Sample records for higher basal level

  1. Elevated basal progesterone levels are associated with increased preovulatory progesterone rise but not with higher pregnancy rates in ICSI cycles with GnRH antagonists.

    PubMed

    Mutlu, Mehmet Firat; Erdem, Mehmet; Mutlu, Ilknur; Bulut, Berk; Erdem, Ahmet

    2017-09-01

    To ascertain the association between basal progesterone (P) levels and the occurrence of preovulatory progesterone rise (PPR) and clinical pregnancy rates (CPRs) in ICSI cycles with GnRH antagonists. Serum P levels of 464 patients were measured on day 2 and day of hCG of cycles. Cycles with basal P levels>1.6ng/mL were cancelled. All embryos were cryopreserved in cycles with P levels≥2ng/mL on the day of hCG. The primary outcome measures were the incidence of PPR (P>1.5ng/mL) and CPR with regard to basal P. Basal P levels were significantly higher in cycles with PPR than in those without PPR (0.63±0.31 vs. 0.48±0.28ng/mL). Area under the curve for basal P according to ROC analysis to discriminate between elevated and normal P levels on the day of hCG was 0.65 (0.58-0.71 95% CI, p<0.01). The cut-off value for basal P levels that best discriminates between cycles with and without PPR was 0.65ng/mL. Cycles with basal P levels above 0.65ng/mL had a significantly higher incidence of PPR (30.9% vs. 13.5%) but similar clinical and cumulative pregnancy rates (38.8% vs. 31.1% and 41.7% vs. 32.6%, respectively) in comparison to cycles with basal P levels below 0.65ng/mL. In multivariate regression analysis, basal P levels, LH level on the first day of antagonist administration, and estradiol levels on the day of hCG trigger were the variables that predicted PPR. Basal P levels were associated with increased incidence of PPR but not with CPR. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Site, gender and age variation in normal skin colour on the back and the forearm: tristimulus colorimeter measurements.

    PubMed

    Fullerton, A; Serup, J

    1997-02-01

    To study whether anatomical location and age and gender of subjects had any influence on the objective skin colour measurements. Baseline colour in prone position was measured with the Minolta ChromaMeter® in the upper, middle and lower level of the upper back and on the forearm of 168 volunteers. These two sites are commonly used in skin testing. Higher basal a* and lower basal L* levels were found on the upper scapular region compared to the lower scapular region and the subscapular region. The basal b* level showed no variation relative to site. The basal a* and the basal b* levels were lower on the forearm compared to the upper back while the basal L* level was higher. Females above 65 years showed a less coloured skin with lower values as compared to those of younger age. Females were found to have a generally lower basal a* level than males both on the upper back and forearm skin. These relatively major differences and sources of variation have to be considered when planning irritancy studies where colour differences between erythema and normal skin is used.

  3. Correlation Between Personality Traits and Testosterone Concentrations in Healthy Population.

    PubMed

    Tajima-Pozo, Kazuhiro; Bayón, Camila; Díaz-Marsá, Marina; Carrasco, Jose Luis

    2015-01-01

    High plasma testosterone levels have been associated with aggression, sexual behaviour and social status. The aim of this paper was to study the correlation between basal plasma testosterone levels and personality variables in healthy participants. Fifty-four participants were randomly enrolled into this study. Basal plasma testosterone levels were measured between 8:30 am and 10 am. After 24 hours of blood drawing, each subject completed personality questionnaires. Positive correlation between basal plasma testosterone levels and anti-social personality traits in both genders was observed (r = 0.336 and P < 0.018). Also, a positive correlation was observed between basal plasmatestosterone levels and criminal thinking traits (r = 0. 376, P < 0.05) and Millon compulsive (r = 0.386, P < 0.010) in both genders. In female participants, a positive correlation between basal plasmatestosterone levels and psychoticism (r = 0. 25, P < 0.019) and Cloninger AUTO TCI (r = 0.507, P < 0.004) was observed. In males participants positive correlation between baseline plasmatic Testosterone levels and Millon Antisocial trait (r = 0. 544, P < 0.19) and Millon Hypomania trait (r = 0. 485, P < 0.41) and Millon Drug Abuse trait (r = 0.632, P < 0.05) was reported. Our results suggest gender differences in clinical and personality variables related with basal plasma testosterone level. In men, high plasma testosterone levels were associated with clinical traits, substance abuse and hypomania. Women with higher basal testosterone levels showed higher scores on personality self-direction traits.

  4. Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease.

    PubMed

    Frejo, Lidia; Gallego-Martinez, Alvaro; Requena, Teresa; Martin-Sanz, Eduardo; Amor-Dorado, Juan Carlos; Soto-Varela, Andres; Santos-Perez, Sofia; Espinosa-Sanchez, Juan Manuel; Batuecas-Caletrio, Angel; Aran, Ismael; Fraile, Jesus; Rossi-Izquierdo, Marcos; Lopez-Escamez, Jose Antonio

    2018-04-13

    Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere's disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.

  5. 50 Hz hippocampal stimulation in refractory epilepsy: Higher level of basal glutamate predicts greater release of glutamate.

    PubMed

    Cavus, Idil; Widi, Gabriel A; Duckrow, Robert B; Zaveri, Hitten; Kennard, Jeremy T; Krystal, John; Spencer, Dennis D

    2016-02-01

    The effect of electrical stimulation on brain glutamate release in humans is unknown. Glutamate is elevated at baseline in the epileptogenic hippocampus of patients with refractory epilepsy, and increases during spontaneous seizures. We examined the effect of 50 Hz stimulation on glutamate release and its relationship to interictal levels in the hippocampus of patients with epilepsy. In addition, we measured basal and stimulated glutamate levels in a subset of these patients where stimulation elicited a seizure. Subjects (n = 10) were patients with medically refractory epilepsy who were undergoing intracranial electroencephalography (EEG) evaluation in an epilepsy monitoring unit. Electrical stimulation (50 Hz) was delivered through implanted hippocampal electrodes (n = 11), and microdialysate samples were collected every 2 min. Basal glutamate, changes in glutamate efflux with stimulation, and the relationships between peak stimulation-associated glutamate concentrations, basal zero-flow levels, and stimulated seizures were examined. Stimulation of epileptic hippocampi in patients with refractory epilepsy caused increases in glutamate efflux (p = 0.005, n = 10), and 4 of ten patients experienced brief stimulated seizures. Stimulation-induced increases in glutamate were not observed during the evoked seizures, but rather were related to the elevation in interictal basal glutamate (R(2) = 0.81, p = 0.001). The evoked-seizure group had lower basal glutamate levels than the no-seizure group (p = 0.04), with no stimulation-induced change in glutamate efflux (p = 0.47, n = 4). Conversely, increased glutamate was observed following stimulation in the no-seizure group (p = 0.005, n = 7). Subjects with an atrophic hippocampus had higher basal glutamate levels (p = 0.03, n = 7) and higher stimulation-induced glutamate efflux. Electrical stimulation of the epileptic hippocampus either increased extracellular glutamate efflux or induced seizures. The magnitude of stimulated glutamate increase was related to elevation in basal interictal glutamate, suggesting a common mechanism, possibly impaired glutamate metabolism. Divergent mechanisms may exist for seizure induction and increased glutamate in patients with epilepsy. These data highlight the potential risk of 50 Hz stimulation in patients with epilepsy. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  6. Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

    PubMed

    Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

    2018-02-14

    The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

    PubMed Central

    Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

    2016-01-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus–pituitary–adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. PMID:26668010

  8. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.

    PubMed

    Lyons, Jonathan J; Yu, Xiaomin; Hughes, Jason D; Le, Quang T; Jamil, Ali; Bai, Yun; Ho, Nancy; Zhao, Ming; Liu, Yihui; O'Connell, Michael P; Trivedi, Neil N; Nelson, Celeste; DiMaggio, Thomas; Jones, Nina; Matthews, Helen; Lewis, Katie L; Oler, Andrew J; Carlson, Ryan J; Arkwright, Peter D; Hong, Celine; Agama, Sherene; Wilson, Todd M; Tucker, Sofie; Zhang, Yu; McElwee, Joshua J; Pao, Maryland; Glover, Sarah C; Rothenberg, Marc E; Hohman, Robert J; Stone, Kelly D; Caughey, George H; Heller, Theo; Metcalfe, Dean D; Biesecker, Leslie G; Schwartz, Lawrence B; Milner, Joshua D

    2016-12-01

    Elevated basal serum tryptase levels are present in 4-6% of the general population, but the cause and relevance of such increases are unknown. Previously, we described subjects with dominantly inherited elevated basal serum tryptase levels associated with multisystem complaints including cutaneous flushing and pruritus, dysautonomia, functional gastrointestinal symptoms, chronic pain, and connective tissue abnormalities, including joint hypermobility. Here we report the identification of germline duplications and triplications in the TPSAB1 gene encoding α-tryptase that segregate with inherited increases in basal serum tryptase levels in 35 families presenting with associated multisystem complaints. Individuals harboring alleles encoding three copies of α-tryptase had higher basal serum levels of tryptase and were more symptomatic than those with alleles encoding two copies, suggesting a gene-dose effect. Further, we found in two additional cohorts (172 individuals) that elevated basal serum tryptase levels were exclusively associated with duplication of α-tryptase-encoding sequence in TPSAB1, and affected individuals reported symptom complexes seen in our initial familial cohort. Thus, our findings link duplications in TPSAB1 with irritable bowel syndrome, cutaneous complaints, connective tissue abnormalities, and dysautonomia.

  9. Three-year efficacy of complex insulin regimens in type 2 diabetes.

    PubMed

    Holman, Rury R; Farmer, Andrew J; Davies, Melanie J; Levy, Jonathan C; Darbyshire, Julie L; Keenan, Joanne F; Paul, Sanjoy K

    2009-10-29

    Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited. In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). [corrected] Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups. Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379.) 2009 Massachusetts Medical Society

  10. Dynamics of Nampt/visfatin and high molecular weight adiponectin in response to oral glucose load in obese and lean women.

    PubMed

    Unlütürk, Uğur; Harmanci, Ayla; Yildiz, Bülent Okan; Bayraktar, Miyase

    2010-04-01

    High molecular weight adiponectin (HMWA) is the active circulating form of adiponectin. Nampt/visfatin is the enzyme secreted from adipocytes in an active form and is one of the putative regulators of insulin secretion. To investigate the dynamics of total adiponectin (TA), HMWA and Nampt/visfatin in obese and lean women during oral glucose tolerance test (OGTT). We studied normal glucose-tolerant (NGT), age-matched, 30 obese and 30 lean women. All subjects underwent a standard 75 g, 2-h OGTT, and area under the curve (AUC) during OGTT for glucose, insulin, Nampt/visfatin, TA and HMWA was calculated. Body fat mass was assessed by bioimpedance analysis. Results Obese women had significantly higher basal and AUC values for insulin and Nampt/visfatin, whereas basal and AUC-HMWA were significantly lower in this group. Alternatively, obese and lean groups had similar basal and AUC values for glucose and TA. Basal insulin levels were negatively correlated with HMWA levels, but not with basal Nampt/visfatin. AUC-insulin was correlated positively with AUC-visfatin, and negatively with AUC-HMWA. Total and truncal body fat mass showed positive correlation with basal and AUC-visfatin, and negative correlation with basal and AUC-HMWA. In the NGT state, obese women have higher Nampt/visfatin and lower HMWA levels, both basally and in response to oral glucose challenge. The dynamics of Nampt/visfatin and HMWA during OGTT appear to be linked with insulin and adiposity. Counter-regulatory adaptations in HMWA and Nampt/visfatin might have an impact on suggested adipoinsular axis, contributing to maintenance of normal glucose tolerance.

  11. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    PubMed

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens.

    PubMed

    Feenstra, M G; Botterblom, M H; Mastenbroek, S

    2000-01-01

    We used on-line microdialysis measurements of dopamine and noradrenaline extracellular concentrations in the medial prefrontal cortex of awake, freely moving rats during the dark and the light period of the day to study whether (i) basal efflux would be higher in the active, dark period than in the inactive, light period; (ii) the activation induced by environmental stimuli would be dependent on these conditions. When determined one day after cannula placement, noradrenaline and dopamine levels were higher during the dark. Maximal relative increases induced by novelty and handling were 150% and 175-200%, respectively, and were very similar in the light and the dark, but the net increases were higher in the dark. Separate groups were tested one week after cannula placement to ensure recovery of possibly disturbed circadian rhythms. While basal levels in the dark were now approximately twice those in the light, the maximal relative and net increases after both novelty and handling were very similar. Basal levels of dopamine in the nucleus accumbens (one day after cannula placement) were not different in the light or dark, but were increased by novelty and handling to about 130% only in the light period, not in the dark. Thus, in the prefrontal cortex, dopamine strongly resembles noradrenaline, in that basal efflux was state dependent, whereas activation by stimuli was not. In the nucleus accumbens, basal dopamine efflux was not state dependent, but activation by stimuli was. These results suggest that there are differential effects of circadian phase on basal activity and responsiveness of the mesolimbic vs the mesocortical dopamine system.

  13. Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone.

    PubMed

    Saggese, G; Cesaretti, G; Franchi, G; Startari, L

    1996-08-01

    Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I, GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which , for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 < p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chronological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and < 0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.

  14. Changes of poststimulatory plasma renin activity in women with hyperthyroidism or hypothyroidism in relation to therapy.

    PubMed

    Marcisz, Czeslaw; Kucharz, Eugene J; Marcisz-Orzel, Magdalena; Poręba, Ryszard; Orzel, Arkadiusz; Sioma-Markowska, Urszula

    2011-01-01

    The influence of thyroid hormones upon renin-angiotensin-aldosterone system is poorly understood. Under basal conditions, individuals belong to normal, low or high plasma renin activity (PRA) subjects. The study was designed to evaluate basal and poststimulatory PRA and serum aldosterone (Aldo) level in patients with hyperthyroidism or hypothyroidism during therapy. We examined 73 women with hyperthyroidism, 27 women with hypothyroidism and 36 healthy controls. The patients were investigated before initiation of therapy and after attainment of euthyroid state. All subjects were investigated under basal conditions (normal-sodium diet) and after application of a low-sodium diet for three days and upright position for 3 hr. PRA, serum Aldo level, blood pressure, serum sodium, potassium and thyroid hormone levels were determined in all subjects. The subjects were classified as low PRA (<1.0 ng/ml/h), normal PRA (1.0-4.0 ng/ml/h) and high PRA (>4.0 ng/ml/h) individuals according to results obtained under basal conditions. Relatively higher poststimulatory enhancement in PRA was found in patients with hyperthyroidism, especially those with low basal PRA, than in those with hypothyroidism. In women with thyroid dysfunctions poststimulatory increase in Aldo were relative lower than poststimulatory enhancement of PRA. After therapy these difference disappeared. The poststimulatory changes in PRA depended on the basal PRA. Poststimulatory PRA is higher in hyperthyroid women, especially those with low basal PRA. In women with hypothyroidism, basal and poststimulatory PRA is low. Blood pressure and severity of thyroid dysfunction was found to be similar in the patients with low, normal or high basic PRA. In women with thyroid dysfunctions, serum Aldo level and its relative poststimulatory increments are inadequate to changes of PRA; it is suggested that the dissociation in the renin-angiotensin-aldosterone system occurs in hyperthyroid and hypothyroid women.

  15. Polyunsaturated fatty acids reduce insulin and very low density lipoprotein levels in broiler chickens.

    PubMed

    Crespo, N; Esteve-Garcia, E

    2003-07-01

    An experiment was conducted to study the effect of different dietary fatty acid profiles on plasma levels of insulin, very low density lipoproteins (VLDL), cholesterol, and glucose. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% and a basal diet without additional fat were administered to female broiler chickens. Serum insulin, cholesterol, and plasma VLDL were affected by the different treatments; however, glucose concentrations were similar among treatments. In the fasted state, broilers fed diets with sunflower or linseed oil presented lower levels of insulin and cholesterol with respect to those fed tallow or olive oil (P < 0.05). VLDL in the fasted state was reduced in broilers fed sunflower and linseed oils (P < 0.05) with respect to those fed tallow, olive oil, or the basal diet. Plasma levels of VLDL were only significantly correlated with abdominal fat in birds fed the basal diet, in the fed and in the fasted state, and in those fed linseed oil in the fed state (P < 0.05). Results of this experiment suggest that higher insulin levels in broilers fed diets rich in saturated fatty acids could be related to higher fat deposition. Fat deposition in birds fed high fat diets was not correlated with circulating VLDL, which suggested direct dietary fat deposition, except for birds fed linseed oil diets. Although birds fed linseed oil diets presented lower levels of VLDL than those fed tallow, olive oil, or the basal diet, the higher correlation with abdominal fat suggests that in these birds, fat deposition is more dependent on hepatic VLDL secretion, despite the high dietary fat level.

  16. Basal testosterone, leadership and dominance: A field study and meta-analysis.

    PubMed

    van der Meij, Leander; Schaveling, Jaap; van Vugt, Mark

    2016-10-01

    This article examines the role of basal testosterone as a potential biological marker of leadership and hierarchy in the workplace. First, we report the result of a study with a sample of male employees from different corporate organizations in the Netherlands (n=125). Results showed that employees with higher basal testosterone levels reported a more authoritarian leadership style, but this relationship was absent among those who currently held a real management position (i.e., they had at least one subordinate). Furthermore, basal testosterone levels were not different between managers and non-managers, and testosterone was not associated with various indicators of status and hierarchy such as number of subordinates, income, and position in the organizational hierarchy. In our meta-analysis (second study), we showed that basal testosterone levels were not associated with leadership in men nor in women (9 studies, n=1103). Taken together, our findings show that basal testosterone is not associated with having a leadership position in the corporate world or related to leadership styles in leaders. We suggest that basal testosterone could play a role in acquiring leadership positions through dominant and authoritarian behavior. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Endocrine Secretory Reserve and Proinsulin Processing in Recipients of Islet of Langerhans Versus Whole Pancreas Transplants

    PubMed Central

    Elkhafif, Nabeel M.; Borot, Sophie; Morel, Philippe; Demuylder-Mischler, Sandrine; Giovannoni, Laurianne; Toso, Christian; Bosco, Domenico; Berney, Thierry

    2013-01-01

    OBJECTIVE β-Cells have demonstrated altered proinsulin processing after islet transplantation. We compare β-cell metabolic responses and proinsulin processing in pancreas and islet transplant recipients with respect to healthy control subjects. RESEARCH DESIGN AND METHODS We studied 15 islet and 32 pancreas transplant recipients. Islet subjects were subdivided into insulin-requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten healthy subjects served as control subjects. Subjects were administered an intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin, intact proinsulin, and proinsulin fragment levels were determined from serum samples. Acute insulin response (AIR) and proinsulin processing rates were calculated. RESULTS We found that basal insulin and C-peptide levels were higher in the pancreas group than in all other groups. II-ISL patients had basal insulin and C-peptide levels similar to healthy control subjects. The IR-ISL group had significantly lower AIRs than all other groups. Basal processing rates were higher in the pancreas and II-ISL groups than in healthy control subjects and the IR-ISL group. After arginine stimulation, all groups had elevated processing rates, with the exception of the IR-ISL group. CONCLUSIONS Our data suggest that II-ISL transplant recipients can maintain basal metabolic parameters similar to healthy control subjects at the cost of a higher rate of proinsulin processing. IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin response and lower basal rates of proinsulin processing even after arginine stimulation. PMID:24041681

  18. Identification and characterization of a gibberellin-regulated protein, which is ASR5, in the basal region of rice leaf sheaths.

    PubMed

    Takasaki, Hironori; Mahmood, Tariq; Matsuoka, Makoto; Matsumoto, Hiroshi; Komatsu, Setsuko

    2008-04-01

    Gibberellins (GAs) regulate growth and development in higher plants. To identify GA-regulated proteins during rice leaf sheath elongation, a proteomic approach was used. Proteins from the basal region of leaf sheath in rice seedling treated with GA(3) were analyzed by fluorescence two-dimensional difference gel electrophoresis. The levels of abscisic acid-stress-ripening-inducible 5 protein (ASR5), elongation factor-1 beta, translationally controlled tumor protein, fructose-bisphosphate aldolase and a novel protein increased; whereas the level of RuBisCO subunit binding-protein decreased by GA(3) treatment. ASR5 out of these six proteins was significantly regulated by GA(3) at the protein level but not at the mRNA level in the basal region of leaf sheaths. Since this protein is regulated not only by abscisic acid but also by GA(3), these results indicate that ASR5 might be involved in plant growth in addition to stress in the basal regions of leaf sheaths.

  19. Comparative endocrinological responses to short transportation of Equidae (Equus asinus and Equus caballus).

    PubMed

    Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Aveni, Francesca; Ferlazzo, Adriana

    2013-03-01

    In order to evaluate the effects of short transportation on β-endorphin, adrenocorticotropic hormone (ACTH) and cortisol changes, 12 healthy stallions of Equidae (Equus asinus and Equus caballus) were studied before and after transportation of 50 km. Blood samples were collected 1 week before transportation in basal conditions, immediately before loading and after transportation and unloading, on their arrival at the breeding station. Compared to basal and before values, donkeys showed an increase in circulating ACTH (P < 0.001) and cortisol (P < 0.0005) levels after transportation and higher ACTH (P < 0.01) levels than horses after transportation. A positive and significant correlation (r = 0.885; P < 0.01) between ACTH and cortisol levels after transportation was found. No significant differences were observed for β-endorphin levels. Compared to basal and before values, horses showed higher cortisol (P < 0.005) levels after transportation and no significant differences were observed for ACTH and β-endorphin levels in donkeys. Horses facing forward (direction of travel) showed higher (P < 0.01) β-endorphin levels after transportation than donkeys; horses facing backward (the opposite direction of travel) showed lower (P < 0.05) ACTH levels after transportation. The results indicate that short transportation induces a preferential activation of the hypothalamus-pituitary-axis (HPA), with significant release of ACTH and cortisol in donkeys and only of cortisol in horses, suggesting that transportation for donkeys may be more stressful than horses. © 2012 The Authors Animal Science Journal © 2012 Japanese Society of Animal Science.

  20. Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

    PubMed

    Demirseren, Duriye Deniz; Cicek, Cagla; Alisik, Murat; Demirseren, Mustafa Erol; Aktaş, Akın; Erel, Ozcan

    2017-09-01

    The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.

  1. Ethanol attracts scolytid beetles to Phytophthora ramorum cankers on coast live oak

    Treesearch

    Rick G. Kelsey; Maia M. Beh; David C. Shaw; Daniel K. Manter

    2013-01-01

    Ethanol in sapwood was analyzed along vertical transects, through small spot cankers and larger basal cankers, of Phytophthora ramorum-infected stems of Quercus agrifolia at three sites in California. Trees with large basal cankers, known to attract scolytid beetles, had a 4.3 times higher ethanol level than trees with spot cankers...

  2. Basal cortisol levels and metabolic syndrome: A systematic review and meta-analysis of observational studies.

    PubMed

    Garcez, Anderson; Leite, Heloísa Marquardt; Weiderpass, Elisabete; Paniz, Vera Maria Vieira; Watte, Guilherme; Canuto, Raquel; Olinto, Maria Teresa Anselmo

    2018-05-17

    To perform a qualitative synthesis (systematic review) and quantitative analysis (meta-analysis) to summarize the evidence regarding the relationship between basal cortisol levels and metabolic syndrome (MetS) in adults. A systematic search was performed in the PubMed, Embase, and PsycINFO databases for observational studies on the association between basal cortisol levels and MetS. The quality of individual studies was assessed by the Newcastle-Ottawa score. A random effects model was used to report pooled quantitative results and the I 2 statistic was used to assess heterogeneity. Egger's and Begg's tests were used to evaluate publication bias. Twenty-six studies (19 cross-sectional and seven case-control) met the inclusion criteria for the systematic review. The majority was classified as having a low risk of bias and used established criteria for the diagnosis of MetS. Twenty-one studies provided data on basal cortisol levels as continuous values and were included in the meta-analysis; they comprised 35 analyses and 11,808 subjects. Pooled results showed no significant difference in basal cortisol levels between subjects with and without MetS (standardized mean difference [SMD] = 0.02, 95% confidence interval [CI]=-0.11 to 0.14). There was high heterogeneity between the studies when all comparisons were considered (I 2  = 83.1%;p < 0.001). Paradoxically, meta-analysis of studies evaluating saliva samples showed no significantly lower basal cortisol levels among subjects with MetS (SMD=-0.18, 95% CI=-0.37 to 0.01), whereas those studies that evaluated serum samples (SMD = 0.11, 95% CI=-0.02 to 0.24) and urine samples (SMD = 0.73, 95% CI=-0.40 to 1.86) showed no significantly higher basal cortisol levels among subjects with MetS. In the subgroup and meta-regression analyses, a significant difference in basal cortisol levels was observed according to study design, population base, age, gender, cortisol level assessment method, and study quality. This systematic review and meta-analysis does not reveal any association between basal cortisol levels and MetS based on results of observational studies. The results of a random-effect meta-analysis showed no significant difference in basal cortisol levels between subjects with and without MetS. The present findings should be considered in order to help future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Children's externalizing and internalizing symptoms over time: the role of individual differences in patterns of RSA responding.

    PubMed

    Hinnant, James Benjamin; El-Sheikh, Mona

    2009-11-01

    We examined associations between basal respiratory sinus arrhythmia (RSA) in conjunction with RSA regulation with the hypothesis that their interaction would explain unique variability in children's prospective adjustment 2 years later. Participants were 176 children (98 girls; 78 boys) in middle childhood. RSA regulation was assessed through social and problem-solving challenges. Parents reported on children's internalizing and externalizing symptoms. Interactions between RSA baseline and regulation to the social stressor predicted children's later internalizing symptoms. Interactions between RSA baseline and responding to the problem-solving stressor predicted children's externalizing symptoms. The highest levels of internalizing symptoms were predicted for children with both lower basal RSA and higher RSA suppression. The highest levels of externalizing symptoms were predicted for children who demonstrated lower basal RSA in conjunction with RSA augmentation. Findings highlight the importance of the contemporaneous consideration of basal RSA and RSA regulation in the prediction of developmental psychopathology symptomology.

  4. The effects of extreme nutritional conditions on the neurochemistry of reward and addiction

    NASA Astrophysics Data System (ADS)

    Pothos, Emmanuel N.

    2001-08-01

    Weight loss is a frequent problem in space flights. We now claim that it may affect performance and drug-seeking behavior by altering midbrain neurochemistry. In food-deprived rats (20-30% underweight) basal extracellular dopamine levels in the nucleus accumbens decrease to 40-50% of normal and locomotion is depressed. However, amphetamine-induced dopamine release and locomotion are higher than in controls (1825% vs. 595% after a 25 μM d-amphetamine intraaccumbens infusion). The lower basal and the higher stimulated dopamine levels suggest that the neurotransmitter accumulates presynaptically in the accumbens of the underweight rats due to subnormal basal release. Psychostimulants are more rewarding for underweight subjects possibly because they release significantly more dopamine from elevated presynaptic stores into the accumbens. Consequently, weight loss can lead both to depression of performance and propensity to substance abuse. These effects should be considered when providing nutritional resources for space flights so that weight loss is limited.

  5. A20 Regulates Atherogenic Interferon (IFN)-γ Signaling in Vascular Cells by Modulating Basal IFNβ Levels*

    PubMed Central

    Moll, Herwig P.; Lee, Andy; Minussi, Darlan C.; da Silva, Cleide G.; Csizmadia, Eva; Bhasin, Manoj; Ferran, Christiane

    2014-01-01

    IFNγ signaling in endothelial (EC) and smooth muscle cells (SMC) is a key culprit of pathologic vascular remodeling. The impact of NF-κB inhibitory protein A20 on IFNγ signaling in vascular cells remains unknown. In gain- and loss-of-function studies, A20 inversely regulated expression of IFNγ-induced atherogenic genes in human EC and SMC by modulating STAT1 transcription. In vivo, inadequate A20 expression in A20 heterozygote mice aggravated intimal hyperplasia following partial carotid artery ligation. This outcome uniquely associated with increased levels of Stat1 and super-induction of Ifnγ-dependent genes. Transcriptome analysis of the aortic media from A20 heterozygote versus wild-type mice revealed increased basal Ifnβ signaling as the likely cause for higher Stat1 transcription. We confirmed higher basal IFNβ levels in A20-silenced human SMC and showed that neutralization or knockdown of IFNβ abrogates heightened STAT1 levels in these cells. Upstream of IFNβ, A20-silenced EC and SMC demonstrated higher levels of phosphorylated/activated TANK-binding kinase-1 (TBK1), a regulator of IFNβ transcription. This suggested that A20 knockdown increased STAT1 transcription by enhancing TBK1 activation and subsequently basal IFNβ levels. Altogether, these results uncover A20 as a key physiologic regulator of atherogenic IFNγ/STAT1 signaling. This novel function of A20 added to its ability to inhibit nuclear factor-κB (NF-κB) activation solidifies its promise as an ideal therapeutic candidate for treatment and prevention of vascular diseases. In light of recently discovered A20/TNFAIP3 (TNFα-induced protein 3) single nucleotide polymorphisms that impart lower A20 expression or function, these results also qualify A20 as a reliable clinical biomarker for vascular risk assessment. PMID:25217635

  6. Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients

    PubMed Central

    Kim, Sung-Tae; Kim, Byung-Joon; Song, In-Geol; Jung, Jang-Han; Lee, Kang-Woo; Park, Keun-Young; Cho, Youn-Zoo; Lee, Dae-Ho; Koh, Gwan-Pyo

    2011-01-01

    Background Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Methods Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. Results A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). Conclusion Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease. PMID:21537412

  7. Development of insulin resistance and endothelin-1 levels in the Zucker fatty rat.

    PubMed

    Berthiaume, Nathalie; Mika, Amanda K; Zinker, Bradley A

    2003-07-01

    In order to determine the effects of increasing insulin resistance on endothelin-1 (ET-1) levels, Zucker lean and fatty rats were studied at basal and during a complete nutrient meal tolerance test (MTT) at 7, 12, and 15 weeks of age. The fatty rats were mildly hyperglycemic, severely hyperinsulinemic and glucose-intolerant at all ages versus lean animals and this progressed with age within groups, as previously published. Basal ET-1 levels, at 7 weeks, were significantly increased in fatty versus lean rats (3.2+/-0.5 v 2.0+/-0.3 pg/mL, respectively; P<.05); however, we did not observe any significant basal difference at 12 or 15 weeks. At 7 weeks, ET-1 levels between fatty and lean rats were not different during the MTT (15 minutes: 2.9+/-0.4 v 2.7+/-0.7; 120 minutes: 6.5+/-0.8 v 6.6+/-0.5 pg/mL, fatty v lean, respectively). At 12 weeks, though there was no difference in basal levels, fatty rats had higher ET-1 levels during the MTT compared to lean animals (15 minutes: 6.9+/-1.4 v 1.8+/-0.4; 120 minutes: 9.4+/-1.7 v 3.2+/-0.5 pg/mL, respectively; P<.01). At 15 weeks, ET-1 levels during the MTT receded to levels similar to those observed at 7 weeks, which were significantly higher in fatty versus lean rats 15 minutes following the challenge (3.4+/-0.4 v 2.4+/-0.2 pg/mL, respectively; P<.05). In conclusion, ET-1 levels in the Zucker fatty rat: (1) were increased in the early stages of the progression of insulin resistance at 7 weeks, but were unchanged under basal conditions with age thereafter, and (2) were increased under nutrient challenge conditions with advanced insulin resistance up to 12 weeks, and were still significantly but to a lesser degree increased at 15 weeks of age. The explanation for these results and their relationship to the observed insulin resistance is unclear and will require further investigation.

  8. Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults

    PubMed Central

    Verstynen, Timothy D.; Lynch, Brighid; Miller, Destiny L.; Voss, Michelle W.; Prakash, Ruchika Shaurya; Chaddock, Laura; Basak, Chandramallika; Szabo, Amanda; Olson, Erin A.; Wojcicki, Thomas R.; Fanning, Jason; Gothe, Neha P.; McAuley, Edward; Kramer, Arthur F.; Erickson, Kirk I.

    2012-01-01

    The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum. PMID:22900181

  9. Plasma catecholamine levels before and after paroxetine treatment in patients with panic disorder.

    PubMed

    Oh, Jae-Young; Yu, Bum-Hee; Heo, Jung-Yoon; Yoo, Ikki; Song, Hyemin; Jeon, Hong Jin

    2015-02-28

    Catecholamines such as norepinephrine, epinephrine, and dopamine are closely related to the autonomic nervous system, suggesting that panic disorder may involve elevated catecholamine levels. This study investigated basal and posttreatment catecholamine levels in patients with panic disorder. A total of 29 patients with panic disorder and 23 healthy controls participated in the study. Panic disorder patients received paroxetine treatment for 12 weeks after clinical tests and examination had been conducted. We investigated the difference in basal levels of catecholamine and measured the changes in catecholamine levels before and after drug treatment in panic disorder patients. The basal plasma epinephrine (48.87±6.18 pg/ml) and dopamine (34.87±3.57 pg/ml) levels of panic disorder patients were significantly higher than those (34.79±4.72 pg/ml and 20.40±3.53 pg/ml) of the control group. However, basal plasma norepinephrine levels did not show statistically significant differences between patients and controls. After drug therapy, plasma catecholamine levels were nonsignificantly decreased and norepinephrine levels showed a tendency toward a decrease that did not reach significance. In conclusion, this study suggests the possibility of a baseline increase of plasma catecholamine levels and activation of sympathetic nervous systems in patients with panic disorder which may normalize after treatment with paroxetine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Fortune favours the bold: a higher predator reduces the impact of a native but not an invasive intermediate predator.

    PubMed

    Barrios-O'Neill, Daniel; Dick, Jaimie T A; Emmerson, Mark C; Ricciardi, Anthony; MacIsaac, Hugh J; Alexander, Mhairi E; Bovy, Helene C

    2014-05-01

    Emergent multiple predator effects (MPEs) might radically alter predictions of predatory impact that are based solely on the impact of individuals. In the context of biological invasions, determining if and how the individual-level impacts of invasive predators relates to their impacts in multiple-individual situations will inform understanding of how such impacts might propagate through recipient communities. Here, we use functional responses (the relationship between prey consumption rate and prey density) to compare the impacts of the invasive freshwater mysid crustacean Hemimysis anomala with a native counterpart Mysis salemaai when feeding on basal cladoceran prey (i) as individuals, (ii) in conspecific groups and (iii) in conspecific groups in the presence of a higher fish predator, Gasterosteus aculeatus. In the absence of the higher predator, the invader consumed significantly more basal prey than the native, and consumption was additive for both mysid species - that is, group consumption was predictable from individual-level consumption. Invaders and natives were themselves equally susceptible to predation when feeding with the higher fish predator, but an MPE occurred only between the natives and higher predator, where consumption of basal prey was significantly reduced. In contrast, consumption by the invaders and higher predator remained additive. The presence of a higher predator serves to exacerbate the existing difference in individual-level consumption between invasive and native mysids. We attribute the mechanism responsible for the MPE associated with the native to a trait-mediated indirect interaction, and further suggest that the relative indifference to predator threat on the part of the invader contributes to its success and impacts within invaded communities. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  11. Ecological Importance of Small-Diameter Trees to the Structure, Diversity and Biomass of a Tropical Evergreen Forest at Rabi, Gabon.

    PubMed

    Memiaghe, Hervé R; Lutz, James A; Korte, Lisa; Alonso, Alfonso; Kenfack, David

    2016-01-01

    Tropical forests have long been recognized for their biodiversity and ecosystem services. Despite their importance, tropical forests, and particularly those of central Africa, remain understudied. Until recently, most forest inventories in Central Africa have focused on trees ≥10 cm in diameter, even though several studies have shown that small-diameter tree population may be important to demographic rates and nutrient cycling. To determine the ecological importance of small-diameter trees in central African forests, we used data from a 25-ha permanent plot that we established in the rainforest of Gabon to study the diversity and dynamics of these forests. Within the plot, we censused 175,830 trees ≥1 cm dbh from 54 families, 192 genera, and 345 species. Average tree density was 7,026 trees/ha, basal area 31.64 m2/ha, and above-ground biomass 369.40 Mg/ha. Fabaceae, Ebenaceae and Euphorbiaceae were the most important families by basal area, density and above-ground biomass. Small-diameter trees (1 cm ≥ dbh <10 cm) comprised 93.7% of the total tree population, 16.5% of basal area, and 4.8% of the above-ground biomass. They also had diversity 18% higher at family level, 34% higher at genus level, and 42% higher at species level than trees ≥10 cm dbh. Although the relative contribution of small-diameter trees to biomass was comparable to other forests globally, their contribution to forest density, and diversity was disproportionately higher. The high levels of diversity within small-diameter classes may give these forests high levels of structural resilience to anthropogenic/natural disturbance and a changing climate.

  12. Ecological Importance of Small-Diameter Trees to the Structure, Diversity and Biomass of a Tropical Evergreen Forest at Rabi, Gabon

    PubMed Central

    Memiaghe, Hervé R.; Lutz, James A.; Korte, Lisa; Alonso, Alfonso; Kenfack, David

    2016-01-01

    Tropical forests have long been recognized for their biodiversity and ecosystem services. Despite their importance, tropical forests, and particularly those of central Africa, remain understudied. Until recently, most forest inventories in Central Africa have focused on trees ≥10 cm in diameter, even though several studies have shown that small-diameter tree population may be important to demographic rates and nutrient cycling. To determine the ecological importance of small-diameter trees in central African forests, we used data from a 25-ha permanent plot that we established in the rainforest of Gabon to study the diversity and dynamics of these forests. Within the plot, we censused 175,830 trees ≥1 cm dbh from 54 families, 192 genera, and 345 species. Average tree density was 7,026 trees/ha, basal area 31.64 m2/ha, and above-ground biomass 369.40 Mg/ha. Fabaceae, Ebenaceae and Euphorbiaceae were the most important families by basal area, density and above-ground biomass. Small-diameter trees (1 cm ≥ dbh <10 cm) comprised 93.7% of the total tree population, 16.5% of basal area, and 4.8% of the above-ground biomass. They also had diversity 18% higher at family level, 34% higher at genus level, and 42% higher at species level than trees ≥10 cm dbh. Although the relative contribution of small-diameter trees to biomass was comparable to other forests globally, their contribution to forest density, and diversity was disproportionately higher. The high levels of diversity within small-diameter classes may give these forests high levels of structural resilience to anthropogenic/natural disturbance and a changing climate. PMID:27186658

  13. Genetic differences in NMDA and D1 receptor levels, and operant responding for food and morphine in Lewis and Fischer 344 rats.

    PubMed

    Martín, Sonsoles; Lyupina, Yulia; Crespo, José Antonio; González, Begoña; García-Lecumberri, Carmen; Ambrosio, Emilio

    2003-05-30

    Previously, we have shown that Lewis (LEW) rats acquire faster than Fischer 344 (F344) rats operant food- and morphine-reinforced tasks under fixed-ratio schedules of reinforcement. The first purpose of the present work has been to study if differences in operant responding behavior may participate in the reported differences in morphine self-administration behavior between both inbred rat strains. To this end, we have analyzed the microstructure of responding obtained under a variable-interval (VI) of food reinforcement by calculating the inter-response time (IRT) for each rat strain. LEW rats exhibited shorter IRTs than F344 rats, suggesting that LEW rats may have an inherent high or compulsive operant responding activity. When subjects of both inbred rat strains were submitted to a schedule of morphine reinforcement of high responding requirements such as progressive ratio schedules, LEW rats also reached significantly higher breaking points and final response ratio than F344 rats for i.v. morphine self-administration. Given that there are neurochemical differences between both rat strains and that glutamatergic N-methyl-D-aspartate (NMDA) and dopaminergic D(1) receptors have been involved in operant responding behavior, a second purpose of this work has been to measure basal NMDA and D(1) receptor levels in these rat strains by quantitative receptor autoradiography. Compared to F344 rats, LEW rats showed higher basal NMDA receptor levels in frontal and cingulate cortex, caudate putamen, central amygdaloid nuclei, and intermediate white layer of superior colliculus, and higher basal D(1) receptor levels in several areas of hippocampus and thalamus, and substantia nigra pars reticulata. Taken together, these results suggest that an inherent high operant responding activity of LEW rats may have a role in the previous reported faster acquisition of opiate-reinforced behavior in operant self-administration paradigms under fixed-ratio schedules of reinforcement. In addition, a basal higher NMDA and D(1) receptor levels of LEW rats compared to F344 rats may participate in the neurochemical background that mediates the behavioral differences between both inbred rat strains.

  14. Total and free iodothyronine changes in response to transport of Equidae (Equus asinus and Equus caballus).

    PubMed

    Fazio, Esterina; Medica, Pietro; Cravana, Cristina; Ferlazzo, Adriana

    2017-03-31

    In this study the effects of short distance road transport on total and free iodothyronine changes in 12 stallions (Equus asinus and Equus caballus) were evaluated. Donkeys (n = 6) and horses (n = 6) were transported for a distance of 50 km. Blood samples were collected 1 week before transport in basal conditions, 1 week later immediately before loading, and after transport and unloading. After transport, donkeys showed significant increases in circulating T4 (P≤0.01), fT3 (P≤0.001), and fT4 (P≤0.01) levels; while horses had significant increases in circulating T3, fT3 and fT4 (P≤0.01) levels. Compared to donkeys' values, horses showed lower T4 values in basal condition, before and after transport (P≤0.001); higher fT3 values in basal condition and before (P≤0.001), and lower values (P≤0.001) after transport; higher fT4 values (P≤0.001) in basal condition. The results indicate that short road transport of donkeys and horses induces the activation of the thyroid gland, with the same release of fT3 and fT4 iodothyronines, but with different preferential release of T3 in horses and T4 in donkeys after transport.

  15. The effect of an adverse psychological environment on salivary cortisol levels in the elderly differs by 5-HTTLPR genotype.

    PubMed

    Ancelin, Marie-Laure; Scali, Jacqueline; Norton, Joanna; Ritchie, Karen; Dupuy, Anne-Marie; Chaudieu, Isabelle; Ryan, Joanne

    2017-12-01

    An adverse psychological environment (e.g. stressful events or depression) has been shown to influence basal cortisol levels and cortisol response to stress. This differs depending on the adverse stimuli, but also varies across individuals and may be influenced by genetic predisposition. An insertion/deletion polymorphism in the serotonin transporter gene ( 5-HTTLPR ) is a strong candidate in this regard. To investigate how stressful life events and depression are associated with diurnal cortisol levels in community-dwelling elderly and determine whether this varies according to genetic variability in the 5-HTTLPR . This population-based study included 334 subjects aged 65 and older (mean (SD) = 76.5 (6.3)). Diurnal cortisol was measured on two separate days, under quiet (basal) and stressful conditions. The number of recent major stressful events experienced during the past year was assessed from a 12-item validated questionnaire as an index of cumulative recent stressful events. Lifetime trauma was evaluated using the validated Watson's PTSD inventory, which evaluates the most severe traumatic or frightening experience according to DSM criteria. Depression was defined as having a Mini-International Neuropsychiatric Interview (MINI) diagnosis of current major depressive disorder or high levels of depressive symptoms (Center for Epidemiologic Studies-Depression Scale ≥16). 5-HTTLPR genotyping was performed on blood samples. Exposure to stressful life events was associated with lower basal evening cortisol levels overall, and in the participants with the 5-HTTLPR L allele but not the SS genotype. The greatest effects (over 50% decrease, p < 0.001) were observed for the LL participants having experienced multiple recent stressful events or severe lifetime traumas. Participants with the L allele also had higher evening cortisol stress response. Conversely, depression tended to be associated with a 42% higher basal morning cortisol in the SS participants specifically, but did not modify the association between stressful events and cortisol levels. An adverse psychological environment is associated with basal cortisol levels and cortisol stress response, but this differs according to 5-HTTLPR genotype.

  16. Cyclic estrogenic fluctuation influences synaptic transmission of the medial vestibular nuclei in female rats.

    PubMed

    Pettorossi, Vito E; Frondaroli, Adele; Grassi, Silvarosa

    2011-04-01

    The estrous cycle in female rats influences the basal synaptic responsiveness and plasticity of the medial vestibular nucleus (MVN) neurons through different levels of circulating 17β-estradiol (cE(2)). The aim of this study was to verify, in the female rat, whether cyclic fluctuations of cE(2) influence long-term synaptic effects induced by high frequency afferent stimulation (HFS) in the MVN, since we found that HFS in the male rat induces fast long-term potentiation (fLTP), which depends on the neural synthesis of E(2) (nE(2)) from testosterone (T). We analyzed the field potential (FP) evoked in the MVN by vestibular afferent stimulation, under basal conditions, and after HFS, in brainstem slices of female rats during high levels (proestrus, PE) and low levels (diestrus, DE) of cE(2). Selective blocking agents of converting T enzymes were used. Unlike in the male rat, HFS induced three effects: fLTP through T conversion into E(2), and slow LTP (sLTP) and long-term depression (LTD), through T conversion into DHT. The occurrence of these effects depended on the estrous cycle phase: the frequency of fLTP was higher in DE, and those of sLTP and LTD were higher in PE. Conversely, the basal FP was also higher in PE than in DE.

  17. Sex differences in salivary cortisol in response to acute stressors among healthy participants, in recreational or pathological gamblers, and in those with posttraumatic stress disorder.

    PubMed

    Paris, Jason J; Franco, Christine; Sodano, Ruthlyn; Freidenberg, Brian; Gordis, Elana; Anderson, Drew A; Forsyth, John P; Wulfert, Edelgard; Frye, Cheryl A

    2010-01-01

    Sex differences in incidence and severity of some stress-related, neuropsychiatric disorders are often reported to favor men, suggesting that women may be more vulnerable to aberrant hypothalamic-pituitary-adrenal (HPA) axis responses to stress. In this review, we discuss several investigations that we, and others, have conducted assessing salivary cortisol as a measure of HPA function. We have examined basal cortisol among healthy men and women and also following acute exposure to stressors. Among healthy participants, men had higher basal cortisol levels than did women. In response to acute stressors, such as carbon dioxide or noise, respectively, cortisol levels were comparable between men and women or higher among women. We have also examined cortisol levels among those with problem eating, gambling, or posttraumatic stress disorder (PTSD). Women with restrained eating habits have higher basal cortisol levels than do women without restrained eating habits. Pathological gamblers have more aberrant stress response to gambling stimuli than do recreational gamblers, and these effects are more prominent among men than women. Men who have motor vehicle accident related PTSD, demonstrate more aberrant cortisol function, than do their female counterparts. Although these sex differences in cortisol seem to vary with type of stress exposure and/or pathophysiological status of the individual, other hormones may influence cortisol response. To address this, cortisol levels among boys and girls with different stress-related experiences, will be the subject of future investigation. 2009 Elsevier Inc. All rights reserved.

  18. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter

    PubMed Central

    de Godoy, Márcio A. F.; Rattan, Neeru; Rattan, Satish

    2009-01-01

    Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1−/− and COX-2−/− mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 ± 3.4% (mean ± SE) by SC-560 (1 × 10−5 M) and 5.4 ± 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 ± 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 ± 0.015 mN/mg) in the IAS from COX-1−/− mice (P < 0.05, n = 5). However, basal tone in COX-2−/− mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone. PMID:19056763

  19. COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

    PubMed

    de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

    2009-02-01

    Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P < 0.05, n = 5). Basal tone was 0.172 +/- 0.021 mN//mg in the IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P < 0.05, n = 5). However, basal tone in COX-2(-/-) mice was not significantly different from that in wild-type mice. We conclude that COX-1-related products contribute significantly to IAS tone.

  20. Microbial biomass and basal respiration in Sub-Antarctic and Antarctic soils in the areas of some Russian polar stations

    NASA Astrophysics Data System (ADS)

    Abakumov, E.; Mukhametova, N.

    2014-03-01

    Antarctica is the unique place for pedological investigations. Soils of Antarctica have been studied intensively during the last century. Antarctic logistic provides the possibility to scientists access the terrestrial landscapes mainly in the places of polar stations. That is why the main and most detailed pedological investigations were conducted in Mc Murdo Valleys, Transantarctic Mountains, South Shetland Islands, Larsemann hills and Schirmacher Oasis. Investigations were conducted during the 53rd and 55th Russian Antarctic expeditions on the base of soil pits and samples collected in Sub-Antarctic and Antarctic regions. Soils of diverse Antarctic landscapes were studied with aim to assess the microbial biomass level, basal respiration rates and metabolic activity of microbial communities. The investigation conducted shows that soils of Antarctic are quite different in profile organization and carbon content. In general, Sub-Antarctic soils are characterized by more developed humus (sod) organo-mineral horizons as well as the upper organic layer. The most developed organic layers were revealed in peat soils of King-George Island, where its thickness reach even 80 cm. These soils as well as soils under guano are characterized by the highest amount of total organic carbon (TOC) 7.22-33.70%. Coastal and continental soils of Antarctic are presented by less developed Leptosols, Gleysols, Regolith and rare Ornhitosol with TOC levels about 0.37-4.67%. The metabolic ratios and basal respiration were higher in Sub-Antarctic soils than in Antarctic ones which can be interpreted as result of higher amounts of fresh organic remnants in organic and organo-mineral horizons. Also the soils of King-George island have higher portion of microbial biomass (max 1.54 mg g-1) than coastal (max 0.26 mg g-1) and continental (max 0.22 mg g-1) Antarctic soils. Sub-Antarctic soils mainly differ from Antarctic ones in increased organic layers thickness and total organic carbon content, higher microbial biomass carbon content, basal respiration and metabolic activity levels.

  1. On the Origin of Tremor in Parkinson’s Disease

    PubMed Central

    Dovzhenok, Andrey; Rubchinsky, Leonid L.

    2012-01-01

    The exact origin of tremor in Parkinson’s disease remains unknown. We explain why the existing data converge on the basal ganglia-thalamo-cortical loop as a tremor generator and consider a conductance-based model of subthalamo-pallidal circuits embedded into a simplified representation of the basal ganglia-thalamo-cortical circuit to investigate the dynamics of this loop. We show how variation of the strength of dopamine-modulated connections in the basal ganglia-thalamo-cortical loop (representing the decreasing dopamine level in Parkinson’s disease) leads to the occurrence of tremor-like burst firing. These tremor-like oscillations are suppressed when the connections are modulated back to represent a higher dopamine level (as it would be the case in dopaminergic therapy), as well as when the basal ganglia-thalamo-cortical loop is broken (as would be the case for ablative anti-parkinsonian surgeries). Thus, the proposed model provides an explanation for the basal ganglia-thalamo-cortical loop mechanism of tremor generation. The strengthening of the loop leads to tremor oscillations, while the weakening or disconnection of the loop suppresses them. The loop origin of parkinsonian tremor also suggests that new tremor-suppression therapies may have anatomical targets in different cortical and subcortical areas as long as they are within the basal ganglia-thalamo-cortical loop. PMID:22848541

  2. Intracochlear Position of Cochlear Implants Determined Using CT Scanning versus Fitting Levels: Higher Threshold Levels at Basal Turn.

    PubMed

    van der Beek, Feddo B; Briaire, Jeroen J; van der Marel, Kim S; Verbist, Berit M; Frijns, Johan H M

    2016-01-01

    In this study, the effects of the intracochlear position of cochlear implants on the clinical fitting levels were analyzed. A total of 130 adult subjects who used a CII/HiRes 90K cochlear implant with a HiFocus 1/1J electrode were included in the study. The insertion angle and the distance to the modiolus of each electrode contact were determined using high-resolution CT scanning. The threshold levels (T-levels) and maximum comfort levels (M-levels) at 1 year of follow-up were determined. The degree of speech perception of the subjects was evaluated during routine clinical follow-up. The depths of insertion of all the electrode contacts were determined. The distance to the modiolus was significantly smaller at the basal and apical cochlear parts compared with that at the middle of the cochlea (p < 0.05). The T-levels increased toward the basal end of the cochlea (3.4 dB). Additionally, the M-levels, which were fitted in our clinic using a standard profile, also increased toward the basal end, although with a lower amplitude (1.3 dB). Accordingly, the dynamic range decreased toward the basal end (2.1 dB). No correlation was found between the distance to the modiolus and the T-level or the M-level. Furthermore, the correlation between the insertion depth and stimulation levels was not affected by the duration of deafness, age at implantation or the time since implantation. Additionally, the T-levels showed a significant correlation with the speech perception scores (p < 0.05). The stimulation levels of the cochlear implants were affected by the intracochlear position of the electrode contacts, which were determined using postoperative CT scanning. Interestingly, these levels depended on the insertion depth, whereas the distance to the modiolus did not affect the stimulation levels. The T-levels increased toward the basal end of the cochlea. The level profiles were independent of the overall stimulation levels and were not affected by the biographical data of the patients, such as the duration of deafness, age at implantation or time since implantation. Further research is required to elucidate how fitting using level profiles with an increase toward the basal end of the cochlea benefits speech perception. Future investigations may elucidate an explanation for the effects of the intracochlear electrode position on the stimulation levels and might facilitate future improvements in electrode design. © 2016 S. Karger AG, Basel.

  3. Growth Performance, Mineral Digestibility, and Blood Characteristics of Ostriches Receiving Drinking Water Supplemented with Varying Levels of Chelated Trace Mineral Complex.

    PubMed

    Seyfori, Hossein; Ghasemi, Hossein Ali; Hajkhodadadi, Iman; Nazaran, Mohammad Hassan; Hafizi, Maryam

    2018-05-01

    The effects of water supplementation of chelated trace minerals (CTM, which is named Bonzaplex designed with chelate compounds technology) on growth performance, apparent total tract digestibility (ATTD) of minerals, and some blood metabolites, TM, and antioxidant enzyme values in African ostriches were investigated from 8 to 12 months of age. A total of 20 8-month-old ostriches (five birds in five replicate pens) was randomly allocated into one of the following four treatments: (1) control (basal diet + tap water), (2) low CTM (basal diet +100 mg/bird/day CTM powder in tap water), (3) medium CTM (basal diet +1 g/bird/day CTM powder in tap water), and (4) high CTM (basal diet +2 g/bird/day CTM powder in tap water). Compared with control, medium CTM improved (P < 0.05) daily weight gain and ATTD of phosphorous, zinc, and copper in 12-month-old ostriches. Furthermore, the feed conversion ratio was lower, and ATTD of magnesium was higher in the medium- and high-CTM groups than that in the control group (P < 0.05). At the end of the trial, ostriches receiving high-CTM treatment exhibited the lower (P < 0.05) serum triglyceride and very low-density lipoprotein cholesterol concentrations and higher copper levels compared to those of the control treatment. Supplementation of higher amounts of CTM (medium and high CTM) also increased the activity of serum superoxide dismutase (P < 0.05). No differences were detected for other blood parameters including glucose, total protein, albumin, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, iron, magnesium, and glutathione peroxidase values. In conclusion, supplementation of CTM at the level of 1 g/bird/day to the drinking water can be recommended for improving growth performance, mineral absorption, and antioxidant status of ostriches fed diets containing the recommended levels of inorganic TM.

  4. Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers.

    PubMed

    Chichilichi, Biswal; Mohanty, G P; Mishra, S K; Pradhan, C R; Behura, N C; Das, A; Behera, K

    2015-09-01

    The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38(th) day of age. At 42(nd) day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers.

  5. Effect of partial supplementation of sun-dried Azolla as a protein source on the immunity and antioxidant status of commercial broilers

    PubMed Central

    Chichilichi, Biswal; Mohanty, G. P.; Mishra, S. K.; Pradhan, C. R.; Behura, N. C.; Das, A.; Behera, K.

    2015-01-01

    Aim: The present study was conducted to evaluate the effect of partial supplementation of sun-dried Azolla as a protein source on the immunity of commercial broilers in coastal Odisha. Materials and Methods: A 180 day-old broiler chicks were distributed in six dietary treatments viz. C1: Basal diet, C2: Basal diet + enzyme, T1: Basal diet +5% protein from Azolla, T2: Basal diet + 5% protein from Azolla + enzyme, T3: Basal diet +10% protein from Azolla, and T4: Basal diet + 10% protein from Azolla + enzyme. Cutaneous basophilc hypersensitivity (CBH) and humoral immunity response were determined at the 38th day of age. At 42nd day, the weight of lymphoid organs, an antioxidant enzyme, and lipid peroxidation activity were determined. Results: The CBH response did not differ significantly among the treated groups, but the sheep red blood cells response was significantly higher in T4. The weight of lymphoid organs or immune organs of all the treated groups did not differ significantly (p>0.05). The erythrocyte catalase level of T4 group was found to be significantly higher than rest of the treated groups except T3. Conclusion: It may be concluded that supplementation of Azolla at 10% of dietary protein requirement along with enzyme supplementation in an isonitrogenous diet showed a better immune response in broilers. PMID:27047208

  6. Neonatal Procedural Pain and Preterm Infant Cortisol Response to Novelty at 8 Months

    PubMed Central

    Weinberg, Joanne; Whitfield, Michael F.

    2005-01-01

    Objectives. Stress systems may be altered in the long term in preterm infants for multiple reasons, including early exposure to procedural pain in neonatal intensive care. This question has received little attention beyond hospital discharge. Stress responses (cortisol) to visual novelty in preterm infants who were born at extremely low gestational age (ELGA; ≤28 weeks), very low gestational age (VLGA; 29–32 weeks), and term were compared at 8 months of age corrected for prematurity (corrected chronological age [CCA]). In addition, among the preterm infants, we evaluated whether cortisol levels at 8 months were related to neonatal exposure to procedural pain and morphine in the neonatal intensive care unit. Methods. Seventy-six infants, 54 preterm (≤32 weeks' GA at birth) and 22 term-born infants who were seen at 8 months CCA composed the study sample, after excluding those with major sensory, motor, or cognitive impairment. Salivary cortisol was measured before (basal) and 20 minutes after introduction of novel toys (post 1) and after developmental assessment (post 2). Results. Salivary cortisol was significantly higher in ELGA infants at 8 months, compared with the VLGA and term groups before and after introduction of visual novelty. Term-born and VLGA infants showed a slight decrease in cortisol when playing with novel toys, whereas the ELGA group showed higher basal and sustained levels of cortisol. After controlling for early illness severity and duration of supplemental oxygen, higher basal cortisol levels in preterm infants at 8 months' CCA were associated with higher number of neonatal skin-breaking procedures. In contrast, cortisol responses to novelty were predicted equally well by neonatal pain or GA at birth. No relationship between morphine dosing and cortisol response was demonstrated in these infants. Conclusions. ELGA preterm infants show a different pattern of cortisol levels before and after positive stimulation of visual novelty than more maturely born, VLGA preterm and term-born infants. Exposure to high numbers of skin-breaking procedures may contribute to “resetting” basal arousal systems in preterm infants. PMID:15231977

  7. Increased R2* in the caudate nucleus of asymptomatic welders

    PubMed Central

    Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Li, Yunqing; Lewis, Mechelle M.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Fry, Rebecca C.; Snyder, Amanda M.; Connor, James R.; Yang, Qing X.; Mailman, Richard B.; Huang, Xuemei

    2017-01-01

    Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neuro-toxicity. Although welding-related airborne Fe levels are about ten-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose-response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain MRI were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole blood Fe levels compared to controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole blood Fe concentration. The present study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance. PMID:27871916

  8. Increased R2* in the Caudate Nucleus of Asymptomatic Welders

    PubMed Central

    Lee, Eun-Young; Flynn, Michael R.; Du, Guangwei; Li, Yunqing; Lewis, Mechelle M.; Herring, Amy H.; Van Buren, Eric; Van Buren, Scott; Kong, Lan; Fry, Rebecca C.; Snyder, Amanda M.; Connor, James R.; Yang, Qing X.; Mailman, Richard B.; Huang, Xuemei

    2016-01-01

    Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose–response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance. PMID:26769335

  9. The Human Airway Epithelial Basal Cell Transcriptome

    PubMed Central

    Wang, Rui; Zwick, Rachel K.; Ferris, Barbara; Witover, Bradley; Salit, Jacqueline; Crystal, Ronald G.

    2011-01-01

    Background The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. Methodology/Principal Findings Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the “human airway basal cell signature” as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. Conclusion/Significance The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium. PMID:21572528

  10. The In Vitro Influence of a Genetic Superoxide-Hydrogen Peroxide Imbalance on Immunosenescence.

    PubMed

    Barbisan, Fernanda; Azzolin, Verônica Farina; Ribeiro, Euler Esteves; Duarte, Marta Maria Medeiros Frescura; da Cruz, Ivana Beatrice Mânica

    2017-08-01

    As superoxide is a key molecule of inflammatory activation, superoxide-hydrogen peroxide (S-HP) imbalance genetically caused could alter immunosenescence patterns. To test this hypothesis, we collected and cultured peripheral blood mononuclear cells (PBMCs) carrier's different genotypes of a genetic polymorphism located in the superoxide dismutase manganese-dependent gene (Val16Ala-SOD2). We used an in vitro genetic model based on previous studies, which suggested an association between homozygous genotypes (AA and VV) and alterations in oxidative-inflammatory mediators. PBMCs collected from young healthy volunteers were cultured in the presence of phytohemagglutinin, as well as the following cell culture passages obtained from the 72-hour initial culture. Each follow passage started with the same cell concentration (1 × 10 5 cells). The general immunosenescence pattern was observed independent of SOD2 genotypes: cellular proliferation until the 15th passage, when cellular arrestment occurred in the G0/G1 phase. From the 10th passage, a higher proliferative state was observed, indicating inflammatory hyperactivation, with an increase in the levels of inflammatory cytokines (IL-1, IL-6, and TNFα), nitric oxide, superoxide, lipoperoxidation, protein carbonylation, reactive oxygen species, and DNA damage. The S-HP imbalance affected the intensity of some immunosenescence parameters. AA cells, which present basal high HP levels, were associated with higher DNA damage and lipoperoxidation levels, whereas VV, which present basal high S levels, was associated with higher proinflammatory cytokine levels. In summary, the results suggested that a basal S-HP imbalance could affect the intensity of some immunosenescence markers, and this influence could explain the potential association between an imbalance of genotypes (AA and VV) and the risk of developing some chronic diseases.

  11. Sex-reversed correlation between stress levels and dominance rank in a captive non-breeder flock of crows.

    PubMed

    Ode, Minami; Asaba, Akari; Miyazawa, Eri; Mogi, Kazutaka; Kikusui, Takefumi; Izawa, Ei-Ichi

    2015-07-01

    Group living has both benefits and costs to individuals; benefits include efficient acquisition of resources, and costs include stress from social conflicts among group members. Such social challenges result in hierarchical dominance ranking among group members as a solution to avoid escalating conflict that causes different levels of basal stress between individuals at different ranks. Stress-associated glucocorticoid (corticosterone in rodents and birds; CORT) levels are known to correlate with dominance rank in diverse taxa and to covary with various social factors, such as sex and dominance maintenance styles. Although there is much evidence for sex differences in the basal levels of CORT in various species, the correlation of sex differences in basal CORT with dominance rank is poorly understood. We investigated the correlation between CORT metabolites (CM) in the droppings and social factors, including rank and sex, in a captive non-breeder group of crows. In this group, all the single males dominated all the single females, and dominance ranks were stable among single males but relatively unstable among single females. CM levels and rank were significantly correlated in a sex-reversed fashion: males at higher rank (i.e., more dominant) had higher CM, whereas females at higher rank exhibited lower CM. This is the first evidence of sex-reversed patterns of CM-rank correlation in birds. The results suggest that different mechanisms of stress-dominance relationships operate on the sexes in non-breeder crow aggregations; in males, stress is associated with the cost of aggressive displays, whereas females experience subordination stress due to males' overt aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Structural and compositional controls on transpiration in 40- and 450-year-old riparian forests in western Oregon, USA.

    PubMed

    Moore, Georgianne W; Bond, Barbara J; Jones, Julia A; Phillips, Nathan; Meinzer, Federick C

    2004-05-01

    Large areas of forests in the Pacific Northwest are being transformed to younger forests, yet little is known about the impact this may have on hydrological cycles. Previous work suggests that old trees use less water per unit leaf area or sapwood area than young mature trees of the same species in similar environments. Do old forests, therefore, use less water than young mature forests in similar environments, or are there other structural or compositional components in the forests that compensate for tree-level differences? We investigated the impacts of tree age, species composition and sapwood basal area on stand-level transpiration in adjacent watersheds at the H.J. Andrews Forest in the western Cascades of Oregon, one containing a young, mature (about 40 years since disturbance) conifer forest and the other an old growth (about 450 years since disturbance) forest. Sap flow measurements were used to evaluate the degree to which differences in age and species composition affect water use. Stand sapwood basal area was evaluated based on a vegetation survey for species, basal area and sapwood basal area in the riparian area of two watersheds. A simple scaling exercise derived from estimated differences in water use as a result of differences in age, species composition and stand sapwood area was used to estimate transpiration from late June through October within the entire riparian area of these watersheds. Transpiration was higher in the young stand because of greater sap flux density (sap flow per unit sapwood area) by age class and species, and greater total stand sapwood area. During the measurement period, mean daily sap flux density was 2.30 times higher in young compared with old Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) trees. Sap flux density was 1.41 times higher in young red alder (Alnus rubra Bong.) compared with young P. menziesii trees, and was 1.45 times higher in old P. menziesii compared with old western hemlock (Tsuga heterophylla (Raf.) Sarg.) trees. Overall, sapwood basal area was 21% higher in the young stand than in the old stand. In the old forest, T. heterophylla is an important co-dominant, accounting for 58% of total sapwood basal area, whereas P. menziesii is the only dominant conifer in the young stand. Angiosperms accounted for 36% of total sapwood basal area in the young stand, but only 7% in the old stand. For all factors combined, we estimated 3.27 times more water use by vegetation in the riparian area of the young stand over the measurement period. Tree age had the greatest effect on stand differences in water use, followed by differences in sapwood basal area, and finally species composition. The large differences in transpiration provide further evidence that forest management alters site water balance via elevated transpiration in vigorous young stands.

  13. A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

    PubMed

    Petznick, Andrea; Evans, Margaret D M; Madigan, Michele C; Markoulli, Maria; Garrett, Qian; Sweeney, Deborah F

    2011-02-01

    To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  14. Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

    PubMed

    Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

    2000-03-01

    Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

  15. Sea-level response to melting of Antarctic ice shelves on multi-centennial timescales with the fast Elementary Thermomechanical Ice Sheet model (f.ETISh v1.0)

    NASA Astrophysics Data System (ADS)

    Pattyn, Frank

    2017-08-01

    The magnitude of the Antarctic ice sheet's contribution to global sea-level rise is dominated by the potential of its marine sectors to become unstable and collapse as a response to ocean (and atmospheric) forcing. This paper presents Antarctic sea-level response to sudden atmospheric and oceanic forcings on multi-centennial timescales with the newly developed fast Elementary Thermomechanical Ice Sheet (f.ETISh) model. The f.ETISh model is a vertically integrated hybrid ice sheet-ice shelf model with vertically integrated thermomechanical coupling, making the model two-dimensional. Its marine boundary is represented by two different flux conditions, coherent with power-law basal sliding and Coulomb basal friction. The model has been compared to existing benchmarks. Modelled Antarctic ice sheet response to forcing is dominated by sub-ice shelf melt and the sensitivity is highly dependent on basal conditions at the grounding line. Coulomb friction in the grounding-line transition zone leads to significantly higher mass loss in both West and East Antarctica on centennial timescales, leading to 1.5 m sea-level rise after 500 years for a limited melt scenario of 10 m a-1 under freely floating ice shelves, up to 6 m for a 50 m a-1 scenario. The higher sensitivity is attributed to higher ice fluxes at the grounding line due to vanishing effective pressure. Removing the ice shelves altogether results in a disintegration of the West Antarctic ice sheet and (partially) marine basins in East Antarctica. After 500 years, this leads to a 5 m and a 16 m sea-level rise for the power-law basal sliding and Coulomb friction conditions at the grounding line, respectively. The latter value agrees with simulations by DeConto and Pollard (2016) over a similar period (but with different forcing and including processes of hydrofracturing and cliff failure). The chosen parametrizations make model results largely independent of spatial resolution so that f.ETISh can potentially be integrated in large-scale Earth system models.

  16. Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study

    PubMed Central

    Petersson, Maria; Uvnäs-Moberg, Kerstin; Nilsson, Anne; Gustafson, Lise-Lotte; Hydbring-Sandberg, Eva; Handlin, Linda

    2017-01-01

    We have previously shown that dog–owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog–owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0–3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog’s positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: Rs = -0.683, p = 0.042; oxytocin maximum: Rs = -0.783, p = 0.013). The lower the dogs’ oxytocin levels during the interaction, the more stroking they received (Rs = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs’ cortisol levels became (15 min: Rs = 0.661, p = 0.038). The higher the owners’ maximum oxytocin level the fewer position changes the dogs made (Rs = -0.817, p = 0.007) and the shorter time they spent sitting (Rs = -0.786, p = 0.036), whereas the higher the owners’ basal cortisol levels, the longer time the dogs spent standing (0 min: Rs = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in their owners, are associated with the way the owners interact with their dogs and also with behaviors caused by the interaction. PMID:29081760

  17. Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study.

    PubMed

    Petersson, Maria; Uvnäs-Moberg, Kerstin; Nilsson, Anne; Gustafson, Lise-Lotte; Hydbring-Sandberg, Eva; Handlin, Linda

    2017-01-01

    We have previously shown that dog-owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog-owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0-3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog's positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: R s = -0.683, p = 0.042; oxytocin maximum: R s = -0.783, p = 0.013). The lower the dogs' oxytocin levels during the interaction, the more stroking they received ( R s = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs' cortisol levels became (15 min: R s = 0.661, p = 0.038). The higher the owners' maximum oxytocin level the fewer position changes the dogs made ( R s = -0.817, p = 0.007) and the shorter time they spent sitting ( R s = -0.786, p = 0.036), whereas the higher the owners' basal cortisol levels, the longer time the dogs spent standing (0 min: R s = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in their owners, are associated with the way the owners interact with their dogs and also with behaviors caused by the interaction.

  18. Effect of acute swim stress on plasma corticosterone and brain monoamine levels in bidirectionally selected DxH recombinant inbred mouse strains differing in fear recall and extinction.

    PubMed

    Browne, Caroline A; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F; Yilmazer-Hanke, Deniz

    2014-12-01

    Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites 3,4-dihydroxyphenyacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 min after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or post-traumatic stress disorder.

  19. Effect of Acute Swim Stress on Plasma Corticosterone and Brain Monoamine Levels in Bidirectionally Selected DxH Recombinant Inbred Mouse Strains Differing in Fear Recall and Extinction

    PubMed Central

    Browne, Caroline A.; Hanke, Joachim; Rose, Claudia; Walsh, Irene; Foley, Tara; Clarke, Gerard; Schwegler, Herbert; Cryan, John F.; Yilmazer-Hanke, Deniz

    2015-01-01

    Stress-induced changes in plasma corticosterone and central monoamine levels were examined in mouse strains that differ in fear-related behaviors. Two DxH recombinant inbred mouse strains with a DBA/2J background, which were originally bred for a high (H-FSS) and low fear-sensitized acoustic startle reflex (L-FSS), were used. Levels of noradrenaline, dopamine, and serotonin and their metabolites (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were studied in the amygdala, hippocampus, medial prefrontal cortex, striatum, hypothalamus, and brainstem. H-FSS mice exhibited increased fear levels and a deficit in fear extinction (within-session) in the auditory fear-conditioning test, and depressive-like behavior in the acute forced swim stress test. They had higher tissue noradrenaline and serotonin levels and lower dopamine and serotonin turnover under basal conditions, although they were largely insensitive to stress-induced changes in neurotransmitter metabolism. In contrast, acute swim stress increased monoamine levels but decreased turnover in the less fearful L-FSS mice. L-FSS mice also showed a trend toward higher basal and stress-induced corticosterone levels and an increase in noradrenaline and serotonin in the hypothalamus and brainstem 30 minutes after stress compared to H-FSS mice. Moreover, the dopaminergic system was activated differentially in the medial prefrontal cortex and striatum of the two strains by acute stress. Thus, H-FSS mice showed increased basal noradrenaline tissue levels compatible with a fear phenotype or chronic stressed condition. Low corticosterone levels and the poor monoamine response to stress in H-FSS mice may point to mechanisms similar to those found in principal fear disorders or posttraumatic stress disorder. PMID:25117886

  20. Metabolic syndrome in children and adolescents with phenylketonuria.

    PubMed

    Kanufre, Viviane C; Soares, Rosângelis D L; Alves, Michelle Rosa A; Aguiar, Marcos J B; Starling, Ana Lúcia P; Norton, Rocksane C

    2015-01-01

    This study aimed to identify markers of metabolic syndrome (MS) in patients with phenylketonuria (PKU). This was a cross-sectional study consisting of 58 PKU patients (ages of 4-15 years): 29 patients with excess weight, and 29 with normal weight. The biochemical variables assessed were phenylalanine (phe), total cholesterol, HDL-c, triglycerides, glucose, and basal insulin. The patients had Homeostasis Model Assessment (HOMA) and waist circumference assessed. No inter-group difference was found for phe. Overweight patients had higher levels of triglycerides, basal insulin, and HOMA, but lower concentrations of HDL-cholesterol, when compared to the eutrophic patients. Total cholesterol/HDL-c was significantly higher in the overweight group. A positive correlation between basal insulin level and HOMA with waist circumference was found only in the overweight group. The results of this study suggest that patients with PKU and excess weight are potentially vulnerable to the development of metabolic syndrome. Therefore, it is necessary to conduct clinical and laboratory monitoring, aiming to prevent metabolic changes, as well as excessive weight gain and its consequences, particularly cardiovascular risk. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  1. Survey of Basal Stem Rot Disease on Oil Palms (Elaeis guineensis Jacq.) in Kebun Bukit Kijang,North Sumatera, Indonesia

    NASA Astrophysics Data System (ADS)

    Lisnawita; Hanum, H.; Tantawi, A. R.

    2016-08-01

    Basal stem rot disease caused by Ganoderma sp. is a significant disease on oil palm plantations in Indonesia, especially in North Sumatera. Currently, the pathogen does not only attack the plants that have produced (old plants) but also attacks the plants that have not produced in the first generation yet. A survey of the distribution of the basal stem rot disease in the plantation of the community has been completed in order to illustrate the distribution and the incidence of the basal stem rot disease in 5 locations of the oil palm plantation of the community in Desa Bukit Kijang, Region of Asahan, North Sumatera, Indonesia. From the research, it is revealed that the basal stem rot disease has spread to all of the observed locations with the level of disease incidence between 0.71% in Kebun Bukit Kijang 3 to 50% in the 17 years old oil palm in Kebun Bukit Kijang 4 and Bukit Kijang 5. The observable symptoms of the basal stem rot disease are chlorotic leaves, the appearance of fruiting body, collapsed plants, and the existence of holes on the basal stem. The incidence of basal stem rot disease is higher on land due to a high sand content (>50%).

  2. Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus).

    PubMed

    Agnvall, Beatrix; Katajamaa, Rebecca; Altimiras, Jordi; Jensen, Per

    2015-09-01

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication. © 2015 The Author(s).

  3. Cost-effectiveness analysis of IDegLira versus basal-bolus insulin for patients with type 2 diabetes in the Slovak health system

    PubMed Central

    Psota, Marek; Psenkova, Maria Bucek; Racekova, Natalia; Ramirez de Arellano, Antonio; Vandebrouck, Tom; Hunt, Barnaby

    2017-01-01

    Aims To investigate the cost-effectiveness of once-daily insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy in patients with type 2 diabetes not meeting glycemic targets on basal insulin from a healthcare payer perspective in Slovakia. Methods Long-term clinical and economic outcomes for patients receiving IDegLira and basal-bolus therapy were estimated using the IMS CORE Diabetes Model based on a published pooled analysis of patient-level data. Results IDegLira was associated with an improvement in quality-adjusted life expectancy of 0.29 quality-adjusted life years (QALYs) compared with basal-bolus therapy. The average lifetime cost per patient in the IDegLira arm was EUR 2,449 higher than in the basal-bolus therapy arm. Increased treatment costs with IDegLira were partially offset by cost savings from avoided diabetes-related complications. IDegLira was highly cost-effective versus basal-bolus therapy with an incremental cost-effectiveness ratio of EUR 8,590 per QALY gained, which is well below the cost-effectiveness threshold set by the law in Slovakia. Conclusion IDegLira is cost-effective in Slovakia, providing a simple option for intensification of basal insulin therapy without increasing the risk of hypoglycemia or weight gain and with fewer daily injections than a basal-bolus regimen. PMID:29276398

  4. Pregnancy - identifying fertile days

    MedlinePlus

    ... mean ovulation is near. TAKING YOUR BASAL BODY TEMPERATURE After you ovulate, your body temperature will rise and stay at a higher level ... can use a special thermometer to take your temperature in the morning before you get out of ...

  5. Importance of serum basal tryptase levels in children with insect venom allergy.

    PubMed

    Yavuz, S T; Sackesen, C; Sahiner, U M; Buyuktiryaki, B; Arik Yilmaz, E; Sekerel, B E; Soyer, O U; Tuncer, A

    2013-03-01

    The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 μg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 μg/l (2.5-4.0)] and healthy control subjects [2.9 μg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 μg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  6. Regulatory peptides in the plasma of patients with chronic cardiac failure at rest and during exercise.

    PubMed

    Nicholls, D P; Riley, M; Elborn, J S; Stanford, C F; Shaw, C; McKillop, J M; Buchanan, K D

    1992-10-01

    The levels of several regulatory peptides were measured in peripheral plasma samples from individuals with chronic cardiac failure (CCF) and matched controls in both the resting state and during a short period of maximal exercise. Basal levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P < 0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all raised in the patients with CCF, and increased further with exercise. Basal circulating levels of atrial natriuretic peptide (ANP) were also significantly higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P < 0.01), but the response to exercise was attenuated, so that at peak exercise, no significant difference was observed. Basal circulating levels of gastrin-releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13 +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group when compared to controls and there was no significant change in the levels of either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY) and neurotensin (NT) were somewhat higher in patients, but the differences were not significant, and there were no changes during exercise. There were also no significant differences in the levels of vasoactive intestinal peptide (VIP), glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either experimental group both before and during exercise. We have therefore identified different circulating levels of certain regulatory peptides in patients with CCF, but the significance of these remains unclear.

  7. Interaction between different sports branches such as taekwondo, box, athletes and serum brain derived neurotrophic factor levels.

    PubMed

    Oztasyonar, Yunus

    2017-04-01

    This study aimed to compare serum brain-derived neurotrophic factor (BDNF) levels "which contributes in both neuron development/regeneration" between combat sport braches, which requires high attention and concentration and can lead micro and macro brain trauma, and athleticism, which requires durability in competition. The study design included 4 groups. Group 1 had sedentary participants, and group 2 athletes (middle and long runners) who exercised for two 2-hour daily training sessions 6 days a week. group 3 included boxers, and group 4 taekwondo fighters. We investigated changes in the blood BDNF levels of taekwondo fighters, boxers, and athletes before and after training and compared them among each other and with measurements of sedentary controls. All athletes had higher basal BDNF levels than sedentary participants. Boxers and taekwondo athletes had especially high basal BDNF levels. When we compared different sports branch each other Pre- and post- training BDNF values are ranked as follows: taekwondo > boxing > athletes > sedentary. In sport branches such as combat sports and athletes, serum BDNF levels have been demonstrated to be higher after training than before. In addition, serum BDNF levels were higher in taekwondo fighters and boxers than athletes. BDNF might have a role in the protection mechanism against brain damage or contributes in occurrence and maintenance of high attention and concentration especially among combat sports.

  8. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

    PubMed

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß

    PubMed Central

    Hurtado-Guerrero, Isaac; Pinto-Medel, Maria Jesús; Urbaneja, Patricia; Rodriguez- Bada, Jose Luis; León, Antonio; Guerrero, Miguel; Fernández, Óscar

    2017-01-01

    Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness. PMID:28103257

  10. Fasting glucose and postprandial glycemia: which is the best target for improving outcomes? The Apollo and 4-T Trials.

    PubMed

    Monnier, Louis; Colette, Claude

    2008-11-01

    Two studies, the Apollo and 4-T Trials, were conducted in order to determine which insulin regimen (basal or prandial) is the most efficient for the treatment of insulin-requiring type 2 diabetic patients. Both trials compared treatments using prandial insulins (aspart or lispro) three times daily with more classical insulin strategies using basal insulin given once daily (glargine or detemir) or twice daily if required (detemir in the 4-T Study). Both studies showed that a therapeutic regimen involving prandial insulin resulted in equal (Apollo Study) or greater (4-T Study) reductions in patients' HbA(1c) levels than basal insulin regimens. However, the prandial insulin strategies were accompanied by higher risks of hypoglycemia and greater weight gain. As a consequence, the investigators of the two studies concluded that basal insulin once daily provides a simple and effective option with less adverse effects than prandial insulin three times a day. Such conclusions are certainly important for guiding strategies in the vast majority of type 2 diabetic patients who require an add-on insulin therapy. However, the authors' opinion is that the choice between either basal or prandial insulin alone and combined insulin regimens with basal and prandial insulin should be tailored according to the patient's clinical status by paying more attention to the respective contributions of basal and prandial hyperglycemia to their overall hyperglycemia. This recommendation seems to be particularly important when insulin treatment is initiated in patients exhibiting HbA(1c) levels between 7.0 and 8.0%.

  11. Sex differences in the phagocytic and migratory activity of microglia and their impairment by palmitic acid.

    PubMed

    Yanguas-Casás, Natalia; Crespo-Castrillo, Andrea; de Ceballos, Maria L; Chowen, Julie A; Azcoitia, Iñigo; Arevalo, Maria Angeles; Garcia-Segura, Luis M

    2018-03-01

    Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade. In this study, we have determined the effect of palmitic acid in the inflammatory profile, motility, and phagocytosis of primary male and female microglia, both in basal conditions and in the presence of a pro-inflammatory stimulus (interferon-γ). Male microglia in vitro showed higher migration than female microglia under basal and stimulated conditions. In contrast, female microglia had higher basal and stimulated phagocytic activity than male microglia. Palmitic acid did not affect basal migration or phagocytosis, but abolished the migration and phagocytic activity of male and female microglia in response to interferon-γ. These findings extend previous observations of sex differences in microglia and suggest that palmitic acid impairs the protective responses of these cells. © 2017 Wiley Periodicals, Inc.

  12. p53 and PCNA Expression in Keratocystic Odontogenic Tumors Compared with Selected Odontogenic Cysts

    PubMed Central

    Seyedmajidi, Maryam; Nafarzadeh, Shima; Siadati, Sepideh; Shafaee, Shahryar; Bijani, Ali; Keshmiri, Nazanin

    2013-01-01

    p53 and PCNA expression in keratocystic odontogenic tumors compared with selected odontogenic cysts Summary: The aim of this study was to evaluate p53 and PCNA expression in different odontogenic lesions regarding their different clinical behaviors. Slices prepared from 94 paraffin-embedded tissue blocks (25 radicular cysts (RC), 23 dentigerous cysts (DC), 23 keratocystic odontogenic tumors (KCOT) and 23 calcifying cystic odontogenic tumors (CCOT)) were stained with p53 and PCNA antibodies using immunohistochemistry procedure. The highest level of p53 expression was in the basal layer of RC, and the highest level of PCNA expression was in the suprabasal layer of KCOT. The differences of p53 expression in basal and suprabasal layers as well as PCNA expression in the suprabasal layer were significant but there was no significant difference in PCNA expression in the basal layer of these lesions. The expression of p53 in the basal layer of RC was higher than in other cysts. This may be due to intensive inflammatory infiltration. Also, the high level of PCNA expression in the suprabasal layer of KCOT may justify its neoplastic nature and tendency to recurrence. KCOT and calcifying cystic odontogenic tumors did not show similar expression of studied biomarkers. PMID:24551811

  13. Light Effects on Behavioural Performance Depend on the Individual State of Vigilance

    PubMed Central

    Barba, Antonio; Padilla, Francisca

    2016-01-01

    Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task—SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants’ behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance. PMID:27820822

  14. Light Effects on Behavioural Performance Depend on the Individual State of Vigilance.

    PubMed

    Correa, Ángel; Barba, Antonio; Padilla, Francisca

    2016-01-01

    Research has shown that exposure to bright white light or blue-enriched light enhances alertness, but this effect is not consistently observed in tasks demanding high-level cognition (e.g., Sustained Attention to Response Task-SART, which measures inhibitory control). Individual differences in sensitivity to light effects might be mediated by variations in the basal level of arousal. We tested this hypothesis by measuring the participants' behavioural state of vigilance before light exposure, through the Psychomotor Vigilance Task. Then we compared the effects of a blue-enriched vs. dim light at nighttime on the performance of the auditory SART, by controlling for individual differences in basal arousal. The results replicated the alerting effects of blue-enriched light, as indexed by lower values of both proximal temperature and distal-proximal gradient. The main finding was that lighting effects on SART performance were highly variable across individuals and depended on their prior state of vigilance. Specifically, participants with higher levels of basal vigilance before light exposure benefited most from blue-enriched lighting, responding faster in the SART. These results highlight the importance of considering basal vigilance to define the boundary conditions of light effects on cognitive performance. Our study adds to current research delineating the complex and reciprocal interactions between lighting effects, arousal, cognitive task demands and behavioural performance.

  15. Optimal cutoff value of basal anti-mullerian hormone in iranian infertile women for prediction of ovarian hyper-stimulation syndrome and poor response to stimulation.

    PubMed

    Aghssa, Malek Mansour; Tarafdari, Azam Manshadi; Tehraninejad, Ensieh Shahrokh; Ezzati, Mohammad; Bagheri, Maryam; Panahi, Zahra; Mahdavi, Saeed; Abbasi, Mehrshad

    2015-09-10

    We intended to establish the threshold of Anti-Mullerian Hormone (AMH) for detection of Ovarian Hyper-Stimulation Syndrome (OHSS) and poor response to treatment in Iranian infertile women. Pre-stimulation menstrual cycle day-3 hormonal indices including basal AMH values were measured in 105 infertile women aged 32.5 ± 4.3 years. Patients underwent long GnRH agonist Controlled Ovarian Hyperstimulation (COH) in a referral infertility center (Tehran, Iran). The gonadotropin dose was determined based on the age and basal serum Follicular Stimulating Hormone (FSH) level. The IVF/ICSI cycles were followed and the clinical and sonographic data were recorded. Sixteen cases developed OHSS. The prevalence of PCOS was higher in subjects with OHSS [62.5 % (38.8-86.2) vs. 17 % (9.2-24.9)]. The patients with OHSS had higher ovarian follicular count [23.7 (3.2) vs. 9.1 (0.5); p < 0.05], collected oocytes [13.5 (1.9) vs. 6.9 (0.5); p < 0.05] and AMH level [7.9 (0.7) vs. 3.6 (0.3); p < 0.05]. Basal AMH level and oocyte yields (but not age, BMI, and PCOS) correlated with occurrence of OHSS; and only the AMH levels were associated with poor ovarian response (oocytes yield ≤ 4). The optimal cutoff value for the prediction of OHSS was 6.95 ng/ml (area under the receiver operating characteristics curve: 0.86; CI: 0.78-0.95; sensitivity: 75 %; specificity: 84 %; odds ratio for occurrence of OHSS: 9 and p < 0.001). The optimal cut point to discriminate poor response (oocytes ≤4) was 1.65 ng/ml ( AUC : 0.8; CI: 0.69-0.91; sensitivity: 89 % specificity : 71 %; and OR = 23.8 and P value <0.001). Iranian women with basal AMH level > 6.95 ng/ml are at high risk of developing OHSS and those with AMH level < 1.65 ng/ml are poor responders.

  16. Ice shelf basal melt rates around Antarctica from simulations and observations

    NASA Astrophysics Data System (ADS)

    Schodlok, M. P.; Menemenlis, D.; Rignot, E. J.

    2016-02-01

    We introduce an explicit representation of Antarctic ice shelf cavities in the Estimating the Circulation and Climate of the Ocean, Phase II (ECCO2) ocean retrospective analysis; and compare resulting basal melt rates and patterns to independent estimates from satellite observations. Two simulations are carried out: the first is based on the original ECCO2 vertical discretization; the second has higher vertical resolution particularly at the depth range of ice shelf cavities. The original ECCO2 vertical discretization produces higher than observed melt rates and leads to a misrepresentation of Southern Ocean water mass properties and transports. In general, thicker levels at the base of the ice shelves lead to increased melting because of their larger heat capacity. This strengthens horizontal gradients and circulation within and outside the cavities and, in turn, warm water transports from the shelf break to the ice shelves. The simulation with more vertical levels produces basal melt rates (1735 ± 164 Gt/a) and patterns that are in better agreement with observations. Thinner levels in the sub-ice-shelf cavities improve the representation of a fresh/cold layer at the ice shelf base and of warm/salty water near the bottom, leading to a sharper pycnocline and reduced vertical mixing underneath the ice shelf. Improved water column properties lead to more accurate melt rates and patterns, especially for melt/freeze patterns under large cold-water ice shelves. At the 18 km grid spacing of the ECCO2 model configuration, the smaller, warm-water ice shelves cannot be properly represented, with higher than observed melt rates in both simulations.

  17. Parental history of depression and higher basal salivary cortisol in unaffected child and adolescent offspring.

    PubMed

    Zhang, Jihui; Lam, Siu Ping; Li, Shirley Xin; Liu, Yaping; Chan, Joey Wing Yan; Chan, Michael Ho Ming; Ho, Chung Shun; Li, Albert Martin; Wing, Yun Kwok

    2018-07-01

    There are contradictory findings regarding the associations of parental depression on the hypothalamic-pituitary-adrenal axis activity of their offspring. We aimed to explore the associations of parental depression on the diurnal salivary cortisol profile in their child and adolescent offspring. A total of 189 unaffected child and adolescent offspring as determined by structured clinical interview were divided into 3 groups according to their parental history of depression, namely current parental depression (CPD, n = 27), past parental depression (PPD, n = 57), and no parental depression (NPD, n = 105). Diurnal saliva samples were collected to measure the cortisol awakening response and diurnal cortisol profile. CPD group had significantly higher basal cortisol level (mean ± SE = 11.9 ± 0.80 nmol/dl) than PPD group (mean ± SE = 9.7 ± 0.73 nmol/dl, post hoc p = .024) and NPD group (mean ± SE = 10.2 ± 0.52 nmol/dl, post hoc p = .031) and lower cortisol level at noon, but comparable cortisol levels in other time points. The cortisol awakening response reference to increase (AUCi) were significantly blunted in CPD group when compared with PPD and NPD (post hoc p < .01). Adjustment for potential confounding factors did not change major findings. Further analyses revealed that main influences were derived from current maternal depression. A single day of saliva sample. Current but not past (lifetime) parental depression is associated with higher basal salivary cortisol and blunted cortisol awakening response in their children and adolescents. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L.

    PubMed

    Lee, You-Jeong; Kim, Chung-Hoon; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2014-11-01

    To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.

  19. Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L

    PubMed Central

    Lee, You-Jeong; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2014-01-01

    Objective To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. Methods This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). Results The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). Conclusion TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH. PMID:25469340

  20. Preliminary characterization of IL32 in basal-like/triple negative compared to other types of breast cell lines and tissues

    PubMed Central

    2014-01-01

    Background Triple negative breast cancer (TNBC) and often basal-like cancers are defined as negative for estrogen receptor, progesterone receptor and Her2 gene expression. Over the past few years an incredible amount of data has been generated defining the molecular characteristics of both cancers. The aim of these studies is to better understand the cancers and identify genes and molecular pathways that might be useful as targeted therapies. In an attempt to contribute to the understanding of basal-like/TNBC, we examined the Gene Expression Omnibus (GEO) public datasets in search of genes that might define basal-like/TNBC. The Il32 gene was identified as a candidate. Findings Analysis of several GEO datasets showed differential expression of IL32 in patient samples previously designated as basal and/or TNBC compared to normal and luminal breast samples. As validation of the GEO results, RNA and protein expression levels were examined using MCF7 and MDA MB231 cell lines and tissue microarrays (TMAs). IL32 gene expression levels were higher in MDA MB231 compared to MCF7. Analysis of TMAs showed 42% of TNBC tissues and 25% of the non-TNBC were positive for IL32, while non-malignant patient samples and all but one hyperplastic tissue sample demonstrated lower levels of IL32 protein expression. Conclusion Data obtained from several publically available GEO datasets showed overexpression of IL32 gene in basal-like/TNBC samples compared to normal and luminal samples. In support of these data, analysis of TMA clinical samples demonstrated a particular pattern of IL32 differential expression. Considered together, these data suggest IL32 is a candidate suitable for further study. PMID:25100201

  1. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter.

    PubMed

    Rattan, Satish; Singh, Jagmohan

    2012-04-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10(-8) to 10(-4) M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC(20) in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC(20), before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

  2. RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

    PubMed Central

    Singh, Jagmohan

    2012-01-01

    The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8 to 10−4 M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20 in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment. PMID:22241857

  3. Selenium-enriched Saccharomyces cerevisiae improves growth, antioxidant status and selenoprotein gene expression in Arbor Acres broilers.

    PubMed

    Chen, F; Zhu, L; Qiu, H; Qin, S

    2017-04-01

    One hundred and fifty 7-day-old Arbor Acres broilers were randomly assigned into five groups: group 1 served as a control that was fed a basal diet without selenium (Se) supplementation; groups 2, 3 and 4 were fed the basal diet supplemented with 0.15, 0.5 and 1.5 mg Se as Se-enriched Saccharomyces cerevisiae (SSC) per kg of diet; and group 5 was fed the basal diet supplemented with 0.15 mg per kg of Se as sodium selenite (SS). Growth performance, glutathione peroxidase (GP X ) and superoxide dismutase (SOD) activities, total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content in plasma and liver, and cellular glutathione peroxidase (GP X -1) and phospholipid hydroperoxide glutathione peroxidase (GP X -4) mRNA levels in liver were determined. Compared with group 1, groups 2-4 exhibited higher body weights (p < 0.05), lower feed/gain ratios, and higher GP X activities in plasma (p < 0.05) and GP X and SOD activities and GP X -1 and GP X -4 mRNA levels in liver (p < 0.05). Compared with group 5, group 2 exhibited higher GP X activity in plasma on day 21 (p < 0.05). Compared with group 2 and 5, group 3 exhibited lower MDA content in plasma on day 7 (p < 0.05), higher GP X activity in plasma, SOD activity and GP X -1 mRNA levels in liver on day 14 and 21 (p < 0.05), and higher GP X -4 mRNA levels on day 14 (p < 0.05). Compared with group 4, group 3 exhibited lower MDA contents in plasma on day 14 (p < 0.05) and in liver on day 21 (p < 0.05), higher T-AOC in plasma and higher GP X -1 mRNA levels on day 14 and 21 (p < 0.05), and higher SOD activity in plasma and higher SOD and GP X activities in liver on day 21 (p < 0.05). Thus, SSC improves growth and antioxidant status of broilers; the short-term bioavailability of SS was faster than that of SSC, but the long-term bioavailability of SSC was greater than SS. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  4. Elevated basal intestinal mucosal cytokine levels in asymptomatic first-degree relatives of patients with Crohn’s disease

    PubMed Central

    Indaram, Anant VK; Nandi, Santa; Weissman, Sam; Lam, Sing; Bailey, Beverly; Blumstein, Meyer; Greenberg, Ronald; Bank, Simmy

    2000-01-01

    AIM: To determine levels of cytokines in colonic mucosa of asymptomatic first degree relatives of Crohn’s disease patients. METHODS: Cytokines (Interleukin (IL) 1-Beta, IL-2, IL-6 and IL-8) were measured using ELISA in biopsy samples of normal looking colonic mucosa of first degree relatives of Crohn’s disease patients (n = 9) and fro m normal controls (n = 10) with no family history of Crohn’s disease. RESULTS: Asymptomatic first degree relatives of patients with Crohn’s disease had significantly higher levels of basal intestinal mucosal cytokines (IL-2, IL-6 and IL-8) than normal controls. Whether these increase d cytokine levels serve as phenotypic markers for a genetic predisposition to de veloping Crohn’s disease later on, or whether they indicate early (pre-cli nical) damage has yet to be further defined. CONCLUSION: Asymptomatic first degree relatives of Crohn’s disease patients have higher levels of cytokines in their normal-looking intestinal mucosa compared to normal controls. This supports the hypothesis that increased cytokines may be a cause or an early event in the inflammatory cascade of Crohn’s disease and are not merely a result of the inflammatory process. PMID:11819521

  5. Insulin secretion at high altitude in man

    NASA Astrophysics Data System (ADS)

    Sawhney, R. C.; Malhotra, A. S.; Singh, T.; Rai, R. M.; Sinha, K. C.

    1986-09-01

    The effect of hypoxia on circulatory levels of insulin, its response to oral glucose administration (100 g) and changes in circadian rhythms of glucose as well as insulin were evaluated in euglycemic males at sea level (SL, 220 m) during their stay at high altitude (3500 m, SJ) and in high altitude natives (HAN). Basal glucose levels were not altered at high altitude but the rise in glucose (δ glucose) after glucose load was significantly higher in SJ and HAN (p<0.01) as compared to SL values. An increase (p<0.01) both in basal as well as glucose induced rise in insulin secretion (δ insulin) was observed at HA. The rise in insulin in SJ was significantly higher (p<0.01) than in HAN. This elevation in glucose and insulin levels was also evident at different times of the day. The circadian rhythmicity of glucose as well as insulin was altered by the altitude stress. The findings of the study show a rise in insulin level at HA but the hyperglycemia in the face of hyper-insulinism require the presumption of a simultaneous and dispropotionate rise of insulin antagonistic hormones upsetting the effect of insulin on glucose metabolism.

  6. Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

    PubMed

    Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

    2018-03-28

    This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

  7. Effects of dietary inclusions of red beet and betaine on the acute stress response and muscle lipid peroxidation in rainbow trout.

    PubMed

    Pinedo-Gil, Julia; Martín-Diana, Ana Belén; Bertotto, Daniela; Sanz-Calvo, Miguel Ángel; Jover-Cerdá, Miguel; Tomás-Vidal, Ana

    2018-06-01

    This study evaluates the effects of red beet (RB) and betaine on rainbow trout submitted to an acute stress challenge. A control diet was compared with four experimental diets in which red beet (14 and 28%) and betaine (0.9 and 1.63%) were incorporated in different concentrations according to a factorial design. Cortisol in plasma and fin, glucose and lactate plasma levels, and malondialdehide (MDA) in muscle were all measured before the stress challenge and 30 min and 6 and 12 h after the stress challenge as parameters to determine the diet effects. RB and betaine had no effect on cortisol, glucose, and MDA basal levels. However, lactate basal levels were significantly lower on fish fed with RB and betaine. Thirty minutes after the stress challenge, there was a significant increase in plasma and fin cortisol, glucose and lactate concentrations, although fish fed with diets containing RB and betaine showed significantly higher plasma cortisol values. MDA values of fish fed with 14% RB and 0.9% betaine were significantly higher than MDA values from fish fed with 28% RB and 1.63% betaine. After 6 and 12 h, plasma and fin cortisol and lactate levels recovered in a similar trend. Glucose plasma levels recovered in almost all groups 12 h after the stress. Also, MDA values recovered basal levels after 6 and 12 h. RB and betaine did not enhance the tolerance to the stress challenge compared to the control group, although the presence of these ingredients had no negative effect on any of the stress indicators.

  8. [Aldosterone response to various stimuli in hyperthyroidism: in vivo and in vitro studies].

    PubMed

    Kigoshi, T; Kaneko, M; Nakano, S; Azukizawa, S; Uchida, K; Morimoto, S

    1993-06-20

    Responses of plasma aldosterone (PA) to alpha-ACTH-(1-24) (250 micrograms, im) injection and graded angiotensin II (AII) infusions (2, 4 and 8ng/kg/min for 30 min at each dose) on a constant sodium intake (170mEq daily) were assessed in 17 patients with Basedow's disease and 13 age-matched normal subjects. Aldosterone production in response to ACTH, AII and potassium in adrenal zona glomerulosa cells from L-thyroxine-induced hyperthyroid rats (H-rats) were also examined. Basal levels of plasma renin activity (PRA) and urinary aldosterone excretion were significantly higher (p < 0.01 and p < 0.05, respectively) in the patients with Basedow's disease than in the normal subjects, whereas basal PA level was similar in the two groups. The ACTH injection induced similar increases in plasma cortisol, plasma 18-hydroxycorticosterone (18-OHB) and PA in the two groups. The graded AII infusions also produced increases in plasma 18-OHB and PA in the two groups. Responses of these two corticosteroids to AII were, however, significantly lower (p < 0.05) in the patients with Basedow's disease than in the normal subjects. In the experimental animal study, basal PRA levels and the adrenal glomerulosa cell count/adrenal were significantly higher (p < 0.05) in the H-rats than in the control rats, whereas basal PA levels were similar in the two groups. Aldosterone production in response to AII, ACTH, and potassium increased in a dose-dependent manner in the two groups. Responses of aldosterone production to AII were, however, significantly lower (p < 0.05) in the H-rats than in the control rats. These results suggest that the impaired responsiveness of adrenal zona glomerulosa cells to AII, as well as an increased metabolic clearance rate of aldosterone, may be involved in the abnormal aldosterone metabolism in hyperthyroidism.

  9. Analysis of formability of Ca-added magnesium alloy sheets at low temperatures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Se-Jong; Lee, Young-Seon; Kim, Daeyong, E-mail: daeyong@kims.re.kr

    The formability of sheets of the Ca-added magnesium alloy AZX311 was analyzed. The parameters affecting the sheet formability, such as the strain-hardening rate and the strain-rate sensitivity, did not seem to be higher in the alloy AZX311 at temperatures of room temperature (RT) and 200 °C. In addition, the critical stress for fracture at RT was lower in AZX311 than in AZ31. However, AZX311 exhibited higher stretchability and formability at low temperatures than AZ31. Electron back-scattered diffraction microscopy revealed that AZX311 had a weaker basal texture as well as broadened basal poles along the transverse direction. Polycrystal plasticity simulations confirmedmore » that this weaker basal texture increases the activity of basal slip over thickness strain, resulting in the higher formability of AZX311. - Highlights: • A weak basal texture with broadening basal poles along the TD in AZX311 • Lower critical stress for fracture at RT in AZX311 than in AZ31 • Lower strain-hardening rates at low temperatures in the AZX311 than in the AZ31 • Higher formability at low temperatures in AZX311 because of the weak basal texture.« less

  10. Brain biochemical correlates of the plasma homocysteine level: a proton magnetic resonance spectroscopy study in the elderly subjects.

    PubMed

    Chen, Cheng-Sheng; Kuo, Yu-Ting; Tsai, Hui-Yi; Li, Chun-Wei; Lee, Chen-Chang; Yen, Cheng-Fang; Lin, Hsiu-Fen; Ko, Chih-Hung; Juo, Suh-Hang Hank; Yeh, Yi-Chun; Liu, Gin-Chung

    2011-07-01

    An elevated plasma homocysteine level has been reported to be associated with various neuropsychiatric diseases. However, little is known about the brain biochemical changes associated with the higher plasma homocysteine level. The main goal of this study was to examine the sex difference in brain biochemical concentrations using brain proton magnetic resonance spectroscopy (H MRS), and to elucidate the biochemical changes associated with plasma homocysteine levels by sex in healthy elderly subjects. Seventy elderly subjects without any clinical psychiatric and neurological disease underwent 3-T brain H MRS. MRS spectra were acquired from voxels placed on the left side of the basal ganglia, frontal lobe, and hippocampus. Brain biochemical concentrations were compared between the elderly male and female participants. Correlations between these biochemical concentrations and plasma homocysteine levels by sex were analyzed. Female participants had significantly higher levels of choline in the left frontal lobe and hippocampus, and lower creatine and myo-inositol, in the left basal ganglia than did males. A higher homocysteine level was correlated with a lower N-acetylaspartate (NAA) concentration in the left hippocampus in elderly women (r = -0.44; p = 0.03) but not in elderly men. This study found that there was a sex difference in brain biochemical concentrations in the elderly participants. A higher plasma homocysteine level was associated with a lower NAA in the hippocampus of elderly women. The sex difference in association between brain biochemical concentrations and plasma homocysteine levels needs further investigation. We speculate that after menopause, women lose protection of estrogen from the neurotoxic effects of homocysteine in the hippocampus. Future studies are required to examine this speculation.

  11. Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia.

    PubMed

    Abi-Saab, Walid M; Maggs, David G; Jones, Tim; Jacob, Ralph; Srihari, Vinod; Thompson, James; Kerr, David; Leone, Paola; Krystal, John H; Spencer, Dennis D; During, Matthew J; Sherwin, Robert S

    2002-03-01

    Brain levels of glucose and lactate in the extracellular fluid (ECF), which reflects the environment to which neurons are exposed, have never been studied in humans under conditions of varying glycemia. The authors used intracerebral microdialysis in conscious human subjects undergoing electrophysiologic evaluation for medically intractable epilepsy and measured ECF levels of glucose and lactate under basal conditions and during a hyperglycemia-hypoglycemia clamp study. Only measurements from nonepileptogenic areas were included. Under basal conditions, the authors found the metabolic milieu in the brain to be strikingly different from that in the circulation. In contrast to plasma, lactate levels in brain ECF were threefold higher than glucose. Results from complementary studies in rats were consistent with the human data. During the hyperglycemia-hypoglycemia clamp study the relationship between plasma and brain ECF levels of glucose remained similar, but changes in brain ECF glucose lagged approximately 30 minutes behind changes in plasma. The data demonstrate that the brain is exposed to substantially lower levels of glucose and higher levels of lactate than those in plasma; moreover, the brain appears to be a site of significant anaerobic glycolysis, raising the possibility that glucose-derived lactate is an important fuel for the brain.

  12. Obesity-driven prepartal hepatic lipid accumulation in dairy cows is associated with increased CD36 and SREBP-1 expression.

    PubMed

    Prodanović, Radiša; Korićanac, Goran; Vujanac, Ivan; Djordjević, Ana; Pantelić, Marija; Romić, Snježana; Stanimirović, Zoran; Kirovski, Danijela

    2016-08-01

    We investigated the hypothesis that obesity in dairy cows enhanced expression of proteins involved in hepatic fatty acid uptake and metabolism. Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their body condition score (BCS) as optimal (3.25≤BCS≤3.5) and high (4.0≤BCS≤4.25). Intravenous glucose tolerance test (GTT) and liver biopsies were carried out at day 10 before calving. Blood samples were collected before (basal) and after glucose infusion, and glucose, insulin and non-esterified fatty acid (NEFA) levels were determined at each sample point. In addition, β-hydroxybutyrate and triglycerides levels were measured in the basal samples. The liver biopsies were analyzed for total lipid content and protein expression of insulin receptor beta (IRβ), fatty acid translocase (FAT/CD36) and sterol regulatory element-binding protein-1 (SREBP-1). Basal glucose and insulin were higher in high-BCS cows, which coincided with higher circulating triglycerides and hepatic lipid content. Clearance rate and AUC for NEFA during GTT were higher in optimal-BCS cows. The development of insulin resistance and fatty liver in obese cows was paralleled by increased hepatic expression of the IRβ, CD36 and SREBP-1. These results suggest that increased expression of hepatic CD36 and SREBP-1 is relevant in the obesity-driven lipid accumulation in the liver of dairy cows during late gestation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Effect of dietary supplementation of l-tryptophan on thermal tolerance and oxygen consumption rate in Cirrhinus mrigala fingerlings under varied stocking density.

    PubMed

    Tejpal, C S; Sumitha, E B; Pal, A K; Shivananda Murthy, H; Sahu, N P; Siddaiah, G M

    2014-04-01

    A 60 day feeding trial was conducted to study the effect of dietary l-tryptophan on thermal tolerance and oxygen consumption rate of freshwater fish, mrigala, Cirrhinus mrigala reared under ambient temperature at low and high stocking density. Four hundred eighty fingerlings were distributed into eight experimental groups. Four groups each of low density group (10 fishes/75L water) and higher density group (30 fishes/75L water) were fed a diet containing 0, 0.68, 1.36 or 2.72% l-tryptophan in the diet, thus forming eight experimental groups namely, Low density control (LC) (basal feed +0% l-tryptophan); LT1 (basal feed+0.68% l-tryptophan); LT2 (basal feed+1.36% l-tryptophan); LT3 (basal feed+2.72% l-tryptophan); high density control (HC) (basal feed+0% l-tryptophan); HT1 (basal feed+0.68% l-tryptophan); HT2 (basal feed+1.36% l-tryptophan); and HT3 (basal feed+2.72% l-tryptophan) were fed at 3% of the body weight. The test diets having crude protein 34.33±0.23 to 35.81±0.18% and lipid 423.49±1.76 to 425.85±0.31KCal/100g were prepared using purified ingredients. The possible role of dietary l-tryptophan on thermal tolerance and oxygen consumption rate was assessed in terms of critical thermal maxima (CTMax), critical thermal minima (CTMin), lethal thermal maxima (LTMax) and lethal thermal minima (LTMin). The CTMax, CTMin, LTMax and LTMin values were found to be significantly higher (p<0.05) in the treatment groups with CTMax 42.94±0.037 (LT2); LT Max 43.18±0.070 (LT2); CTMin 10.47±0.088 (LT2) and LTMin 9.42±0.062 (LT3), whereas the control group showed a lower tolerance level. The same trend was observed in the high density group (CTMax 42.09±0.066 (LT3); LTMax 43 23±0.067 (HT3); CTMin 10.98±0.040 (HT3) and LTMin 9.74±0.037 (HT3). However, gradual supplementation of dietary l-tryptophan in the diet significantly reduced the oxygen consumption rate in both the low density group (Y=-26.74x+222.4, r²=0.915) and the high density group (Y=-32.96x+296.5, r²=0.8923). Dietary supplementation of l-tryptophan at a level of 1.36% improved the thermal tolerance level and reduced the oxygen consumption rate in C. mrigala fingerlings. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

    PubMed Central

    Kim, Bo Ram; Van de Laar, Emily; Tarumi, Shintaro; Hasenoeder, Stefan; Wang, Dennis; Virtanen, Carl; Bandarchi, Bizhan; Pham, Nhu An; Lee, Sharon; Keshavjee, Shaf; Tsao, Ming-Sound; Moghal, Nadeem

    2016-01-01

    Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages. PMID:27880766

  15. Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

    PubMed

    Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

    2011-08-01

    To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the corresponding basal ganglia-thalamocortical circuit. © RSNA, 2011.

  16. Study of adrenal function in patients with tuberculosis.

    PubMed

    Sarin, Bipan Chander; Sibia, Keerat; Kukreja, Sahiba

    2018-07-01

    Although subclinical adrenal insufficiency has been documented in tuberculosis but it has been neglected in mainstream management of TB due to inconclusive data on its prevalence in TB. The fact that adrenal insufficiency may result not only in poor general condition of the patient but also sudden death due to adrenal crisis, makes it all the more important to address this issue seriously. In this non-randomized interventional study comprising of 100 cases of TB, our aim was to assess the adreno-cortical functions in patients with pulmonary TB (50 cases) and extra-pulmonary TB (50 cases) in an attempt to determine if there is any compromise of adrenal function. In this study, 100 cases of active TB were investigated for adrenal insufficiency by measuring morning fasting basal serum cortisol levels, followed by low dose ACTH stimulation test using 1μg synacthen (synthetic ACTH analog). The post-stimulation serum cortisol levels were estimated. Basal serum cortisol levels<220nmol/L or post-stimulation test serum cortisol level increment<200nmol/L or post-stimulation serum cortisol levels<500nmol/L were suggestive of adrenal insufficiency. Basal serum cortisol level was low in 16% cases and after low dose ACTH stimulation test, cortisol response was subnormal in 76% cases. Incidence of adrenal insufficiency in pulmonary TB (74%) and extra-pulmonary TB (78%) were comparable. The number of females having adrenal insufficiency in both the groups was higher than the males (67.3% males and 83.3% females) but the difference was statistically significant only in extra-pulmonary TB group (p=0.011). On analysing the data, the sensitivity of basal serum cortisol level estimation in diagnosing adrenal insufficiency was observed to be 21.05% and its specificity was 100%. Positive predictive value was 100% and negative predictive value was 28.57%. Diagnostic accuracy of basal serum cortisol level estimation was observed to be 40%. The incidence of subclinical adrenal insufficiency in TB cases attending chest department at a tertiary care hospital was significantly high but comparable in both pulmonary and extra-pulmonary type of TB. Females in general and particularly those with extra-pulmonary TB were observed to be at increased risk of adrenal insufficiency. The low dose ACTH stimulation test was able to identify cases with adrenal insufficiency which had normal basal serum cortisol levels. Screening all TB cases for adrenal insufficiency by measuring both morning basal serum cortisol levels and low dose ACTH stimulation test can help identify cases at risk of fatal adrenal crisis and institute timely management, thus improving disease prognosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  17. Regional variations of basal cell carcinoma incidence in the U.K. using The Health Improvement Network database (2004-10).

    PubMed

    Musah, A; Gibson, J E; Leonardi-Bee, J; Cave, M R; Ander, E L; Bath-Hextall, F

    2013-11-01

    Basal cell carcinoma (BCC) is one of the most common types of nonmelanoma skin cancer affecting the white population; however, little is known about how the incidence varies across the U.K. To determine the variation in BCC throughout the U.K. Data from 2004 to 2010 were obtained from The Health Improvement Network database. European and world age-standardized incidence rates (EASRs and WASRs, respectively) were obtained for country-level estimates and levels of socioeconomic deprivation, while strategic health-authority-level estimates were directly age and sex standardized to the U.K. standard population. Incidence-rate ratios were estimated using multivariable Poisson regression models. The overall EASR and WASR of BCC in the U.K. were 98.6 per 100,000 person-years and 66.9 per 100,000 person-years, respectively. Regional-level incidence rates indicated a significant geographical variation in the distribution of BCC, which was more pronounced in the southern parts of the country. The South East Coast had the highest BCC rate followed by South Central, Wales and the South West. Incidence rates were substantially higher in the least deprived groups and we observed a trend of decreasing incidence with increasing levels of deprivation (P < 0.001). Finally, in terms of age groups, the largest annual increase was observed among those aged 30-49 years. Basal cell carcinoma is an increasing health problem in the U.K.; the southern regions of the U.K. and those in the least deprived groups had a higher incidence of BCC. Our findings indicate an increased incidence of BCC for younger age groups below 49 years. © 2013 British Association of Dermatologists.

  18. Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with insulin glargine: pooled analyses of five randomized controlled trials.

    PubMed

    Rosenstock, Julio; Marre, Michel; Qu, Yongming; Zhang, Shuyu; Bastyr, Edward J; Prince, Melvin J; Chang, Annette M

    2016-11-01

    Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential action, resulting from reduced peripheral effects. This report summarizes hypoglycaemia data from five BIL phase III studies with insulin glargine as the comparator, including three double-blind trials. Prespecified pooled analyses (n = 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin only, those with T2D on basal-bolus therapy, and those with type 1 diabetes (T1D). BIL treatment resulted in a 36-45% lower nocturnal hypoglycaemia rate compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c) and higher basal insulin dosing. The total hypoglycaemia rate was similar in patients with T2D on basal treatment only, trended towards being higher (10%) in patients with T2D on basal-bolus treatment (p = .053), and was 15% higher (p < .001) with BIL versus glargine in patients with T1D, with more daytime hypoglycaemia in the T1D and T2D groups who were receiving basal-bolus therapy. In T1D, during the maintenance treatment period (26-52 weeks), the total hypoglycaemia rate was not significantly different. There were no differences in severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia in all patient populations, higher daytime hypoglycaemia with basal-bolus therapy in the T1D and T2D groups, and an associated increase in total hypoglycaemia in the patients with T1D. © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  19. Microbial biomass and basal respiration of selected Sub-Antarctic and Antarctic soils in the areas of some Russian polar stations

    NASA Astrophysics Data System (ADS)

    Abakumov, E.; Mukhametova, N.

    2014-07-01

    Antarctica is a unique place for soil, biological, and ecological investigations. Soils of Antarctica have been studied intensively during the last century, when different national Antarctic expeditions visited the sixth continent with the aim of investigating nature and the environment. Antarctic investigations are comprised of field surveys mainly in the terrestrial landscapes, where the polar stations of different countries are situated. That is why the main and most detailed soil surveys were conducted in the McMurdo Valleys, Transantarctic Mountains, South Shetland Islands, Larsemann Hills and the Schirmacher Oasis. Our investigations were conducted during the 53rd and 55th Russian Antarctic expeditions in the base of soil pits, and samples were collected in Sub-Antarctic and Antarctic regions. Sub-Antarctic or maritime landscapes are considered to be very different from Antarctic landscapes due to differing climatic and geogenic conditions. Soils of diverse zonal landscapes were studied with the aim of assessing the microbial biomass level, basal respiration rates and metabolic activity of microbial communities. This investigation shows that Antarctic soils are quite diverse in profile organization and carbon content. In general, Sub-Antarctic soils are characterized by more developed humus (sod) organo-mineral horizons as well as by an upper organic layer. The most developed organic layers were revealed in peat soils of King George Island, where its thickness reach, in some cases, was 80 cm. These soils as well as soils formed under guano are characterized by the highest amount of total organic carbon (TOC), between 7.22 and 33.70%. Coastal and continental Antarctic soils exhibit less developed Leptosols, Gleysols, Regolith and rare Ornhitosol, with TOC levels between 0.37 and 4.67%. The metabolic ratios and basal respiration were higher in Sub-Antarctic soils than in Antarctic ones, which can be interpreted as a result of higher amounts of fresh organic remnants in organic and organo-mineral horizons. The soils of King George Island also have higher portions of microbial biomass (max 1.54 mg g-1) compared to coastal (max 0.26 mg g-1) and continental (max 0.22 mg g-1) Antarctic soils. Sub-Antarctic soils differ from Antarctic ones mainly by having increased organic layer thickness and total organic carbon content, higher microbial biomass carbon content, basal respiration, and metabolic activity levels.

  20. Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes.

    PubMed

    De Palo, E F; Gatti, R; Cappellin, E; Schiraldi, C; De Palo, C B; Spinella, P

    2001-01-01

    Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 gkg(-1) of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO2 max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6+/-0.8 mmol L(-1) after vs 12.8+/-1.0 mmol L(-1) before treatment; p < 0.05 [mean +/- std. err.]). The end-exercise pGH of each athlete was higher than basal (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pGH was higher (but not significantly, p = 0.08) than before this treatment (12.2+/-2.0 ng mL(-1) before vs 33.8+/-13.6 ngmL(-1) after treatment). The end-exercise pGHBP was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end-exercise pGHBP was 738+/-85 pmol L(-1) before vs 1691+/-555 pmol L(-1) after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis.

  1. Impact of Basal Conditions on Grounding-Line Retreat

    NASA Astrophysics Data System (ADS)

    Koellner, S. J.; Parizek, B. R.; Alley, R. B.; Muto, A.; Holschuh, N.; Nowicki, S.

    2017-12-01

    An often-made assumption included in ice-sheet models used for sea-level projections is that basal rheology is constant throughout the domain of the simulation. The justification in support of this assumption is that physical data for determining basal rheology is limited and a constant basal flow law can adequately approximate current as well as past behavior of an ice-sheet. Prior studies indicate that beneath Thwaites Glacier (TG) there is a ridge-and-valley bedrock structure which likely promotes deformation of soft tills within the troughs and sliding, more akin to creep, over the harder peaks; giving rise to a spatially variable basal flow law. Furthermore, it has been shown that the stability of an outlet glacier varies with the assumed basal rheology, so accurate projections almost certainly need to account for basal conditions. To test the impact of basal conditions on grounding-line evolution forced by ice-shelf perturbations, we modified the PSU 2-D flowline model to enable the inclusion of spatially variable basal rheology along an idealized bedrock profile akin to TG. Synthetic outlet glacier "data" were first generated under steady-state conditions assuming a constant basal flow law and a constant basal friction coefficient field on either a linear or bumpy sloping bed. In following standard procedures, a suite of models were then initialized by assuming different basal rheologies and then determining the basal friction coefficients that produce surface velocities matching those from the synthetic "data". After running each of these to steady state, the standard and full suite of models were forced by drastically reducing ice-shelf buttressing through side-shear and prescribed basal-melting perturbations. In agreement with previous findings, results suggest a more plastic basal flow law enhances stability in response to ice-shelf perturbations by flushing ice from farther upstream to sustain the grounding-zone mass balance required to prolong the current grounding-line position. Mixed rheology beds tend to mimic the retreat of the higher-exponent bed, a behavior enhanced over bumps as the stabilizing ridges tap into ice from local valleys. Thus, accounting for variable basal conditions in ice-sheet model projections is critical for improving both the timing and magnitude of retreat.

  2. [Effect of acute hypoxia on the intensity of free radical processes in the basal nuclei of the brain, and the rat behaviour in the open field test under conditions of altered photoperiod].

    PubMed

    Sopova, I Iu; Zamorskiĭ, I I

    2011-03-01

    The effect of acute hypoxia on the intensity of free radical processes in the basal nuclei (the nucleus caudatus, globus pallidus. nucleus accumbens. amygdaloid complex) of the brain, and the rat behaviour in the open field test has been studied under conditions of altered photoperiod. It has been shown that constant darkness levels the effect of acute hypoxia on the intensity of lipid peroxidation, preserves the activity of superoxide dismutase and catalase at a higher level, lowers the activity of glutathione peroxidase. Under light, the sensitivity of basal nuclei neurons to acute hypoxia is enhanced, the latter being reflected in intensification of lipid peroxidation at the expense of increased formation of dien conjugates. The activity of catalase at that considerably exceeds the level of even intact rats in all the structures. It has been established that an altered photoperiod modulates the effect of acute hypoxia on the parameters of rat's activity in the open field, the character of their change depending on the nature of a photophase change.

  3. Altered adrenal steroid metabolism underlying hypercortisolism in female endurance athletes.

    PubMed

    Lindholm, C; Hirschberg, A L; Carlström, K; von Schoultz, B

    1995-06-01

    To explore possible changes in adrenal steroid metabolism and androgenic-anabolic status in female endurance athletes as a mechanism for their hypercortisolism. Adrenal steroids and androgenic-anabolic factors were studied during basal conditions and in response to ACTH stimulation related to menstrual status. Department of Obstetrics and Gynecology, Karolinska Hospital, Stockholm, Sweden. Thirteen female elite middle to long distance runners (six eumenorrheic, seven oligoamenorrheic) and seven regularly menstruating controls. Blood samples were collected before and after an injection of 250 micrograms IV synthetic ACTH 1-24. Body weight, height, and body fat were measured. Basal serum concentrations of cortisol, androstenedione (A), DHEA, DHEAS, 17 alpha-hydroxyprogesterone (17-OHP), T, steroid-binding proteins, and insulin-like growth factor I and ACTH-induced response (area under the curve) of cortisol, DHEA, and 17-OHP. Oligoamenorrheic athletes had higher basal cortisol and A concentrations compared with healthy controls, whereas basal levels of DHEA and DHEAS were normal. Important findings in the oligoamenorrheic athletes were a significantly lower ratio between the ACTH-induced increments of DHEA and 17-OHP and an increased ratio between basal A and DHEAS. Insulin-like growth factor I was correlated negatively to sex hormone-binding globulin and to the amount of body fat in the combined material. The results indicate a redistribution of adrenal steroid metabolism in favor of glucocorticoid production in female endurance athletes. We suggest that hypercortisolism in female endurance athletes is a physiological adaptation to maintain adequate blood glucose levels during a condition of energy deficiency.

  4. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas.

    PubMed

    Goncharova, N D; Vengerin, A A; Khavinson, V Kh; Lapin, B A

    2005-01-01

    The purpose of this research was to study age-related changes in functioning of pineal and pancreatic glands of non-human primates, rhesus monkeys, and to elucidate the possibility of their corrections with the help of epitalon, a synthetic analogue of the pharmacopoeia drug epithalamin. In old (20-27 years) animals, the basal plasma levels of glucose and insulin were found to be higher, while the night melatonin level was lower in comparison with (6-8 years) young animals. After the glucose administration to old monkeys, a larger area under the curve of the plasma glucose response, a reduced glucose 'disappearance' rate, and a reduced insulin peak (5 min after the glucose administration) were observed in comparison with young animals in similar experiments. The epitalon administration to old monkeys caused the decrease in the basal levels of glucose and insulin and the increase in the basal night melatonin level. Additionally, in the case of old monkeys, epitalon decreased the area under the plasma glucose response curve, markedly increased the glucose 'disappearance' rate and normalized the plasma insulin dynamics in response to glucose administration. Yet, it has not affected the hormonal and metabolic changes in young animals. Thus, epitalon is a promising factor for restoring the age-related endocrine dysfunctions of primates.

  5. Choline acetyltransferase expression during periods of behavioral activity and across natural sleep-wake states in the basal forebrain.

    PubMed

    Greco, M A; McCarley, R W; Shiromani, P J

    1999-01-01

    The present study examined whether the expression of the messenger RNA encoding the protein responsible for acetylcholine synthesis is associated with sleep-wakefulness. Choline acetyltransferase messenger RNA levels were analysed using a semi-quantitative assay in which reverse transcription was coupled to complementary DNA amplification using the polymerase chain reaction. To examine the relationship between steady-state messenger RNA and behavioral activity, rats were killed during the day (4.00 p.m.) or night (4.00 a.m.), and tissue from the vertical and horizontal limbs of the diagonal bands of Broca was analysed. Choline acetyltransferase messenger RNA levels were higher during the day than during the night. The second study examined more closely the association between choline acetyltransferase messenger RNA levels and individual bouts of wakefulness, slow-wave sleep or rapid eye movement sleep. Choline acetyltransferase messenger RNA levels were low during wakefulness, intermediate in slow-wave sleep and high during rapid eye movement sleep. In contrast, protein activity, measured at a projection site of cholinergic neurons of the basal forebrain, was higher during wakefulness than during sleep. These findings suggest that choline acetyltransferase protein and messenger RNA levels exhibit an inverse relationship during sleep and wakefulness. The increased messenger RNA expression during sleep is consistent with a restorative function of sleep.

  6. Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis study.

    PubMed

    Nedvidkova, Jara; Haluzik, Martin; Bartak, Vladimir; Dostalova, Ivana; Vlcek, Petr; Racek, Pavel; Taus, Michal; Behanova, Magdalena; Svacina, Stepan; Alesci, Salvatore; Pacak, Karel

    2004-06-01

    Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline-stimulated local lipolysis and to determine local concentrations of lipolysis-regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four-fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

  7. Social-emotional competence and early adolescents' peer acceptance in school: Examining the role of afternoon cortisol.

    PubMed

    Oberle, Eva

    2018-01-01

    The present study investigated the role of afternoon cortisol in social-emotional competence and peer acceptance in early adolescence. To date, research on basal cortisol activity and social development in childhood and adolescence has predominately focused on understanding maladjustment and dysfunction in development. The degree to which basal cortisol is also involved in positive adjustment and social functioning remains largely unexplored. A total of 154 early adolescents (46% female; Mean age = 11.26; SD = .65) from diverse ethnic backgrounds provided self-reports of perspective taking, peer reports of acceptance by classmates, peer reports of prosocial behaviors, and saliva samples to assess basal cortisol. As expected and in alignment with previous research, afternoon cortisol, perspective taking, prosocial behaviors, and peer acceptance were all positively correlated. Path analyses followed by bootstrapping analyses revealed that the direct path from higher afternoon cortisol to higher levels of prosocial behavior was fully mediated by perspective taking skills. The direct path from higher afternoon cortisol to peer acceptance was fully mediated by perspective taking skills and prosocial behavior. The findings are discussed within the broader context of previous research on cortisol and social adjustment in childhood and early adolescence. The practical relevance of the findings is considered.

  8. Associations between basal cortisol levels and memory retrieval in healthy young individuals.

    PubMed

    Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J F; Rasch, Björn

    2013-11-01

    Cortisol is known to affect memory processes. On the one hand, stress-induced or pharmacologically induced elevations of cortisol levels enhance memory consolidation. On the other hand, such experimentally induced elevations of cortisol levels have been shown to impair memory retrieval. However, the effects of individual differences in basal cortisol levels on memory processes remain largely unknown. Here we tested whether individual differences in cortisol levels predict picture learning and recall in a large sample. A total of 1225 healthy young women and men viewed two different sets of emotional and neutral pictures on two consecutive days. Both sets were recalled after a short delay (10 min). On Day 2, the pictures seen on Day 1 were additionally recalled, resulting in a long-delay (20 hr) recall condition. Cortisol levels were measured three times on Days 1 and 2 via saliva samples before encoding, between encoding and recall as well as after recall testing. We show that stronger decreases in cortisol levels during retrieval testing were associated with better recall performance of pictures, regardless of emotional valence of the pictures or length of the retention interval (i.e., 10 min vs. 20 hr). In contrast, average cortisol levels during retrieval were not related to picture recall. Remarkably during encoding, individual differences in average cortisol levels as well as changes in cortisol did not predict memory recall. Our results support previous findings indicating that higher cortisol levels during retrieval testing hinders recall of episodic memories and extend this view onto interindividual changes in basal cortisol levels.

  9. Differential response of DU145 and PC3 prostate cancer cells to ionizing radiation: role of reactive oxygen species, GSH and Nrf2 in radiosensitivity.

    PubMed

    Jayakumar, Sundarraj; Kunwar, Amit; Sandur, Santosh K; Pandey, Badri N; Chaubey, Ramesh C

    2014-01-01

    Radioresistance is the major impediment in radiotherapy of many cancers including prostate cancer, necessitating the need to understand the factors contributing to radioresistance in tumor cells. In the present study, the role of cellular redox and redox sensitive transcription factor, Nrf2 in the radiosensitivity of prostate cancer cell lines PC3 and DU145, has been investigated. Differential radiosensitivity of PC3 and DU145 cells was assessed using clonogenic assay, flow cytometry, and comet assay. Their redox status was measured using DCFDA and DHR probes. Expression of Nrf2 and its dependent genes was measured by EMSA and real time PCR. Knockdown studies were done using shRNA transfection. PC3 and DU145 cells differed significantly in their radiosensitivity as observed by clonogenic survival, apoptosis and neutral comet assays. Both basal and inducible levels of ROS were higher in PC3 cells than that of DU145 cells. DU145 cells showed higher level of basal GSH content and GSH/GSSG ratio than that of PC3 cells. Further, significant increase in both basal and induced levels of Nrf2 and its dependent genes was observed in DU145 cells. Knock-down experiments and pharmacological intervention studies revealed the involvement of Nrf2 in differential radio-resistance of these cells. Cellular redox status and Nrf2 levels play a causal role in radio-resistance of prostate cancer cells. The pivotal role Nrf2 has been shown in the radioresistance of tumor cells and this study will further help in exploiting this factor in radiosensitization of other tumor cell types. © 2013.

  10. Altered cellular magnesium responsiveness to hyperglycemia in hypertensive subjects.

    PubMed

    Barbagallo, M; Dominguez, L J; Bardicef, O; Resnick, L M

    2001-09-01

    Previous studies by our group have identified ionic aspects of insulin resistance in hypertension, in which cellular responses to insulin were influenced by the basal intracellular ionic environment-the lower the cytosolic free magnesium (Mg(i)), the less Mg(i) increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mg(i) responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used (31)P-nuclear magnetic resonance (NMR) spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=14) and hypertensive (HTN, n=12) subjects before and 30, 60, 120, and 180 minutes after in vitro glucose incubations. Basal Mg(i) levels were significantly lower in HTN subjects than in NL subjects (169+/-10 versus 205+/-8 micromol.L(-1), P<0.01). In NL cells, hyperglycemia significantly lowered Mg(i), from 205+/-8 micromol.L(-1) (basal, T=0) to 181+/-8, 162+/-6, 152+/-7, and 175+/-9 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mg(i) responses to hyperglycemia were blunted, from 169+/-10 micromol.L(-1) (basal, T=0) to 170+/-11, 179+/-12, 181+/-14, and 173+/-15 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mg(i) responses to hyperglycemia were closely related to basal Mg(i) levels: the higher the Mg(i), the greater the response (n=26, r=0.620, P<0.001). Thus, (1) erythrocytes from hypertensive vis-à-vis normotensive subjects are resistant to the ionic effects of extracellular hyperglycemia on Mg(i) levels, and (2) cellular ionic responses to glucose depend on the basal Mg(i) environment. Altogether, these data support a role for altered extracellular glucose levels in regulating cellular magnesium metabolism and also suggest the importance of ionic factors in determining cellular responsiveness to nonhormonal as well as hormonal signals.

  11. Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer

    PubMed Central

    2013-01-01

    Introduction The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancer cells through numerous mutations and epigenetic changes. The recent development of inhibitors targeting different components of the PI3K pathway may represent a valuable treatment alternative. However, predicting efficacy of these drugs is challenging, and methods for therapy monitoring are needed. Basal-like breast cancer (BLBC) is an aggressive breast cancer subtype, frequently associated with PI3K pathway activation. The objectives of this study were to quantify the PI3K pathway activity in tissue sections from xenografts representing basal-like and luminal-like breast cancer before and immediately after treatment with PI3K inhibitors, and to identify metabolic biomarkers for treatment response. Methods Tumor-bearing animals (n = 8 per treatment group) received MK-2206 (120 mg/kg/day) or BEZ235 (50 mg/kg/day) for 3 days. Activity in the PI3K/Akt/mammalian target of rapamycin pathway in xenografts and human biopsies was evaluated using a novel method for semiquantitative assessment of Aktser473 phosphorylation. Metabolic changes were assessed by ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy. Results Using a novel dual near-infrared immunofluorescent imaging method, basal-like xenografts had a 4.5-fold higher baseline level of pAktser473 than luminal-like xenografts. Following treatment, basal-like xenografts demonstrated reduced levels of pAktser473 and decreased proliferation. This correlated with metabolic changes, as both MK-2206 and BEZ235 reduced lactate concentration and increased phosphocholine concentration in the basal-like tumors. BEZ235 also caused increased glucose and glycerophosphocholine concentrations. No response to treatment or change in metabolic profile was seen in luminal-like xenografts. Analyzing tumor sections from five patients with BLBC demonstrated that two of these patients had an elevated pAktser473 level. Conclusion The activity of the PI3K pathway can be determined in tissue sections by quantitative imaging using an antibody towards pAktser473. Long-term treatment with MK-2206 or BEZ235 resulted in significant growth inhibition in basal-like, but not luminal-like, xenografts. This indicates that PI3K inhibitors may have selective efficacy in basal-like breast cancer with increased PI3K signaling, and identifies lactate, phosphocholine and glycerophosphocholine as potential metabolic biomarkers for early therapy monitoring. In human biopsies, variable pAktser473 levels were observed, suggesting heterogeneous PI3K signaling activity in BLBC. PMID:23448424

  12. Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells.

    PubMed

    Chan, S A; Smith, C

    2001-12-15

    1. Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. 2. The sAPs evoked inward Na(+) and Ca(2+) currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (tau = 560 ms). 3. Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. 4. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. 5. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506.

  13. Physiological stimuli evoke two forms of endocytosis in bovine chromaffin cells

    PubMed Central

    Chan, Shyue-An; Smith, Corey

    2001-01-01

    Exocytosis and endocytosis were measured following single, or trains of, simulated action potentials (sAP) in bovine adrenal chromaffin cells. Catecholamine secretion was measured by oxidative amperometry and cell membrane turnover was measured by voltage clamp cell capacitance measurements. The sAPs evoked inward Na+ and Ca2+ currents that were statistically identical to those evoked by native action potential waveforms. On average, a single secretory granule underwent fusion following sAP stimulation. An equivalent amount of membrane was then quickly internalised (τ = 560 ms). Stimulation with sAP trains revealed a biphasic relationship between cell firing rate and endocytic activity. At basal stimulus frequencies (single to 0.5 Hz) cells exhibited a robust membrane internalisation that then diminished as firing increased to intermediate levels (1.9 and 6 Hz). However at the higher stimulation rates (10 and 16 Hz) endocytic activity rebounded and was again able to effectively maintain cell surface near pre-stimulus levels. Treatment with cyclosporin A and FK506, inhibitors of the phosphatase calcineurin, left endocytosis characteristics unaltered at the lower basal stimulus levels, but blocked the resurgence in endocytosis seen in control cells at higher sAP frequencies. Based on these findings we propose that, under physiological electrical stimulation, chromaffin cells internalise membrane via two distinct pathways that are separable. One is prevalent at basal stimulus frequencies, is lessened with increased firing, and is insensitive to cyclosporin A and FK506. A second endocytic form is activated by increased firing frequencies, and is selectively blocked by cyclosporin A and FK506. PMID:11744761

  14. Effects of inclusion levels of banana (Musa spp.) peelings on feed degradability and rumen environment of cattle fed basal elephant grass.

    PubMed

    Nambi-Kasozi, Justine; Sabiiti, Elly Nyambobo; Bareeba, Felix Budara; Sporndly, Eva; Kabi, Fred

    2016-04-01

    The effect of feeding varying banana peeling (BP) levels on rumen environment and feed degradation characteristics was evaluated using three rumen fistulated steers in four treatments. The steers were fed BP at 0, 20, 40, and 60% levels of the daily ration with basal elephant grass (EG) to constitute four diets. Maize bran, cotton seed cake, and Gliricidia sepium were offered to make the diets iso-nitrogenous. The nylon bag technique was used to measure BP and EG dry matter (DM), crude protein (CP), and neutral detergent fiber (NDF) degradabilities at 0, 6, 12, 24, 48, 72, 96, and 120 h. Rumen fluid samples were collected to determine pH and volatile fatty acid (VFA) concentrations. Effective DM, CP, and NDF degradabilities of BP ranged between 574 and 807, 629-802, and 527-689 g/kg, respectively, being lower at higher BP levels. Elephant grass degradability behaved similarly with relatively high effective CP degradability (548-569 g/kg) but low effective DM and NDF degradability (381-403 and 336-373 g/kg, respectively). Rumen pH and VFA reduced with increasing BP in the diets. Rumen pH dropped to 5.8 and 5.9 at the 40 and 60% BP feeding levels, respectively. Banana peelings were better degraded than EG but higher BP levels negatively affected feed degradability and rumen environment.

  15. Does hierarchy stability influence testosterone and cortisol levels of bearded capuchin monkeys (Sapajus libidinosus) adult males? A comparison between two wild groups.

    PubMed

    Mendonça-Furtado, Olívia; Edaes, Mariana; Palme, Rupert; Rodrigues, Agatha; Siqueira, José; Izar, Patrícia

    2014-11-01

    Testosterone and cortisol are hormones expected to play a major role in competitive behaviours (i.e. aggression), and are related to rank and hierarchical stability. Through a non-invasive technique, we analyzed faecal testosterone (FTM(1)) and cortisol (FCM(2)) metabolites of dominant and subordinate males from two wild groups of bearded capuchin monkeys. One group had a stable dominance hierarchy while the other had an unstable hierarchy, with a marked conflict period related to a male take-over. In the unstable hierarchy group (1) the dominant male had higher FTM peaks than subordinates, and (2) basal FTM levels were higher than in the stable group. These findings are in accordance with the Challenge Hypothesis and rank-based predictions, and confirm that in Sapajus libidinosus hierarchy stability, social status, aggression rates and testosterone are closely related. Dominants of both groups had higher basal and peak FCM levels, suggesting that in S. libidinosus the dominant male has a higher allostatic load than subordinates, related to his role in protection against predators, intragroup appeasement, and control of food sources. Finally, we suggest that males of S. libidinosus are resistant to testosterone suppression by cortisol, because in the unstable group in spite of an increase in FCM there was also an increase in FTM during the conflict period. This article is part of a Special Issue entitled: Neotropical Behaviour. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Athletes with higher VO2max present reduced oxLDL after a marathon race

    PubMed Central

    Bachi, André L L; Sierra, Ana Paula R; Rios, Francisco J O; Gonçalves, Danieli A; Ghorayeb, Nabil; Abud, Ronaldo L; Victorino, Angélica B; dos Santos, Juliana M B; Kiss, Maria Augusta D P; Pithon-Curi, Tania C; Vaisberg, Mauro

    2015-01-01

    Background During a session of prolonged and exhaustive exercise, such as a marathon race, large quantities of free radicals are produced and can oxidise (ox) several molecules, such as low-density lipoprotein (LDL). To prevent oxidative damage, athletes present higher antioxidant levels. However, the effect of marathon running on the natural IgM or IgG anti-oxLDL autoantibodies is not understood. Thus, we investigated the effect of a marathon race on oxidative stress and the mechanisms of control of this stress. Methods Blood samples of 20 marathon runners were collected 24 hours before, immediately and 72 hours after a marathon race to evaluate: plasma lipid profile; serum levels of oxLDL and anti-oxLDL autoantibodies (IgM and IgG isotype) and total antioxidant capacity (TAC). Maximum oxygen uptake (VO2max) was also determined. Results Immediately after the race, oxLDL and TAC levels decreased in comparison to the basal levels; however, the IgM or IgG anti-oxLDL levels remain unchanged. Whereas no differences were observed in the IgM or IgG anti-oxLDL levels 72h after the marathon, the oxLDL and TAC levels returned to the basal values. Significant positive correlations were observed between oxLDL and LDL-cholesterol before, and 72h after the marathon. Significant negative correlations were observed between oxLDL and VO2max immediately after the marathon and 72 h later, as well as between oxLDL and TAC 72 h after the race. Conclusions Athletes with a higher VO2max and total antioxidant activity presented reduced LDL oxidation. The levels of IgM or IgG anti-oxLDL autoantibodies were not affected by running the marathon. PMID:27900109

  17. Increased adrenal steroid secretion in response to CRF in women with hypothalamic amenorrhea.

    PubMed

    Genazzani, A D; Bersi, C; Luisi, S; Fruzzetti, F; Malavasi, B; Luisi, M; Petraglia, F; Genazzani, A R

    2001-09-01

    To evaluate adrenal steroid hormone secretion in response to corticotropin-releasing factor (CRF) or to adrenocorticotropin hormone in women with hypothalamic amenorrhea. Controlled clinical study. Department of Reproductive Medicine and Child Development, Section of Gynecology and Obstetrics, University of Pisa, Italy. Fifteen women with hypothalamic amenorrhea were enrolled in the study. Eight normal cycling women were used as control group. Blood samples were collected before and after an injection of ovine CRF (0.1 microg/kg iv bolus) or after synthetic ACTH (0.25 mg iv). Plasma levels of ACTH, 17-hydroxypregnenolone (17OHPe), progesterone (P), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), cortisol (F), 11-deoxycortisol (S) and androstenedione (A). Basal plasma concentrations of ACTH, cortisol, 11-deoxycortisol, DHEA and 17OHPe were significantly higher in patients than in controls, whereas plasma levels of progesterone and 17-OHP were significantly lower in patients than in controls. In amenorrheic women the ratio of 17-OHPe/DHEA, of 17-OHPe/17-OHP and of 11-deoxycortisol/cortisol were significantly higher than in controls, while a significant reduction in the ratio of 17-OHP/androstenedione, of 17-OHP/11-deoxycortisol was obtained. In response to corticotropin-releasing factor test, plasma levels of ACTH, cortisol, 17-OHP, 11-deoxycortisol, DHEA and androstenedione were significantly lower in patients than in controls. In response to adrenocorticotropin hormone, plasma levels of 17-OHP, androstenedione and androstenedione/cortisol were significantly higher in patients than in controls. Patients suffering for hypothalamic amenorrhea showed an increased activation of hypothalamus-pituitary-adrenal (HPA) axis, as shown by the higher basal levels and by augmented adrenal hormone response to corticotropin-releasing factor administration. These data suggest a possible derangement of adrenal androgen enzymatic pathway.

  18. A Small Molecule Inverse Agonist for the Human Thyroid-Stimulating Hormone Receptor

    PubMed Central

    Neumann, Susanne; Huang, Wenwei; Eliseeva, Elena; Titus, Steve; Thomas, Craig J.; Gershengorn, Marvin C.

    2010-01-01

    Small molecule inverse agonists for the TSH receptor (TSHR) may be used as probes of the role of basal (or agonist-independent or constitutive) signaling and may have therapeutic potential as orally active drugs to inhibit basal signaling in patients with thyroid cancer and in some patients with hyperthyroidism. We describe the first small-molecule ligand [1;2-(3-((2,6-dimethylphenoxy)methyl)-4-methoxyphenyl)-3-(furan-2-ylmethyl)-2,3-dihydroquinazolin-4(1H)-one] that exhibits inverse agonist properties at TSHR. 1 inhibits basal and TSH-stimulated signaling, measured as cAMP production, by TSHRs in HEK-EM 293 cells stably expressing wild-type TSHRs; the antagonism of TSH-mediated signaling is competitive. 1 also inhibits basal signaling by wild-type TSHRs, and four constitutively active mutants of TSHR expressed transiently in HEK-EM 293 cells. 1 was active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs where it inhibited basal levels of mRNA transcripts for thyroglobulin, thyroperoxidase, sodium iodide symporter, and TSHR. These data serve as proof of principle that small, drug-like molecules can inhibit basal signaling by TSHR. We suggest that this small molecule is a lead compound for the development of higher-potency inverse agonists that can be used as probes of TSHR biology with therapeutic potential. PMID:20427476

  19. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds.

    PubMed

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D

    2014-10-13

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations.

  20. [The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

    PubMed

    Cui, Jia; Dou, Jingtao; Yang, Guoqing; Zang, Li; Jin, Nan; Chen, Kang; Du, Jin; Gu, Weijun; Wang, Xianling; Yang, Lijuan; Lyu, Zhaohui; Ba, Jianming; Mu, Yiming; Lu, Juming; Li, Jiangyuan; Pan, Changyu

    2015-07-01

    Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.

  1. Enhanced Stress Response in 5-HT1AR Overexpressing Mice: Altered HPA Function and Hippocampal Long-Term Potentiation.

    PubMed

    Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Díaz, Álvaro; Garro-Martínez, Emilio; Linge, Raquel; Castro, Elena; Haberzettl, Robert; Fink, Heidrun; Bert, Bettina; Brosda, Jan; Romero, Beatriz; Crespo-Facorro, Benedicto; Pazos, Ángel

    2017-11-15

    Postsynaptic 5-HT 1A receptors (5-HT 1A R) play an important role in anxiety and stress, although their contribution is still controversial. Previous studies report that mice overexpressing postsynaptic 5-HT 1A Rs show no changes in basal anxiety, though the influence of stress conditions has not been addressed yet. In this study, we used this animal model to evaluate the role of 5-HT 1A Rs in anxiety response after pre-exposure to an acute stressor. Under basal conditions, 5-HT 1A R overexpressing animals presented high corticosterone levels and a lower mineralocorticoid/glucocorticoid receptor ratio. After pre-exposure to a single stressor, they showed a high anxiety-like response, associated with a blunted increase in corticosterone levels and higher c-Fos activation in the prefrontal cortex. Moreover, these mice also presented a lack of downregulation of hippocampal long-term potentiation after stress exposure. Therefore, higher postsynaptic 5-HT 1A R activation might predispose to a high anxious phenotype and an impaired stress coping behavior.

  2. Influence of chestnut tannins on welfare, carcass characteristics, meat quality, and lipid oxidation in rabbits under high ambient temperature.

    PubMed

    Liu, Huawei; Zhou, Daowei; Tong, Jianming; Vaddella, Venkata

    2012-01-01

    A study was conducted to evaluate the influence of chestnut tannins (CT) on welfare, carcass characteristics, meat quality, and lipid oxidation in rabbits under high ambient temperature. Rabbits in one group were raised at 20°C and fed with basal diet (N) and other three groups (33°C) were fed basal diet with 0 (C), 5 (CT5), and 10 g (CT10) of CT/kg of diet. Compared with the C group, rabbits in CT10 had higher pH(24) and lower cooking loss and thiobarbituric acid reacting substance values at 0, 30, and 60 min of forced oxidation. Rabbits in C group had higher cortisol levels, creatine kinase activities, white blood cell counts, neutrophil percentage, neutrophil:lymphocyte ratio and lower T(3), T(4) levels, lymphocyte percentage than N and CT10 groups. Supplementation of CT seemed to have a positive effect on growth performance, welfare, and meat quality of rabbits under high ambient temperature. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Antioxidants Supplementation in Elderly Cardiovascular Patients

    PubMed Central

    Vila, Susana; Azzato, F.; Milei, José

    2013-01-01

    Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), β-carotene (βC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and βC levels. Increase in α-TP and βC levels was observed only in patients with basal levels <18 μM for α-TP (P < 0.01) and <0.30 μM for βC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F 1,110 = 3.611, P < 0.06, and N.S.), glutathione (+21%, F 1,110 = 2.92, P < 0.09, and N.S.), and TBARS (−29%, F 1,110 = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F 1,110 = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F 32,80 = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α-TP and βC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation). PMID:24489984

  4. Higher ambulatory systolic blood pressure independently associated with enlarged perivascular spaces in basal ganglia.

    PubMed

    Yang, Shuna; Yuan, Junliang; Zhang, Xiaoyu; Fan, Huimin; Li, Yue; Yin, Jiangmei; Hu, Wenli

    2017-09-01

    Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear. This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM). We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS. A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO. Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.

  5. Cross-Country Differences in Basal and Stress-Induced Cortisol Secretion in Older Adults

    PubMed Central

    Lupien, Sonia J.; Fiocco, Alexandra; Suchecki, Deborah

    2014-01-01

    Objective Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Methods Salivary cortisol of 260 older adults from Canada and Brazil were nalyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Results Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. Conclusion These findings suggest that country context may modulate cortisol secretion and could impact the population health. PMID:25153322

  6. Cross-country differences in basal and stress-induced cortisol secretion in older adults.

    PubMed

    Souza-Talarico, Juliana N; Plusquellec, Pierrich; Lupien, Sonia J; Fiocco, Alexandra; Suchecki, Deborah

    2014-01-01

    Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Salivary cortisol of 260 older adults from Canada and Brazil were analyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. These findings suggest that country context may modulate cortisol secretion and could impact the population health.

  7. Exacerbated Glial Response in the Aged Mouse Hippocampus Following Controlled Cortical Impact Injury

    PubMed Central

    Sandhir, Rajat; Onyszchuk, Gregory; Berman, Nancy E. J.

    2008-01-01

    Old age is associated with enhanced susceptibility to and poor recovery from brain injury. An exacerbated microglial and astrocyte response to brain injury might be involved in poor outcomes observed in the elderly. The present study was therefore designed to quantitate the expression of markers of microglia and astrocyte activation using real-time RT-PCR, immunoblot and immunohistochemical analysis in aging brain in response to brain injury. We examined the hippocampus, a region that undergoes secondary neuron death, in aged (21–24 month) and adult (5–6 month) mice following controlled cortical impact (CCI) injury to the sensorimotor cortex. Basal mRNA expression of CD11b and Iba1, markers of activated microglia, was higher in aged hippocampus as compared to the adult. The mRNA expression of microglial markers increased and reached maximum 3 days post injury in both adult and aged mice, but was higher in the aged mice at all time points studied, and in the aged mice the return to baseline levels was delayed. Basal mRNA expression of GFAP and S100B, markers of activated astrocytes, was higher in aged mice. Both markers increased and reached maximum 7 days post injury. The mRNA expression of astrocyte markers returned to near basal levels rapidly after injury in the adult mice, whereas again in the aged mice return to baseline was delayed. Immunochemical analysis using Iba1 and GFAP antibodies indicate accentuated glial responses in the aged hippocampus after injury. The pronounced and prolonged activation of microglia and astrocytes in hippocampus may contribute to worse cognitive outcomes in the elderly following TBI. PMID:18692046

  8. Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation.

    PubMed

    Mirkov, Ivana; Popov Aleksandrov, Aleksandra; Subota, Vesna; Kataranovski, Dragan; Kataranovski, Milena

    2018-03-01

    Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage. © 2017 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  9. Number of Langerhans cells is decreased in premalignant keratosis and skin cancers.

    PubMed

    Shevchuk, Z; Filip, A; Shevchuk, V; Kashuba, E

    2014-03-01

    It was shown earlier that a number of CD207 positive Langerhans cells was lower in basal cell carcinomas than in the normal epidermis. Moreover, benign skin lesions presented a higher number of Langerhans cells when they were compared to malignant tumors. To count Langerhans cells, assessing expression levels of CD1A and CD207 markers in actinic keratosis, basal and squamous cell carcinomas, compared with the normal skin. Comparison of Langerhans cells might give a valuable prognostic marker for skin cancer. Immunohistochemistry and methods of statistics were used. Expression of CD1A and CD207 markers was assessed in tumor samples of actinic keratosis, cutaneous basal and squamous cell carcinomas, in comparison with the normal skin. In each cohort there were 40 patients (and 11 healthy individuals). We have shown that the number of Langerhans cells is considerably lower in cutaneous basal and squamous cell carcinomas, compared with their number in the normal skin (p < 0.0001). CD1A expression correlated with CD207 expression only in the control group. There was no correlation in actinic keratosis, basal and squamous cell carcinoma. This may suggest an alteration of Langerhans cells phenotype in skin neoplastic diseases, making the number of Langerhans cells a valuable prognostic factor for skin tumors.

  10. Effects of dietary β-glucan and glycyrrhizin on non-specific immunity and disease resistance of the sea cucumber ( Apostichopus japonicus Selenka) challenged with Vibrio splendidus

    NASA Astrophysics Data System (ADS)

    Chang, Jie; Zhang, Wenbing; Mai, Kangsen; Ma, Hongming; Xu, Wei

    2010-12-01

    Sea cucumbers, Apostichopus japonicus Selenka, were fed diets containing non-immunostimulant (basal diet), 0.2% β-glucan and 0.02% glycyrrhizin in a recirculatory water system for 45 days, and subsequently challenged with Vibrio splendidus by injection at 1.0×108 cfu / sea cucumber for 15 days. Phagocytic capacity (PC), intracellular superoxide anion production (ISAP), lysozyme (LSZ) activity and superoxide dismutase (SOD) activity in the coelomic fluid were analyzed on the 0th, 5th, 10th and 15th days after injection. Results showed that after the 45-day feeding period, PC, ISAP, LSZ activity and SOD activity in sea cucumbers fed with dietary β-glucan or glycyrrhizin were significantly higher than in those fed with the basal diet. On the 5th day after infection, all the immune parameters examined in the sea cucumbers injected with V. splendidus decreased in value significantly. On the 15th day, PC, ISAP and LSZ activity returned to levels similar to those on the 0th day. For the sea cucumbers injected with saline, there were no significant differences in all the immune parameters examined and in the cumulative morbidity during the 15-day challenging trial. After injecting with V. splendidus, the cumulative morbidity of sea cucumbers fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin when challenged with V. splendidus challenged sea cucumber fed with the basal diet was significantly higher than those fed with dietary β-glucan or glycyrrhizin. There was no significant difference in cumulative morbidity between the dietary β-glucan and glycyrrhizin treatments over time.

  11. Baseline Levels and Trimestral Variation of Triiodothyronine and Thyroxine and Their Association with Mortality in Maintenance Hemodialysis Patients

    PubMed Central

    Meuwese, Christiaan L.; Dekker, Friedo W.; Lindholm, Bengt; Qureshi, Abdul R.; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J.

    2012-01-01

    Summary Background and objectives Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. Design, setting, participants, & measurements In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan–Meier curves and Cox proportional hazard models. Results During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Conclusions Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect. PMID:22246282

  12. Baseline levels and trimestral variation of triiodothyronine and thyroxine and their association with mortality in maintenance hemodialysis patients.

    PubMed

    Meuwese, Christiaan L; Dekker, Friedo W; Lindholm, Bengt; Qureshi, Abdul R; Heimburger, Olof; Barany, Peter; Stenvinkel, Peter; Carrero, Juan J

    2012-01-01

    Conflicting evidence exists with regard to the association of thyroid hormones and mortality in dialysis patients. This study assesses the association between basal and trimestral variation of thyroid stimulating hormone, triiodothyronine, and thyroxine and mortality. In 210 prevalent hemodialysis patients, serum triiodothyronine, thyroxine, thyroid stimulating hormone, and interleukin-6 were measured 3 months apart. Cardiovascular and non-cardiovascular deaths were registered during follow-up. Based on fluctuations along tertiles of distribution, four trimestral patterns were defined for each thyroid hormone: persistently low, decrease, increase, and persistently high. The association of baseline levels and trimestral variation with mortality was investigated with Kaplan-Meier curves and Cox proportional hazard models. During follow-up, 103 deaths occurred. Thyroid stimulating hormone levels did not associate with mortality. Patients with relatively low basal triiodothyronine concentrations had higher hazards of dying than patients with high levels. Longitudinally, patients with persistently low levels of triiodothyronine during the 3-month period had higher mortality hazards than those having persistently high levels. These associations were mainly attributable to cardiovascular-related mortality. The association between thyroxine and mortality was not altered after adjustment for triiodothyronine. Hemodialysis patients with reduced triiodothyronine or thyroxine levels bear an increased mortality risk, especially due to cardiovascular causes. This was true when considering both baseline measurements and trimestral variation patterns. Our longitudinal design adds observational evidence supporting the hypothesis that the link may underlie a causal effect.

  13. Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus.

    PubMed

    Laimer, Markus; Melmer, Andreas; Mader, Julia K; Schütz-Fuhrmann, Ingrid; Engels, Heide-Rose; Götz, Gabriele; Pfeifer, Martin; Hermann, Julia M; Stettler, Christoph; Holl, Reinhard W

    2016-01-01

    Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p<0.001) and diabetic ketoacidosis (β = 0.012; p = 0.017). Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

  14. Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

    PubMed Central

    Floquet, Célia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

    2012-01-01

    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

  15. The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals.

    PubMed

    Juncal-Ruiz, María; Riesco-Dávila, Laura; de la Foz, Víctor Ortiz-García; Ramírez-Bonilla, Mariluz; Martínez-García, Obdulia; Irure-Ventura, Juan; Leza, Juan Carlos; López-Hoyos, Marcos; Crespo-Facorro, Benedicto

    2018-02-28

    Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1β, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1β, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.

  16. Effects of various feeding patterns of Bacillus coagulans on growth performance, antioxidant response and Nrf2-Keap1 signaling pathway in juvenile gibel carp (Carassius auratus gibelio).

    PubMed

    Yu, Yebing; Wang, Changhai; Wang, Aimin; Yang, Wenping; Lv, Fu; Liu, Fei; Liu, Bo; Sun, Cunxin

    2018-02-01

    The present study was conducted to evaluate the effects of various Bacillus coagulans feeding patterns on growth, antioxidant parameter and Nrf2 pathway in juvenile gibel carp. The similar size of gibel carp (initial weight: 14.33 ± 0.15 g) were subjected to three levels of B. coagulans supplementation (0, 500, and 1000 mg/kg) and two feeding modes (supplementing B. coagulans continuously or for two days of B. coagulans after 5 days of a basal diet) according to a 3 × 2 factorial design. The fish that were continuously fed 500 mg/kg B. coagulans (P2) and those fed the first basal diet for 5 days followed by 500 mg/kg or 1000 mg/kg B.coagulans for 2 days (P4 or P5) showed higher weight gain rate and specific growth rate than the other groups. Blood respiratory burst (RB), myeloperoxidase (MPO), and anti-superoxide anion free radical (AFASER) activities in the P4 group were higher than those of the control. White blood cell count (WBC), RB activity, MPO activity, and glutathione (GSH) content in the P5 group were also higher than those of the control. A similar higher trend was observed in the gene expressions of NADPH oxidase 2 (NOX2), NFE2-related factor (Nrf2), Kelch-like-ECH-associated protein(Keap1) in the P4 and NOX2, NRF2, CNC homolog 1 (Bach1), peroxiredoxin 2 (Prx2) in the P5 group compared with the control. Additionally, we observed a significantly lower level of plasma aspartate aminotransferase (AST), lower activity of alanine aminotransferase (ALT), a higher level of MPO, higher GPX activity, and increased NRF2 and Prx2 expression were all observed in the P2 treatment group compared with the control. Furthermore, the malondialdehyde (MDA) content in the P2, P3, and P4 groups was lower than that of the control. These results indicate that a diet supplemented with appropriate levels of B.coagulans could improve the growth, immune response, and antioxidant capability of gibel carp. We concluded that the pattern of two days of 500 or 1000 mg/kg B. coagulans after 5 days of a basal diet was recommended for gibel carp. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effects of prebiotics, probiotics, and their combination on growth performance, small intestine morphology, and resident Lactobacillus of male broilers.

    PubMed

    Wang, X; Farnell, Y Z; Peebles, E D; Kiess, A S; Wamsley, K G S; Zhai, W

    2016-06-01

    Effects of commercial antimicrobials and the individual and combinational use of commercial prebiotics and probiotics in feed from d zero to 41 on the growth performance, small intestine size, jejunal morphology, and ileal resident bacteria population of broiler chickens were determined. A total of 1,040 one-day-old male Ross × Ross 708 broilers were randomly distributed to 80 floor pens (5 treatments, 16 replications per treatment, 13 chicks per pen). Five dietary treatments were employed: 1) a corn soybean-meal basal diet (served as a negative control diet, NC); 2) a basal diet supplemented with a commercial prebiotic product (Pre); 3) a basal diet supplemented with a probiotic product containing Bacillus subtilis spores (Pro); 4) a basal diet supplemented with both prebiotic and probiotic products (Pre + Pro); and 5) a basal diet supplemented with commercial antimicrobials (served as a positive control diet, PC). At d 14, Pre diets improved the relative level of Lactobacillus in ileal mucosa as compared to NC, Pro, or PC diets (P = 0.045) without improving broiler BW. Broilers fed PC diets exhibited the highest BW gain from d 15 to 27, the lowest duodenum, jejunum, and ileum relative weights as percentage of BW at d 27, and the highest breast weight at d 42 (P = 0.026, 0.035, 0.002, 0.025, and 0.035, respectively). Broilers fed Pro or Pre + Pro diets exhibited higher BW gain from d 28 to 41 (P = 0.005) and higher overall BW gain from d zero to 41 (P = 0.039) than those fed other diets. Dietary treatments did not affect jejunal morphology or ileal resident Escherichia coli level at any age. From our results, including spores of Bacillus subtilis in feed may stimulate growth at a later age and may facilitate broilers in reaching their target weight sooner. Therefore, probiotics are recommended as potential alternatives to antimicrobials in chicken diets, especially in grower and finisher feed. © 2016 Poultry Science Association Inc.

  18. Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication.

    PubMed

    Gil, Hyo-wook; Kang, Eun-jung; Lee, Kwon-hyun; Yang, Jong-oh; Lee, Eun-young; Hong, Sae-yong

    2011-01-01

    In order to evaluate the efficiency and renal protective effects of glutathione during Ca(++)-EDTA chelation therapy for chronic cadmium intoxication, we measured the renal excretion of cadmium, β(2)-microglobulin, proteinuria, and hematuria during intravenous administration of glutathione with Ca(++)-EDTA in a 54-year-old patient with chronic cadmium intoxication. We administered 500 mg of Ca(++)-EDTA and 50 mg/kg of glutathione alone or in 1 L of normal saline over the next 24 hours and repeated this over 12 consecutive days. During the first 3 days, the basal levels (only saline administration) were determined; during the second 3 days, Ca(++)-EDTA only was administered, for the third sequence of 3 days, Ca(++)-EDTA with glutathione was provided, and for the last 3 days, glutathione alone was given. One month later, the same protocol was repeated. There were six blood and urine samples to analyze in each group. The blood cadmium level was higher when the EDTA was infused together with glutathione (7.44 ± 0.73 µg/L, p < 0.01) compared to the basal level of 4.6 ± 0.44 µg/L. Also, the renal cadmium excretion was significantly higher in the EDTA with glutathione group than in the basal group (23.4 ± 15.81 µg/g creatinine vs 89.23 ± 58.52 µg/g creatinine, p < 0.01). There was no difference in the protein/creatinine and β(2)-microglobulin/creatinine ratio in the urine (p > 0.05) among the groups. Furthermore, microhematuria and proteinuria did not develop over the observation period of 6 months. These results suggest that glutathione administration with EDTA might be an effective treatment modality for patients with cadmium intoxication.

  19. Erythropoietin during hypoglycaemia in type 1 diabetes: relation to basal renin-angiotensin system activity and cognitive function.

    PubMed

    Kristensen, Peter Lommer; Høi-Hansen, Thomas; Olsen, Niels Vidiendal; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2009-07-01

    Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function. We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1 diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion. Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia. Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia.

  20. Readability Levels of First and Second Grade Basal Texts.

    ERIC Educational Resources Information Center

    Langan, Yvette

    The Fry Readability Formula was used to determine the readability levels of 12 first and second grade basal texts. These texts were part of the Ginn 360, Ginn 720, and Macmillan Series "r" basal reader series. The results showed that 4 of the 12 books tested did not correspond closely to the publisher's readability levels. The Ginn 720 text for…

  1. Exploring the effects of inclusion of dietary fresh Azolla on the performance of White Pekin broiler ducks.

    PubMed

    Acharya, Parag; Mohanty, G P; Pradhan, C R; Mishra, S K; Beura, N C; Moharana, B

    2015-11-01

    The objective of this study was to investigate the dietary advantages of inclusion of unconventional nutrient source, i.e., Azolla in the basal diet of White Pekin broilers. All ducklings were randomly distributed into three treatment groups with three replicates each and each replicate having 12 ducklings and were reared in deep litter system. Groups were subjected to three dietary treatments such as G1: Basal diet, G2: Basal diet + 5% fresh Azolla of basal diet, G3: Basal diet + 10% fresh Azolla of basal diet. During experimental period, parameters, such as bodyweight, bodyweight gain, feed consumption,feed conversion ratio(FCR), and economic of production,wererecorded. The result showed that body weights in every week, except the 5(th) week, did not differ significantly between groups. However, no significant difference was observed between the groups in any week in terms of absolute body weight gain and feed consumption. As regard to FCR, the 10% Azolla group (G3) showed the best feed efficiency followed by the 5% Azolla group (G2) and the control group (G1). On the basis of profit/bird or profit/kg live weight, each of the Azolla-fed group showed a higher economic efficiency than the control. From the experiment, it was concluded that Azollaat 5 or 10% level can be included in the diet to economize the White Pekin broiler farming, and it can be great impetus to poultry farming to include unconventional nutrient source as a dietary supplement.

  2. Striatal GABA-MRS predicts response inhibition performance and its cortical electrophysiological correlates.

    PubMed

    Quetscher, Clara; Yildiz, Ali; Dharmadhikari, Shalmali; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Dydak, Ulrike; Beste, Christian

    2015-11-01

    Response inhibition processes are important for performance monitoring and are mediated via a network constituted by different cortical areas and basal ganglia nuclei. At the basal ganglia level, striatal GABAergic medium spiny neurons are known to be important for response selection, but the importance of the striatal GABAergic system for response inhibition processes remains elusive. Using a novel combination of behavior al, EEG and magnetic resonance spectroscopy (MRS) data, we examine the relevance of the striatal GABAergic system for response inhibition processes. The study shows that striatal GABA levels modulate the efficacy of response inhibition processes. Higher striatal GABA levels were related to better response inhibition performance. We show that striatal GABA modulate specific subprocesses of response inhibition related to pre-motor inhibitory processes through the modulation of neuronal synchronization processes. To our knowledge, this is the first study providing direct evidence for the relevance of the striatal GABAergic system for response inhibition functions and their cortical electrophysiological correlates in humans.

  3. Thyroid-stimulating hormone, 5-HTTLPR genotype, and antidepressant response in depressed women.

    PubMed

    Gressier, Florence; Trabado, Séverine; Verstuyft, Céline; Bouaziz, Elodie; Hardy, Patrick; Fève, Bruno; Becquemont, Laurent; Corruble, Emmanuelle

    2011-10-01

    Basal serum thyroid-stimulating hormone (TSH) levels may predict antidepressant efficacy in patients with major depressive episodes (MDE), but data are inconsistent. As the SS genotype of the 5-HTTLPR polymorphism has been associated with a lower antidepressant efficacy in women with MDE, we aimed at assessing the relationship between normal basal TSH, 5-HTTLPR, and antidepressant efficacy in women. A total of 71 women and 28 men, with normal baseline TSH serum levels, hospitalized for a MDE, were assessed for 5-HTTLPR genotypes and prospectively followed for short-term antidepressant efficacy. Women with SS genotype had higher TSH levels (P=0.002) and a worse antidepressant response (P=0.046) than the women with LL/LS genotype, whereas no significant difference was shown in men. In multivariate analyses, antidepressant response in women was explained by TSH and 5-HTTLPR, but not by other variables. Further research is needed to understand the underlying mechanism explaining interactions between sex, TSH, and serotonergic function.

  4. PubMed Central

    Carbonneau, Roch; Demers, Jean-Marie

    1965-01-01

    The object of this experiment was to study the influence of essential amino acids on the growth, fatty infiltration of liver and cholesterol level of the serum in ducklings. A 11 per cent protein basal diet, deficient in many essential amino acids, given to ducklings, resulted in poor growth, fatty infiltration of liver and high cholesterol level of the serum. In our experimental design, three amino acids, lysine, methionine and threonine were promoting growth whereas lysine and threonine were preventing fatty infiltration of liver but methionine failed to do so. Rather than a deficiency in lysine alone, simultaneous deficiencies in valine, arginine and lysine resulted in better growth for ducklings. This protective effect of deficiency in valine and arginine together with one in lysine was not effective against fatty infiltration of liver. The cholesterolemia found for the ducklings given basal diet or diets with deficiency in many essential amino acids was higher than that found for the ducklings given diets without essential amino acids deficiency. PMID:4220644

  5. Changes in circulating cytokines and markers of muscle damage in elite cyclists during a multi-stage competition.

    PubMed

    Córdova Martínez, Alfredo; Martorell Pons, Miquel; Sureda Gomila, Antoni; Tur Marí, Josep A; Pons Biescas, Antoni

    2015-09-01

    The purpose of this study was to determine the changes in the basal and post-exercise plasma markers of muscular damage, lipid peroxidation and cytokines in eight male well-trained semiprofessional cyclists, in response to a three consecutive-day cycling competition. Serum markers of oxidative and muscular damage - creatine kinase activity, lactate dehydrogenase activity, myoglobin and malondialdehyde (MDA), creatinine and nitrite levels - followed a sawtooth-type representation throughout the competition. MDA showed an accumulative pattern, evidenced in the post-race values of the third stage which were significantly higher with respect to the values of the first stage. Cortisol levels were significantly influenced by an interaction between the exercise and the stage factors, with higher values on the 4th day. Plasma cytokine levels were only determined before the first stage and post-race, after the third stage. The exercise increased TNFα, IL6, IL2 and IFNγ levels, whereas IL1β was unchanged. In conclusion, cyclist stages induced oxidative and cellular muscle damage which is partially recovered to basal values by the next morning. Repetitive stages during the cycling competition accumulated plasma muscular damage and lipid peroxidation markers and pro-inflammatory cytokines, probably as a result of local inflammatory responses. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  6. Hypoxia Induces an Increase in Intracellular Magnesium via Transient Receptor Potential Melastatin 7 (TRPM7) Channels in Rat Hippocampal Neurons in Vitro*

    PubMed Central

    Zhang, Jing; Zhao, Fengbo; Zhao, Yin; Wang, Jing; Pei, Lei; Sun, Ning; Shi, Jing

    2011-01-01

    TRPM7, a divalent cation channel, plays an important role in neurons damaged from cerebral ischemia due to permitting intracellular calcium overload. This study aimed to explore whether magnesium was transported via a TRPM7 channel into the intracellular space of rat hippocampal neurons after 1 h of oxygen-glucose deprivation (OGD) and acute chemical ischemia (CI) by using methods of the Mg2+ fluorescent probe Mag-Fura-2 to detect intracellular magnesium concentration ([Mg2+]i) and flame atomic absorption spectrometry to measure extracellular magnesium concentration ([Mg2+]o). The results showed that the neuronal [Mg2+]i was 1.51-fold higher after 1 h of OGD at a basal level, and the increase of neuronal [Mg2+]i reached a peak after 1 h of OGD and was kept for 60 min with re-oxygenation. Meanwhile, the [Mg2+]o decreased after 1 h of OGD and recovered to the pre-ischemic level within 15 min after re-oxygenation. In the case of CI, the [Mg2+]i peak immediately appeared in hippocampal neurons. This increase of [Mg2+]i declined by removing extracellular magnesium in OGD or CI. Furthermore, by using Gd3+ or 2-aminoethoxydiphenyl borate to inhibit TRPM7 channels, the [Mg2+]i increase, which was induced by OGD or CI, was attenuated without altering the basal level of [Mg2+]i. By silencing TRPM7 with shRNA in hippocampal neurons, it was found that not only was the increase of [Mg2+]i induced by OGD or CI but also the basal levels of [Mg2+]i were attenuated. In contrast, overexpression of TRPM7 in HEK293 cells exaggerated both the basal levels and increased [Mg2+]i after 1 h of OGD/CI. These results suggest that anoxia induced the increase of [Mg2+]i via TRPM7 channels in rat hippocampal neurons. PMID:21487014

  7. Rehabilitation program based on sensorimotor recovery improves the static and dynamic balance and modifies the basal ganglia neurochemistry

    PubMed Central

    Delli Pizzi, Stefano; Bellomo, Rosa Grazia; Carmignano, Simona Maria; Ancona, Emilio; Franciotti, Raffaella; Supplizi, Marco; Barassi, Giovanni; Onofrj, Marco; Bonanni, Laura; Saggini, Raoul

    2017-01-01

    Abstract Rehabilitation interventions represent an alternative strategy to pharmacological treatment in order to slow or reverse some functional aspects of disability in Parkinson's disease (PD). To date, the neurophysiological mechanisms underlying rehabilitation-mediated improvement in PD patients are still poorly understood. Interestingly, growing evidence has highlighted a key role of the glutamate in neurogenesis and brain plasticity. The brain levels of glutamate, and of its precursor glutamine, can be detected in vivo and noninvasively as “Glx” by means of proton magnetic resonance spectroscopy (1H-MRS). In the present pilot study, 7 PD patients with frequent falls and axial dystonia underwent 8-week rehabilitative protocol focused on sensorimotor improvement. Clinical evaluation and Glx quantification were performed before and after rehabilitation. The Glx assessment was focused on the basal ganglia in agreement with their key role in the motor functions. We found that the rehabilitation program improves the static and dynamic balance in PD patients, promoting a better global motor performance. Moreover, we observed that the levels of Glx within the left basal ganglia were higher after rehabilitation as compared with baseline. Thus, we posit that our sensorimotor rehabilitative protocol could stimulate the glutamate metabolism in basal ganglia and, in turn, neuroplasticity processes. We also hypothesize that these mechanisms could prepare the ground to restore the functional interaction among brain areas deputed to motor controls, which are affected in PD. PMID:29390267

  8. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  9. Association of basal serum androgen levels with ovarian response and ICSI cycle outcome.

    PubMed

    Abide Yayla, C; Ozkaya, E; Kayatas Eser, S; Sanverdi, I; Devranoglu, B; Kutlu, T

    2018-05-01

    The purpose of this study was to assess the predictive value of basal serum testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) levels during follicular phase for ovarian response and outcome in intracytoplasmic sperm injection (ICSI) cycles of women with diminished ovarian reserve. We prospectively gathered data of basal serum androgen levels and ICSI cycle characteristics of 120 women with diminished ovarian reserve. Association of basal serum T and DHEAS levels with ovarian response was analyzed. Basal T and DHEAS levels were similar between pregnant and non-pregnant cases (P > 0.05). There were significant differences between groups with and without successful embryo implantation in terms of serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), gonadotropin starting and total dose, and peak estradiol level (P < 0.05). There were 58 (49.2%) cases who did not reach to the embryo transfer stage due to several reasons including cancelation of stimulation due to unresponsiveness (n = 26, 21.7%), no oocyte at oocyte pickup (n = 11, 9.2%), no mature oocyte (n = 6, 5%), and failure of fertilization or embryo development (n = 15, 12.5%). Basal androgen levels were not significant predictors for any of the cycle outcome. AMH level was a significant predictor for failure of fertilization or embryo development (AUC 0.722, P = 0.01) and cancelation of stimulation (AUC 0.801, P < 0.001). FSH was a significant predictor for cancelation of stimulation (AUC 0.774, P < 0.001). In women with diminished ovarian reserve, basal T and DHEAS levels have no value in predicting any of the cycle outcome parameters.

  10. Binge-Like Ethanol Consumption Increases Corticosterone Levels and Neurodegneration whereas occupancy of Type II Glucocorticoid Receptors with Mifepristone is Neuroprotective

    PubMed Central

    Cippitelli, Andrea; Damadzic, Ruslan; Hamelink, Carol; Brunnquell, Michael; Thorsell, Annika; Heilig, Markus; Eskay, Robert L

    2012-01-01

    Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing basal, medium or high Cort. Intragastric EtOH or an isocaloric control solution was given 3 times daily for 4 days to achieve blood alcohol levels (BALs) ranging between 200-350 mg/dl. Mean 24 hour (24-hr) plasma Cort levels were ~110 ng/ml and ~40 ng/ml in intact EtOH treated and intact control, respectively. Basal Cort replacement in EtOH-treated Adx animals animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement resulting in levels 2-fold higher (medium) than normal, or higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocortocoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone treated animals in the EC, as determined by Fluoro Jade B staining. These results suggest that Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors. PMID:22500955

  11. Basal ganglia function, stuttering, sequencing, and repair in adult songbirds

    PubMed Central

    Kubikova, Lubica; Bosikova, Eva; Cvikova, Martina; Lukacova, Kristina; Scharff, Constance; Jarvis, Erich D.

    2014-01-01

    A pallial-basal-ganglia-thalamic-pallial loop in songbirds is involved in vocal motor learning. Damage to its basal ganglia part, Area X, in adult zebra finches has been noted to have no strong effects on song and its function is unclear. Here we report that neurotoxic damage to adult Area X induced changes in singing tempo and global syllable sequencing in all animals, and considerably increased syllable repetition in birds whose song motifs ended with minor repetitions before lesioning. This stuttering-like behavior started at one month, and improved over six months. Unexpectedly, the lesioned region showed considerable recovery, including immigration of newly generated or repaired neurons that became active during singing. The timing of the recovery and stuttering suggest that immature recovering activity of the circuit might be associated with stuttering. These findings indicate that even after juvenile learning is complete, the adult striatum plays a role in higher level organization of learned vocalizations. PMID:25307086

  12. Integrin-mediated traction force enhances paxillin molecular associations and adhesion dynamics that increase the invasiveness of tumor cells into a three-dimensional extracellular matrix

    PubMed Central

    Mekhdjian, Armen H.; Kai, FuiBoon; Rubashkin, Matthew G.; Prahl, Louis S.; Przybyla, Laralynne M.; McGregor, Alexandra L.; Bell, Emily S.; Barnes, J. Matthew; DuFort, Christopher C.; Ou, Guanqing; Chang, Alice C.; Cassereau, Luke; Tan, Steven J.; Pickup, Michael W.; Lakins, Jonathan N.; Ye, Xin; Davidson, Michael W.; Lammerding, Jan; Odde, David J.; Dunn, Alexander R.; Weaver, Valerie M.

    2017-01-01

    Metastasis requires tumor cells to navigate through a stiff stroma and squeeze through confined microenvironments. Whether tumors exploit unique biophysical properties to metastasize remains unclear. Data show that invading mammary tumor cells, when cultured in a stiffened three-dimensional extracellular matrix that recapitulates the primary tumor stroma, adopt a basal-like phenotype. Metastatic tumor cells and basal-like tumor cells exert higher integrin-mediated traction forces at the bulk and molecular levels, consistent with a motor-clutch model in which motors and clutches are both increased. Basal-like nonmalignant mammary epithelial cells also display an altered integrin adhesion molecular organization at the nanoscale and recruit a suite of paxillin-associated proteins implicated in invasion and metastasis. Phosphorylation of paxillin by Src family kinases, which regulates adhesion turnover, is similarly enhanced in the metastatic and basal-like tumor cells, fostered by a stiff matrix, and critical for tumor cell invasion in our assays. Bioinformatics reveals an unappreciated relationship between Src kinases, paxillin, and survival of breast cancer patients. Thus adoption of the basal-like adhesion phenotype may favor the recruitment of molecules that facilitate tumor metastasis to integrin-based adhesions. Analysis of the physical properties of tumor cells and integrin adhesion composition in biopsies may be predictive of patient outcome. PMID:28381423

  13. Neurotransmitter activity is linked to outcome following subthalamic deep brain stimulation in Parkinson's disease.

    PubMed

    O'Gorman Tuura, Ruth L; Baumann, Christian R; Baumann-Vogel, Heide

    2018-05-01

    While the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's Disease (PD) are not yet fully understood, DBS appears to exert a wide range of neurochemical effects on the network level, thought to arise from activation of inhibitory and excitatory pathways. The activity within the primary inhibitory (GABAergic) and excitatory (glutamatergic) neurotransmitter systems may therefore play an important role in the therapeutic efficacy of DBS in PD. The purpose of this study was to investigate abnormalities in GABA-ergic and glutamatergic neurotransmission in PD, and to examine the link between neurotransmitter levels and outcome following DBS. Magnetic resonance spectra were acquired from the pons and basal ganglia in sixteen patients with PD and sixteen matched control participants. GABA and glutamate levels were quantified with LCModel, an automated spectral fitting package. Fourteen patients subsequently underwent DBS, and PD symptoms were evaluated with the MDS-UPDRS at baseline and six months after surgery. The efficacy of DBS treatment was evaluated from the percentage improvement in MDS-UPDRS scores. Basal ganglia GABA levels were significantly higher in PD patients relative to control participants (p < 0.01), while pontine glutamate + glutamine (Glx) levels were significantly lower in patients with PD (p < 0.05). While GABA levels were not significantly related to outcome post-surgery, basal ganglia glutamate levels emerged as a significant predictor of outcome, suggesting a possible role for glutamatergic neurotransmission in the therapeutic mechanism of DBS. GABAergic and glutamatergic neurotransmission is altered in PD, and glutamatergic activity in particular may influence outcome post-surgery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. β-Cells with relative low HIMP1 overexpression levels in a transgenic mouse line enhance basal insulin production and hypoxia/hypoglycemia tolerance.

    PubMed

    Zhang, Xiaoping; Degenstein, Linda; Cao, Yun; Stein, Jeffrey; Osei, Kwame; Wang, Jie

    2012-01-01

    Rodent pancreatic β-cells that naturally lack hypoglycemia/hypoxia inducible mitochondrial protein 1 (HIMP1) are susceptible to hypoglycemia and hypoxia influences. A linkage between the hypoglycemia/hypoxia susceptibility and the lack of HIMP1 is suggested in a recent study using transformed β-cells lines. To further illuminate this linkage, we applied mouse insulin 1 gene promoter (MIP) to control HIMP1-a isoform cDNA and have generated three lines (L1 to L3) of heterozygous HIMP1 transgenic (Tg) mice by breeding of three founders with C57BL/6J mice. In HIMP1-Tg mice/islets, we performed quantitative polymerase chain reaction (PCR), immunoblot, histology, and physiology studies to investigate HIMP1 overexpression and its link to β-cell function/survival and body glucose homeostasis. We found that the HIMP1 level increased steadily in β-cells of L1 to L3 heterozygous HIMP1-Tg mice. HIMP1 overexpression at relatively lower levels in L1 heterozygotes results in a negligible decline in blood glucose concentrations and an insignificant elevation in blood insulin levels, while HIMP1 overexpression at higher levels are toxic, causing hyperglycemia in L2/3 heterozygotes. Follow-up studies in 5-30-week-old L1 heterozygous mice/islets found that HIMP1 overexpression at relatively lower levels in β-cells has enhanced basal insulin biosynthesis, basal insulin secretion, and tolerances to low oxygen/glucose influences. The findings enforced the linkage between the hypoglycemia/hypoxia susceptibility and the lack of HIMP1 in β-cells, and show a potential value of HIMP1 overexpression at relatively lower levels in modulating β-cell function and survival.

  15. HDAC1 and HDAC2 are Differentially Expressed in Endometriosis

    PubMed Central

    Colón-Díaz, Maricarmen; Báez-Vega, Perla; García, Miosotis; Ruiz, Abigail; Monteiro, Janice B.; Fourquet, Jessica; Bayona, Manuel; Alvarez-Garriga, Carolina; Achille, Alexandra; Seto, Edward; Flores, Idhaliz

    2012-01-01

    Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormone-regulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue microarray (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 + P4 in endometrial stromal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs. PMID:22344732

  16. Inorganic phosphorus (Pi) in CSF is a biomarker for SLC20A2-associated idiopathic basal ganglia calcification (IBGC1).

    PubMed

    Hozumi, Isao; Kurita, Hisaka; Ozawa, Kazuhiro; Furuta, Nobuyuki; Inden, Masatoshi; Sekine, Shin-Ichiro; Yamada, Megumi; Hayashi, Yuichi; Kimura, Akio; Inuzuka, Takashi; Seishima, Mitsuru

    2018-05-15

    Idiopathic basal ganglia calcification (IBGC), also called Fahr's disease or recently primary familial brain calcification (PFBC), is characterized by abnormal deposits of minerals including calcium mainly and phosphate in the brain. Mutations in SLC20A2 (IBGC1 (merged with former IBGC2 and IBGC3)), which encodes PiT-2, a phosphate transporter, is the major cause of IBGC. Recently, Slc20a2-KO mice have been showed to have elevated levels of inorganic phosphorus (Pi) in cerebrospinal fluid (CSF); however, CSF Pi levels in patients with IBGC have not been fully examined. We investigated the cases of 29 patients with IBGC including six patients with SLC20A2 mutation and three patients with PDGFB mutation, and 13 controls. The levels of sodium (Na), potassium (K), chloride (Cl), calcium (Ca), and Pi in sera and CSF were determined by potentiometry and colorimetry. Moreover, clinical manifestations were investigated in the IBGC patients with high Pi levels in CSF. The study revealed that the average level of Pi in the CSF of the total group of patients with IBGC is significantly higher than that of the control group, and the levels of Pi in CSF of the IBGC patients with SLC20A2 mutations are significantly higher than those of the IBGC patients with PDGFB mutations, the other IBGC patients and controls. Results of this study suggest that the levels of CSF Pi will be a good biomarker for IBGC1. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Dental Pulp Stem Cell-Derived, Scaffold-Free Constructs for Bone Regeneration.

    PubMed

    Tatsuhiro, Fukushima; Seiko, Tatehara; Yusuke, Takebe; Reiko, Tokuyama-Toda; Kazuhito, Satomura

    2018-06-22

    In the present study, a scaffold-free tissue construct was developed as an approach for the regeneration of tissue defects, which produced good outcomes. We fabricated a scaffold-free tissue construct from human dental pulp stem cells (hDPSCs construct), and examined the characteristics of the construct. For its fabrication, basal sheets prepared by 4-week hDPSCs culturing were subjected to 1-week three-dimensional culture, with or without osteogenic induction, whereas hDPSC sheets (control) were fabricated by 1-week culturing of basal sheets on monolayer culture. The hDPSC constructs formed a spherical structure and calcified matrix that are absent in the control. The expression levels for bone-related genes in the hDPSC constructs were significantly upregulated compared with those in the control. Moreover, the hDPSC constructs with osteogenic induction had a higher degree of calcified matrix formation, and higher expression levels for bone-related genes, than those for the hDPSC constructs without osteogenic induction. These results suggest that the hDPSC constructs with osteogenic induction are composed of cells and extracellular and calcified matrices, and that they can be a possible scaffold-free material for bone regeneration.

  18. Developing Higher Order Reading Comprehension Skills in the Learning Disabled Student: A Non-Basal Approach.

    ERIC Educational Resources Information Center

    Solomon, Sheila

    This practicum study evaluated a non-basal, multidisciplinary, multisensory approach to teaching higher order reading comprehension skills to eight fifth-grade learning-disabled students from low socioeconomic minority group backgrounds. The four comprehension skills were: (1) identifying the main idea; (2) determining cause and effect; (3) making…

  19. Exploring the effects of inclusion of dietary fresh Azolla on the performance of White Pekin broiler ducks

    PubMed Central

    Acharya, Parag; Mohanty, G. P.; Pradhan, C. R.; Mishra, S. K.; Beura, N. C.; Moharana, B.

    2015-01-01

    Aim: The objective of this study was to investigate the dietary advantages of inclusion of unconventional nutrient source, i.e., Azolla in the basal diet of White Pekin broilers. Materials and Methods: All ducklings were randomly distributed into three treatment groups with three replicates each and each replicate having 12 ducklings and were reared in deep litter system. Groups were subjected to three dietary treatments such as G1: Basal diet, G2: Basal diet + 5% fresh Azolla of basal diet, G3: Basal diet + 10% fresh Azolla of basal diet. During experimental period, parameters, such as bodyweight, bodyweight gain, feed consumption,feed conversion ratio(FCR), and economic of production,wererecorded. Results: The result showed that body weights in every week, except the 5th week, did not differ significantly between groups. However, no significant difference was observed between the groups in any week in terms of absolute body weight gain and feed consumption. As regard to FCR, the 10% Azolla group (G3) showed the best feed efficiency followed by the 5% Azolla group (G2) and the control group (G1). On the basis of profit/bird or profit/kg live weight, each of the Azolla-fed group showed a higher economic efficiency than the control. Conclusion: From the experiment, it was concluded that Azollaat 5 or 10% level can be included in the diet to economize the White Pekin broiler farming, and it can be great impetus to poultry farming to include unconventional nutrient source as a dietary supplement. PMID:27047032

  20. Saccharomyces boulardii and Bacillus subtilis B10 modulate TLRs and cytokines expression patterns in jejunum and ileum of broilers

    PubMed Central

    Yajing, Sun; Arain, Muhammad Asif; Weifen, Li; Ping, Li; Bloch, Dost Muhammad; Wenhua, Liu

    2017-01-01

    The present study was designed to evaluate the effects of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on intestinal epithelial Toll like receptors (TLR), and Cytokine expression response to understand the intestinal epithelial innate immune mechanism in broilers. A total of 300 birds (Sanhuang broilers) were allotted into three groups (n = 100) and each divided into five replications (n = 20). Control group (Ctr) birds were fed basal diet, broilers in experimental groups received (1×108cfu/kg feed) Sb and Bs respectively in addition to basal diet for 72 days. The result showed significant increase in mRNA expression level of TLR2, TLR4 and TLR15. Down streaming MyD88, TRAF6, TAB2 and NF-κB mRNA level noted higher, in the jejunum and ileum as compared to control group. Meanwhile, IL-6, TNFα, IL-10, TGF-β expression levels showed high expression in the jejunum of Sb and Bs groups. IL-10 expression level increased in the ileum and IL-6, TNFα, IL-10 and TGF-β expression levels increased in the jejunum of Sb group. Levels of IL-1 β, IL-17, and IL-4, increased merely in Sb group. Ileal cytokines IL-1β, IL-17 and IL-4concentration were noted higher in Sb group, and IL-1β, and IL-4 levels were up-regulated in Bs group. The results indicated that the INF-γ and IL-8 level decreased in Sb and BS groups. Serum IgA and sIgA level increased in both treatment groups. Our findings illustrated that S. boulardii and B. subtilis B10 may have a role to induce mucosal immunity by activating the TLRs and cytokines expressions in broilers. PMID:28319123

  1. Saccharomyces boulardii and Bacillus subtilis B10 modulate TLRs and cytokines expression patterns in jejunum and ileum of broilers.

    PubMed

    Rajput, Imran Rashid; Ying, Huang; Yajing, Sun; Arain, Muhammad Asif; Weifen, Li; Ping, Li; Bloch, Dost Muhammad; Wenhua, Liu

    2017-01-01

    The present study was designed to evaluate the effects of Saccharomyces boulardii (Sb) and Bacillus subtilis B10 (Bs) on intestinal epithelial Toll like receptors (TLR), and Cytokine expression response to understand the intestinal epithelial innate immune mechanism in broilers. A total of 300 birds (Sanhuang broilers) were allotted into three groups (n = 100) and each divided into five replications (n = 20). Control group (Ctr) birds were fed basal diet, broilers in experimental groups received (1×108cfu/kg feed) Sb and Bs respectively in addition to basal diet for 72 days. The result showed significant increase in mRNA expression level of TLR2, TLR4 and TLR15. Down streaming MyD88, TRAF6, TAB2 and NF-κB mRNA level noted higher, in the jejunum and ileum as compared to control group. Meanwhile, IL-6, TNFα, IL-10, TGF-β expression levels showed high expression in the jejunum of Sb and Bs groups. IL-10 expression level increased in the ileum and IL-6, TNFα, IL-10 and TGF-β expression levels increased in the jejunum of Sb group. Levels of IL-1 β, IL-17, and IL-4, increased merely in Sb group. Ileal cytokines IL-1β, IL-17 and IL-4concentration were noted higher in Sb group, and IL-1β, and IL-4 levels were up-regulated in Bs group. The results indicated that the INF-γ and IL-8 level decreased in Sb and BS groups. Serum IgA and sIgA level increased in both treatment groups. Our findings illustrated that S. boulardii and B. subtilis B10 may have a role to induce mucosal immunity by activating the TLRs and cytokines expressions in broilers.

  2. The decrease in the population of Gluconacetobacter diazotrophicus in sugarcane after nitrogen fertilization is related to plant physiology in split root experiments.

    PubMed

    Rodríguez-Andrade, Osvaldo; Fuentes-Ramírez, Luis E; Morales-García, Yolanda E; Molina-Romero, Dalia; Bustillos-Cristales, María R; Martínez-Contreras, Rebeca D; Muñoz-Rojas, Jesús

    2015-01-01

    It has been established that a decrease in the population of Gluconacetobacter diazotrophicus associated with sugarcane occurs after nitrogen fertilization. This fact could be due to a direct influence of NH(4)NO(3) on bacterial cells or to changes in plant physiology after fertilizer addition, affecting bacterial establishment. In this work, we observed that survival of G. diazotrophicus was directly influenced when 44.8mM of NH(4)NO(3) (640mgN/plant) was used for in vitro experiments. Furthermore, micropropagated sugarcane plantlets were inoculated with G. diazotrophicus and used for split root experiments, in which both ends of the system were fertilized with a basal level of NH(4)NO(3) (0.35mM; 10mgN/plant). Twenty days post inoculation (dpi) one half of the plants were fertilized with a high dose of NH(4)NO(3) (6.3mM; 180 mgN/plant) on one end of the system. This nitrogen level was lower than that directly affecting G. diazotrophicus cells; however, it caused a decrease in the bacterial population in comparison with control plants fertilized with basal nitrogen levels. The decrease in the population of G. diazotrophicus was higher in pots fertilized with a basal nitrogen level when compared with the corresponding end supplied with high levels of NH4NO3 (100dpi; 80 days post fertilization) of the same plant system. These observations suggest that the high nitrogen level added to the plants induce systemic physiological changes that affect the establishment of G. diazotrophicus. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Identification and analysis of low molecular weight dissolved organic carbon in subglacial basal ice ecosystems by ion chromatography

    NASA Astrophysics Data System (ADS)

    Lawson, E. C.; Wadham, J. L.; Lis, G. P.; Tranter, M.; Pickard, A. E.; Stibal, M.; Dewsbury, P.; Fitzsimons, S.

    2015-08-01

    Glacial runoff is an important source of dissolved organic carbon (DOC) for downstream heterotrophic activity, despite the low overall DOC concentrations. This is because of the abundance of bioavailable, low molecular weight (LMW) DOC species. However, the provenance and character of LMW-DOC is not fully understood. We investigated the abundance and composition of DOC in subglacial environments via a molecular level DOC analysis of basal ice, which forms by water/sediment freeze-on to the glacier sole. Spectrofluorometry and a novel ion chromatographic method, which has been little utilised in glacial science for LMW-DOC determinations, were employed to identify and quantify the major LMW fractions (free amino acids, carbohydrates and carboxylic acids) in basal ice from four glaciers, each with a different basal debris type. Basal ice from Joyce Glacier (Antarctica) was unique in that 98 % of the LMW-DOC was derived from the extremely diverse FAA pool, comprising 14 FAAs. LMW-DOC concentrations in basal ice were dependent on the bioavailability of the overridden organic carbon (OC), which in turn, was influenced by the type of overridden material. Mean LMW-DOC concentrations in basal ice from Russell Glacier (Greenland), Finsterwalderbreen (Svalbard) and Engabreen (Norway) were low (0-417 nM C), attributed to the relatively refractory nature of the OC in the overridden paleosols and bedrock. In contrast, mean LMW-DOC concentrations were an order of magnitude higher (4430 nM C) in basal ice from Joyce Glacier, a reflection of the high bioavailability of the overridden lacustrine material (>17 % of the sediment OC comprised extractable carbohydrates, a proxy for bioavailable OC). We find that the overridden material may act as a direct (via abiotic leaching) and indirect (via microbial cycling) source of DOC to the subglacial environment and provides a range of LMW-DOC compounds that may stimulate microbial activity in wet sediments in current subglacial environments.

  4. Neural nitric oxide gene inactivation affects the release profile of oxytocin into the blood in response to forced swimming.

    PubMed

    Orlando, G F; Langnaese, K; Landgraf, R; Spina, M G; Wolf, G; Engelmann, M

    2007-02-01

    This study was undertaken to examine the importance of nitric oxide (NO) generated by the neural isoform of the nitric oxide synthase (nNOS) on the activity of the hypothalamic neurohypophyseal system in neural nitric oxide synthase knock-out (KO) and wild-type (WT) mice under basal conditions and in response to forced swimming. The intensity of the hybridisation signal for vasopressin (AVP) in the hypothalamic supraoptic nucleus (SON) was significantly higher in KO mice when compared with WT, whereas oxytocin (OXT) basal mRNA levels were similar in both groups. Although the basal peripheral release of AVP and OXT was equivalent in both genotypes, we observed in KO mice a significant drop of AVP and OXT plasma values 15 min after stressor onset and a robust increase in the OXT plasma concentration at 60 min. These findings suggest that in the male mouse, NO inhibits AVP gene transcription in magnocellular neurones of the SON and collaborates in maintaining constant AVP and OXT plasma levels following acute stressor exposure, exerting a bimodal regulatory action on OXT secretion. We conclude that NO is involved in the regulation of magnocellular neurones of the SON, and it is preferentially implicated in the attenuation of the peripheral release of OXT induced by acute stressor exposure.

  5. Endolysosomal two‐pore channels regulate autophagy in cardiomyocytes

    PubMed Central

    García‐Rúa, Vanessa; Feijóo‐Bandín, Sandra; Rodríguez‐Penas, Diego; Mosquera‐Leal, Ana; Abu‐Assi, Emad; Beiras, Andrés; María Seoane, Luisa; Lear, Pamela; Parrington, John; Portolés, Manuel; Roselló‐Lletí, Esther; Rivera, Miguel; Gualillo, Oreste; Parra, Valentina; Hill, Joseph A.; Rothermel, Beverly; González‐Juanatey, José Ramón

    2016-01-01

    Key points Two‐pore channels (TPCs) were identified as a novel family of endolysosome‐targeted calcium release channels gated by nicotinic acid adenine dinucleotide phosphate, as also as intracellular Na+ channels able to control endolysosomal fusion, a key process in autophagic flux.Autophagy, an evolutionarily ancient response to cellular stress, has been implicated in the pathogenesis of a wide range of cardiovascular pathologies, including heart failure.We report direct evidence indicating that TPCs are involved in regulating autophagy in cardiomyocytes, and that TPC knockout mice show alterations in the cardiac lysosomal system. TPC downregulation implies a decrease in the viability of cardiomyocytes under starvation conditions. In cardiac tissues from both humans and rats, TPC transcripts and protein levels were higher in females than in males, and correlated negatively with markers of autophagy.We conclude that the endolysosomal channels TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts. Abstract Autophagy participates in physiological and pathological remodelling of the heart. The endolysosomal two‐pore channels (TPCs), TPC1 and TPC2, have been implicated in the regulation of autophagy. The present study aimed to investigate the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. In cultured cardiomyocytes, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagy identified by increased LC3‐II and decreased p62 levels. Small interfering RNA depletion of TPC2 alone or together with TPC1 increased both LC3II and p62 levels under basal conditions and in response to serum starvation, suggesting that, under conditions of severe energy depletion (serum plus glucose starvation), changes in the autophagic flux (as assessed by use of bafilomycin A1) occurred either when TPC1 or TPC2 were downregulated. The knockdown of TPCs diminished cardiomyocyte viability under starvation and simulated ischaemia. Electron micrographs of hearts from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild‐type mice. In cardiac tissues from humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males. Furthermore, transcript levels of TPCs correlated negatively with p62 levels in heart tissues. TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes (i.e. there is a negative effect on cell viability under stress conditions in their absence) and they are differentially expressed in male and female human and murine hearts, where they correlate with markers of autophagy. PMID:26757341

  6. Right ventricular function and N-terminal pro-brain natriuretic peptide levels in adult patients with simple dextro-transposition of the great arteries.

    PubMed

    Martínez-Quintana, Efrén; Marrero-Negrín, Natalia; Gopar-Gopar, Silvia; Rodríguez-González, Fayna

    2017-06-01

    Dextro-transposition of the great arteries (d-TGA) patients is at high risk of developing right ventricular dysfunction and tricuspid regurgitation in adulthood. Determining the relation between echocardiographic parameters, N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels and the New York Heart Association (NYHA) functional class may help determining the best time to operate them. Patients with simple d-TGA operated in infancy with an atrial switch procedure (Mustard or Senning operation) were followed up in our Adult Congenital Heart Disease Unit. Analytical, echocardiographic, and clinical parameters were determined to evaluate the correlation between right echocardiographic ventricular function, NT-pro-BNP levels, and NYHA functional class. Twenty-four patients with d-TGA were operated in infancy of whom 17 alive patients had simple d-TGA. Nine patients had NT-pro-BNP levels lower than 200 pg/mL and eight patients were above 200 pg/mL. Patients with lower hemoglobin concentration, higher right ventricular diameter or under diuretic treatment showed significant higher NT-pro-BNP levels (above 200 pg/dL). The Spearman test showed a positive correlation between basal right ventricular diameter and tricuspid regurgitation with pro NT BNP levels (correlation coefficient of .624; P=.017 and .490; P=.046, respectively) and a negative correlation with the right ventricle fractional area change (-.508, P=.045). No correlation was seen between NT-pro-BNP levels and the rest of echocardiographic parameters or the NYHA functional class. NT-pro-BNP levels showed a positive correlation with basal right ventricular diameter and tricuspid regurgitation but not with NYHA association functional class in d-TGA patients. © 2017, Wiley Periodicals, Inc.

  7. Cytokine production capacity in depression and anxiety.

    PubMed

    Vogelzangs, N; de Jonge, P; Smit, J H; Bahn, S; Penninx, B W

    2016-05-31

    Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including persons (18-65 years; 66% women) with current (that is, past month; N=591) or remitted (N=354) DSM-IV depressive or anxiety disorders and healthy controls (N=297). Depressive and anxiety symptoms were measured by means of the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Using Multi-Analyte Profiling technology, plasma levels of 13 cytokines were assayed after whole blood stimulation by addition of LPS. Basal plasma levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α were also available. A basal and a LPS summary index were created. Results show that LPS-stimulated inflammation was associated with increased odds of current depressive/anxiety disorders (odds ratio (OR)=1.28, P=0.009), as was the case for basal inflammation (OR=1.28, P=0.001). These associations were no longer significant after adjustment for lifestyle and health (OR=1.13, P=0.21; OR=1.07, P=0.45, respectively). After adjustment for lifestyle and health, interleukin-8 was associated with both remitted (OR=1.25, P=0.02) and current (OR=1.28, P=0.005) disorders. In addition, LPS-stimulated inflammation was associated with more severe depressive (β=0.129, P<0.001) and anxiety (β=0.165, P<0.001) symptoms, as was basal inflammation. Unlike basal inflammation, LPS-stimulated inflammation was still associated with (anxiety) symptom severity after adjustment for lifestyle and health (IDS: interleukin (IL)-8, MCP-1, MMP2; BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β). To conclude, lifestyle and health factors may partly explain higher levels of basal, as well as LPS-stimulated inflammation in persons with depressive and anxiety disorders. However, production capacity of several cytokines was positively associated with severity of depressive and in particular anxiety symptoms, even while taking lifestyle and health factors into account. Elevated IL-8 production capacity in both previously and currently depressed and anxious persons might indicate a genetic vulnerability for these disorders.

  8. The effects of Bacillus coagulans-fermented and non-fermented Ginkgo biloba on abdominal fat deposition and meat quality of Peking duck.

    PubMed

    Liu, Xiaoyan; Cao, Guanjun; Zhou, Jinglong; Yao, Xuan; Fang, Binghu

    2017-07-01

    In order to evaluate the effects of Bacillus coagulans-fermented Ginkgo biloba (FG) and non-fermented G. biloba (NFG) on abdominal fat deposition and meat quality, 270 female Peking ducks were randomly assigned to the following experimental groups: a control group (fed a basal diet), an NFG group (fed a basal diet + 0.3% NFG), and an FG group (fed a basal diet + 0.3% FG). Body weight and feed intake were recorded weekly, and feed conversion ratio was calculated to assess growth performance. After 6 wk, 18 ducks from each group were killed. Abdominal fat ratio and pH (at 45 min and 24 h postmortem), color parameters (lightness, redness, and yellowness), water-holding capacity, cooking loss, shear force, and intramuscular fat and fatty acid contents were measured. Six more ducks were killed to isolate RNA from their abdominal fat tissue for measurements of peroxisome proliferator-activated receptor-γ (PPARγ), obese (leptin), and adiponectin (ADP) expression using real-time polymerase chain reaction. The results revealed that body weight gain was higher in the FG group than in the control and NFG groups, whereas feed conversion ratio was lower (P < 0.05). The abdominal fat contents were lower in the NFG and FG groups than in the control group (P < 0.05). The NFG and FG groups had lower levels of saturated fatty acids (mainly palmitic acid) and higher levels of polyunsaturated fatty acids (mainly linoleic acid and arachidonic acid) than the control group. The mRNA expressions of PPARγ, leptin, and ADP in abdominal fat tissue were significantly increased in the NFG and FG groups, and the mRNA expression of PPARγ was higher in the FG group than in the NFG group (P < 0.05). These results suggest that fermenting G. biloba reduces the deposition of abdominal fat and improves the fatty acid profile of Peking duck meat. © 2017 Poultry Science Association Inc.

  9. The incidence of satellite cysts in keratocystic odontogenic tumors.

    PubMed

    Pavelić, Boiidar; Katunarić, Marina; Segović, Sanja; Karadole, Maja Cimas; Katanec, Davor; Saban, Aida; Puhar, Ivan

    2014-03-01

    Renaming of the Odontogenic Keratocyst as the Keratocystic Odontogenic Tumor by the World Health Organization (WHO) is based on the aggressive nature of this lesion. Satellite cysts founded in the walls of the original cysts may give rise to a new lesion formation. The aim of this retrospecitve study was to identify the existence of specific features according incidence of satellite cysts and the pallisading of the basal layer of the epithelium and to establish their mutual correlation. The histopathologic data of Keratocystic Odontogenic Tumor on the basis of new WHO's classification (2005) were analized. Prominent palisade basal cell layer was found in 415 (94.75%) and partially absent palisade basal cell layer in 23 (5.25%) cases. Satellite cysts were presented in prominent palisade basal cell layer in 85 specimens (20.5%) and in cases with partial absent of the palisade basal layer in 3 spicemens (13%). The higher the frequency of pallisading was the higher the frequency of satellite cysts was (p > 0.05).

  10. The regulation of thermal stress induced apoptosis in corals reveals high similarities in gene expression and function to higher animals

    NASA Astrophysics Data System (ADS)

    Kvitt, Hagit; Rosenfeld, Hanna; Tchernov, Dan

    2016-07-01

    Recent studies suggest that controlled apoptotic response provides an essential mechanism, enabling corals to respond to global warming and ocean acidification. However, the molecules involved and their functions are still unclear. To better characterize the apoptotic response in basal metazoans, we studied the expression profiles of selected genes that encode for putative pro- and anti-apoptotic mediators in the coral Stylophora pistillata under thermal stress and bleaching conditions. Upon thermal stress, as attested by the elevation of the heat-shock protein gene HSP70’s mRNA levels, the expression of all studied genes, including caspase, Bcl-2, Bax, APAF-1 and BI-1, peaked at 6-24 h of thermal stress (hts) and declined at 72 hts. Adversely, the expression levels of the survivin gene showed a shifted pattern, with elevation at 48-72 hts and a return to basal levels at 168 hts. Overall, we show the quantitative anti-apoptotic traits of the coral Bcl-2 protein, which resemble those of its mammalian counterpart. Altogether, our results highlight the similarities between apoptotic networks operating in simple metazoans and in higher animals and clearly demonstrate the activation of pro-cell survival regulators at early stages of the apoptotic response, contributing to the decline of apoptosis and the acclimation to chronic stress.

  11. The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

    PubMed

    Harrison-Findik, Duygu Dee; Lu, Sizhao

    2015-05-06

    This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

  12. Peptide YY abnormalities in gastrointestinal diseases.

    PubMed

    Adrian, T E; Savage, A P; Bacarese-Hamilton, A J; Wolfe, K; Besterman, H S; Bloom, S R

    1986-02-01

    Plasma concentrations of peptide YY (PYY), a newly isolated peptide produced by ileal and colonic endocrine cells, were measured in several groups of patients with digestive disorders after a standardized normal breakfast. Peptide YY levels were found to be grossly elevated in patients with steatorrhea due to small intestinal mucosal atrophy (tropical sprue). Basal levels in these patients were 79 +/- 18 pM, which was nearly 10-fold higher than those seen in healthy controls (8.5 +/- 0.8 pM). Patients with steatorrhea due to chronic destructive pancreatitis also had substantially increased basal PYY levels (47.5 +/- 6.3 pM), and their postprandial response was also greater than that of normal subjects. Moderately elevated plasma PYY concentrations were seen in patients with inflammatory bowel disease and patients recovering from acute infective diarrhea. In contrast, patients with diverticular disease, duodenal ulcer, and functional bowel disease had normal PYY responses. These changes in the secretion of PYY responses. These changes in the secretion, may shed light on the physiologic role of this newly discovered peptide and on intestinal adaptation to common digestive disorders.

  13. Temperature, energy metabolism, and adaptive divergence in two oyster subspecies.

    PubMed

    Li, Ao; Li, Li; Song, Kai; Wang, Wei; Zhang, Guofan

    2017-08-01

    Comparisons of related species that have diverse spatial distributions provide an efficient way to investigate adaptive evolution in face of increasing global warming. The oyster subjected to high environmental selections is a model species as sessile marine invertebrate. This study aimed to detect the adaptive divergence of energy metabolism in two oyster subspecies from the genus Crassostrea - C. gigas gigas and C. gigas angulata -which are broadly distributed along the northern and southern coasts of China, respectively. We examined the effects of acute thermal stress on energy metabolism in two oyster subspecies after being common gardened for one generation in identical conditions. Thermal responses were assessed by incorporating physiological, molecular, and genomic approaches. Southern oysters exhibited higher fluctuations in metabolic rate, activities of key energetic enzymes, and levels of thermally induced gene expression than northern oysters. For genes involved in energy metabolism, the former displayed higher basal levels of gene expression and a more pronounced downregulation of thermally induced expression, while the later exhibited lower basal levels and a less pronounced downregulation of gene expression. Contrary expression pattern was observed in oxidative stress gene. Besides, energy metabolic tradeoffs were detected in both subspecies. Furthermore, the genetic divergence of a nonsynonymous SNP ( SOD-132 ) and five synonymous SNPs in other genes was identified and validated in these two subspecies, which possibly affects downstream functions and explains the aforementioned phenotypic variations. Our study demonstrates that differentiations in energy metabolism underlie the plasticity of adaptive divergence in two oyster subspecies and suggest C. gigas angulata with moderate phenotypic plasticity has higher adaptive potential to cope with exacerbated global warming.

  14. Site condition, structure, and growth of baldcypress along tidal/non-tidal salinity gradients

    USGS Publications Warehouse

    Krauss, K.W.; Duberstein, J.A.; Doyle, T.W.; Conner, W.H.; Day, Richard H.; Inabinette, L.W.; Whitbeck, J.L.

    2009-01-01

    This report documents changes in forest structure and growth potential of dominant trees in salt-impacted tidal and non-tidal baldcypress wetlands of the southeastern United States. We inventoried basal area and tree height, and monitored incremental growth (in basal area) of codominant baldcypress (Taxodium distichum) trees monthly, for over four years, to examine the inter-relationships among growth, site fertility, and soil physico-chemical characteristics. We found that salinity, soil total nitrogen (TN), flood duration, and flood frequency affected forest structure and growth the greatest. While mean annual site salinity ranged from 0.1 to 3.4 ppt, sites with salinity concentrations of 1.3 ppt or greater supported a basal area of less than 40 m2/ha. Where salinity was < 0.7 ppt, basal area was as high as 87 m2/ha. Stand height was also negatively affected by higher salinity. However, salinity related only to soil TN concentrations or to the relative balance between soil TN and total phosphorus (TP), which reached a maximum concentration between 1.2 and 2.0 ppt salinity. As estuarine influence shifts inland with sea-level rise, forest growth may become more strongly linked to salinity, not only due to salt effects but also as a consequence of site nitrogen imbalance.

  15. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

    PubMed Central

    Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S.; Falk, Gary W.; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A.; Peters, Jeffrey H.; Lan, Xiaopeng; Que, Jianwen

    2015-01-01

    Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

  16. Pavlovian autoshaping procedures increase plasma corticosterone levels in rats.

    PubMed

    Tomie, Arthur; Silberman, Yuval; Williams, Kayon; Pohorecky, Larissa A

    2002-06-01

    Pavlovian autoshaping conditioned responses (CRs) are complex sequences of conditioned stimulus (CS)-directed skeletal-motor responses that are elicited by CS objects predictive of food unconditioned stimulus (US). Autoshaping CRs are observed under conditions known to be conducive to elevations in plasma corticosterone levels, as, for example, in response to the eating of food as well as in response to signals predictive of food. Two experiments investigated the relationships between Pavlovian autoshaping procedures, the performance of Pavlovian autoshaping CRs, and plasma corticosterone levels in male Long-Evans rats. In Experiment 1, rats in the CS-US paired group (n=30) were given 20 daily sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of the food US. Tail blood samples obtained after the 20th autoshaping session revealed higher plasma corticosterone levels in the CS-US paired group than in the CS-US random control group (n=10). In Experiment 2, rats (n=35) were assessed for basal plasma corticosterone levels 2 weeks prior to autoshaping training. Plasma samples obtained immediately following the first autoshaping session, and prior to the acquisition of lever-press autoshaping CR performance, revealed higher plasma corticosterone levels in the CS-US paired group (n=24) relative to basal levels. This effect was not observed in the CS-US random control group (n=11). Data suggest that corticosterone release is a physiological endocrine Pavlovian CR induced by lever CS-food US pairings during Pavlovian autoshaping procedures, rather than a by-product of autoshaping CR performance. Implications of the link between autoshaping procedures and corticosterone release are discussed.

  17. Predicting stress from the ability to eavesdrop on feelings: Emotional intelligence and testosterone jointly predict cortisol reactivity.

    PubMed

    Bechtoldt, Myriam N; Schneider, Vanessa K

    2016-09-01

    While emotional intelligence (EI) is recognized as a resource in social interactions, we hypothesized a positive association with stress in socially evaluative contexts. In particular, we expected emotion recognition, the core component of EI, to inflict stress on individuals in negatively valenced interactions. We expected this association to be stronger for status-driven individuals, that is, for individuals scoring high on basal testosterone. In a laboratory experiment, N = 166 male participants underwent the Trier Social Stress Test (Kirschbaum, Pirke, & Hellhammer, 1993). As expected, EI measured by the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT V2.0; Mayer et al., 2003) predicted higher cortisol reactivity, including slower recovery from stress. The effect was moderated by basal testosterone, such that the association was positive when basal testosterone was high but not when it was low. On the component level of EI, the interaction was replicated for negative emotion recognition. These findings lend support to the hypothesis that EI is associated with higher activity of the hypothalamic-pituitary-adrenal axis in contexts where social status is at stake, particularly for those individuals who are more status-driven. Thus, the effects of EI are not unequivocally positive: While EI may positively affect the course of social interactions, it also inflicts stress on the emotionally intelligent individuals themselves. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  18. Effect of selenium supplementation on the level of glutathione-peroxidase (GSH-Px) activity in the nursing rat

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Barron, S.P.; Hittner, H.M.; Strength, D.R.

    Prevention of retinopathy of prematurity using vitamin E as an antioxidant has been demonstrated. The purpose of this experiment was to study the antioxidant system, GSH-Px, (a selenoenzyme), in the retina. The effect of i.p. administration and dietary Se as selenite or selenomethionine (selmet) on tissue GSH-Px activity was determined in nursing pups. Dams were randomized into 3 dietary treatments (Basal, 0.15 ppm selenite, and 0.15 ppm selmet) and mated. Pups were sacrificed at 0, 7, and 14 days after delivery and GSH-Px was measured in pup eyes, hearts, livers, and kidneys, and dam livers. The pups of the damsmore » consuming the Basal diet were divided into 4 i.p. groups: none, saline, selenite, and selmet (3 ..mu..g Se/kg body wt). The i.p. Se had no effect on GSH-Px activity in eye or heart, but significantly increased GSH-Px activity in liver and kidney with no difference between selenite and selmet. The pups of the dams consuming selenite and selmet diets showed significantly higher GSH-Px activity in all tissues studied than those consuming the Basal diet. For all tissues GSH-Px activity was higher for pups and dams fed selmet than those fed selenite. This research demonstrates that there was a difference in selenium availability between diet and i.p. administration.« less

  19. Stimulatory effect of clebopride on human prolactin secretion.

    PubMed

    Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

    1980-11-01

    Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

  20. Occult pneumothoraces in Chinese patients with significant blunt chest trauma: radiological classification and proposed clinical significance.

    PubMed

    Lee, Ryan K L; Graham, Colin A; Yeung, Janice H H; Ahuja, Anil T; Rainer, Timothy H

    2012-12-01

    An occult pneumothorax (OP) is a pneumothorax not seen on a supine chest X-ray (CXR) but detected on abdominal or thoracic computed tomography (CT) scanning. With the increasing use of CT in the management of significantly injured trauma patients, more OPs are being detected. The aim of this study was to classify OPs diagnosed on thoracic CT (TCT) and correlate them with their clinical significance. Retrospective analysis of prospectively collected trauma registry data. Total 36 (N=36) consecutive significantly injured trauma patients admitted through the emergency department (ED) who sustained blunt chest trauma and underwent TCT between 1 January 2007 and 31 December 2008 were included. OP was defined as the identification (by a consultant radiologist) of a pneumothorax on TCT that had not been detected on supine CXR. OPs were classified by laterality (unilateral/bilateral) and location (apical, basal, non apical/basal). The size of pneumothoraces, severity of injury [including number of associated thoracic injuries and injury severity score (ISS)], length of hospital stay and mortality were compared between groups. The need for tube thoracostomy and clinical outcome were also analysed. Patients with bilateral OPs (N=8) had significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 23, p=0.02) and longer hospital stay (median: 20 days vs. 11 days, p=0.01) than those with a unilateral OP (N=28). Basal OPs (N=7) were significantly larger than apical (N=10) and non-apical/basal Ops (N=11). Basal OPs were associated with significantly more associated thoracic injuries (median: 2 vs. 1, p=0.01), higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 17 days, p=0.02) than apical Ops, which had higher ISS (median: 35 vs. 25, p=0.04) and longer hospital stays (median: 23 days vs. 15 days, p=0.02) than non-apical/basal OPs. Non-apical/basal OPs were associated with more related injuries (median: 2 vs. 1, p=0.02) than apical OPs. All apical and non-apical/basal OPs were successfully managed expectantly without associated mortality. This TCT classification of OP is proposed to help clinicians to decide on subsequent management of the OP. Basal OPs are significantly larger in size, and both basal and bilateral OPs are associated with higher severity of injury and longer hospital stay. These groups of patient may benefit from prophylactic tube thoracostomy instead of conservative treatment. On the other hand, apical and non-apical/basal groups is smaller in size, less severely injured and thus can be successfully managed expectantly. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Dark exposure of petunia cuttings strongly improves adventitious root formation and enhances carbohydrate availability during rooting in the light.

    PubMed

    Klopotek, Yvonne; Haensch, Klaus-Thomas; Hause, Bettina; Hajirezaei, Mohammad-Reza; Druege, Uwe

    2010-05-01

    The effect of temporary dark exposure on adventitious root formation (ARF) in Petuniaxhybrida 'Mitchell' cuttings was investigated. Histological and metabolic changes in the cuttings during the dark treatment and subsequent rooting in the light were recorded. Excised cuttings were exposed to the dark for seven days at 10 degrees C followed by a nine-day rooting period in perlite or were rooted immediately for 16 days in a climate chamber at 22/20 degrees C (day/night) and a photosynthetic photon flux density (PPFD) of 100micromolm(-2)s(-1). Dark exposure prior to rooting increased, accelerated and synchronized ARF. The rooting period was reduced from 16 days (non-treated cuttings) to 9 days (treated cuttings). Under optimum conditions, despite the reduced rooting period, dark-exposed cuttings produced a higher number and length of roots than non-treated cuttings. An increase in temperature to 20 degrees C during the dark treatment or extending the cold dark exposure to 14 days caused a similar enhancement of root development compared to non-treated cuttings. Root meristem formation had already started during the dark treatment and was enhanced during the subsequent rooting period. Levels of soluble sugars (glucose, fructose and sucrose) and starch in leaf and basal stem tissues significantly decreased during the seven days of dark exposure. This depletion was, however, compensated during rooting after 6 and 24h for soluble sugars in leaves and the basal stem, respectively, whereas the sucrose level in the basal stem was already increased at 6h. The association of higher carbohydrate levels with improved rooting in previously dark-exposed versus non-treated cuttings indicates that increased post-darkness carbohydrate availability and allocation towards the stem base contribute to ARF under the influence of dark treatment and provide energy for cell growth subject to a rising sink intensity in the base of the cutting. Copyright 2009 Elsevier GmbH. All rights reserved.

  2. Estrogen Regulation of Duodenal Bicarbonate Secretion and Sex-Specific Protection of Human Duodenum

    PubMed Central

    Tuo, Biguang; Wen, Guorong; Wei, Jinqi; Liu, Xuemei; Wang, Xue; Zhang, Yalin; Wu, Huichao; Dong, Xiao; Chow, Jimmy Y.C.; Vallon, Volker; Dong, Hui

    2011-01-01

    BACKGROUND & AIMS The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. METHODS We performed an epidemiological study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. RESULTS Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20–49 years), who were 3.91–5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to ≤1.32-fold among subjects 60 years or older. Premenopausal (20–29 years), but not post-menopausal (60–69 years) women, had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20–29 years) were significantly higher than in post-menopausal women (60–69 years), whereas there were no significant differences in basal or acid-stimulated DBS between men that were 20–29 years old or 60–69 years old. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors- and - were detected on plasma membrane and in cytosol of human duodenal epithelial cells. CONCLUSIONS Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in prevalence of duodenal ulcer. PMID:21699784

  3. Estrogen regulation of duodenal bicarbonate secretion and sex-specific protection of human duodenum.

    PubMed

    Tuo, Biguang; Wen, Guorong; Wei, Jinqi; Liu, Xuemei; Wang, Xue; Zhang, Yalin; Wu, Huichao; Dong, Xiao; Chow, Jimmy Y C; Vallon, Volker; Dong, Hui

    2011-09-01

    The reason that women have a lower prevalence of duodenal ulcer is not clear. We investigated whether estrogen regulates human duodenal bicarbonate secretion (DBS) and whether this process accounts for sex differences in the prevalence of duodenal ulcer. We performed an epidemiologic study to correlate duodenal ulcer prevalence with sex and age. Proximal DBS was measured from healthy subjects. Estrogen-receptor expression was examined in human duodenal mucosa by immunoblot and immunohistochemical analyses. Among women, the prevalence of duodenal ulcer was significantly lower than among men. The reduced prevalence was greatest among premenopausal women (20-49 y), who were 3.91- to 5.09-fold less likely to develop duodenal ulcers than age-matched men; the difference was reduced to 1.32-fold or less among subjects aged 60 years or older. Premenopausal (20-29 y), but not postmenopausal (60-69 y), women had significantly higher basal and acid-stimulated DBS than the age-matched men. Basal and acid-stimulated DBS in premenopausal women (20-29 y) were significantly higher than in postmenopausal women (60-69 y), whereas there were no significant differences in basal or acid-stimulated DBS between men who were aged 20-29 years or 60-69 years. Serum levels of estradiol changed in parallel with basal and acid-stimulated DBS during the physiological menstrual cycle in premenopausal women. 17β-estradiol-stimulated DBS was independent of age or sex. Estrogen receptors α and β were detected on plasma membranes and in the cytosol of human duodenal epithelial cells. Estrogen regulates human DBS, which could reduce the risk for duodenal ulcer in women and contribute to sex differences in the prevalence of duodenal ulcer. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Role of Arginine decarboxylase (ADC) in Arabidopsis thaliana defence against the pathogenic bacterium Pseudomonas viridiflava.

    PubMed

    Rossi, F R; Marina, M; Pieckenstain, F L

    2015-07-01

    Polyamine biosynthesis starts with putrescine production through the decarboxylation of arginine or ornithine. In Arabidopsis thaliana, putrescine is synthesised exclusively by arginine decarboxylase (ADC), which exists as two isoforms (ADC1 and 2) that are differentially regulated by abiotic stimuli, but their role in defence against pathogens has not been studied in depth. This work analysed the participation of ADC in Arabidopsis defence against Pseudomonas viridiflava. ADC activity and expression, polyamine levels and bacterial resistance were analysed in null mutants of each ADC isoform. In non-infected wild-type (WT) plants, ADC2 expression was much higher than ADC1. Analysis of adc mutants demonstrated that ADC2 contributes to a much higher extent than ADC1 to basal ADC activity and putrescine biosynthesis. In addition, adc2 mutants showed increased basal expression of salicylic acid- and jasmonic acid-dependent PR genes. Bacterial infection induced putrescine accumulation and ADC1 expression in WT plants, but pathogen-induced putrescine accumulation was blocked in adc1 mutants. Results suggest a specific participation of ADC1 in defence, although basal resistance was not decreased by dysfunction of either of the two ADC genes. In addition, and as opposed to WT plants, bacterial infection increased ADC2 expression and ADC activity in adc1 mutants, which could counterbalance the lack of ADC1. Results demonstrate a major contribution of ADC2 to total ADC activity and the specific induction of ADC1 in response to infection. A certain degree of functional redundancy between the two isoforms in relation to their contribution to basal resistance is also evident. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  5. Molecular analysis of the differential hepatic expression of rat kininogen family genes.

    PubMed Central

    Chen, H M; Liao, W S

    1993-01-01

    Serum concentration of rat T1 kininogen increases 20- to 30-fold in response to acute inflammation, an induced hepatic synthesis regulated primarily at the transcriptional level. We have demonstrated by transient transfection analyses that rat T1 kininogen gene/chloramphenicol acetyltransferase (T1K/CAT) constructs are highly responsive to interleukin-6 and dexamethasone. In these studies we examined the regulation of a highly homologous K kininogen gene promoter and showed that it is minimally induced under identical conditions. The basal expression of the KK/CAT construct was, however, five- to sevenfold higher than that of the analogous T1K/CAT construct. Promoter-swapping experiments to examine the molecular basis of this differentially regulated basal expression showed that at least two K kininogen promoter regions are important for conferring its high basal expression: a distal 19-bp region (C box) constituted a binding site for C/EBP family proteins, and a proximal 66-bp region contained two adjacent binding sites for hepatocyte nuclear factor 3 (HNF-3). While the C box in the K kininogen promoter was able to interact with C/EBP transcription factors, the T1 kininogen promoter C box could not. In addition, HNF-3 binding sites of the K kininogen promoter demonstrated stronger affinities than those of the T1 kininogen promoter. Since C/EBP and HNF-3 are highly enriched in the liver and are known to enhance transcription of liver-specific genes, these differences in their binding activities thus accounted for the K kininogen gene's higher basal expression. Our studies demonstrated that evolutionary divergence of a few critical nucleotides may lead to subtle changes in the binding affinities of a transcription factor to its recognition site, profoundly altering expression of the downstream gene. Images PMID:8413271

  6. Effects of nanostructured zeolite and aflatoxin B1 in growth performance, immune parameters and pathological conditions of rainbow trout Oncorhynchus mykiss.

    PubMed

    Alinezhad, S; Faridi, M; Falahatkar, B; Nabizadeh, R; Davoodi, D

    2017-11-01

    The reduction of Aflatoxin B 1 (AF) in juvenile rainbow trout (Oncorhynchus mykiss) diet was analyzed after supplementing Nanostructured Zeolite (NZ) in a 56-day experiment. Two hundred and seventy juveniles with an average weight of 23 ± 3.7 g were placed in 6 different groups of C (control as a basal diet), NZ 0.5 (basal diet + 0.5% NZ), NZ 1 (basal diet + 1% NZ), AF 5 (basal diet + 5 mg AFB 1 ), AF 5 NZ 0.5 (basal diet + 5 mg AFB 1  + 0.5% NZ), AF 5 NZ 1 (basal diet + 5 mg AFB 1  + 1% NZ) with three replications and were fed four times a day based on their satiation. No significant differences were observed in terms of growth performance among the experimental groups (P > 0.05). However, hepatosomatic index in fish fed by AF 5 NZ 0.5 was reduced compared with NZ 0.5 group (P < 0.05). The carcass moisture content showed a higher amount in treatment AF 5 NZ 0.5 compared to the control group (P < 0.05). There was a decrease in fat content in treatment AF 5 compared to that of the control group (P < 0.05). Serum total protein, albumin and globulin levels in fish fed with aflatoxin were lower than in fish fed the diet without AF for all levels of NZ (P < 0.05); however, the interaction between AF and NZ was not significant (P > 0.05). Concentrations of C 3 , C 4 and immunoglobulin M together with serum lysozyme activity showed no significant differences among all treatments (P > 0.05). No considerable histopathological lesions were observed in liver, kidney and spleen for all treatments. Based on the results, NZ showed some effects on physiological functions in juvenile rainbow trout fed by 0.5% dietary NZ which could improve performance in this species. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Loss of Dickkopf 3 Promotes the Tumorigenesis of Basal Breast Cancer

    PubMed Central

    Lorsy, Eva; Topuz, Aylin Sophie; Geisler, Cordelia; Stahl, Sarah; Garczyk, Stefan; von Stillfried, Saskia; Hoss, Mareike; Gluz, Oleg; Hartmann, Arndt; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    Dickkopf 3 (DKK3) has been associated with tumor suppression of various tumor entities including breast cancer. However, the functional impact of DKK3 on the tumorigenesis of distinct molecular breast cancer subtypes has not been considered so far. Therefore, we initiated a study analyzing the subtype-specific DKK3 expression pattern as well as its prognostic and functional impact with respect to breast cancer subtypes. Based on three independent tissue cohorts including one in silico dataset (n = 30, n = 463 and n = 791) we observed a clear down-regulation of DKK3 expression in breast cancer samples compared to healthy breast tissue controls on mRNA and protein level. Interestingly, most abundant reduction of DKK3 expression was detected in the highly aggressive basal breast cancer subtype. Analyzing a large in silico dataset comprising 3,554 cases showed that low DKK3 mRNA expression was significantly associated with reduced recurrence free survival (RFS) of luminal and basal-like breast cancer cases. Functionally, DKK3 re-expression in human breast cancer cell lines led to suppression of cell growth possibly mediated by up-regulation of apoptosis in basal-like but not in luminal-like breast cancer cell lines. Moreover, ectopic DKK3 expression in mesenchymal basal breast cancer cells resulted in partial restoration of epithelial cell morphology which was molecularly supported by higher expression of epithelial markers like E-Cadherin and down-regulation of mesenchymal markers such as Snail 1. Hence, we provide evidence that down-regulation of DKK3 especially promotes tumorigenesis of the aggressive basal breast cancer subtype. Further studies decoding the underlying molecular mechanisms of DKK3-mediated effects may help to identify novel targeted therapies for this clinically highly relevant breast cancer subtype. PMID:27467270

  8. Fetuin-A levels in hyperthyroidism.

    PubMed

    Pamuk, Bariş Onder; Yilmaz, Hamiyet; Topcuoglu, Tugba; Bilgir, Oktay; Çalan, Ozlem; Pamuk, Gulseren; Ertugrul, Derun Taner

    2013-01-01

    Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1). Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. Our findings suggest that hyperthyroidism influences fetuin-A levels.

  9. Long-term follow-up of functional hypothalamic amenorrhea and prognostic factors.

    PubMed

    Falsetti, Leopoldo; Gambera, Alessandro; Barbetti, Lorena; Specchia, Cristina

    2002-02-01

    This study evaluated the prognosis of functional hypothalamic amenorrhea (FHA) and the predictive factors of recovery, through a long-term follow-up. Ninety-three women affected by FHA underwent a follow-up for an average period of 8.1 yr (range 7-9 yr). At the end of the follow-up, 65 (70.7%) patients recovered. Statistical analysis showed that there was no association between recovery and anamnestic causes of FHA or with the echographic ovarian morphology but identified the predictive factors of recovery as the basal body mass index (BMI), the basal cortisol, and androstenedione plasma levels. A higher basal BMI and A, and lower cortisol values are positive prognostic factors for the recovery. Also the BMI, acquired during the follow-up, is important for FHA resolution: in fact, in recovered women the BMI increased or remained stable, whereas in nonrecovered women it decreased or remained stable. At the end of the follow-up, 52 (74.3%) patients treated with hormone replacement therapy and 8 (80%) with no therapy recovered, but only 5 (41.7%) with oral contraceptive pills recovered.

  10. Airborne copper exposure in school environments associated with poorer motor performance and altered basal ganglia.

    PubMed

    Pujol, Jesus; Fenoll, Raquel; Macià, Dídac; Martínez-Vilavella, Gerard; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Deus, Joan; Blanco-Hinojo, Laura; Querol, Xavier; Sunyer, Jordi

    2016-06-01

    Children are more vulnerable to the effects of environmental elements. A variety of air pollutants are among the identified factors causing neural damage at toxic concentrations. It is not obvious, however, to what extent the tolerated high levels of air pollutants are able to alter brain development. We have specifically investigated the neurotoxic effects of airborne copper exposure in school environments. Speed and consistency of motor response were assessed in 2836 children aged from 8 to 12 years. Anatomical MRI, diffusion tensor imaging, and functional MRI were used to directly test the brain repercussions in a subgroup of 263 children. Higher copper exposure was associated with poorer motor performance and altered structure of the basal ganglia. Specifically, the architecture of the caudate nucleus region was less complete in terms of both tissue composition and neural track water diffusion. Functional MRI consistently showed a reciprocal connectivity reduction between the caudate nucleus and the frontal cortex. The results establish an association between environmental copper exposure in children and alterations of basal ganglia structure and function.

  11. Diagnostic accuracy of basal TSH determinations based on the intravenous TRH stimulation test: an evaluation of 2570 tests and comparison with the literature.

    PubMed

    Moncayo, Helga; Dapunt, Otto; Moncayo, Roy

    2007-08-02

    Basal TSH levels reflect the metabolic status of thyroid function, however the definition and interpretation of the basal levels of TSH is a matter of controversial debate. The aim of this study was to evaluate basal TSH levels in relation to the physiological response to i.v. TRH stimulation. A series of 2570 women attending a specialized endocrine unit were evaluated. A standardized i.v. TRH stimulation test was carried out by applying 200 mug of TRH. TSH levels were measured both in the basal and the 30 minute blood sample. The normal response to TRH stimulation had been previously determined to be an absolute value lying between 2.5 and 20 mIU/l. Both TSH values were analyzed by cross tabulation. In addition the results were compared to reference values taken from the literature. Basal TSH values were within the normal range (0.3 to 3.5 mIU/l) in 91,5% of cases, diminished in 3,8% and elevated in 4.7%. Based on the response to TRH, 82.4% were considered euthyroid, 3.3% were latent hyperthyroid, and 14.3% were latent hypothyroid. Combining the data on basal and stimulated TSH levels, latent hypothyroidism was found in the following proportions for different TSH levels: 5.4% for TSH < 2.0 mIU/l, 30.2% for TSH between 2.0 and 3.0 mIU/l, 65,5% for TSH between 3.0 and 3.50 mIU/l, 87.5% for TSH between 3.5 and 4.0 mIU/l, and 88.2% for TSH between 4 and 5 mIU/l. The use of an upper normal range for TSH of 2.5 mIU/l, as recommended in the literature, misclassified 7.7% of euthyroid cases. Our analysis strategy allows us to delineate the predictive value of basal TSH levels in relation to latent hypothyroidism. A grey area can be identified for values between 3.0 and 3.5 mIU/l.

  12. Phylogenetic analyses of complete mitochondrial genome sequences suggest a basal divergence of the enigmatic rodent Anomalurus

    PubMed Central

    Horner, David S; Lefkimmiatis, Konstantinos; Reyes, Aurelio; Gissi, Carmela; Saccone, Cecilia; Pesole, Graziano

    2007-01-01

    Background Phylogenetic relationships between Lagomorpha, Rodentia and Primates and their allies (Euarchontoglires) have long been debated. While it is now generally agreed that Rodentia constitutes a monophyletic sister-group of Lagomorpha and that this clade (Glires) is sister to Primates and Dermoptera, higher-level relationships within Rodentia remain contentious. Results We have sequenced and performed extensive evolutionary analyses on the mitochondrial genome of the scaly-tailed flying squirrel Anomalurus sp., an enigmatic rodent whose phylogenetic affinities have been obscure and extensively debated. Our phylogenetic analyses of the coding regions of available complete mitochondrial genome sequences from Euarchontoglires suggest that Anomalurus is a sister taxon to the Hystricognathi, and that this clade represents the most basal divergence among sampled Rodentia. Bayesian dating methods incorporating a relaxed molecular clock provide divergence-time estimates which are consistently in agreement with the fossil record and which indicate a rapid radiation within Glires around 60 million years ago. Conclusion Taken together, the data presented provide a working hypothesis as to the phylogenetic placement of Anomalurus, underline the utility of mitochondrial sequences in the resolution of even relatively deep divergences and go some way to explaining the difficulty of conclusively resolving higher-level relationships within Glires with available data and methodologies. PMID:17288612

  13. Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults

    PubMed Central

    Reijman, Sophie; Bakermans-Kranenburg, Marian J.; Hiraoka, Regina; Crouch, Julie L.; Milner, Joel S.; van IJzendoorn, Marinus H.

    2016-01-01

    We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner’s curse. Most studies were underpowered. Future directions for research are suggested. PMID:27462035

  14. Sea-level response to abrupt ocean warming of Antarctic ice shelves

    NASA Astrophysics Data System (ADS)

    Pattyn, Frank

    2016-04-01

    Antarctica's contribution to global sea-level rise increases steadily. A fundamental question remains whether the ice discharge will lead to marine ice sheet instability (MISI) and collapse of certain sectors of the ice sheet or whether ice loss will increase linearly with the warming trends. Therefore, we employ a newly developed ice sheet model of the Antarctic ice sheet, called f.ETISh (fast Elementary Thermomechanical Ice Sheet model) to simulate ice sheet response to abrupt perturbations in ocean and atmospheric temperature. The f.ETISh model is a vertically integrated hybrid (SSA/SIA) ice sheet model including ice shelves. Although vertically integrated, thermomechanical coupling is ensured through a simplified representation of ice sheet thermodynamics based on an analytical solution of the vertical temperature profile, including strain heating and horizontal advection. The marine boundary is represented by a flux condition either coherent with power-law basal sliding (Pollard & Deconto (2012) based on Schoof (2007)) or according to Coulomb basal friction (Tsai et al., 2015), both taking into account ice-shelf buttressing. Model initialization is based on optimization of the basal friction field. Besides the traditional MISMIP tests, new tests with respect to MISI in plan-view models have been devised. The model is forced with stepwise ocean and atmosphere temperature perturbations. The former is based on a parametrised sub-shelf melt (limited to ice shelves), while the latter is based on present-day mass balance/surface temperature and corrected for elevation changes. Surface melting is introduced using a PDD model. Results show a general linear response in mass loss to ocean warming. Nonlinear response due to MISI occurs under specific conditions and is highly sensitive to the basal conditions near the grounding line, governed by both the initial conditions and the basal sliding/deformation model. The Coulomb friction model leads to significantly higher sensitivity compared to power-law sliding. On longer time scales, West-antarctic inter-basin connections favor nonlinear response.

  15. Effects of supplementation with two sources and two levels of copper on meat lipid oxidation, meat colour and superoxide dismutase and glutathione peroxidase enzyme activities in Nellore beef cattle.

    PubMed

    Correa, Lísia Bertonha; Zanetti, Marcus Antonio; Del Claro, Gustavo Ribeiro; de Paiva, Fernanda Alves; da Luz e Silva, Saulo; Netto, Arlindo Saran

    2014-10-28

    In the present study, thirty-five Nellore bulls were used to determine the effects of two levels and two sources (organic and inorganic) of Cu supplementation on the oxidative stability of lipids, measured by the thiobarbituric acid-reactive substance (TBARS) test, meat colour and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities. The following treatments were used: (1) control (C) - basal diet without supplementation of Cu (7 mg Cu/kg DM); (2) I10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper sulphate (inorganic form); (3) I40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper sulphate; (4) O10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper proteinate (organic form); (5) O40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper proteinate. Lipid oxidation was determined in meat samples exposed to display, modified atmosphere (MA) and vacuum packaging (VC) conditions and in liver samples using the TBARS test. These samples were also evaluated for meat discolouration after exposure to air. The activities of SOD and GSH-Px enzymes were determined in liver samples. In display, MA and VC conditions, the TBARS values of samples from animals supplemented with 40 mg Cu/kg DM were lower than those of samples from control animals. There was no effect of treatment on the colour variables (L*, a*, b*). There was also no significant effect of treatment on hepatic TBARS concentrations and GSH-Px activity. Supplementation with Cu at 40 mg/kg, regardless of the source, induced higher hepatic SOD activity compared with the control treatment. In conclusion, Cu supplementation improved the oxidative stability of lipids in samples exposed to display, MA and VC conditions, demonstrating the antioxidant effect of this mineral.

  16. Endurance exercise training induces fat depot-specific differences in basal autophagic activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tanaka, Goki; Kato, Hisashi; Izawa, Tetsuya, E-mail: tizawa@mail.doshisha.ac.jp

    The purpose of this study was to uncover the effect of exercise training on the expression of autophagy marker proteins in epididymal white adipose tissue (eWAT), inguinal WAT (iWAT), and the stromal vascular fraction (SVF) collected from eWAT. Male Wistar rats aged 4–5 weeks were randomly divided into two groups, sedentary control (n = 7) and exercise-trained (n = 7). Rats in the exercise-trained group were exercised on a treadmill set at a 5° incline 5 days/week for 9 weeks. We determined that the expression levels of an autophagosome-associating form of microtubule-associated protein 1 light chain 3 (LC3)-II and of p62 were significantly highermore » in eWAT from exercise-trained than from control rats, while those of adipose-specific deletion of autophagy-related protein (ATG7) and lysosomal-associated membrane protein type 2A (LAMP2a) showed no difference between groups. However, in iWAT, the expression levels of LC3-II and ATG7 were significantly higher in exercise-trained than in control rats. The expression of p62 was highly correlated with that of peroxisome proliferator-activated receptor γ (PPARγ), a master regulator of adipogenesis and lipid metabolism, in both WAT types (eWAT, r = 0.856, P < 0.05; iWAT, r = 0.762, P < 0.05), whereas LC3-II and PPARγ levels were highly correlated in eWAT (r = 0.765, P < 0.05) but not in iWAT (r = −0.306, ns). In SVF, the expression levels of LC3II, ATG7, and LAMP2a were significantly higher in exercise-trained than in control rats. These results suggest that exercise training suppresses basal autophagy activity in eWAT, but that this activity is enhanced in iWAT and SVF collected from eWAT. Thus, the adaptation of basal autophagic activity following exercise training exhibits fat depot-specific differences. - Highlights: • Autophagy has been associated with obesity and associated diseases. • We examined exercise-associated rat white adipose tissue (WAT) autophagy markers. • Exercise increased autophagosome associated LC3-II in WAT. • Exercise-induced changes in p62 and ATG7 were WAT-type specific. • Exercise-induced basal autophagic activity shows fat depot-specific differences.« less

  17. Lowered quality of life in mood disorders is associated with increased neuro-oxidative stress and basal thyroid-stimulating hormone levels and use of anticonvulsant mood stabilizers.

    PubMed

    Nunes, Caroline Sampaio; Maes, Michael; Roomruangwong, Chutima; Moraes, Juliana Brum; Bonifacio, Kamila Landucci; Vargas, Heber Odebrecht; Barbosa, Decio Sabbatini; Anderson, George; de Melo, Luiz Gustavo Piccoli; Drozdstoj, Stoyanov; Moreira, Estefania; Carvalho, André F; Nunes, Sandra Odebrecht Vargas

    2018-04-17

    Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH. © 2018 John Wiley & Sons, Ltd.

  18. Beam hardening artifact reduction using dual energy computed tomography: implications for myocardial perfusion studies

    PubMed Central

    Carrascosa, Patricia; Cipriano, Silvina; De Zan, Macarena; Deviggiano, Alejandro; Capunay, Carlos; Cury, Ricardo C.

    2015-01-01

    Background Myocardial computed tomography perfusion (CTP) using conventional single energy (SE) imaging is influenced by the presence of beam hardening artifacts (BHA), occasionally resembling perfusion defects and commonly observed at the left ventricular posterobasal wall (PB). We therefore sought to explore the ability of dual energy (DE) CTP to attenuate the presence of BHA. Methods Consecutive patients without history of coronary artery disease who were referred for computed tomography coronary angiography (CTCA) due to atypical chest pain and a normal stress-rest SPECT and had absence or mild coronary atherosclerosis constituted the study population. The study group was acquired using DE and the control group using SE imaging. Results Demographical characteristics were similar between groups, as well as the heart rate and the effective radiation dose. Myocardial signal density (SD) levels were evaluated in 280 basal segments among the DE group (140 PB segments for each energy level from 40 to 100 keV; and 140 reference segments), and in 40 basal segments (at the same locations) among the SE group. Among the DE group, myocardial SD levels and myocardial SD ratio evaluated at the reference segment were higher at low energy levels, with significantly lower SD levels at increasing energy levels. Myocardial signal-to-noise ratio was not significantly influenced by the energy level applied, although 70 keV was identified as the energy level with the best overall signal-to-noise ratio. Significant differences were identified between the PB segment and the reference segment among the lower energy levels, whereas at ≥70 keV myocardial SD levels were similar. Compared to DE reconstructions at the best energy level (70 keV), SE acquisitions showed no significant differences overall regarding myocardial SD levels among the reference segments. Conclusions BHA that influence the assessment of myocardial perfusion can be attenuated using DE at 70 keV or higher. PMID:25774354

  19. Outcome of Microscopic Transsphenoidal Surgery in Cushing Disease: A Case Series of 96 Patients.

    PubMed

    Shirvani, Manochehr; Motiei-Langroudi, Rouzbeh; Sadeghian, Homa

    2016-03-01

    To analyze the results of transsphenoidal surgery in patients with Cushing disease and outcome. Retrospective analysis of the records of 96 patients with Cushing disease from 1997 to 2012. There were 73 females and 23 males, with a mean follow-up of 44 months (range, 3-13 years). The sex ratio was significantly different in children and teenagers versus adults. Magnetic resonance imaging showed microadenoma, macroadenoma, and no adenoma in 66, 18, and 12 patients, respectively. There was no surgical mortality. Early remission (normal 24-hour urinary free cortisol and basal serum cortisol <5 μg/dL) was achieved in 94.8%. Regression analysis showed that only tumor size, cavernous sinus extension, and tumor consistency influenced remission. Recurrence was seen in 21.9%. Regression analysis showed that age, preoperative basal cortisol levels, and follow-up duration influenced recurrence. Correlation analysis showed that there was a significant negative correlation between patient age and the follow-up period. After detection of recurrence, 17 patients underwent repeat transsphenoidal surgery that resulted in remission in 12 patients (70.6%). The other 5 patients were referred for gamma knife radiosurgery or bilateral adrenalectomy. Transsphenoidal surgery is a safe and highly efficient procedure in the treatment of Cushing disease. Macroadenomas, cavernous sinus invasion, and harder tumor consistencies, however, are associated with lower remission rates (higher disease persistence) and younger age, higher preoperative cortisol levels, and longer follow-up periods are associated with higher recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effects of Anti-diarrhoeal Herbs on Growth Performance, Nutrient Digestibility, and Meat Quality in Pigs

    PubMed Central

    Cho, J. H.; Zhang, S.; Kim, I. H.

    2012-01-01

    Two studies were conducted to investigate the effects of anti-diarrhoeal herbs on growth performance, nutrient digestibility, and meat quality in pigs. In Exp 1, 150 weanling-growing piglets (average BW = 7.5±0.24 kg, average age = 27±1 d) were allotted into one of the five dietary treatments, including: i) CON, basal diet, ii) DP, basal diet+1 g/kg date pits, iii) JH, basal diet+0.5 g/kg Japanese-honeysuckle, iv) HCT, basal diet+1 g/kg houttuynia cordata thunb, and v) LE, basal diet+1 g/kg laquer tree extract. From wk 0 to 5, the JH, HCT and LE groups presented higher (p<0.05) ADFI, ADG and gain/feed ratio (G/F) than CON and DP groups. During wk 5 to 10, Pigs fed JH, HCT and LE diets indicated higher (p<0.05) ADG and ADFI than the pigs fed CON and DP diets. During the entire experimental period, a significant increase of ADG appeared in JH, HCT and LE (p<0.05). Pigs fed JH, HCT and LE diets got a higher (p<0.05) ADFI than the pigs fed CON and DP diets. Pigs fed diets with supplementations of herb additives revealled lower (p<0.05) score of diarrhea pigs during d 2 to d 6 compared with pigs fed CON diet. In Exp 2, 60 growing-finishing barrows and gilts (average BW = 54.10±1.20 kg, average age = 54±3 d) were allotted to three treatments: i) CON, basal diet; ii) YG, basal diet+1 g/kg yellow ginger and iii) HR, basal dietary+1 g/kg hoantchy root, respectively. From wk 0 to 5, Dietary supplementation of YG and HR enhanced (p<0.05) ADG. No difference was found between YG and HR treatments. During, wk 5 to 10, ADG also was observed higher in YG and HR treatments than CON group (p<0.05). Additional, YG had the highest ADG (p<0.05) among treatments. There was always an increase of ADG in YG and HR (p<0.05) through all periods. HR treatment showed a lower (p<0.05) score of diarrhoeal pigs on d 1and d 2 compared with CON treatment. Pigs fed YG and HR diets had a higher (p<0.05) longissimus muscle area (LMA) than pigs fed CON diet. In conclusion, anti-diarrhoeal herbs can improve growth performance, and prevent diarrhea incidence in pigs, it can also increase LMA in finishing pigs. PMID:25049522

  1. The effect of dietary bacterial organic selenium on growth performance, antioxidant capacity, and Selenoproteins gene expression in broiler chickens.

    PubMed

    Dalia, A M; Loh, T C; Sazili, A Q; Jahromi, M F; Samsudin, A A

    2017-08-18

    Selenium (Se) is an essential trace mineral in broilers, which has several important roles in biological processes. Organic forms of Se are more efficient than inorganic forms and can be produced biologically via Se microbial reduction. Hence, the possibility of using Se-enriched bacteria as feed supplement may provide an interesting source of organic Se, and benefit broiler antioxidant system and other biological processes. The objective of this study was to examine the impacts of inorganic Se and different bacterial organic Se sources on the performance, serum and tissues Se status, antioxidant capacity, and liver mRNA expression of selenoproteins in broilers. Results indicated that different Se sources did not significantly (P ≤ 0.05) affect broiler growth performance. However, bacterial organic Se of T5 (basal diet +0.3 mg /kg feed ADS18 Se), T4 (basal diet +0.3 mg /kg feed ADS2 Se), and T3 (basal diet +0.3 mg /kg feed ADS1 Se) exhibited significantly (P ≤ 0.05) highest Se concentration in serum, liver, and kidney respectively. Dietary inorganic Se and bacterial organic Se were observed to significantly affect broiler serum ALT, AST, LDH activities and serum creatinine level. ADS18 supplemented Se of (Stenotrophomonas maltophilia) bacterial strain showed the highest GSH-Px activity with the lowest MDA content in serum, and the highest GSH-Px and catalase activity in the kidney, while bacterial Se of ADS2 (Klebsiella pneumoniae) resulted in a higher level of GSH-Px1 and catalase in liver. Moreover, our study showed that in comparison with sodium selenite, only ADS18 bacterial Se showed a significantly higher mRNA level in GSH-Px1, GSH-Px4, DIO1, and TXNDR1, while both ADS18 and ADS2 showed high level of mRNA of DIO2 compared to sodium selenite. The supplementation of bacterial organic Se in broiler chicken, improved tissue Se deposition, antioxidant status, and selenoproteins gene expression, and can be considered as an effective alternative source of Se in broiler chickens.

  2. Dissociable Frontal–Striatal and Frontal–Parietal Networks Involved in Updating Hierarchical Contexts in Working Memory

    PubMed Central

    Nee, Derek Evan; Brown, Joshua W.

    2013-01-01

    Recent theories propose that the prefrontal cortex (PFC) is organized in a hierarchical fashion with more abstract, higher level information represented in anterior regions and more concrete, lower level information represented in posterior regions. This hierarchical organization affords flexible adjustments of action plans based on the context. Computational models suggest that such hierarchical organization in the PFC is achieved through interactions with the basal ganglia (BG) wherein the BG gate relevant contexts into the PFC. Here, we tested this proposal using functional magnetic resonance imaging (fMRI). Participants were scanned while updating working memory (WM) with 2 levels of hierarchical contexts. Consistent with PFC abstraction proposals, higher level context updates involved anterior portions of the PFC (BA 46), whereas lower level context updates involved posterior portions of the PFC (BA 6). Computational models were only partially supported as the BG were sensitive to higher, but not lower level context updates. The posterior parietal cortex (PPC) showed the opposite pattern. Analyses examining changes in functional connectivity confirmed dissociable roles of the anterior PFC–BG during higher level context updates and posterior PFC–PPC during lower level context updates. These results suggest that hierarchical contexts are organized by distinct frontal–striatal and frontal–parietal networks. PMID:22798339

  3. Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease.

    PubMed

    Benjamin, F; Deutsch, S; Saperstein, H; Seltzer, V L

    1986-08-01

    To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.

  4. Influence of Dietary Selenium Species on Selenoamino Acid Levels in Rainbow Trout.

    PubMed

    Godin, Simon; Fontagné-Dicharry, Stéphanie; Bueno, Maïté; Tacon, Philippe; Prabhu, Philip Antony Jesu; Kaushik, Sachi; Médale, Françoise; Bouyssiere, Brice

    2015-07-22

    Two forms of selenium (Se) supplementation of fish feeds were compared in two different basal diets. A 12-week feeding trial was performed with rainbow trout fry using either a plant-based or a fish meal-based diet. Se yeast and selenite were used for Se supplementation. Total Se and Se speciation were determined in both diets and whole body of trout fry using inductively coupled plasma mass spectrometry (ICP MS) and high-performance liquid chromatography (HPLC). The two selenoamino acids, selenomethionine (SeMet) and selenocysteine (SeCys), were determined in whole body of fry after enzymatic digestion using protease type XIV with a prior derivatization step in the case of SeCys. The plant-based basal diet was found to have a much lower total Se than the fish meal-based basal diet with concentrations of 496 and 1222 μg(Se) kg(-1), respectively. Dietary Se yeast had a higher ability to raise whole body Se compared to selenite. SeMet concentration in the fry was increased only in the case of Se yeast supplementation, whereas SeCys levels were similar at the end of the feeding trial for both Se supplemented forms. The results show that the fate of dietary Se in fry is highly dependent on the form brought through supplementation and that a plant-based diet clearly benefits from Se supplementation.

  5. Qualitative evaluation of the iris and ciliary body by ultrasound biomicroscopy in subjects with angle closure.

    PubMed

    Ku, Judy Y; Nongpiur, Monisha E; Park, Judy; Narayanaswamy, Arun K; Perera, Shamira A; Tun, Tin A; Kumar, Rajesh S; Baskaran, Mani; Aung, Tin

    2014-12-01

    To qualitatively analyze anterior chamber structures imaged by ultrasound biomicroscopy (UBM) in primary angle-closure patients. Subjects diagnosed as primary angle-closure suspect (PACS), primary angle-closure glaucoma (PACG), and previous acute primary angle closure (APAC) were recruited prospectively along with a group of normal controls. UBM was performed under standardized dark room conditions and qualitative assessment was carried out using a set of reference photographs of standard UBM images to categorize the various anatomic features related to angle configuration. These included overall and basal iris thicknesses, iris convexity, iris angulation, ciliary body size, and ciliary sulcus. A total of 60 PACS, 114 PACG, 41 APAC, and 33 normal controls were included. Patients were predominantly older Chinese females. After controlling the confounding effect of age and sex, eyes with overall thicker irides [medium odds ratio (OR) 3.58, thick OR 2.84] when compared with thin irides have a significantly higher likelihood of having PACS/PACG/APAC versus controls. Thicker basal iris component (medium OR 4.13, thick OR 3.39) also have higher likelihood of having angle closure when compared with thin basal iris thickness. Subjects with basal iris insertion, mild iris angulation, and large ciliary body have a higher OR of having angle closure. In contrast, the presence/absence of a ciliary sulcus did not influence the likelihood of angle closure. Eyes with thicker overall and basal iris thicknesses are more likely to have angle closure than controls. Other features that increase the likelihood of angle closure include basal iris insertion, mild iris angulation, and large ciliary body.

  6. Beta-lactoglobulin secretion in human milk varies widely after cow's milk ingestion in mothers of infants with cow's milk allergy.

    PubMed

    Sorva, R; Mäkinen-Kiljunen, S; Juntunen-Backman, K

    1994-04-01

    Cow's milk proteins secreted in human milk may cause cow's milk allergy (CMA) even during exclusive breast-feeding. We studied beta-lactoglobulin levels in human milk of mothers of infants with CMA. We also studied intestinal absorption of macromolecules in the same mothers to see whether it is related to the secretion of beta-lactoglobulin in human milk. CMA was verified with oral challenge in 46 of 55 infants assessed. beta-Lactoglobulin levels were assessed in human milk from 53 of 55 mothers of the infants before (basal sample) and 1 and 2 hours after an oral cow's milk load, which was given after a 24-hour milk-free diet. beta-Lactoglobulin was determined by an ELISA with a detection limit of 0.002 microgram/L. The 6-hour urine recovery of a high-molecular-weight polyethylene glycol (PEG) 3000 was assessed after an oral load of PEG in 45 of 55 mothers. beta-Lactoglobulin was found in the 1- or 2-hour samples in 75% of the mothers. beta-Lactoglobulin levels were increased in the 1- or 2-hour samples as compared with the basal levels in about half of the mothers. The respective levels were decreased in one third of the mothers whose basal beta-lactoglobulin levels were higher than in the others. beta-Lactoglobulin was found in none of the three human milk samples in 15% of the mothers. After an oral load of a high-molecular-weight PEG 3000, the 6-hour urine recovery of PEG was similar in the mothers of the infants with CMA and the mothers of infants without CMA. Neither was the urinary recovery of PEG related to the beta-lactoglobulin levels in human milk. The results support the view that beta-lactoglobulin in human milk may contribute to, but does not alone explain, the development of CMA in breast-fed infants.

  7. Hormonal underpinnings of status conflict: Testosterone and cortisol are related to decisions and satisfaction in the hawk-dove game.

    PubMed

    Mehta, Pranjal H; Lawless DesJardins, Nicole M; van Vugt, Mark; Josephs, Robert A

    2017-06-01

    A contribution to a special issue on Hormones and Human Competition.Testosterone is theorized to influence status-seeking behaviors such as social dominance and competitive behavior, but supporting evidence is mixed. The present study tested the roles of testosterone and cortisol in the hawk-dove game, a dyadic economic decision-making paradigm in which earnings depend on one's own and the other player's choices. If one person selects the hawk strategy and the other person selects the dove strategy, the player who selected hawk attains a greater financial pay-off (status differentiation). The worst financial outcome occurs when both players choose the hawk strategy (status confrontation). Ninety-eight undergraduate students (42 men) provided saliva samples and played ten rounds of the hawk-dove game with another same-sex participant. In support of the hypothesis that testosterone is related to status concern, individuals higher in basal testosterone made more hawk decisions - decisions that harmed the other player. Acute decreases in cortisol were also associated with more hawk decisions. There was some empirical support for the dual-hormone hypothesis as well: basal testosterone was positively related to satisfaction in the game among low basal-cortisol individuals but not among high basal-cortisol individuals. There were no significant sex differences in these hormonal effects. The present findings align with theories of hormones and status-seeking behavior at the individual level, but they also open up new avenues for research on hormone profiles at the collective level. Our results suggest that the presence of two or more high-testosterone members increases the likelihood of status confrontations over a limited resource that can undermine collective outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Dysregulated responses to emotions among abstinent heroin users: correlation with childhood neglect and addiction severity.

    PubMed

    Gerra, G; Somaini, L; Manfredini, M; Raggi, M A; Saracino, M A; Amore, M; Leonardi, C; Cortese, E; Donnini, C

    2014-01-03

    The aim of this paper was to investigate the subjective responses of abstinent heroin users to both neutral and negative stimuli and the related hypothalamus-pituitary-adrenal reactions to emotional experience in relationship to their perception of childhood adverse experiences. Thirty male abstinent heroin dependents were included in the study. Emotional responses and childhood neglect perception were measured utilizing the State-Trait Anxiety Inventory Y-1 and the Child Experience of Care and Abuse Questionnaire. Neutral and unpleasant pictures selected from the International Affective Picture System and the Self-Assessment Manikin procedure have been used to determine ratings of pleasure and arousal. These ratings were compared with normative values obtained from healthy volunteers used as control. Blood samples were collected before and after the experimental sessions to determine both adrenocorticotropic hormone and cortisol plasma levels. Basal anxiety scores, cortisol and adrenocorticotropic hormone levels were higher in abstinent heroin users than in controls. Tests showed that anxiety scores did not change in controls after the vision of neutral slides, whilst they did in abstinent heroin addicts, increasing significantly; and increased less significantly after the unpleasant task, in comparison to controls. Abstinent heroin users showed significantly higher levels of parent antipathy and childhood emotional neglect perception than controls for both the father and the mother. Plasma adrenocorticotropic hormone and cortisol levels did not significantly increase after unpleasant slide set viewing among addicted individuals, because of the significantly higher basal levels characterizing the addicted subjects in comparison with controls. Multiple regression correlation showed a significant relationship between childhood neglect perception, arousal reaction, impaired hypothalamus-pituitary-adrenal axis response and addiction severity. Early adverse experiences seem to affect the entire interaction between hyper-arousal, reduced hormonal response to stress and addiction severity. Our findings, although obtained in a small number of subjects, indicate a significant link between the perception of parental style/care/support during childhood and the ability to cope with stressful emotional stimuli in adulthood and addiction severity. © 2013.

  9. Fetuin-A levels in hyperthyroidism

    PubMed Central

    Pamuk, Barış Onder; Yılmaz, Hamiyet; Topcuoglu, Tugba; Bilgir, Oktay; Çalan, Ozlem; Pamuk, Gulseren; Ertugrul, Derun Taner

    2013-01-01

    OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1. Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels. PMID:23644859

  10. Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

    PubMed

    de Oliveira Poswar, Fabiano; de Carvalho Fraga, Carlos Alberto; Gomes, Emisael Stênio Batista; Farias, Lucyana Conceição; Souza, Linton Wallis Figueiredo; Santos, Sérgio Henrique Souza; Gomez, Ricardo Santiago; de-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

    2015-02-01

    Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC. © The Author(s) 2014.

  11. Identification and analysis of low-molecular-weight dissolved organic carbon in subglacial basal ice ecosystems by ion chromatography

    NASA Astrophysics Data System (ADS)

    O'Donnell, Emily C.; Wadham, Jemma L.; Lis, Grzegorz P.; Tranter, Martyn; Pickard, Amy E.; Stibal, Marek; Dewsbury, Paul; Fitzsimons, Sean

    2016-07-01

    Determining the concentration and composition of dissolved organic carbon (DOC) in glacial ecosystems is important for assessments of in situ microbial activity and contributions to wider biogeochemical cycles. Nonetheless, there is limited knowledge of the abundance and character of DOC in basal ice and the subglacial environment and a lack of quantitative data on low-molecular-weight (LMW) DOC components, which are believed to be highly bioavailable to microorganisms. We investigated the abundance and composition of DOC in basal ice via a molecular-level DOC analysis. Spectrofluorometry and a novel ion chromatographic method, which has been little utilized in glacial science for LMW-DOC determinations, were employed to identify and quantify the major LMW fractions (free amino acids, carbohydrates, and carboxylic acids) in basal ice from four glaciers, each with a different type of overridden material (i.e. the pre-entrainment sedimentary type such as lacustrine material or palaeosols). Basal ice from Joyce Glacier (Antarctica) was unique in that 98 % of the LMW-DOC was derived from the extremely diverse free amino acid (FAA) pool, comprising 14 FAAs. LMW-DOC concentrations in basal ice were dependent on the bioavailability of the overridden organic carbon (OC), which in turn was influenced by the type of overridden material. Mean LMW-DOC concentrations in basal ice from Russell Glacier (Greenland), Finsterwalderbreen (Svalbard), and Engabreen (Norway) were low (0-417 nM C), attributed to the relatively refractory nature of the OC in the overridden palaeosols and bedrock. In contrast, mean LMW-DOC concentrations were an order of magnitude higher (4430 nM C) in basal ice from Joyce Glacier, a reflection of the high bioavailability of the overridden lacustrine material (> 17 % of the sediment OC comprised extractable carbohydrates, a proxy for bioavailable OC). We find that the overridden material may act as a direct (via abiotic leaching) and indirect (via microbial cycling) source of DOC to the subglacial environment and provides a range of LMW-DOC compounds that may stimulate microbial activity in wet subglacial sediments.

  12. Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

    PubMed

    Chico, A; Herranz, L; Corcoy, R; Ramírez, O; Goya, M M; Bellart, J; González-Romero, S; Codina, M; Sánchez, P; Cortázar, A; Acosta, D; Picón, M J; Rubio, J A; Megía, A; Sancho, M A; Balsells, M; Solá, E; González, N L; López-López, J

    2016-11-01

    To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA 1c ) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AM Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

    NASA Technical Reports Server (NTRS)

    Young, R. B.; Bridge, K. Y.; Wuethrich, A. J.; Hancock, D. L.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Broiler chickens at 35 days of age were fed 1 ppm clenbuterol for 14 days. This level of dietary clenbuterol led to 5-7% increases in weights of leg and breast muscle tissue. At the end of the 14-day period, serum was prepared from both control and clenbuterol-treated chickens and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and breast muscle groups of twelve-day chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 micron clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 days beginning on the seventh day in culture. Neither the percent fusion nor the number of nuclei in myotubes were significantly affected by any of the treatments. The quantity of MHC was not increased by serum from clenbuterol-treated chickens in either breast and leg muscle cultures; however, MHC quantity was 50- 100% higher in cultures grown in control chicken serum to which 10 nM and 50 nM clenbuterol had also been added. The Beta-AR population was 4,000-7,000 Beta-AR per cell in cultures grown in chicken serum, with leg muscle cultures having approximately 25-30% more receptors than breast muscle cultures. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the Beta-AR population in leg and breast muscle cultures grown in the presence of 10% horse serum was 18,000-20,000 Beta-AR per cell. Basal concentration of cAMP was not significantly affected by any of the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 micron isoproterenol, limited increases of 12-20% in cAMP concentration above basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 micron isoproterenol, increases of 600-800 % in cAMP concentration above basal levels were observed. Thus, not only did cells grown in horse serum have a higher Beta-AR population, each receptor had a higher capacity for cAMP synthesis following isoproterenol stimulation. Finally, the hypothesis was tested that clenbuterol exerts its action on muscle protein content by changes in cAMP concentration. No correlation was apparent between basal cAMP concentration and MHC content.

  14. Effect of Serum from Chickens Treated with Clenbuterol on Myosin Accumulation, Beta-Adrenergic Receptor Population, and Cyclic AMP Synthesis in Embryonic Chicken Skeletal Muscle Cell Cultures

    NASA Technical Reports Server (NTRS)

    Young, Ronald B.; Bridge, Kristin Y.; Wuethrich, Andrew J.; Hancock, Deana L.

    2002-01-01

    Broiler chickens at 35 d of age were fed 1 ppm clenbuterol for 14 d. This level of dietary clenbuterol led to 5-7% increases in the weights of leg and breast muscle tissue. At the end of the 14-d period, serum was prepared from both control and clenbuterol-treated chickens, and was then employed as a component of cell culture media at a final concentration of 20% (v/v). Muscle cell cultures were prepared from both the leg and the breast muscle groups of 12-d chick embryos. Treatment groups included control chicken serum to which 10 nM, 50 nM, and 1 uM clenbuterol had been added, as well as cells grown in media containing 10% horse serum. Cultures were subjected to each treatment for 3 d, beginning on the seventh d in culture. Neither the percent fusion nor the number of nuclei in myotubes was significantly affected by any of the treatments. The quantity of myosin heavy chains (MHCs) was not increased by serum from clenbuterol-treated chickens in either breast or leg muscle cultures; however, the MHC quantity was 50-150% higher in cultures grown in control chicken serum to which 10 and 50 nM clenbuterol had also been added. The B-adrenergic receptor (betaAR) population was 4000-7000 betaARs per cell in cultures grown in chicken serum with leg muscle cultures having approximately 25-30% more receptors than breast muscle Culture. Receptor population was not significantly affected by the presence of clenbuterol or by the presence of serum from clenbuterol-treated chickens. In contrast, the betaAR Population in leg and breast muscle cultures grown in the presence of 10% horse serum was 16,000-18,000 betaARs per cell. Basal concentration of cyclic adenosine 3':5'monophosphate (cAMP) was not significantly affected by the treatments. When cultures grown in chicken serum were stimulated for 10 min with 1 uM isoproterenol, limited increases of 12-20% in cAMP Concentration above the. basal levels were observed. However, when cultures grown in the presence of horse serum were stimulated with 1 uM isoproterenol, cAMP concentration was stimulated 5- to 9-fold above the basal levels. Thus, not only did cells, grown in horse serum have a higher PAR population, but also each receptor had a higher capacity for cAMP synthesis following isoproterenol stimulation. Finally, the hypothesis that clenbuterol exerts its action on muscle protein content by changes in cAMP concentration was tested. No correlation was apparent between basal cAMP concentration and MHC content.

  15. Glioblastoma recurrence correlates with NLGN3 levels.

    PubMed

    Liu, Rui; Qin, Xing-Ping; Zhuang, Yang; Zhang, Ya; Liao, Hua-Bao; Tang, Jun-Chun; Pan, Meng-Xian; Zeng, Fei-Fei; Lei, Yang; Lei, Rui-Xue; Wang, Shu; Liu, An-Chun; Chen, Juan; Zhang, Zhi-Feng; Zhao, Dan; Wu, Song-Lin; Liu, Ren-Zhong; Wang, Ze-Fen; Wan, Qi

    2018-05-18

    Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain. In contrast, NLGN3 levels in the deep brain regions of GBM patients are high. We also show that an increase in NLGN3 concentration promotes the growth of U251 cells and U87-MG cells. Respective use of the cortex neuron culture medium (C-NCM) and basal ganglia neuron culture medium (BG-NCM) with DMEM to cultivate U251, U87-MG and GBM cells isolated from patients, we found that these cells grew faster after treatment with C-NCM and BG-NCM in which the cells treated with C-NCM grew faster than the ones treated with BG-NCM group. Inhibition of NLGN3 release by ADAM10i prevents NCM-induced cell growth. Together, this study suggests that increased levels of NLGN3 in the deep brain region under the GBM pathological circumstances may contribute to GBM recurrence in the basal ganglia, thalamus, and corpus callosum. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana

    PubMed Central

    Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela

    2010-01-01

    Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes. PMID:20101514

  17. Quantitative expression analysis of selected transcription factors in pavement, basal and trichome cells of mature leaves from Arabidopsis thaliana.

    PubMed

    Schliep, Martin; Ebert, Berit; Simon-Rosin, Ulrike; Zoeller, Daniela; Fisahn, Joachim

    2010-05-01

    Gene expression levels of several transcription factors from Arabidopsis thaliana that were described previously to be involved in leaf development and trichome formation were analysed in trichome, basal and pavement cells of mature leaves. Single cell samples of these three cells types were collected by glass micro-capillaries. Real-time reverse transcription (RT)-PCR was used to analyse expression patterns of the following transcription factors: MYB23, MYB55, AtHB1, FILAMENTOUS FLOWER (FIL)/YABBY1 (YAB1), TRIPTYCHON (TRY) and CAPRICE (CPC). A difference in the expression patterns of TRY and CPC was revealed. Contrary to the CPC expression pattern, no transcripts of TRY could be detected in pavement cells. FIL/YAB1 was exclusively expressed in trichome cells. AtHB1 was highly expressed throughout all three cell types. MYB55 was higher expressed in basal cells than in trichome and pavement cells. MYB23 showed a pattern of low expression in pavement cells, medium in basal cells and high expression in trichomes. Expression patterns obtained by single cell sampling and real-time RT-PCR were compared to promoter GUS fusions of the selected transcription factors. Therefore, we regenerated two transgenic Arabidopsis lines that expressed the GUS reporter gene under control of the promoters of MYB55 and YAB1. In conclusion, despite their function in leaf morphogenesis, all six transcription factors were detected in mature leaves. Furthermore, single cell sampling and promoter GUS staining patterns demonstrated the predominant presence of MYB55 in basal cells as compared to pavement cells and trichomes.

  18. Direct and indirect trophic effects of predator depletion on basal trophic levels.

    PubMed

    Chen, Huili; Hagerty, Steven; Crotty, Sinead M; Bertness, Mark D

    2016-02-01

    Human population growth and development have heavily degraded coastal ecosystems with cascading impacts across multiple trophic levels. Understanding both the direct and indirect trophic effects of human activities is important for coastal conservation. In New England, recreational overfishing has triggered a regional trophic cascade. Predator depletion releases the herbivorous purple marsh crab from consumer control and leads to overgrazing of marsh cordgrass and salt marsh die-off. The direct and indirect trophic effects of predator depletion on basal trophic levels, however, are not understood. Using observational and experimental data, we examined the hypotheses that (1) direct trophic effects of predator depletion decrease meiofaunal abundance by releasing deposit feeding fiddler crabs from consumer control, and/or (2) indirect trophic effects of predator depletion increase meiofaunal abundance by releasing blue carbon via the erosion of centuries of accreted marsh peat. Experimental deposit feeder removal led to 23% higher meiofaunal density at die-off than at healthy sites, while reciprocally transplanting sediment from die-off and healthy sites revealed that carbon-rich die-off sediment increased meiofauna density by over 164%: six times stronger than direct trophic effects. Recovering sites had both carbon-rich sediment and reduced deposit feeding leading to higher meiofauna densities than both die-off and healthy sites. This suggests that consequences of the trophic downgrading of coastal habitats can be driven by both direct and indirect trophic mechanisms that may vary in direction and magnitude, making their elucidation dependent on experimental manipulations.

  19. Altered expression of Matrix Remodeling Associated 7 (MXRA7) in psoriatic epidermis: evidence for a protective role in the psoriasis imiquimod mouse model.

    PubMed

    Ning, Jinling; Shen, Ying; Wang, Ting; Wang, Mengru; Liu, Wei; Sun, Yonghu; Zhang, Furen; Chen, Lingling; Wang, Yiqiang

    2018-05-21

    Preliminary datamining performed with Gene Expression Omnibus datasets implied that psoriasis may involve the matrix remodeling associated 7 (MXRA7), a gene with little function information yet. To test that hypothesis, studies were performed in human samples and murine models. Immunohistochemistry in normal human skin showed that MXRA7 proteins were present across the full epidermal layer, with highest expression level detected in the basal layer. In psoriatic samples, MXRA7 proteins were absent in the basal stem cells layer while suprabasal keratinocytes stained at a higher level than in normal tissues. In an imiquimod-induced psoriasis-like disease model in mice, diseased skins manifested similar MXRA7 expression pattern and change as in human samples, and MXRA7-deficient mice developed severer psoriasis-like diseases than wild-type mice did. While levels of pro-psoriatic genes (e.g. IL17, IL22, IL23, etc) in imiquimod-stimulated MXRA7-deficient mice were higher than in wild-type mice, keratinocytes isolated from MXRA7-deficient mice showed increased proliferation upon differentiation induction in culture. These data demonstrated that MXRA7 gene might function as a negative modulator in psoriasis development when pro-psoriatic factors attack, presumably via expression alteration or redistribution of MXRA7 proteins in keratinocytes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Football fan aggression: the importance of low Basal cortisol and a fair referee.

    PubMed

    van der Meij, Leander; Klauke, Fabian; Moore, Hannah L; Ludwig, Yannick S; Almela, Mercedes; van Lange, Paul A M

    2015-01-01

    Fan aggression in football (soccer) is a societal problem that affects many countries worldwide. However, to date, most studies use an epidemiological or survey approach to explain football fan aggression. This study used a controlled laboratory study to advance a model of predictors for fan aggression. To do so, football fans (n = 74) saw a match summary in which their favorite team lost against their most important rival. Next, we measured levels of aggression with the hot sauce paradigm, in which fans were given the opportunity to administer a sample of hot sauce that a rival football supporter had to consume. To investigate if media exposure had the ability to reduce aggression, before the match fans saw a video in which fans of the rival team commented in a neutral, negative, or positive manner on their favorite team. Results showed that the media exposure did not affect aggression. However, participants displayed high levels of aggression and anger after having watched the match. Also, aggression was higher in fans with lower basal cortisol levels, which suggests that part of the aggression displayed was proactive and related to anti-social behavior. Furthermore, aggression was higher when the referee was blamed and aggression was lower when the performance of the participants' favorite team was blamed for the match result. These results indicate that aggression increased when the match result was perceived as unfair. Interventions that aim to reduce football fan aggression should give special attention to the perceived fairness of the match result.

  1. Effects of phenylalanine, histidine, and leucine on basal and GHRH-stimulated GH secretion and on PRL, insulin, and glucose levels in short children. Comparison with the effects of arginine.

    PubMed

    Bellone, J; Valetto, M R; Aimaretti, G; Segni, M; Volta, C; Cardimale, G; Baffoni, C; Pasquino, A M; Bernasconi, S; Bartolotta, E; Mucci, M; Ghigo, E

    1996-01-01

    Of the amino acids arginine is the most potent GH secretagogue in man. It potentiates the GH response to GHRH, exerts a weaker PRL-releasing effect, stimulates insulin and glucagon and induces a biphasic glucose variation. The potency and effects of other amino acids on pituitary and pancreatic hormones need to be clarified. In 43 children with normal short stature (5.3-14.0 yr; 30 M and 13 F) the effects of the infusion of phenylalanine (Phe, 0.08 g/kg), histidine (His, 0.1 g/kg), and leucine (Leu, 0.08 g/kg) on basal and GHRH-stimulated GH secretion and on PRL, insulin and glucose levels were studied and compared with those of arginine at high (hArg, 0.5 g/kg) or low dose (lArg, 0.2 g/kg). Phe increased basal (p < 0.05) but not GHRH-stimulated GH levels, induced PRL and insulin rises (p < 0.03 and p < 0.03), and did not change glycemia. Though a trend toward an increase in basal GH levels was found after His, His and Leu did not significantly modify either basal or GHRH-induced GH secretion nor basal PRL, insulin and glucose levels. Both hArg and lArg increased basal (p < 0.0001 and p < 0.05, respectively) and GHRH-stimulated GH levels (p < 0.006 and p < 0.006). hArg increased both PRL (p < 0.002) and insulin levels (p < 0.005) more (p < 0.0005 and p < 0.004) than lArg (p < 0.005 and p < 0.005), while glucose levels showed a similar increase followed by a similar decrease. We conclude that in childhood: a) Phe significantly increases GH secretion but, differently from Arg, does not potentiate the response to GHRH, suggesting different mechanisms of action of these amino acids; b) differently from His and Leu, Phe is a PRL and insulin secretagogue but is less potent than Arg; c) Arg has the highest stimulatory effect on pituitary and pancreatic hormones.

  2. Time course of saliva and serum melatonin levels after ingestion of melatonin.

    PubMed

    Shirakawa, S; Tsuchiya, S; Tsutsumi, Y; Kotorii, T; Uchimura, N; Sakamoto, T; Yamada, S

    1998-04-01

    Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561+/-1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177+/-403 pg/mL) which was one-third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period (r=0.82, P=0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.

  3. Common Features of Neural Activity during Singing and Sleep Periods in a Basal Ganglia Nucleus Critical for Vocal Learning in a Juvenile Songbird

    PubMed Central

    Yanagihara, Shin; Hessler, Neal A.

    2011-01-01

    Reactivations of waking experiences during sleep have been considered fundamental neural processes for memory consolidation. In songbirds, evidence suggests the importance of sleep-related neuronal activity in song system motor pathway nuclei for both juvenile vocal learning and maintenance of adult song. Like those in singing motor nuclei, neurons in the basal ganglia nucleus Area X, part of the basal ganglia-thalamocortical circuit essential for vocal plasticity, exhibit singing-related activity. It is unclear, however, whether Area X neurons show any distinctive spiking activity during sleep similar to that during singing. Here we demonstrate that, during sleep, Area X pallidal neurons exhibit phasic spiking activity, which shares some firing properties with activity during singing. Shorter interspike intervals that almost exclusively occurred during singing in awake periods were also observed during sleep. The level of firing variability was consistently higher during singing and sleep than during awake non-singing states. Moreover, deceleration of firing rate, which is considered to be an important firing property for transmitting signals from Area X to the thalamic nucleus DLM, was observed mainly during sleep as well as during singing. These results suggest that songbird basal ganglia circuitry may be involved in the off-line processing potentially critical for vocal learning during sensorimotor learning phase. PMID:21991379

  4. Cytokine production capacity in depression and anxiety

    PubMed Central

    Vogelzangs, N; de Jonge, P; Smit, J H; Bahn, S; Penninx, B W

    2016-01-01

    Recent studies have suggested that immune function may be dysregulated in persons with depressive and anxiety disorders. Few studies examined the expression of cytokines in response to ex vivo stimulation of blood by lipopolysaccharide (LPS) to study the innate production capacity of cytokines in depression and anxiety. To investigate this, baseline data from the Netherlands Study of Depression and Anxiety (NESDA) were used, including persons (18–65 years; 66% women) with current (that is, past month; N=591) or remitted (N=354) DSM-IV depressive or anxiety disorders and healthy controls (N=297). Depressive and anxiety symptoms were measured by means of the Inventory of Depressive Symptomatology (IDS) and the Beck Anxiety Inventory (BAI). Using Multi-Analyte Profiling technology, plasma levels of 13 cytokines were assayed after whole blood stimulation by addition of LPS. Basal plasma levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α were also available. A basal and a LPS summary index were created. Results show that LPS-stimulated inflammation was associated with increased odds of current depressive/anxiety disorders (odds ratio (OR)=1.28, P=0.009), as was the case for basal inflammation (OR=1.28, P=0.001). These associations were no longer significant after adjustment for lifestyle and health (OR=1.13, P=0.21; OR=1.07, P=0.45, respectively). After adjustment for lifestyle and health, interleukin-8 was associated with both remitted (OR=1.25, P=0.02) and current (OR=1.28, P=0.005) disorders. In addition, LPS-stimulated inflammation was associated with more severe depressive (β=0.129, P<0.001) and anxiety (β=0.165, P<0.001) symptoms, as was basal inflammation. Unlike basal inflammation, LPS-stimulated inflammation was still associated with (anxiety) symptom severity after adjustment for lifestyle and health (IDS: IL-8, MCP-1, MMP2; BAI: LPS index, IL-6, IL-8, IL-10, IL-18, MCP-1, MMP2, TNF-β). To conclude, lifestyle and health factors may partly explain higher levels of basal, as well as LPS-stimulated inflammation in persons with depressive and anxiety disorders. However, production capacity of several cytokines was positively associated with severity of depressive and in particular anxiety symptoms, even while taking lifestyle and health factors into account. Elevated IL-8 production capacity in both previously and currently depressed and anxious persons might indicate a genetic vulnerability for these disorders. PMID:27244234

  5. Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells.

    PubMed

    Ede, Christopher; Chen, Ximin; Lin, Meng-Yin; Chen, Yvonne Y

    2016-05-20

    Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning 2 orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality.

  6. Age Differences of Salivary Alpha-Amylase Levels of Basal and Acute Responses to Citric Acid Stimulation Between Chinese Children and Adults.

    PubMed

    Yang, Ze-Min; Chen, Long-Hui; Zhang, Min; Lin, Jing; Zhang, Jie; Chen, Wei-Wen; Yang, Xiao-Rong

    2015-01-01

    It remains unclear how salivary alpha-amylase (sAA) levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1) copy number and protein expression (glycosylated and non-glycosylated) in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount) in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them. Interestingly, adults showed attenuated sAA activity levels increase over those of children after stimulation. Correlation analysis showed that total sAA amount, glycosylated sAA amount, and AMY1 copy number × total sAA amount were all positively correlated with sAA activity before and after stimulation in both groups. Interestingly, correlation r between sAA levels (glycosylated sAA amount and total sAA amount) and sAA activity decreased after stimulation in children, while adults showed an increase in correlation r. In addition, the correlation r between AMY1 copy number × total sAA amount and sAA activity was higher than that between AMY1 copy number, total sAA amount, and sAA activity, respectively. Taken together, our results suggest that total sAA amount, glycosylated sAA amount, and the positive interaction between AMY1 copy number and total sAA amount are crucial in influencing sAA activity before and after stimulation in children and adults.

  7. Age Differences of Salivary Alpha-Amylase Levels of Basal and Acute Responses to Citric Acid Stimulation Between Chinese Children and Adults

    PubMed Central

    Yang, Ze-Min; Chen, Long-Hui; Zhang, Min; Lin, Jing; Zhang, Jie; Chen, Wei-Wen; Yang, Xiao-Rong

    2015-01-01

    It remains unclear how salivary alpha-amylase (sAA) levels respond to mechanical stimuli in different age groups. In addition, the role played by the sAA gene (AMY1) copy number and protein expression (glycosylated and non-glycosylated) in sAA activity has also been rarely reported. In this study, we analyzed saliva samples collected before and after citric acid stimulation from 47 child and 47 adult Chinese subjects. We observed that adults had higher sAA activity and sAA glycosylated levels (glycosylated sAA amount/total sAA amount) in basal and stimulated saliva when compared with children, while no differences were found in total or glycosylated sAA amount between them. Interestingly, adults showed attenuated sAA activity levels increase over those of children after stimulation. Correlation analysis showed that total sAA amount, glycosylated sAA amount, and AMY1 copy number × total sAA amount were all positively correlated with sAA activity before and after stimulation in both groups. Interestingly, correlation r between sAA levels (glycosylated sAA amount and total sAA amount) and sAA activity decreased after stimulation in children, while adults showed an increase in correlation r. In addition, the correlation r between AMY1 copy number × total sAA amount and sAA activity was higher than that between AMY1 copy number, total sAA amount, and sAA activity, respectively. Taken together, our results suggest that total sAA amount, glycosylated sAA amount, and the positive interaction between AMY1 copy number and total sAA amount are crucial in influencing sAA activity before and after stimulation in children and adults. PMID:26635626

  8. Streptococcus pneumoniae-induced ototoxicity in organ of Corti explant cultures.

    PubMed

    Perny, Michael; Solyga, Magdalena; Grandgirard, Denis; Roccio, Marta; Leib, Stephen L; Senn, Pascal

    2017-07-01

    Hearing loss remains the most common long-term complication of pneumococcal meningitis (PM) reported in up to 30% of survivors. Streptococcus pneumoniae have been shown to possess different ototoxic properties. Here we present a novel ex vivo experimental setup to examine in detail the pattern of hair cell loss upon exposure to different S. pneumoniae strains, therefore recapitulating pathogen derived aspects of PM-induced hearing loss. Our results show a higher susceptibility towards S. pneumoniae-induced cochlear damage for outer hair cells (OHC) compared to inner hair cells (IHC), which is consistent with in vivo data. S. pneumoniae-induced hair cell loss was both time and dose-dependent. Moreover, we have found significant differences in the level of cell damage between tissue from the basal and the apical turns. This shows that the higher vulnerability of hair cells located at high frequency regions observed in vivo cannot be explained solely by the spatial organisation and bacterial infiltration from the basal portion of the cochlea. Using a wild type D39 strain and a mutant defective for the pneumolysin (PLY) gene, we also have shown that the toxin PLY is an important factor involved in ototoxic damages. The obtained results indicate that PLY can cause both IHC and OHC loss. Finally, we are reporting here for the first time a higher vulnerability of HC located at the basal and middle cochlear region to pneumolysin-induced damage. The detailed description of the susceptibility of hair cells to Streptococcus pneumoniae provided in this report can in the future determine the choice and the development of novel otoprotective therapies during pneumococcal meningitis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study.

    PubMed

    O'Brien, Katie M; Cole, Stephen R; Tse, Chiu-Kit; Perou, Charles M; Carey, Lisa A; Foulkes, William D; Dressler, Lynn G; Geradts, Joseph; Millikan, Robert C

    2010-12-15

    Previous research identified differences in breast cancer-specific mortality across 4 intrinsic tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2(+)/ER(-)). We used immunohistochemical markers to subtype 1,149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Cancer subtypes luminal A, luminal B, basal-like, and HER2(+)/ER(-) were distributed as 64%, 11%, 11%, and 5% for whites, and 48%, 8%, 22%, and 7% for African Americans, respectively. Breast cancer mortality was higher for participants with HER2(+)/ER(-) and basal-like breast cancer compared with luminal A and B. African Americans had higher breast cancer-specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared with the luminal A subtype within racial categories, mortality for participants with basal-like breast cancer was higher among whites (HR = 2.0, 95% CI: 1.2-3.4) than African Americans (HR = 1.5, 95% CI: 1.0-2.4), with the strongest effect seen in postmenopausal white women (HR = 3.9, 95% CI: 1.5-10.0). Our results confirm the association of basal-like breast cancer with poor prognosis and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared with whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. ©2010 AACR.

  10. FTO rs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents

    PubMed Central

    Leite, Neiva; Furtado-Alle, Lupe; Teixeira, Mayza Dalcin; de Souza, Ricardo Lehtonen Rodrigues; da Silva, Larissa Rosa; Pizzi, Juliana; Lopes, Maria de Fátima Aguiar; Titski, Ana Cláudia Kapp

    2018-01-01

    Purpose The rs9939609 SNP (T > A) in FTO gene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables. Methods The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay. Results The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise. Conclusions In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise. PMID:29854435

  11. Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

    PubMed

    Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

    2018-05-01

    We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Diurnal testosterone variability is differentially associated with parenting quality in mothers and fathers.

    PubMed

    Endendijk, Joyce J; Hallers-Haalboom, Elizabeth T; Groeneveld, Marleen G; van Berkel, Sheila R; van der Pol, Lotte D; Bakermans-Kranenburg, Marian J; Mesman, Judi

    2016-04-01

    Previous studies on the relation between testosterone (T) levels and parenting have found ample evidence for the challenge hypothesis, demonstrating that high T levels inhibit parental involvement and that becoming a parent is related to a decrease in T levels in both mothers and fathers. However, less is known about the relation between T levels and more qualitative aspects of parenting. In the current study we examined basal T levels and diurnal variability in T levels in relation to mothers' and fathers' parenting quality. Participants included 217 fathers and 124 mothers with two children (3 and 5years of age). Evening and morning salivary T samples were analyzed with radio-immunoassays to determine circulating T levels. Parental sensitivity (i.e., child-centered responsiveness) and respect for children's autonomy were observed during free play in the family home. The results showed that higher evening T levels in mothers were associated with more sensitivity to the oldest and youngest child. Diurnal T variability was more consistently associated with parenting behavior towards their children than basal T levels. For fathers, more diurnal variability in T was associated with more sensitivity and more respect for autonomy with their youngest children. For mothers, more diurnal variability in T was associated with less sensitivity to both children and less respect for the youngest child's autonomy. These findings suggest that the T system might act differently in relation to parenting behavior in males and females. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Differences in Fine-Root Biomass of Trees and Understory Vegetation among Stand Types in Subtropical Forests

    PubMed Central

    Fu, Xiaoli; Wang, Jianlei; Di, Yuebao; Wang, Huimin

    2015-01-01

    Variation of total fine-root biomass among types of tree stands has previously been attributed to the characteristics of the stand layers. The effects of the understory vegetation on total fine-root biomass are less well studied. We examined the variation of total fine-root biomass in subtropical tree stands at two sites of Datian and Huitong in China. The two sites have similar humid monsoon climate but different soil organic carbon. One examination compared two categories of basal areas (high vs. low basal area) in stands of single species. A second examination compared single-species and mixed stands with comparable basal areas. Low basal area did not correlate with low total fine-root biomass in the single-species stands. The increase in seedling density but decrease in stem density for the low basal area stands at Datian and the quite similar stand structures for the basal-area contrast at Huitong helped in the lack of association between basal area and total fine-root biomass at the two sites, respectively. The mixed stands also did not yield higher total fine-root biomasses. In addition to the lack of niche complementarity between tree species, the differences in stem and seedling densities and the belowground competition between the tree and non-tree species also contributed to the similarity of the total fine-root biomasses in the mixed and single-species stands. Across stand types, the more fertile site Datian yielded higher tree, non-tree and total fine-root biomasses than Huitong. However, the contribution of non-tree fine-root biomass to the total fine-root biomass was higher at Huitong (29.4%) than that at Datian (16.7%). This study suggests that the variation of total fine-root biomass across stand types not only was associated with the characteristics of trees, but also may be highly dependent on the understory layer. PMID:26047358

  14. Differences in Fine-Root Biomass of Trees and Understory Vegetation among Stand Types in Subtropical Forests.

    PubMed

    Fu, Xiaoli; Wang, Jianlei; Di, Yuebao; Wang, Huimin

    2015-01-01

    Variation of total fine-root biomass among types of tree stands has previously been attributed to the characteristics of the stand layers. The effects of the understory vegetation on total fine-root biomass are less well studied. We examined the variation of total fine-root biomass in subtropical tree stands at two sites of Datian and Huitong in China. The two sites have similar humid monsoon climate but different soil organic carbon. One examination compared two categories of basal areas (high vs. low basal area) in stands of single species. A second examination compared single-species and mixed stands with comparable basal areas. Low basal area did not correlate with low total fine-root biomass in the single-species stands. The increase in seedling density but decrease in stem density for the low basal area stands at Datian and the quite similar stand structures for the basal-area contrast at Huitong helped in the lack of association between basal area and total fine-root biomass at the two sites, respectively. The mixed stands also did not yield higher total fine-root biomasses. In addition to the lack of niche complementarity between tree species, the differences in stem and seedling densities and the belowground competition between the tree and non-tree species also contributed to the similarity of the total fine-root biomasses in the mixed and single-species stands. Across stand types, the more fertile site Datian yielded higher tree, non-tree and total fine-root biomasses than Huitong. However, the contribution of non-tree fine-root biomass to the total fine-root biomass was higher at Huitong (29.4%) than that at Datian (16.7%). This study suggests that the variation of total fine-root biomass across stand types not only was associated with the characteristics of trees, but also may be highly dependent on the understory layer.

  15. Effects of dietary supplementation of selenium and iodine on growth performance, carcass characteristics and histology of thyroid gland in goats.

    PubMed

    Aghwan, Zeiad Amjad; Sazili, Awis Qurni; Kadhim, Khalid Kamil; Alimon, Abdul Razak; Goh, Yong Meng; Adeyemi, Kazeem Dauda

    2016-05-01

    This study assessed the effects of dietary selenium (Se), iodine (I) and a combination of both on growth performance, thyroid gland activity, carcass characteristics and the concentration of iodine and selenium in Longissimus lumborum (LL) muscle in goats. Twenty-four bucks were randomly assigned to four dietary treatments: control (CON), basal diet without supplementation, basal diet + 0.6 mg Se/kg dry matter (DM) (SS), 0.6 mg I/kg DM (IP), or combination of 0.6 mg/kg DM Se and 0.6 mg/kg DM I (SSIP) and fed for 100 days. Animals fed diet SSIP exhibited higher (P < 0.05) body weight and better feed conversion ratio (FCR) than those fed other diets. Dressing percentage of goats fed the supplemented diets was higher (P < 0.05) than that of the control. Carcasses from the IP group had higher (P < 0.05) total fat proportion than the SSIP group. The levels of both elements were significantly elevated (P < 0.05) in LL muscle in supplemented goats. Thyroid follicular epithelial cells of IP and SSIP animals were significantly higher than those of CON and SS groups. The study demonstrated that the combined Se and I dietary supplementation improves growth performance, carcass dressing percentage and increases the retention of Se and I in goat meat. © 2015 Japanese Society of Animal Science.

  16. Brewers dried yeast as a source of mannan oligosaccharides for weanling pigs.

    PubMed

    White, L A; Newman, M C; Cromwell, G L; Lindemann, M D

    2002-10-01

    Brewers dried yeast, a source of mannan oligosaccharides (MOS), was assessed as an alternative to an antimicrobial agent (carbadox) for young pigs in two experiments. The yeast contained 5.2% MOS. Agglutination tests confirmed adsorption of several serovars of E. coli and Salmonella spp. onto the yeast product. In Exp. 1, seven replicates (five pigs per pen) of 22-d-old pigs were fed a nonmedicated basal diet or the basal diet with carbadox (55 mg/kg), yeast (3%), or a combination of 3% yeast and 2% citric acid for 28 d. Carbadox did not improve growth performance. Growth rate and feed intake were depressed (P < 0.05) in pigs fed yeast alone or in combination with acid. Log counts of total coliforms, Escherichia coli, and Clostridium perfringens in feces were not affected by diet, but Bifidobacteria spp. counts were lower (P < 0.05) in pigs fed the yeast + acid diet and lactobacilli counts were higher (P < 0.05) in pigs fed yeast. Fecal pH and VFA concentrations and intestinal morphological traits were not consistently affected by diet. Serum IgG levels were elevated in the yeast + acid (P < 0.01) group. In Exp. 2, the effects of yeast and carbadox additions to the diet on enteric microbial populations in young pigs housed in isolation units were evaluated. Pigs (n = 24) were weaned at 11 d of age (4.1 kg BW) and placed in isolation chambers (two pigs per chamber) equipped with individual air filtering systems and excrement containers. Treatments were a nonmedicated basal diet and the basal diet with 55 mg/kg of carbadox or with 3% yeast. Diets were fed for 29 d, then each pig was orally dosed with approximately 9.5 x 10(8) CFU of E. coli K88. Daily fecal E. coli K88 counts were not different (P > 0.05) among treatments, but fecal shedding of carbadox-resistant coliforms was higher (P < 0.01) during the 9-d period in pigs fed carbadox. Total fecal coliforms were consistently lower throughout the postinoculation period in pigs fed yeast (P < 0.05). Yeast reduced colonization oftotal coliforms in the duodenum,jejunum, cecum, and colon, but it did not have a consistent effect on colonization of E. coli K88. Pigs fed yeast tended (P < 0.10) to have higher serum IgG levels than controls. In these experiments, brewers dried yeast and carbadox had minimal effects on growth, microbial populations, and intestinal health traits of early-weaned pigs, but certain serum immunological traits were enhanced by feeding yeast.

  17. Endocannabinergic modulation of interleukin-1β in mouse hippocampus under basal conditions and after in vivo systemic lipopolysaccharide stimulation.

    PubMed

    Csölle, Cecília; Sperlágh, Beáta

    2011-01-01

    Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1β levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 μg/kg i.p.). IL-1β levels were determined in the hippocampi of wild-type (WT), CB1R-/- and P2X₇ receptor (P2X₇R)-/- mice using an ELISA kit. Basal but not LPS-induced IL-1β levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1β content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1β protein in WT but not in CB1R-/- mice. In the absence of P2X₇R, LPS-induced IL-1β production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1β was significantly attenuated. The LPS-induced elevation in IL-1β production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X₇R-/- mice. CB1Rs are responsible for the modulation of basal IL-1β levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1β concentrations are independent of CB1Rs. Copyright © 2011 S. Karger AG, Basel.

  18. Regular exercise prevents the development of hyperglucocorticoidemia via adaptations in the brain and adrenal glands in male Zucker diabetic fatty rats.

    PubMed

    Campbell, Jonathan E; Király, Michael A; Atkinson, Daniel J; D'souza, Anna M; Vranic, Mladen; Riddell, Michael C

    2010-07-01

    We determined the effects of voluntary wheel running on the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral determinants of glucocorticoids action, in male Zucker diabetic fatty (ZDF) rats. Six-week-old euglycemic ZDF rats were divided into Basal, Sedentary, and Exercise groups (n = 8-9 per group). Basal animals were immediately killed, whereas Sedentary and Exercising rats were monitored for 10 wk. Basal (i.e., approximately 0900 AM in the resting state) glucocorticoid levels increased 2.3-fold by week 3 in Sedentary rats where they remained elevated for the duration of the study. After an initial elevation in basal glucocorticoid levels at week 1, Exercise rats maintained low glucocorticoid levels from week 3 through week 10. Hyperglycemia was evident in Sedentary animals by week 7, whereas Exercising animals maintained euglycemia throughout. At the time of death, the Sedentary group had approximately 40% lower glucocorticoid receptor (GR) content in the hippocampus, compared with the Basal and Exercise groups (P < 0.05), suggesting that the former group had impaired negative feedback regulation of the HPA axis. Both Sedentary and Exercise groups had elevated ACTH compared with Basal rats, indicating that central drive of the axis was similar between groups. However, Sedentary, but not Exercise, animals had elevated adrenal ACTH receptor and steroidogenic acute regulatory protein content compared with the Basal animals, suggesting that regular exercise protects against elevations in glucocorticoids by a downregulation of adrenal sensitivity to ACTH. GR and 11beta-hydroxysteroid dehydrogenase type 1 content in skeletal muscle and liver were similar between groups, however, GR content in adipose tissue was elevated in the Sedentary groups compared with the Basal and Exercise (P < 0.05) groups. Thus, the gradual elevations in glucocorticoid levels associated with the development of insulin resistance in male ZDF rats can be prevented with regular exercise, likely because of adaptations that occur primarily in the adrenal glands.

  19. African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

    PubMed

    Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

    2002-04-01

    African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

  20. African Swine Fever Virus IAP-Like Protein Induces the Activation of Nuclear Factor Kappa B

    PubMed Central

    Rodríguez, Clara I.; Nogal, María L.; Carrascosa, Angel L.; Salas, María L.; Fresno, Manuel; Revilla, Yolanda

    2002-01-01

    African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-κB. Thus, transient transfection of the viral IAP increases the activity of an NF-κB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-κB-dependent gene. NF-κB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-κB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-κB activity seems to be the consequence of higher IκB kinase (IKK) basal activity in these cells. The NF-κB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2. PMID:11907233

  1. What next after basal insulin? Treatment intensification with lixisenatide in Asian patients with type 2 diabetes mellitus.

    PubMed

    Chan, Wing B; Luk, Andrea; Chow, Wing S; Yeung, Vincent T F

    2017-06-01

    There is increasing evidence that the pathophysiology of type 2 diabetes mellitus (T2DM) in Asian patients differs from that in Western patients, with early phase insulin deficiencies, increased postprandial glucose excursions, and increased sensitivity to insulin. Asian patients may also experience higher rates of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as nausea and vomiting, compared with their Western counterparts. These factors should be taken into consideration when selecting therapy for basal insulin treatment intensification in Asian patients. However, the majority of studies to establish various agents for treatment intensification in T2DM have been conducted in predominantly Western populations, and the levels of evidence available in Chinese or Asian patients are limited. This review discusses the different mechanisms of action of short-acting, prandial, and long-acting GLP-1RAs in addressing hyperglycemia, and describes the rationale and available clinical data for basal insulin in combination with the short-acting prandial GLP-1RA lixisenatide, with a focus on treatment of Asian patients with T2DM. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  2. Brain angiogenic gene-expression in congenital heart disease.

    PubMed

    Sánchez, Olga; Ruiz-Romero, Aina; Domínguez, Carmen; Ferrer, Queralt; Ribera, Irene; Rodríguez-Sureda, Víctor; Alijotas, Jaume; Arévalo, Sílvia; Carreras, Elena; Cabero, Lluís; Llurba, Elisa

    2017-12-05

    To analyze potential differences in the expression of antiangiogenic and angiogenic factors and of genes associated with chronic hypoxia in cerebral tissue from euploid fetuses with congenital heart disease (CHD) and control fetuses. Cerebral tissue was obtained from 15 fetuses with CHD and 12 control fetuses undergoing termination of pregnancy. Expression profiles of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1), the angiogenic vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PlGF), and genes associated with chronic hypoxia were determined by real-time PCR in tissue from the frontal cortex and from basal ganglia-hypothalamus. sFlt-1 expression was 48% higher in the frontal cortex (p=0.0431) and 72% higher in the basal ganglia-hypothalamus (p=0.0369) of CHD fetuses than controls. VEGF-A expression was 60% higher in the basal ganglia-hypothalamus (p=0.0432) of CHD fetuses. The expression of hypoxia-inducible factor-2α (HIF-2α) in the basal ganglia-hypothalamus was 98% higher in CHD fetuses (p=0.0456). An overall dysregulation of angiogenesis with a net balance towards an antiangiogenic environment was observed in the cerebral tissue from fetuses with CHD, suggesting that these fetuses may have an intrinsic angiogenic impairment that could contribute to impaired brain perfusion and abnormal neurological development later in life. This article is protected by copyright. All rights reserved.

  3. Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

    PubMed

    Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

    1988-01-01

    Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

  4. Cortisol in the morning and dimensions of anxiety, depression, and aggression in children from a general population and clinic-referred cohort: An integrated analysis. The TRAILS study.

    PubMed

    Dietrich, Andrea; Ormel, Johan; Buitelaar, Jan K; Verhulst, Frank C; Hoekstra, Pieter J; Hartman, Catharina A

    2013-08-01

    Anxiety and depressive problems have often been related to higher hypothalamic-pituitary-adrenal (HPA)-axis activity (basal morning cortisol levels and cortisol awakening response [CAR]) and externalizing problems to lower HPA-axis activity. However, associations appear weaker and more inconsistent than initially assumed. Previous studies from the Tracking Adolescents Individual Lives Study (TRAILS) suggested sex-differences in these relationships and differential associations with specific dimensions of depressive problems in a general population sample of children (10-12 years). Using the TRAILS population sample (n=1604), we tested hypotheses on the association between single day cortisol (basal morning levels and CAR) and specifically constructed dimensions of anxiety (cognitive versus somatic), depressive (cognitive-affective versus somatic), and externalizing problems (reactive versus proactive aggression), and explored the modifying role of sex. Moreover, we repeated analyses in an independent same-aged clinic-referred sample (n=357). Structural Equation Modeling was used to investigate the association between cortisol and higher- and lower-order (thus, broad and specific) problem dimensions based on self-reports in an integrated model. Overall, findings were consistent across the population and clinic-referred samples, as well as with the existing literature. Most support was found for higher cortisol (mainly CAR) in relation to depressive problems. However, in general, associations were weak in both samples. Therefore, the present results shed doubt on the relevance of single day cortisol measurements for problem behaviors in the milder range. Associations may be stronger in more severe or persistent psychopathology. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. The Combined Efficiency of Dietary Isomaltooligosaccharides and Bacillus spp. on the Growth, Hemato-Serological, and Intestinal Microbiota Indices of Caspian Brown Trout (Salmo trutta caspius Kessler, 1877).

    PubMed

    Aftabgard, Maryam; Salarzadeh, Alireza; Mohseni, Mahmoud; Bahri Shabanipour, Amir Houshang; Zorriehzahra, Mohammad Ebrahim Jalil

    2017-12-01

    The combined effects of a commercial probiotic, BetaPlus®, and a prebiotic, isomaltooligosaccharides (IMOS) on the growth, survival rate, intestinal microbiota, and hemato-immunological parameters were evaluated in Caspian brown trout (Salmo trutta caspius Kessler, 1877). Caspian brown trout fingerlings (~ 9 g) were fed a control diet (basal diet) or a synbiotic diet (the basal diet + 2 g kg -1 IMOS + 1 g kg -1 BetaPlus®) for 7 weeks. At the end of this trial, fish fed the synbiotic diet showed significant improvements in body weight increase, feed conversion ratio, and survival rate compared with fish fed the control diet (P < 0.05). In addition, fish fed the synbiotic diet had the highest levels of white blood cells, monocytes, and neutrophils (P < 0.05), while the red blood cells, hemoglobin, hematrocrit, mean corpuscular volume, and lymphocytes were significantly higher in the control group (P < 0.05). The serum triglycerides, cholesterol, total protein, albumin, albumin/globulin ratio, and immunoglobulin M levels, as well as alanine aminotransferase and lactate dehydrogenase activities were higher in the synbiotic group than in the control group (P < 0.05). In addition, fish fed the synbiotic diet showed significantly higher gut total viable aerobic bacterial counts and lactic acid bacteria (P < 0.05). The results demonstrated that BetaPlus® in combination with IMOS enhanced the growth, survival rate, intestinal microbiota, and some haemato-immunological parameters in Caspian brown trout fingerlings.

  6. Differential metallothionein expression in oral lichen planus and amalgam-associated oral lichenoid lesions.

    PubMed

    Mendes, G-G; Servato, J-P-S; Borges, F-C; Rosa, R-R; Siqueira, C-S; de Faria, P-R; Loyola, A-M; Cardoso, S-V

    2018-05-01

    Oral lichen planus (OLP) is a chronic inflammatory disease mediated by T cells, which manifests as reticular (white) or erosive (red) lesions, that are eventually painful. Oral lichenoid lesion (OLL) are distinguished from OLP by the presence of precipitating factors. The aim of this study was to evaluate whether the presence of metallothionein, which is involved in anti-apoptotic pathways and the anti-oxidative response, could serve as a differential diagnostic for OLP and OLL. We evaluated the expression of metallothionein in 40 cases of OLP and 20 cases of OLL using immunohistochemistry. White OLP has higher concentrations of metallothionein than red OLP in basal and parabasal layers. Moreover, metallothionein was more frequently observed in the cytoplasm and nuclei of basal cells in OLP patients compared to the same regions of OLL cases. Metallothionein levels are related to OLP severity and may contribute to a differential diagnosis between OLP and OLL.

  7. The determination of sulfite levels and its oxidation in plant leaves.

    PubMed

    Brychkova, Galina; Yarmolinsky, Dmitry; Fluhr, Robert; Sagi, Moshe

    2012-07-01

    Sulfur is the sixth most abundant element in life and an important building block of proteins and cellular metabolites. Plants like bacteria can synthesize their sulfur-containing biomolecules from sulfate, where sulfite is an intermediate of the sulfur assimilation pathway. Above a certain threshold SO(2)/sulfite is cytotoxic and is rapidly metabolized to avoid damage. However, the existing data show considerable differences in basal sulfite levels both between species and apparent discrepancies in measured levels in the same species. In order to resolve this question we employed a sulfite detection method using chicken sulfite oxidase and developed an independent enzymatic assay, based on the specific detection of sulfite by sulfite reductase and compared those measurements to a modified colorimetric fuchsin-based method, specific for sulfite detection. We show here that when properly used the sulfite levels detected by the three methods can yield identical results. Furthermore, to examine the capacity of the plant to detoxify sulfite we injected sub-lethal sulfite solutions (yet, several folds higher than the basal levels) into Arabidopsis and tomato leaves and monitored the excess sulfite turnover. Within 3h of sulfite injection, more than 80% of the injected sulfite in Arabidopsis and 91% in tomato were oxidized to sulfate, demonstrating the high capacity of the sulfite oxidation mechanism/s in plants. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. A Drosophila heat shock response represents an exception rather than a rule amongst Diptera species.

    PubMed

    Zatsepina, O G; Przhiboro, A A; Yushenova, I A; Shilova, V; Zelentsova, E S; Shostak, N G; Evgen'ev, M B; Garbuz, D G

    2016-08-01

    Heat shock protein 70 (Hsp70) is the major player that underlies adaptive response to hyperthermia in all organisms studied to date. We investigated patterns of Hsp70 expression in larvae of dipteran species collected from natural populations of species belonging to four families from different evolutionary lineages of the order Diptera: Stratiomyidae, Tabanidae, Chironomidae and Ceratopogonidae. All investigated species showed a Hsp70 expression pattern that was different from the pattern in Drosophila. In contrast to Drosophila, all of the species in the families studied were characterized by high constitutive levels of Hsp70, which was more stable than that in Drosophila. When Stratiomyidae Hsp70 proteins were expressed in Drosophila cells, they became as short-lived as the endogenous Hsp70. Interestingly, three species of Ceratopogonidae and a cold-water species of Chironomidae exhibited high constitutive levels of Hsp70 mRNA and high basal levels of Hsp70. Furthermore, two species of Tabanidae were characterized by significant constitutive levels of Hsp70 and highly stable Hsp70 mRNA. In most cases, heat-resistant species were characterized by a higher basal level of Hsp70 than more thermosensitive species. These data suggest that different trends were realized during the evolution of the molecular mechanisms underlying the regulation of the responses of Hsp70 genes to temperature fluctuations in the studied families. © 2016 The Royal Entomological Society.

  9. Enhanced basal lubrication and the contribution of the Greenland ice sheet to future sea-level rise

    PubMed Central

    Shannon, Sarah R.; Payne, Antony J.; Bartholomew, Ian D.; van den Broeke, Michiel R.; Edwards, Tamsin L.; Fettweis, Xavier; Gagliardini, Olivier; Gillet-Chaulet, Fabien; Goelzer, Heiko; Hoffman, Matthew J.; Huybrechts, Philippe; Mair, Douglas W. F.; Nienow, Peter W.; Perego, Mauro; Price, Stephen F.; Smeets, C. J. P. Paul; Sole, Andrew J.; van de Wal, Roderik S. W.; Zwinger, Thomas

    2013-01-01

    We assess the effect of enhanced basal sliding on the flow and mass budget of the Greenland ice sheet, using a newly developed parameterization of the relation between meltwater runoff and ice flow. A wide range of observations suggest that water generated by melt at the surface of the ice sheet reaches its bed by both fracture and drainage through moulins. Once at the bed, this water is likely to affect lubrication, although current observations are insufficient to determine whether changes in subglacial hydraulics will limit the potential for the speedup of flow. An uncertainty analysis based on our best-fit parameterization admits both possibilities: continuously increasing or bounded lubrication. We apply the parameterization to four higher-order ice-sheet models in a series of experiments forced by changes in both lubrication and surface mass budget and determine the additional mass loss brought about by lubrication in comparison with experiments forced only by changes in surface mass balance. We use forcing from a regional climate model, itself forced by output from the European Centre Hamburg Model (ECHAM5) global climate model run under scenario A1B. Although changes in lubrication generate widespread effects on the flow and form of the ice sheet, they do not affect substantial net mass loss; increase in the ice sheet’s contribution to sea-level rise from basal lubrication is projected by all models to be no more than 5% of the contribution from surface mass budget forcing alone. PMID:23940337

  10. Impact of inflammation on iron stores in involved and non-involved psoriatic skin

    NASA Astrophysics Data System (ADS)

    Pinheiro, T.; Ynsa, M. D.; Alves, L. C.; Teixeira, P.; Ferreira, J.; Filipe, P.

    2015-04-01

    Accumulating evidence supports a role for cellular Fe in cell proliferation, inflammation, and disease tolerance. Psoriasis is a severe inflammatory and hyper proliferative condition of human skin whose aetiology remains poorly understood. Herein, we performed nuclear microscopy techniques to quantify with cellular resolution and high sensitivity the concentration of Fe in lesional (psoriatic plaques) and non-lesional adjacent skin of psoriatic patients. Fe contents were measured across skin depth and along epidermal strata either by quantitatively imaging Fe distribution in regions of interest, or by determining Fe profiles through analysis of sequential points along selected transepts. Both procedures require deconvolution of spectra to project quantitative elemental data through the application of different software codes. Using these approaches a detailed quantitative distribution of Fe was resolved. We show that in both lesional and non-lesional skin, the epidermal profiles of Fe contents showed a peak at the basal layer and that Fe concentration along the basal layer was not uniformly distributed. Typically, Fe levels were significantly higher in epidermal ridges relative to regions above dermal papillae. Lesional skin displayed excess Fe over extended regions above basal layer. In conclusion, we found significantly increased Fe deposits in the epidermis of psoriatic patients, particularly in areas of epidermal hyper proliferation. These findings suggest an important role for Fe in the pathogenesis of psoriasis. They also raise the possibility that manipulation of Fe levels in the skin may become relevant for the clinical management of psoriasis.

  11. Enhanced basal lubrication and the contribution of the Greenland ice sheet to future sea-level rise.

    PubMed

    Shannon, Sarah R; Payne, Antony J; Bartholomew, Ian D; van den Broeke, Michiel R; Edwards, Tamsin L; Fettweis, Xavier; Gagliardini, Olivier; Gillet-Chaulet, Fabien; Goelzer, Heiko; Hoffman, Matthew J; Huybrechts, Philippe; Mair, Douglas W F; Nienow, Peter W; Perego, Mauro; Price, Stephen F; Smeets, C J P Paul; Sole, Andrew J; van de Wal, Roderik S W; Zwinger, Thomas

    2013-08-27

    We assess the effect of enhanced basal sliding on the flow and mass budget of the Greenland ice sheet, using a newly developed parameterization of the relation between meltwater runoff and ice flow. A wide range of observations suggest that water generated by melt at the surface of the ice sheet reaches its bed by both fracture and drainage through moulins. Once at the bed, this water is likely to affect lubrication, although current observations are insufficient to determine whether changes in subglacial hydraulics will limit the potential for the speedup of flow. An uncertainty analysis based on our best-fit parameterization admits both possibilities: continuously increasing or bounded lubrication. We apply the parameterization to four higher-order ice-sheet models in a series of experiments forced by changes in both lubrication and surface mass budget and determine the additional mass loss brought about by lubrication in comparison with experiments forced only by changes in surface mass balance. We use forcing from a regional climate model, itself forced by output from the European Centre Hamburg Model (ECHAM5) global climate model run under scenario A1B. Although changes in lubrication generate widespread effects on the flow and form of the ice sheet, they do not affect substantial net mass loss; increase in the ice sheet's contribution to sea-level rise from basal lubrication is projected by all models to be no more than 5% of the contribution from surface mass budget forcing alone.

  12. Gentamicin concentration gradients in scala tympani perilymph following systemic applications.

    PubMed

    Hahn, Hartmut; Salt, Alec N; Schumacher, Ulrike; Plontke, Stefan K

    2013-01-01

    It has been shown in prior studies that round window membrane (RWM) application of gentamicin produced a robust basal-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Ménière's disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg body weight (BW) over a period of 3 h or as a 300 mg/kg BW subcutaneous bolus injection. At 3 and 5 h after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively, and 10 sequential 1-µl perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in the highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with the amount of drug applied and time before sampling. While it is likely that the basal-apical gradient measured after local drug applications to the round window niche is the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from the blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of ST relative to endolymph in the apical turns. © 2013 S. Karger AG, Basel.

  13. Plastic and evolutionary responses to heat stress in a temperate dung fly: negative correlation between basal and induced heat tolerance?

    PubMed

    Esperk, T; Kjaersgaard, A; Walters, R J; Berger, D; Blanckenhorn, W U

    2016-05-01

    Extreme weather events such as heat waves are becoming more frequent and intense. Populations can cope with elevated heat stress by evolving higher basal heat tolerance (evolutionary response) and/or stronger induced heat tolerance (plastic response). However, there is ongoing debate about whether basal and induced heat tolerance are negatively correlated and whether adaptive potential in heat tolerance is sufficient under ongoing climate warming. To evaluate the evolutionary potential of basal and induced heat tolerance, we performed experimental evolution on a temperate source population of the dung fly Sepsis punctum. Offspring of flies adapted to three thermal selection regimes (Hot, Cold and Reference) were subjected to acute heat stress after having been exposed to either a hot-acclimation or non-acclimation pretreatment. As different traits may respond differently to temperature stress, several physiological and life history traits were assessed. Condition dependence of the response was evaluated by exposing juveniles to different levels of developmental (food restriction/rearing density) stress. Heat knockdown times were highest, whereas acclimation effects were lowest in the Hot selection regime, indicating a negative association between basal and induced heat tolerance. However, survival, adult longevity, fecundity and fertility did not show such a pattern. Acclimation had positive effects in heat-shocked flies, but in the absence of heat stress hot-acclimated flies had reduced life spans relative to non-acclimated ones, thereby revealing a potential cost of acclimation. Moreover, body size positively affected heat tolerance and unstressed individuals were less prone to heat stress than stressed flies, offering support for energetic costs associated with heat tolerance. Overall, our results indicate that heat tolerance of temperate insects can evolve under rising temperatures, but this response could be limited by a negative relationship between basal and induced thermotolerance, and may involve some but not other fitness-related traits. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  14. Parkinson's disease and other basal ganglia or movement disorders in a large nationwide cohort of Swedish welders

    PubMed Central

    Fored, C M; Fryzek, J P; Brandt, L; Nise, G; Sjögren, B; McLaughlin, J K; Blot, W J; Ekbom, A

    2006-01-01

    Introduction Although it has been hypothesised that metal welding and flame cutting are associated with an increased risk for Parkinson's disease due to manganese released in the welding fume, few rigorous cohort studies have evaluated this risk. Methods The authors examined the relation between employment as a welder and all basal ganglia and movement disorders (ICD‐10, G20–26) in Sweden using nationwide and population based registers. All men recorded as welders or flame cutters (n = 49 488) in the 1960 or 1970 Swedish National Census were identified and their rates of specific basal ganglia and movement disorders between 1964 and 2003 were compared with those in an age and geographical area matched general population comparison cohort of gainfully employed men (n = 489 572). Results The overall rate for basal ganglia and movement disorders combined was similar for the welders and flame cutters compared with the general population (adjusted rate ratio (aRR) = 0.91 (95% CI 0.81 to 1.01). Similarly, the rate ratio for PD was 0.89 (95% CI 0.79 to 0.99). Adjusted rate ratios for other individual basal ganglia and movement disorders were also not significantly increased or decreased. Further analyses of Parkinson's disease by attained age, time period of follow up, geographical area of residency, and educational level revealed no significant differences between the welders and the general population. Rates for Parkinson's disease among welders in shipyards, where exposures to welding fumes are higher, were also similar to the general population (aRR = 0.95; 95% CI 0.70 to 1.28). Conclusion This nationwide record linkage study offers no support for a relation between welding and Parkinson's disease or any other specific basal ganglia and movement disorders. PMID:16421393

  15. Chronic effect of static stretching on strength performance and basal serum IGF-1 levels.

    PubMed

    Borges Bastos, Carmen L; Miranda, Humberto; Vale, Rodrigo Gomes de Souza; Portal, Maria de Nazaré; Gomes, M Thiago; Novaes, Jefferson da Silva; Winchester, Jason B

    2013-09-01

    Improving the process of how physical performance is enhanced is one of the main topics evaluated by physiologists. This process often involves athletes and nonathletic populations. The purpose of this study was to assess the chronic response to 10 weeks of static stretching exercises carried out before and during a strength training program for 8 exercises on an 8 repetition maximum (8RM) test performance, and basal serum insulinlike growth factor (IGF-1) levels. Thirty recreationally trained volunteers were randomly assigned to 1 of 3 training groups: (a) SBST (performed a warm-up with a static stretching protocol before each strength training session); (b) SDST (before each training set, a static stretching exercise was performed); and (c) OST (entire session was performed without any type of stretching exercise). Strength and IGF-1 levels were collected at the beginning (pretest) and end (posttest) of the entire experimental procedure. All the exercises showed a significant increase in muscle strength for the OST group. However, the results revealed a significant increase in the muscle strength for only a few exercises in the SBST (LP, LE) and SDST (LP) experimental conditions. Significant statistical differences were found between SBST and SDST for all the exercises in the OST experimental condition. Furthermore, the IGF-1 expression showed no significant differences in the intragroup analysis. However, the OST group showed higher values (p < 0.05) in the posttest when compared with those of the other groups (increased significantly only in the OST experimental condition). It has been concluded that, although all the groups showed an increase in muscular strength, the strength training performed without any type of stretching exercise, regardless of whether the stretching is performed before or during the lifting session, can more effectively increase muscle strength and basal serum IGF-1 levels. It was concluded that strength training, with or without the use of stretching exercises, increased muscular strength in the studied groups, and can induce an increase in IGF-1 levels.

  16. The Effects of Phosphatidylserine and Omega-3 Fatty Acid-Containing Supplement on Late Life Depression

    PubMed Central

    Komori, Teruhisa

    2015-01-01

    Late life depression is often associated with a poor response to antidepressants; therefore an alternative strategy for therapy is required. Although several studies have reported that phosphatidylserine (PS) may be effective for late life depression and that omega-3 fatty acids DHA and EPA have also proven beneficial for many higher mental functions, including depression, no concrete conclusion has been reached. This study was performed to clarify the effect of PS and omega-3 fatty acid-containing supplement for late life depression by not only clinical evaluation but also salivary cortisol levels. Eighteen elderly subjects with major depression were selected for the study. In all, insufficient improvement had been obtained by antidepressant therapy for at least 6 months. The exclusion criteria from prior brain magnetic resonance images (MRI) included the presence of structural MRI findings compatible with stroke or other gross brain lesions or malformations, but not white matter hypersensitivities. They took a supplement containing PS 100 mg, DHA 119 mg and EPA 70 mg three times a day for 12 weeks. The effects of the supplement were assessed using the 17-item Hamilton depression scale (HAM-D17) and the basal levels and circadian rhythm of salivary cortisol. The study adopted them as indices because: salivary cortisol levels are high in patients with depression, their circadian rhythm related to salivary cortisol is often irregular, and these symptoms are alleviated as depression improves. The mean HAM-D17 in all subjects taking the supplement was significantly improved after 12 weeks of taking the supplement. These subjects were divided into 10 non-responders and 8 responders. The basal levels and circadian rhythm of salivary cortisol were normalized in the responders while not in non-responders. PS and omega-3 fatty acids, or other elements of the supplement, may be effective for late life depression, associated with the correction of basal levels and circadian rhythm of salivary cortisol. PMID:26266022

  17. Protease Activated Receptor-2 Expression and Function in Asthmatic Bronchial Smooth Muscle

    PubMed Central

    Gilbert, Guillaume; Carvalho, Gabrielle; Trian, Thomas; Ozier, Annaig; Gillibert-Duplantier, Jennifer; Ousova, Olga; Maurat, Elise; Thumerel, Matthieu; Quignard, Jean-François; Girodet, Pierre-Olivier; Marthan, Roger; Berger, Patrick

    2014-01-01

    Asthmatic bronchial smooth muscle (BSM) is characterized by structural remodeling associated with mast cell infiltration displaying features of chronic degranulation. Mast cell-derived tryptase can activate protease activated receptor type-2 (PAR-2) of BSM cells. The aims of the present study were (i) to evaluate the expression of PAR-2 in both asthmatic and non asthmatic BSM cells and, (ii) to analyze the effect of prolonged stimulation of PAR-2 in asthmatic BSM cells on cell signaling and proliferation. BSM cells were obtained from both 33 control subjects and 22 asthmatic patients. PAR-2 expression was assessed by flow cytometry, western blot and quantitative RT-PCR. Calcium response, transduction pathways and proliferation were evaluated before and following PAR-2 stimulation by SLIGKV-NH2 or trypsin for 1 to 3 days. Asthmatic BSM cells expressed higher basal levels of functional PAR-2 compared to controls in terms of mRNA, protein expression and calcium response. When PAR-2 expression was increased by means of lentivirus in control BSM cells to a level similar to that of asthmatic cells, PAR-2-induced calcium response was then similar in both types of cell. However, repeated PAR-2 stimulations increased the proliferation of asthmatic BSM cells but not that of control BSM cells even following lentiviral over-expression of PAR-2. Such an increased proliferation was related to an increased phosphorylation of ERK in asthmatic BSM cells. In conclusion, we have demonstrated that asthmatic BSM cells express increased baseline levels of functional PAR-2. This higher basal level of PAR-2 accounts for the increased calcium response to PAR-2 stimulation, whereas the increased proliferation to repeated PAR-2 stimulation is related to increased ERK phosphorylation. PMID:24551046

  18. The Effect of Alcohol and Hydrogen Peroxide on Liver Hepcidin Gene Expression in Mice Lacking Antioxidant Enzymes, Glutathione Peroxidase-1 or Catalase

    PubMed Central

    Harrison-Findik, Duygu Dee; Lu, Sizhao

    2015-01-01

    This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1−/−) and catalase (catalase−/−) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1−/− displayed significantly higher hepatic H2O2 levels than catalase−/− compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1−/− mice. Alcohol increased H2O2 production in catalase−/− and wild-type, but not gpx-1−/−, mice. Hepcidin expression was inhibited in alcohol-fed catalase−/− and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1−/− mice. Gpx-1−/− mice also displayed higher level of basal liver CHOP protein expression than catalase−/− mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1−/− mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1−/− mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH. PMID:25955433

  19. CITED2 modulates estrogen receptor transcriptional activity in breast cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lau, Wen Min; Doucet, Michele; Huang, David

    2013-07-26

    Highlights: •The effects of elevated CITED2 on ER function in breast cancer cells are examined. •CITED2 enhances cell growth in the absence of estrogen and presence of tamoxifen. •CITED2 functions as a transcriptional co-activator of ER in breast cancer cells. -- Abstract: Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) is a member of the CITED family of non-DNA binding transcriptional co-activators of the p300/CBP-mediated transcription complex. Previously, we identified CITED2 as being overexpressed in human breast tumors relative to normal mammary epithelium. Upon further investigation within the estrogen receptor (ER)-positive subset of these breast tumor samples, we found thatmore » CITED2 mRNA expression was elevated in those associated with poor survival. In light of this observation, we investigated the effect of elevated CITED2 levels on ER function. While ectopic overexpression of CITED2 in three ER-positive breast cancer cell lines (MCF-7, T47D, and CAMA-1) did not alter cell proliferation in complete media, growth was markedly enhanced in the absence of exogenous estrogen. Correspondingly, cells overexpressing CITED2 demonstrated reduced sensitivity to the growth inhibitory effects of the selective estrogen receptor modulator, 4-hydroxytamoxifen. Subsequent studies revealed that basal ER transcriptional activity was elevated in CITED2-overexpressing cells and was further increased upon the addition of estrogen. Similarly, basal and estrogen-induced expression of the ER-regulated genes trefoil factor 1 (TFF1) and progesterone receptor (PGR) was higher in cells overexpressing CITED2. Concordant with this observation, ChIP analysis revealed higher basal levels of CITED2 localized to the TFF-1 and PGR promoters in cells with ectopic overexpression of CITED2, and these levels were elevated further in response to estrogen stimulation. Taken together, these data indicate that CITED2 functions as a transcriptional co-activator of ER in breast cancer cells and that its increased expression in tumors may result in estrogen-independent ER activation, thereby reducing estrogen dependence and response to anti-estrogen therapy.« less

  20. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    PubMed

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. Field trial on glucose-induced insulin and metabolite responses in Estonian Holstein and Estonian Red dairy cows in two herds

    PubMed Central

    2010-01-01

    Background Insulin secretion and tissue sensitivity to insulin is considered to be one of the factors controlling lipid metabolism post partum. The objective of this study was to compare glucose-induced blood insulin and metabolite responses in Estonian Holstein (EH, n = 14) and Estonian Red (ER, n = 14) cows. Methods The study was carried out using the glucose tolerance test (GTT) performed at 31 ± 1.9 days post partum during negative energy balance. Blood samples were obtained at -15, -5, 5, 10, 20, 30, 40, 50 and 60 min relative to infusion of 0.15 g/kg BW glucose and analysed for glucose, insulin, triglycerides (TG), non-esterified fatty acids (NEFA), cholesterol and β-hydroxybutyrate (BHB). Applying the MIXED Procedure with the SAS System the basal concentration of cholesterol, and basal concentration and concentrations at post-infusion time points for other metabolites, area under the curve (AUC) for glucose and insulin, clearance rate (CR) for glucose, and maximum increase from basal concentration for glucose and insulin were compared between breeds. Results There was a breed effect on blood NEFA (P < 0.05) and a time effect on all metabolites concentration (P < 0.01). The following differences were observed in EH compared to ER: lower blood insulin concentration 5 min after glucose infusion (P < 0.05), higher glucose concentration 20 (P < 0.01) and 30 min (P < 0.05) after infusion, and higher NEFA concentration before (P < 0.01) and 5 min after infusion (P < 0.05). Blood TG concentration in ER remained stable, while in EH there was a decrease from the basal level to the 40th min nadir (P < 0.01), followed by an increase to the 60th min postinfusion (P < 0.01). Conclusion Our results imply that glucose-induced changes in insulin concentration and metabolite responses to insulin differ between EH and ER dairy cows. PMID:20089161

  2. Effects of inclusion level on nutrient digestibility and energy content of wheat middlings and soya bean meal for growing pigs.

    PubMed

    Huang, Qiang; Piao, Xiangshu; Liu, Ling; Li, Defa

    2013-01-01

    Two experiments were conducted to determine the effects of inclusion level of wheat middlings and soya bean meal on apparent total tract digestibility (ATTD) of energy and chemical components of these ingredients in growing pigs. Furthermore, the effects of the inclusion level on their contents of digestible energy (DE) and metabolisable energy (ME) were also determined by the difference method. In Experiment 1, six diets were fed to 36 growing pigs according to a completely randomised design. The basal diet was a corn-soya bean meal diet while the other five diets contained 9.6%, 19.2%, 28.8%, 38.4% or 48.0% of wheat middlings added at the expense of corn and soya bean meal. The measured digestibility of energy and most nutrients of wheat middlings increased (p < 0.05) with increasing levels of that ingredient. Equations were obtained to predict digestibility by inclusion level. At an inclusion level of 9.6% wheat middlings, their DE contents were significantly lower (8.9 MJ/kg DM) than for the higher levels (10.7 to 11.9 MJ/kg DM, p < 0.01). In Experiment 2, three diets were fed to 18 growing pigs according to a completely randomised block design. The basal diet was a corn-based diet while the other two diets were based on corn and two levels of soya bean meal (22.2% and 33.6%). The content of DE in soya bean meal did not differ at 22.2% and 33.6% inclusion levels (16.2 and 16.3 MJ/kg DM, respectively), but the digestibility of dry matter (DM), organic matter and carbohydrates was increased at a higher inclusion level (p < 0.05). This study revealed that the estimated digestibility of nutrients from soya bean meal and wheat middlings was affected by their dietary inclusion levels. For soya bean meal, the estimated energy contents was independent of its inclusion level, but not for wheat middlings. Therefore, the inclusion level of wheat middlings has to be considered for estimating their energy value.

  3. Effects of domestication on biobehavioural profiles: a comparison of domestic guinea pigs and wild cavies from early to late adolescence

    PubMed Central

    2014-01-01

    Introduction Domestication can lead to marked alterations in the biobehavioural profile of a species. Furthermore, during ontogeny, the individual phenotype of an animal can be shaped by the environment in important phases such as adolescence. We investigated differences in biobehavioural profiles between domestic guinea pigs and their ancestor, the wild cavy, over the course of adolescence. At this age, comparisons between the two groups have not been conducted yet. Male guinea pigs and cavies were subjected to a series of tests twice: during the early and late phase of adolescence. We analysed emotional and social behaviours as well as cortisol reactivity and testosterone levels. Results Concerning emotional behaviour, cavies were more explorative and showed more anxiety-like behaviour in the open field test and dark-light test. They also were more risk-taking when having to jump off an elevated platform. Regarding social behaviour, cavies showed less social activity towards unfamiliar females and infants. Furthermore, while guinea pigs and cavies did not differ in basal cortisol levels, cavies showed distinctly higher and prolonged cortisol responses when exposed to an unfamiliar environment. Cavies also had lower basal testosterone titres. No substantial changes in biobehavioural profiles were revealed over the course of adolescence in both groups. Conclusions Domestication led to a substantial shift in the biobehavioural profile of the guinea pig regarding all investigated domains in early and late adolescence. Hence, the differentiation between guinea pigs and cavies emerges early in ontogeny, well before the attainment of sexual maturity. The young individuals already show adaptations that reflect the differences between the natural habitat of cavies and the man-made housing conditions guinea pigs are exposed to. Higher levels of exploration and risk-taking and lower levels of anxiety-like behaviour are necessary for cavies in order to cope with their challenging environment. Their high cortisol reactivity can be interpreted as an energy provisioning mechanism that is needed to meet these demands. By contrast, guinea pigs are adapted to a less challenging environment with much higher population densities. Hence, their biobehavioural profile is characterised by higher levels of social activity and lower levels of exploration, risk-taking, and cortisol reactivity. PMID:24716471

  4. Alterations in soil microbial community composition and biomass following agricultural land use change.

    PubMed

    Zhang, Qian; Wu, Junjun; Yang, Fan; Lei, Yao; Zhang, Quanfa; Cheng, Xiaoli

    2016-11-04

    The effect of agricultural land use change on soil microbial community composition and biomass remains a widely debated topic. Here, we investigated soil microbial community composition and biomass [e.g., bacteria (B), fungi (F), Arbuscular mycorrhizal fungi (AMF) and Actinomycete (ACT)] using phospholipid fatty acids (PLFAs) analysis, and basal microbial respiration in afforested, cropland and adjacent uncultivated soils in central China. We also investigated soil organic carbon and nitrogen (SOC and SON), labile carbon and nitrogen (LC and LN), recalcitrant carbon and nitrogen (RC and RN), pH, moisture, and temperature. Afforestation averaged higher microbial PLFA biomass compared with cropland and uncultivated soils with higher values in top soils than deep soils. The microbial PLFA biomass was strongly correlated with SON and LC. Higher SOC, SON, LC, LN, moisture and lower pH in afforested soils could be explained approximately 87.3% of total variation of higher total PLFAs. Afforestation also enhanced the F: B ratios compared with cropland. The basal microbial respiration was higher while the basal microbial respiration on a per-unit-PLFA basis was lower in afforested land than adjacent cropland and uncultivated land, suggesting afforestation may increase soil C utilization efficiency and decrease respiration loss in afforested soils.

  5. Alterations in soil microbial community composition and biomass following agricultural land use change

    NASA Astrophysics Data System (ADS)

    Zhang, Qian; Wu, Junjun; Yang, Fan; Lei, Yao; Zhang, Quanfa; Cheng, Xiaoli

    2016-11-01

    The effect of agricultural land use change on soil microbial community composition and biomass remains a widely debated topic. Here, we investigated soil microbial community composition and biomass [e.g., bacteria (B), fungi (F), Arbuscular mycorrhizal fungi (AMF) and Actinomycete (ACT)] using phospholipid fatty acids (PLFAs) analysis, and basal microbial respiration in afforested, cropland and adjacent uncultivated soils in central China. We also investigated soil organic carbon and nitrogen (SOC and SON), labile carbon and nitrogen (LC and LN), recalcitrant carbon and nitrogen (RC and RN), pH, moisture, and temperature. Afforestation averaged higher microbial PLFA biomass compared with cropland and uncultivated soils with higher values in top soils than deep soils. The microbial PLFA biomass was strongly correlated with SON and LC. Higher SOC, SON, LC, LN, moisture and lower pH in afforested soils could be explained approximately 87.3% of total variation of higher total PLFAs. Afforestation also enhanced the F: B ratios compared with cropland. The basal microbial respiration was higher while the basal microbial respiration on a per-unit-PLFA basis was lower in afforested land than adjacent cropland and uncultivated land, suggesting afforestation may increase soil C utilization efficiency and decrease respiration loss in afforested soils.

  6. The Readability Levels of the 1981 Scott, Foresman and Co. Basal Texts and Their Comparison with the 1978 Edition.

    ERIC Educational Resources Information Center

    Ackerman, Bonnie

    Fry's Readability Graph was used to determine the readability levels of the 1981 Scott, Foresman and Co. basal textbook series for grades one through six. The readability levels were then compared to those established for the 1978 edition. In the 1981 edition, all stories were handscored. Poems, skill lessons, and plays were not examined in order…

  7. Transcultural adaptation and validation of the patient empowerment in long-term conditions questionnaire.

    PubMed

    Garcimartin, Paloma; Comin-Colet, Josep; Delgado-Hito, Pilar; Badosa-Marcé, Neus; Linas-Alonso, Anna

    2017-05-04

    Patient empowerment is a key element to improve the results in health, increase satisfaction amongst users and obtain higher treatment compliance. The main objective of this study is to validate the Spanish version of the questionnaire "Patient empowerment in long-term conditions" which evaluates the patients' level of empowerment of chronic diseases. The secondary objective is to identify factors which predict basal empowerment and changes (improvement or deterioration) in patients with Heart Failure (HF). An observational and prospective design of psychometric type to validate a questionnaire (aim 1) and a prospective study of cohorts (aim 2). The study will include 121 patients with confirmed diagnosis of HF. Three measurements (basal, at 15 days and at 3 months) will be carried out: quality of life, self-care and empowerment. Descriptive and inferential analyses will be used. For the first aim of the study (validation), the test-retest reproducibility will be assessed through intraclass correlation coefficient; internal consistency will be assessed through Cronbach's alpha coefficient; construct validity through Pearson's correlation coefficient; and sensibility to change through effect size coefficient. Set a valid questionnaire to measure the level of empowerment of patients with chronic diseases could be an effective tool to assess the results from the provision of the health care services. It will also allow us to identify at an early stage, those groups of patients with a low level of empowerment. Hence, they could become a risk group due to poor management of the disease, with a high rate of decompensation and a higher use rate of the health system resources.

  8. Football Fan Aggression: The Importance of Low Basal Cortisol and a Fair Referee

    PubMed Central

    van der Meij, Leander; Almela, Mercedes; van Lange, Paul A. M.

    2015-01-01

    Fan aggression in football (soccer) is a societal problem that affects many countries worldwide. However, to date, most studies use an epidemiological or survey approach to explain football fan aggression. This study used a controlled laboratory study to advance a model of predictors for fan aggression. To do so, football fans (n = 74) saw a match summary in which their favorite team lost against their most important rival. Next, we measured levels of aggression with the hot sauce paradigm, in which fans were given the opportunity to administer a sample of hot sauce that a rival football supporter had to consume. To investigate if media exposure had the ability to reduce aggression, before the match fans saw a video in which fans of the rival team commented in a neutral, negative, or positive manner on their favorite team. Results showed that the media exposure did not affect aggression. However, participants displayed high levels of aggression and anger after having watched the match. Also, aggression was higher in fans with lower basal cortisol levels, which suggests that part of the aggression displayed was proactive and related to anti-social behavior. Furthermore, aggression was higher when the referee was blamed and aggression was lower when the performance of the participants’ favorite team was blamed for the match result. These results indicate that aggression increased when the match result was perceived as unfair. Interventions that aim to reduce football fan aggression should give special attention to the perceived fairness of the match result. PMID:25844939

  9. iTRAQ-Based Proteomic Analysis Reveals Potential Regulation Networks of IBA-Induced Adventitious Root Formation in Apple

    PubMed Central

    Lei, Chao; Fan, Sheng; Li, Ke; Meng, Yuan; Mao, Jiangping; Han, Mingyu; Zhao, Caiping; Bao, Lu; Zhang, Dong

    2018-01-01

    Adventitious root (AR) formation, which is controlled by endogenous and environmental factors, is indispensable for vegetative asexual propagation. However, comprehensive proteomic data on AR formation are still lacking. The aim of this work was to study indole-3-butyric acid (IBA)-induced AR formation in the dwarf apple rootstock ‘T337’. In this study, the effect of IBA on AR formation was analysed. Subsequent to treatment with IBA, both the rooting rate and root length of ‘T337’ increased significantly. An assessment of hormone levels in basal stem cuttings suggested that auxin, abscisic acid, and brassinolide were higher in basal stem cuttings that received the exogenous IBA application; while zeatin riboside, gibberellins, and jasmonic acid were lower than non-treated basal stem cuttings. To explore the underlying molecular mechanism, an isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic technique was employed to identify the expression profiles of proteins at a key period of adventitious root induction (three days after IBA treatment). In total, 3355 differentially expressed proteins (DEPs) were identified. Many DEPs were closely related to carbohydrate metabolism and energy production, protein homeostasis, reactive oxygen and nitric oxide signaling, and cell wall remodeling biological processes; as well as the phytohormone signaling, which was the most critical process in response to IBA treatment. Further, RT-qPCR analysis was used to evaluate the expression level of nine genes that are involved in phytohormone signaling and their transcriptional levels were mostly in accordance with the protein patterns. Finally, a putative work model was proposed. Our study establishes a foundation for further research and sheds light on IBA-mediated AR formation in apple as well as other fruit rootstock cuttings. PMID:29495482

  10. c-Myc and AMPK Control Cellular Energy Levels by Cooperatively Regulating Mitochondrial Structure and Function

    PubMed Central

    Edmunds, Lia R.; Sharma, Lokendra; Wang, Huabo; Kang, Audry; d’Souza, Sonia; Lu, Jie; McLaughlin, Michael; Dolezal, James M.; Gao, Xiaoli; Weintraub, Susan T.; Ding, Ying; Zeng, Xuemei; Yates, Nathan; Prochownik, Edward V.

    2015-01-01

    The c-Myc (Myc) oncoprotein and AMP-activated protein kinase (AMPK) regulate glycolysis and oxidative phosphorylation (Oxphos) although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored the potential co-dependency of and cross-talk between these proteins by comparing the consequences of acute Myc induction in ampk+/+ (WT) and ampk-/- (KO) murine embryo fibroblasts (MEFs). KO MEFs showed a higher basal rate of glycolysis than WT MEFs and an appropriate increase in response to activation of a Myc-estrogen receptor (MycER) fusion protein. However, KO MEFs had a diminished ability to increase Oxphos, mitochondrial mass and reactive oxygen species in response to MycER activation. Other differences between WT and KO MEFs, either in the basal state or following MycER induction, included abnormalities in electron transport chain function, levels of TCA cycle-related oxidoreductases and cytoplasmic and mitochondrial redox states. Transcriptional profiling of pathways pertinent to glycolysis, Oxphos and mitochondrial structure and function also uncovered significant differences between WT and KO MEFs and their response to MycER activation. Finally, an unbiased mass-spectrometry (MS)-based survey capable of quantifying ~40% of all mitochondrial proteins, showed about 15% of them to be AMPK- and/or Myc-dependent in their steady state. Significant differences in the activities of the rate-limiting enzymes pyruvate kinase and pyruvate dehydrogenase, which dictate pyruvate and acetyl coenzyme A abundance, were also differentially responsive to Myc and AMPK and could account for some of the differences in basal metabolite levels that were also detected by MS. Thus, Myc and AMPK are highly co-dependent and appear to engage in significant cross-talk across numerous pathways which support metabolic and ATP-generating functions. PMID:26230505

  11. Effects of pegylated recombinant human megakaryocyte growth and development factor on thrombocytopenia induced by a new myelosuppressive chemotherapy regimen in mice.

    PubMed

    Akahori, H; Shibuya, K; Ozai, M; Ida, M; Kabaya, K; Kato, T; Miyazaki, H

    1996-11-01

    Thrombopoietin, the endogenous c-Mpl ligand, is a novel lineage-specific hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In this study, we examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human c-Mpl ligand derivatized with polyethylene glycol, on myelosuppressive chemotherapy-induced thrombocytopenia in mice. We developed a new murine model of thrombocytopenia induced by i.v. injections of mitomycin C (MMC) for two consecutive days. In control mice, platelet counts began to decrease on day 6, reached a nadir of less than 5% of basal level on day 14, and could not recover to basal level by day 26. Administration of PEG-rHuMGDF greatly enhanced recovery of the number of megakaryocyte progenitor cells and the megakaryocytes in bone marrow, and markedly reduced the severity of thrombocytopenia; it also accelerated platelet recovery in a dose-dependent manner in myelosuppressed mice. Mice receiving consecutive administration of higher doses of PEG-rHuMGDF showed no thrombocytopenia but rather had platelet counts being increased over basal level. Although absolute neutrophil counts and red cell counts also were decreased following MMC treatment, administration of PEG-rHuMGDF also improved neutropenia and anemia. Administration of PEG-rHuMGDF on alternate days or once a week after chemotherapy was almost as effective as consecutive administration in improving thrombocytopenia. Combined administration of PEG-rHuMGDF and rHuG-CSF had an additive effect on improvement of thrombocytopenia and neutropenia. These results suggest that PEG-rHuMGDF is a therapeutically effective agent in the treatment of thrombocytopenia associated with chemotherapy.

  12. A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2.

    PubMed

    de França, Suélem A; dos Santos, Maísa P; Przygodda, Franciele; Garófalo, Maria Antonieta R; Kettelhut, Isis C; Magalhães, Diego A; Bezerra, Kalinne S; Colodel, Edson M; Flouris, Andreas D; Andrade, Cláudia M B; Kawashita, Nair H

    2016-03-01

    The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic stimulation in this process. Male rats (~100 g) were submitted to LPHC (6%-protein; 74%-carbohydrate) or control (C; 17%-protein; 63%-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w(-1) min(-1)). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student's t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60% in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40% increase in the levels of p38-MAPK and a 30% decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.

  13. The effect of Bacillus coagulans-fermented and nonfermented Ginkgo biloba on the immunity status of broiler chickens.

    PubMed

    Liu, Xiaoyan; Cao, Guanjun; Wang, Qin; Yao, Xuan; Fang, Binghu

    2015-07-01

    To evaluate and compare the effects of Bacillus coagulans-fermented Ginkgo biloba (FG) and nonfermented Ginkgo biloba (NFG) on the immunity status of broiler chickens, 180 1-d-old female Arbor Acres chicks were divided into 3 groups and fed either a basal diet, a basal diet supplemented with 0.3% NFG, or a basal diet supplemented with 0.3% FG. Blood samples were taken on the seventh (before vaccination), 14th, 21st, 28th and 35th day for the assessment of serum IL-18 and interferon γ (IFN-γ) levels by ELISA. In addition, Newcastle disease antibody titer analysis was made via hemagglutination and hemagglutination inhibition test methods. On d 35, 6 chickens from each group were sacrificed and the thymus, liver, spleen, small intestine (jejunum segment), cecum, and bursa of Fabricius from each chicken were removed for analysis. RNA was isolated for defensin expression detection by real-time PCR (q-PCR). The results showed that serum IL-18 and IFN-γ levels decreased after treatment with NFG and FG compared with untreated control chickens. The ND antibody titers did not differ significantly between the 3 groups on the seventh, 14th, 21st and 28th day; however, on the 35th day, the ND antibody titers of the NFG and FG chickens were both significantly higher than those of control group chickens. Defensin RNA expression levels were inhibited by NFG; however, they were induced by FG. In conclusion, fermentation of Ginkgo biloba with Bacillus coagulans can promote the beneficial effect of Gingko biloba on the immunity status of broiler chickens.

  14. Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

    PubMed

    Huang, Shu-Yi; Chou, Pai-Chien; Wang, Tsai-Yu; Lo, Yu-Lun; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Chung, Kian Fan; Wang, Chun-Hua; Kuo, Han-Pin

    2016-04-01

    Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = -0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.

  15. Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation

    PubMed Central

    Huang, Shu-Yi; Chou, Pai-Chien; Wang, Tsai-Yu; Lo, Yu-Lun; Joa, Wen-Ching; Chen, Li-Fei; Sheng, Te-Fang; Chung, Kian Fan; Wang, Chun-Hua; Kuo, Han-Pin

    2016-01-01

    Abstract Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 μg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = −0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction. PMID:27082615

  16. [Chronic noise exposure and the cardiovascular system in aircraft pilots].

    PubMed

    Tomei, F; Papaleo, B; Baccolo, T P; Tomao, E; Alfi, P; Fantini, S

    1996-01-01

    The aim of this study was to assess whether pilots are exposed to any risk of effects on the cardiovascular apparatus, whether chronic exposure to noise can be a risk factor for this occupation, the importance of intensity, length and type of exposure to noise, and if any relationship exists between audiometric deficits and cardiovascular effects. The study comprised 416 pilots subdivided into two groups according to the different levels of chronic exposure to noise, and a group of 150 control subjects not exposed to noise. The results showed: a) a higher prevalence of hypertension, nearly always diastolic, and of ECG abnormalities in the group of pilots of turboprop aircraft compared to jet plane pilots and to controls (p < 0.005 and p < 0.01 respectively); b) a higher prevalence of orthostatic hypotension in the two groups of pilots than in the controls (p < 0.05); c) a higher prevalence of hypertension with audiometric deficit compared to hypertension without audiometric deficit both in the more heavily and in the less heavily exposed to noise (p < 0.05), and a higher prevalence of hypertension with audiometric deficit in subjects exposed to higher levels of noise compared to hypertension with deficit but in subjects with lower levels of exposure (p < 0.05); d) a higher prevalence of abnormalities of basal, maximum effort and recovery ECG in pilots exposed to higher noise intensity (p < 0.05); e) improved hypertensive response to ergometric test in pilots with basal hypertension; f) subjects with a maximal load up to 120 W belonged prevalently to the group exposed to more intense noise (p < 0.001), while those with maximal load up to 210 W (p < 0.001) belonged to the group exposed to less intense noise. Considering that pilots are comparable for traditional cardiovascular risk factors, including age, both within the group and with the controls, the results confirm 1) that pilots could be exposed to the risk of effects on the cardiovascular apparatus, 2) that noise could be one of the risk factors and that cardiovascular effects could be related to intensity, type and length of exposure, age being the same, 3) that vascular damage is often accompanied by hearing loss even if the response of the auditory apparatus is different from the response of the cardiovascular apparatus, 4) that the postural diminution of arterial blood pressure might be a sign of a cardiovascular effect of noise. Lastly, a higher hypertensive response in hypertensive pilots suggests that basal hypertension is not reversible. Also a longer exposure to noise seems to influence the cardiovascular apparatus, causing a decrease in the response to work loads due to a lower sympathetic adaptability. The altered response of sympathetic activity to the postural modifications in the more exposed subjects and the response to lower work loads in pilots exposed to more intense noise, suggests a hypothesis of catecholamine depletion and alteration of baroceptor sensitivity as a consequence of chronic sympathetic activation due to chronic exposure to noise.

  17. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

    DTIC Science & Technology

    2001-07-01

    Rogers, H. Ragde, G. M. Kenny, et al. 1999. Follow-up evaluation of a phase II prostate cancer vaccine trial. Prostate 40: 125-129. 69. Troyer, J. K., M...Slusher, D. Price, and J. T. Coyle. 1993. Abnormal acidic amino acids and N-acetylaspartylglutamate in hereditary canine motoneuron disease. Brain Res...levels were at least 10-fold higher, re- promoter, that of the herpesvirus thymidine kinase flecting the greater basal activity of these promoters in gene

  18. Members of the Oral Microbiota Are Associated with IL-8 Release by Gingival Epithelial Cells in Healthy Individuals

    PubMed Central

    Schueller, Katharina; Riva, Alessandra; Pfeiffer, Stefanie; Berry, David; Somoza, Veronika

    2017-01-01

    The triggers for the onset of oral diseases are still poorly understood. The aim of this study was to characterize the oral bacterial community in healthy humans and its association with nutrition, oral hygiene habits, and the release of the inflammatory marker IL-8 from gingival epithelial cells (GECs) with and without stimulation by bacterial endotoxins to identify possible indicator operational taxonomic units (OTUs) associated with inflammatory marker status. GECs from 21 healthy participants (13 females, 8 males) were incubated with or without addition of bacterial lipopolysaccharides (LPSs), and the oral microbiota was profiled using 16S rRNA gene-targeted sequencing. The basal IL-8 release after 6 h was between 9.9 and 98.2 pg/ml, and bacterial communities were characteristic for healthy oral microbiota. The composition of the oral microbiota was associated with basal IL-8 levels, the intake of meat, tea, white wine, sweets and the use of chewing gum, as well as flossing habits, allergies, gender and body mass index. Additionally, eight OTUs were associated with high basal levels of IL-8 and GEC response to LPS, with high basal levels of IL-8, and 1 with low basal levels of IL8. The identification of indicator bacteria in healthy subjects with high levels of IL-8 release is of importance as they may be promising early warning indicators for the possible onset of oral diseases. PMID:28360899

  19. Effects of antimicrobial peptides (AMPs) on blood biochemical parameters, antioxidase activity, and immune function in the common carp (Cyprinus carpio).

    PubMed

    Dong, Xiao-Qing; Zhang, Dong-Ming; Chen, Yu-Ke; Wang, Qiu-Ju; Yang, Yi-Yu

    2015-11-01

    Antibiotic use in livestock feed additives has resulted in harmful residue accumulation and spread of drug-resistance. We examined the use of antimicrobial peptides (AMPs) as a safer alternative to antibiotics in feeding the common carp. AMPs were added to common carp basal diets (Control) as additives at four concentrations: 100 mg kg(-1) (B1), 200 mg kg(-1) (B2), 400 mg kg(-1) (B3), 600 mg kg(-1) (B4) by dry weight of basal diet. After a 60-day feeding experiment, the final weight, DG and SGR of carps on B1, B2 and B3 diet were significantly higher than the control (p < 0.05). The FCR of carps on B1, B2 and B3 diet were significantly lower than the control (p < 0.05). Carps on B2, B3, and B4 diets showed significantly lower (p < 0.05) levels of triglyceride than the control. B4-fed carps showed significantly lower (p < 0.05) levels of total protein, albumin, and total cholesterol than the control. However there was no remarkable difference (p > 0.05) in levels of uric ammonia, globulin, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, lactic dehydrogenase and blood glucose in all groups. The serum superoxide dismutase and catalase activity of B1-fed carps was significantly higher (p < 0.05) than the control and B4-fed carps. The serum alkaline phosphate activity of carps on B1 diets was significantly higher (p < 0.05) than B4-fed carps. The serum acid phosphatase activity of B1-fed carps was significantly higher (p < 0.05) than the control and other antimicrobial peptide-fed groups. The serum lysozyme activity of carps on B1, B2, and B3 diets was significantly higher (p < 0.05) than the control- and B4-fed carps. Regarding immune factors in serum, the levels of immunoglobulin (Ig) and interleukin (IL)-1β in B1-fed carps were significantly higher (p < 0.05) than the control and other groups, while IL-1α levels in B1-fed carps was significantly higher (p < 0.05) than the control-, B2-, and B3-fed carps. Furthermore, there were no significant differences in the content of MHC among the five groups. In conclusion, antimicrobial peptide can reduce triglyceride levels in serum, enrich oxidation resistance, and improve immunity of the common carp. It showed that appropriate concentration of antibacterial peptide as supplements in diets for common carp increased the final weight, DG, SGR and decreased the FCR. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Tree species diversity and its relationship to stand parameters and geomorphology features in the eastern Black Sea region forests of Turkey.

    PubMed

    Ozcelik, Ramazan; Gul, Altay Ugur; Merganic, Jan; Merganicova, Katarina

    2008-05-01

    We studied the effects of stand parameters (crown closure, basal area, stand volume, age, mean stand diameter number of trees, and heterogeneity index) and geomorphology features (elevation, aspect and slope) on tree species diversity in an example of untreated natural mixed forest stands in the eastern Black Sea region of Turkey. Tree species diversity and basal area heterogeneity in forest ecosystems are quantified using the Shannon-Weaver and Simpson indices. The relationship between tree species diversity basal area heterogeneity stand parameters and geomorphology features are examined using regression analysis. Our work revealed that the relationship between tree species diversity and stand parameters is loose with a correlation coefficient between 0.02 and 0.70. The correlation of basal area heterogeneity with stand parameters fluctuated between 0.004 and 0.77 (R2). According to our results, stands with higher tree species diversity are characterised by higher mean stand diameter number of diameter classes, basal area and lower homogeneity index value. Considering the effect of geomorphology features on tree species or basal area heterogeneity we found that all investigated relationships are loose with R < or = 0.24. A significant correlation was detected only between tree species diversity and aspect. Future work is required to verify the detected trends in behaviour of tree species diversity if it is to estimate from the usual forest stand parameters and topography characteristics.

  1. Distinct tumor protein p53 mutants in breast cancer subgroups.

    PubMed

    Dumay, Anne; Feugeas, Jean-Paul; Wittmer, Evelyne; Lehmann-Che, Jacqueline; Bertheau, Philippe; Espié, Marc; Plassa, Louis-François; Cottu, Paul; Marty, Michel; André, Fabrice; Sotiriou, Christos; Pusztai, Lajos; de Thé, Hugues

    2013-03-01

    Tumor protein p53 (TP53) is mutated in approximately 30% of breast cancers, but this frequency fluctuates widely between subclasses. We investigated the p53 mutation status in 572 breast tumors, classified into luminal, basal and molecular apocrine subgroups. As expected, the lowest mutation frequency was observed in luminal (26%), and the highest in basal (88%) tumors. Luminal tumors showed significantly higher frequency of substitutions (82 vs. 65%), notably A/T to G/C transitions (31 vs. 15%), whereas molecular apocrine and basal tumors presented much higher frequencies of complex mutations (deletions/insertions) (36 and 33%, respectively, vs. 18%). Accordingly, missense mutations were significantly more frequent in luminal tumors (75 vs. 54%), whereas basal tumors displayed significantly increased rates of TP53 truncations (43 vs. 25%), resulting in loss of function and/or expression. Interestingly, as basal tumors, molecular apocrine tumors presented with a high rate of complex mutations, but paradoxically, these were not associated with increased frequency of p53 truncation. As in luminal tumors, this could reflect a selective pressure for p53 gain of function, possibly through P63/P73 inactivation. Collectively, these observations point not only to different mechanisms of TP53 alterations, but also to different functional consequences in the different breast cancer subtypes. Copyright © 2012 UICC.

  2. Feeding Jerusalem artichoke reduced skatole level and changed intestinal microbiota in the gut of entire male pigs.

    PubMed

    Vhile, S G; Kjos, N P; Sørum, H; Overland, M

    2012-05-01

    Different levels of dried Jerusalem artichoke were fed to entire male pigs 1 week before slaughter. The objective was to investigate the effect on skatole level in the hindgut and in adipose tissue, as well as the effect on microflora and short-chain fatty acids (SCFA) in the hindgut. Five experimental groups (n = 11) were given different dietary treatments 7 days before slaughtering: negative control (basal diet), positive control (basal diet + 9% chicory-inulin), basal diet + 4.1% Jerusalem artichoke, basal diet + 8.1% Jerusalem artichoke and basal diet + 12.2% Jerusalem artichoke. Samples from colon, rectum, faeces and adipose tissue were collected. Effect of dietary treatment on skatole, indole and androstenone levels in adipose tissue and on skatole, indole, pH, dry matter (DM), microbiota and SCFA in the hindgut was evaluated. Feeding increasing levels of Jerusalem artichoke to entire male pigs reduced skatole in digesta from colon and in faeces (linear, P < 0.01). There was also a tendency towards a decreased level of skatole in adipose tissue (linear, P = 0.06). Feeding Jerusalem artichoke decreased DM content in colon and faeces and pH in colon (linear, P < 0.01). Increasing levels of Jerusalem artichoke resulted in a reduced level of Clostridium perfringens in both colon and rectum (linear, P < 0.05) and a tendency towards decreased levels of enterobacteria in colon (linear, P = 0.05). Further, there was an increase in total amount of SCFA (linear, P < 0.05), acetic acid (linear, P < 0.05) and valerianic acid (linear, P < 0.01) in faeces. In conclusion, adding dried Jerusalem artichoke to diets for entire male pigs 1 week before slaughter resulted in a dose-dependent decrease in skatole levels in the hindgut and adipose tissue. The reduced skatole levels might be related to the decrease in C. perfringens and the increase in SCFA with subsequent reduction in pH.

  3. A study of the action of amlodipine on adrenergically regulated sodium handling by the kidney in normotensive and hypertensive rats.

    PubMed Central

    Johns, E. J.

    1988-01-01

    1. An investigation was undertaken to examine the effect of calcium channel blockade, induced by amlodipine, on the ability of the renal sympathetic nerves to cause an antidiuresis and anti-natriuresis in normotensive Sprague Dawley and spontaneously hypertensive rats anaesthetized with pentobarbitone. 2. Low frequency renal nerve stimulation in normotensive rats, which did not change renal blood flow, caused a 15% reduction in glomerular filtration rate and was associated with falls in urine flow of 37%, absolute sodium excretion of 47%, and fractional sodium excretion of 38%. The magnitude of these renal excretory changes was unaffected by prior administration of amlodipine at either 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1. Amlodipine given in the higher dose, decreased basal levels of blood pressure and increased basal urine flow and sodium excretion. 3. In spontaneously hypertensive rats, renal nerve stimulation minimally affected renal haemodynamics but decreased urine flow, absolute and fractional sodium excretion by 29%, 31% and 24%, respectively. 4. Similar renal nerve stimulation in spontaneously hypertensive rats given amlodipine at 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1 caused minimal changes in renal haemodynamics and in the excretion of water and sodium. The higher dose of drug resulted in decreased blood pressure and increased basal rates of urine flow and sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2967097

  4. Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease.

    PubMed

    Mahabeer, S; Jialal, I; Norman, R J; Naidoo, C; Reddi, K; Joubert, S M

    1989-09-01

    Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

  5. Effect of dietary supplementation of sea buckthorn and giloe leaf meal on the body weight gain, feed conversion ratio, biochemical attributes, and meat composition of turkey poults

    PubMed Central

    Sharma, Aditya; Shukla, Pankaj Kumar; Bhattacharyya, Amitav; Kumar, Upendra; Roy, Debashis; Yadav, Brijesh; Prakash, Atul

    2018-01-01

    Aim: In the recent past, few studies have been carried out about sea buckthorn (SBT) and giloe in chicken as a part of the quest for suitable alternatives to antibiotics. However, studies in turkeys are lacking. Hence, the present study was conducted to evaluate the effects of SBT and giloe leaf meal by dietary feed supplementation in turkey poults. Materials and Methods: A total of 1-day-old turkey poults (n=84) of small white variety were distributed into four dietary treatments having three replicates each with seven birds. The study was conducted in turkey poults during 0-8 weeks of age. During the experiment, the poults were fed basal ration (28% crude protein [CP], 2800 Kcal/kg ME) T1, T2-basal ration was supplemented with SBT leaf meal powder at 0.5%, T3-basal ration was supplemented with giloe leaf meal powder at 0.5%, and T4-basal ration was fed along with supplementation of both SBT at 0.5% and giloe leaf meal powder at 0.5%. Results: T2 turkey poults had a significantly higher (p<0.01) body weight gain than T3 and T4 at 7th week of age. Weekly body weight gain was significantly higher (p<0.05) in T2 than T3 during 5th-8th week and 0-8th week of the growth phase. Feed conversion ratio (FCR) was significantly better (p<0.01) in T2 than other treatment groups during 4th-8th week phase of growth (2.09 vs. 2.36, 2.29 and 2.31). Further, FCR was significantly better (p<0.01) in T2 group as compared to other treatment groups during 0-8th week of growth phase (1.95 vs. 2.21, 2.21 and 2.12). Plasma uric acid was found significantly increased (p<0.05) in T1 than T3 and T4, and alkaline phosphatase value was significantly higher (p<0.05) in T1 and T3 than T2. Zinc content of breast (pectoralis major) muscles was significantly higher (p<0.05) in T2 and T4 as compared to T1, while ether extract (EE) in thigh (ilio tibialis) muscles was significantly higher (p<0.05) in T2 as compared to the other treatment groups. Conclusion: It may be concluded that supplementation of SBT leaf meal at 0.5% may improve production performance of turkey poults. Supplementation of 0.5% SBT leaf meal may result in higher levels of zinc and EE in the breast and thigh cuts of turkey poults. PMID:29479163

  6. Effect of dietary supplementation of sea buckthorn and giloe leaf meal on the body weight gain, feed conversion ratio, biochemical attributes, and meat composition of turkey poults.

    PubMed

    Sharma, Aditya; Shukla, Pankaj Kumar; Bhattacharyya, Amitav; Kumar, Upendra; Roy, Debashis; Yadav, Brijesh; Prakash, Atul

    2018-01-01

    In the recent past, few studies have been carried out about sea buckthorn (SBT) and giloe in chicken as a part of the quest for suitable alternatives to antibiotics. However, studies in turkeys are lacking. Hence, the present study was conducted to evaluate the effects of SBT and giloe leaf meal by dietary feed supplementation in turkey poults. A total of 1-day-old turkey poults (n=84) of small white variety were distributed into four dietary treatments having three replicates each with seven birds. The study was conducted in turkey poults during 0-8 weeks of age. During the experiment, the poults were fed basal ration (28% crude protein [CP], 2800 Kcal/kg ME) T1, T2-basal ration was supplemented with SBT leaf meal powder at 0.5%, T3-basal ration was supplemented with giloe leaf meal powder at 0.5%, and T4-basal ration was fed along with supplementation of both SBT at 0.5% and giloe leaf meal powder at 0.5%. T2 turkey poults had a significantly higher (p<0.01) body weight gain than T3 and T4 at 7 th week of age. Weekly body weight gain was significantly higher (p<0.05) in T2 than T3 during 5 th -8 th week and 0-8 th week of the growth phase. Feed conversion ratio (FCR) was significantly better (p<0.01) in T2 than other treatment groups during 4 th -8 th week phase of growth (2.09 vs. 2.36, 2.29 and 2.31). Further, FCR was significantly better (p<0.01) in T2 group as compared to other treatment groups during 0-8 th week of growth phase (1.95 vs. 2.21, 2.21 and 2.12). Plasma uric acid was found significantly increased (p<0.05) in T1 than T3 and T4, and alkaline phosphatase value was significantly higher (p<0.05) in T1 and T3 than T2. Zinc content of breast (pectoralis major) muscles was significantly higher (p<0.05) in T2 and T4 as compared to T1, while ether extract (EE) in thigh (ilio tibialis) muscles was significantly higher (p<0.05) in T2 as compared to the other treatment groups. It may be concluded that supplementation of SBT leaf meal at 0.5% may improve production performance of turkey poults. Supplementation of 0.5% SBT leaf meal may result in higher levels of zinc and EE in the breast and thigh cuts of turkey poults.

  7. Effects of different dl-selenomethionine and sodium selenite levels on growth performance, immune functions and serum thyroid hormones concentrations in broilers.

    PubMed

    Wang, Y; Wang, H; Zhan, X

    2016-06-01

    This trial was conducted in a 2 × 3 + 1 factorial arrangement based on a completely randomized design to evaluate the effects of different dl-selenomethionine (dl-Se-Met) and sodium selenite (SS) levels on growth performance, immune functions and serum thyroid hormones concentrations in broilers. A total of 840 Ross 308 broilers (7 days old) were allocated by body weight to seven treatments (three replicates of 40 birds each treatment) including (1) basal diet (containing 0.04 mg of selenium (Se)/kg; control) without supplementary Se; (2, 3 and 4) basal diet + 0.05, 0.15 or 0.25 mg/kg Se as SS; (5, 6 and 7) basal diet + 0.05, 0.15 or 0.25 mg/kg Se as dl-Se-Met. The experiment lasted 42 days. The results revealed that dietary Se supplementation improved (p < 0.05) average daily gain, feed efficiency, immune organ index, serum immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM) and triiodothyronine (T3 ) concentrations and decreased (p < 0.01) thyroxine (T4 )/T3 ratio in serum compared with the control. Broilers receiving the dl-Se-Met-supplemented diets had higher (p < 0.05) feed efficiency, thymus index, the amounts of IgA, IgG, IgM and T3 as well as lower (p < 0.05) serum T4 concentrations and T4 /T3 ratio than those consuming the SS-supplemented diets. Serum IgA and IgM levels of broilers fed 0.15 mg Se/kg were significantly higher (p < 0.05) than those of broilers fed 0.05 or 0.25 mg Se/kg. In summary, we concluded that dl-Se-Met is more effective than SS in increasing immunity and promoting conversion of T4 to T3 , thus providing an effective way to improve the growth performance of broilers. Besides, based on a consideration of all experiment indices, 0.15 mg Se/kg was suggested to be the optimal level of Se supplementation under the conditions of this study. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  8. Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

    PubMed

    Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

    2016-01-01

    To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p < 0.05 for all comparisons). Total healthcare costs were similar across the three cohorts. Findings for the second year post-index were similar. The majority of people in this study interrupted or discontinued basal insulin treatment in the year after initiation; and incurred higher medical resource use and costs than continuers. The findings are limited to the commercially insured population in the US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help clinicians manage care for T2DM more effectively.

  9. Effects of grazing management treatment on grassland plant communities and prairie grouse habitat

    Treesearch

    Llewellyn L. Manske; William T. Barker; Mario E. Biondini

    1988-01-01

    Seasonlong grazing treatments show no benefit to grass basal cover and visual obstruction is not adequate. Pastures with one grazing period in mid season show no positive change in grass basal cover but have better visual obstruction than seasonlong. Deferred grazing decreases basal cover of warm season grasses and visual obstruction reduced to inadequate levels the...

  10. Oil biosynthesis in a basal angiosperm: transcriptome analysis of Persea Americana mesocarp.

    PubMed

    Kilaru, Aruna; Cao, Xia; Dabbs, Parker B; Sung, Ha-Jung; Rahman, Md Mahbubur; Thrower, Nicholas; Zynda, Greg; Podicheti, Ram; Ibarra-Laclette, Enrique; Herrera-Estrella, Luis; Mockaitis, Keithanne; Ohlrogge, John B

    2015-08-16

    The mechanism by which plants synthesize and store high amounts of triacylglycerols (TAG) in tissues other than seeds is not well understood. The comprehension of controls for carbon partitioning and oil accumulation in nonseed tissues is essential to generate oil-rich biomass in perennial bioenergy crops. Persea americana (avocado), a basal angiosperm with unique features that are ancestral to most flowering plants, stores ~ 70 % TAG per dry weight in its mesocarp, a nonseed tissue. Transcriptome analyses of select pathways, from generation of pyruvate and leading up to TAG accumulation, in mesocarp tissues of avocado was conducted and compared with that of oil-rich monocot (oil palm) and dicot (rapeseed and castor) tissues to identify tissue- and species-specific regulation and biosynthesis of TAG in plants. RNA-Seq analyses of select lipid metabolic pathways of avocado mesocarp revealed patterns similar to that of other oil-rich species. However, only some predominant orthologs of the fatty acid biosynthetic pathway genes in this basal angiosperm were similar to those of monocots and dicots. The accumulation of TAG, rich in oleic acid, was associated with higher transcript levels for a putative stearoyl-ACP desaturase and endoplasmic reticulum (ER)-associated acyl-CoA synthetases, during fruit development. Gene expression levels for enzymes involved in terminal steps to TAG biosynthesis in the ER further indicated that both acyl-CoA-dependent and -independent mechanisms might play a role in TAG assembly, depending on the developmental stage of the fruit. Furthermore, in addition to the expression of an ortholog of WRINKLED1 (WRI1), a regulator of fatty acid biosynthesis, high transcript levels for WRI2-like and WRI3-like suggest a role for additional transcription factors in nonseed oil accumulation. Plastid pyruvate necessary for fatty acid synthesis is likely driven by the upregulation of genes involved in glycolysis and transport of its intermediates. Together, a comparative transcriptome analyses for storage oil biosynthesis in diverse plants and tissues suggested that several distinct and conserved features in this basal angiosperm species might contribute towards its rich TAG content. Our work represents a comprehensive transcriptome resource for a basal angiosperm species and provides insight into their lipid metabolism in mesocarp tissues. Furthermore, comparison of the transcriptome of oil-rich mesocarp of avocado, with oil-rich seed and nonseed tissues of monocot and dicot species, revealed lipid gene orthologs that are highly conserved during evolution. The orthologs that are distinctively expressed in oil-rich mesocarp tissues of this basal angiosperm, such as WRI2, ER-associated acyl-CoA synthetases, and lipid-droplet associated proteins were also identified. This study provides a foundation for future investigations to increase oil-content and has implications for metabolic engineering to enhance storage oil content in nonseed tissues of diverse species.

  11. Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437.

    PubMed

    Nandi, Nilay; Tyra, Lauren K; Stenesen, Drew; Krämer, Helmut

    2017-12-11

    Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels. The phospho-mimetic S437D mutation stabilizes Acn and promotes basal autophagy. In p35 mutants, basal autophagy and lifespan are reduced, but restored to near wild-type levels in the presence of stabilized Acn S437D . Expression of aggregation-prone polyQ-containing proteins or the Amyloid-β42 peptide, but not alpha-Synuclein, enhances Cdk5-dependent phosphorylation of S437-Acn. Our data indicate that Cdk5 is required to maintain the protective role of basal autophagy in the initial responses to a subset of neurodegenerative challenges.

  12. Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

    PubMed

    Andres, Daniela S; Darbin, Olivier

    2018-01-01

    The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

  13. [Evaluation of the nutritional status, insulin resistance and cardiovascular risk in a population of adolescents in the cities of Granada and Almeria (Spain)].

    PubMed

    Montero Alonso, Miguel A; González-Jiménez, Emilio

    2013-01-01

    The first objective of this study was to evaluate the nutritional status and insulin resistance index in a population of adolescents as calculated by Homeostatic Model Assessment (HOMA). The second objective was to establish correlations between the nutritional status of the subjects, the possible existence of insulin resistance, and the risk of high blood pressure. POPULATION SAMPLE AND METHODOLOGY: The sample was composed of 1001 adolescents, 9-17 years of age, from 18 schools in the provinces of Granada and Almeria. Their nutritional status was determined by means of anthropometric evaluation. For the metabolic study, a blood sample was collected from each subject by venipuncture. An analysis was performed of the basal glucose and insulin levels as well as the Homeostatic Model Assessment- Insulin Resistance (HOMAIR) index. Also evaluated were the levels of glycosylated haemoglobin (HbA1c), serum lipoprotein (a), and non-esterified fatty acids (NEFAs). Insulin resistance was calculated with the formula, proposed by Matthews et al. (1985) : HOMA-IR = (insulin[mmol/L] x glucose[mU/L])/22.5. The evaluation of the nutritional status of the subjects reflected a progressive increase in the values of anthropometric variables as the nutritional status of the subjects worsened. The results of this study showed, regardless of age and gender, 85.01% of the subjects were of normal weight, whereas 9.99% were overweight, and 4.99% were obese. The metabolic study reflected that in comparison to normal-weight and overweight students, obese students had significantly higher serum levels (p < 0,0001) of HbA1c, basal insulin, basal glycemia, basal NEFA, lipoprotein (a), and HOMA-IR. Obesity was found to be a serious health problem in the population of adolescents studied, especially given the high cardiovascular risk that is characteristic of this condition. As reflected in the results of this study, obesity led to the premature development of metabolic disorders, which generally do not appear until adulthood. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  14. Protein Kinase-C Beta Contributes to Impaired Endothelial Insulin Signaling in Humans with Diabetes Mellitus

    PubMed Central

    Tabit, Corey E; Shenouda, Sherene M; Holbrook, Monica; Fetterman, Jessica L; Kiani, Soroosh; Frame, Alissa A; Kluge, Matthew A; Held, Aaron; Dohadwala, Mustali; Gokce, Noyan; Farb, Melissa; Rosenzweig, James; Ruderman, Neil; Vita, Joseph A; Hamburg, Naomi M

    2013-01-01

    Background Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of endothelial insulin signaling through the activity of protein kinase C-β (PKCβ) and nuclear factor κB (NFκB) reduces nitric oxide availability. We sought to establish whether similar mechanisms operate in the endothelium in human diabetes mellitus. Methods and Results We measured protein expression and insulin response in freshly isolated endothelial cells from patients with Type 2 diabetes mellitus (n=40) and non-diabetic controls (n=36). Unexpectedly, we observed 1.7-fold higher basal endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 in patients with diabetes (P=0.007) without a difference in total eNOS expression. Insulin stimulation increased eNOS phosphorylation in non-diabetic subjects but not in diabetic patients (P=0.003) consistent with endothelial insulin resistance. Nitrotyrosine levels were higher in diabetic patients indicating endothelial oxidative stress. PKCβ expression was higher in diabetic patients and was associated with lower flow-mediated dilation (r=−0.541, P=0.02) Inhibition of PKCβ with LY379196 reduced basal eNOS phosphorylation and improved insulin-mediated eNOS activation in patients with diabetes. Endothelial NFκB activation was higher in diabetes and was reduced with PKCβ inhibition. Conclusions We provide evidence for the presence of altered eNOS activation, reduced insulin action and inflammatory activation in the endothelium of patients with diabetes. Our findings implicate PKCβ activity in endothelial insulin resistance. PMID:23204109

  15. Phylogenetic evidence for an ancestral coevolution between a major clade of coccidian parasites and elasmobranch hosts.

    PubMed

    Xavier, Raquel; Santos, Joana L; Veríssimo, Ana

    2018-05-01

    Cartilaginous fishes are the oldest jawed vertebrates and are also reported to be the hosts of some of the most basal lineages of Cestoda and Aporocotylidae (Digenea) parasites. Recently a phylogenetic analysis of the coccidia (Apicomplexa) infecting marine vertebrates revealed that the lesser spotted dogfish harbours parasite lineages basal to Eimeria Schneider, 1875 and the group formed by Schellackia Reichenow, 1919, Lankesterella Ames, 1923, Caryospora Leger, 1904 and Isospora Schneider, 1881. In the present study we have found additional lineages of coccidian parasites infecting the cownose ray Rhinoptera bonasus Mitchill and the blue shark Prionace glauca Linnaeus. These lineages were also found as basal to species from the genera Lankesterella, Schellackia, Caryospora and Isospora infecting higher vertebrates. These results confirm previous phylogenetic assessments and suggest that these parasitic lineages first evolved in basal vertebrate hosts (i.e. Chondrichthyes), and that the more derived lineages infect higher vertebrates (e.g. birds and mammals) conforming to the evolution of their hosts. We hypothesise that elasmobranchs might host further ancestral parasite lineages harbouring unknown links of parasite evolution.

  16. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect.

    PubMed

    Crespin, S R; Greenough, W B; Steinberg, D

    1973-08-01

    A continuous-flow centrifuge was used to infuse sodium salts of oleic, linoleic, lauric, or palmitic acid into the pancreatic artery of anesthetized dogs. In these regional perfusion studies there was no increase in FFA levels in the general circulation. Elevation of pancreatic FFA levels produced an immediate increase in pancreatic venous immunoreactive insulin (IRI). After 10 min of FFA infusion. IRI levels declined somewhat from the initial peak response but soon rose again to high levels which were then sustained until the infusion was terminated. All four long-chain FFA tested produced a similar biphasic IRI response. Clearcut increases in IRI were associated with absolute FFA levels (measured in pancreaticoduodenal venous plasma) as low as 0.6-0.8 mueq/ml and with increments over basal levels of as little as 0.4-0.5 mueq/ml. At higher levels of FFA, absolute IRI levels in the pancreatic venous effluent exceeded 1,000 muU/ml in some experiments and 5- to 10-fold increases over basal values were observed. These studies indicate that long-chain FFA, in physiological concentrations, can markedly stimulate insulin secretion by a direct effect on the pancreas. The results lend support to the concept of insulin as a hormone that is importantly involved in regulating the metabolism of all three principal classes of metabolic substrates and whose release is in turn regulated by all of them. The relative importance and precise nature of its physiologic role in the regulation of lipolysis, lipid deposition, and ketone body formation remains to be established.

  17. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  18. Regulation of ethanol intake under chronic mild stress: roles of dopamine receptors and transporters.

    PubMed

    Delis, Foteini; Rombola, Christina; Bellezza, Robert; Rosko, Lauren; Grandy, David K; Volkow, Nora D; Thanos, Panayotis K

    2015-01-01

    Studies have shown that exposure to chronic mild stress decreases ethanol intake and preference in dopamine D2 receptor wild-type mice (Drd2 (+/+)), while it increases intake in heterozygous (Drd2 (+/-)) and knockout (Drd2 (-/-)) mice. Dopaminergic neurotransmission in the basal forebrain plays a major role in the reinforcing actions of ethanol as well as in brain responses to stress. In order to identify neurochemical changes associated with the regulation of ethanol intake, we used in vitro receptor autoradiography to measure the levels and distribution of dopamine D1 and D2 receptors and dopamine transporters (DAT). Receptor levels were measured in the basal forebrain of Drd2 (+/+), Drd2 (+/-), and Drd2 (-/-) mice belonging to one of four groups: control (C), ethanol intake (E), chronic mild stress exposure (S), and ethanol intake under chronic mild stress (ES). D2 receptor levels were higher in the lateral and medial striatum of Drd2 (+/+) ES mice, compared with Drd2 (+/+) E mice. Ethanol intake in Drd2 (+/+) mice was negatively correlated with striatal D2 receptor levels. D2 receptor levels in Drd2(+/-) mice were the same among the four treatment groups. DAT levels were lower in Drd2(+/-) C and Drd2 (-/-) C mice, compared with Drd2 (+/+) C mice. Among Drd2(+/-) mice, S and ES groups had higher DAT levels compared with C and E groups in most regions examined. In Drd2(-/-) mice, ethanol intake was positively correlated with DAT levels in all regions studied. D1 receptor levels were lower in Drd2(+/-) and Drd2(-/-) mice, compared with Drd2(+/+), in all regions examined and remained unaffected by all treatments. The results suggest that in normal mice, ethanol intake is associated with D2 receptor-mediated neurotransmission, which exerts a protective effect against ethanol overconsumption under stress. In mice with low Drd2 expression, where DRD2 levels are not further modulated, ethanol intake is associated with DAT function which is upregulated under stress leading to ethanol overconsumption.

  19. Treatment persistence in the use of basal insulins in Poland and Germany
.

    PubMed

    Rathmann, Wolfgang; Czech, Marcin; Franek, Edward; Kostev, Karel

    2017-02-01

    To compare short-term basal insulin therapy persistence and its predictors in Poland and Germany. Persistence was defined as proportions of patients remaining on the initial basal insulin (analogs: Poland: n = 6,889, Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n = 50,761, Germany: n = 226,064) over 2 years based on nationwide prescription databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence was evaluated by Kaplan-Meier curves (log-rank tests). Risk of discontinuation of initial basal insulin was investigated using Cox regression models adjusting for age, sex, comedication with other glucose-lowering agents and baseline or comedication with antihypertensives, lipid-lowering drugs, antidepressants, and antiepileptics. In Poland, 2-year persistence was 83.0% in analog insulin and 73.3% in NPH users (p < 0.001). In Germany, persistence was also higher in patients with analog insulins (92.6% vs. 79.0%; p < 0.001). Analog insulin users were less likely to discontinue basal insulin compared with NPH users (adjusted hazard ratio (95%CI): Poland: 0.73 (0.67 - 0.79); Germany: 0.27 (0.27 - 0.28)). Higher age (> 75 vs. ≤ 60 years: Poland: 1.24 (1.16 - 1.33), Germany: 1.09 (1.07 - 1.11)) and GLP-1 receptor agonist use (Poland: 2.76 (1.38 - 5.53), Germany: 1.21 (1.16 - 1.26)) were related to higher risk of discontinuation. Male sex, metformin, sulfonylurea, thiazolidinedione, and short-acting insulin prescriptions as well as antihypertensive, anti-epileptic, and lipid-lowering drug use were associated with lower risk of discontinuation in both countries (all p < 0.05). This real-world study shows that both in Poland and Germany treatment persistence of newly-prescribed basal insulin is influenced by type of insulin (analog vs. NPH) and by glucose-lowering and other comedications.
.

  20. Estimating parameters for tree basal area growth with a system of equations and seemingly unrelated regressions

    Treesearch

    Charles E. Rose; Thomas B. Lynch

    2001-01-01

    A method was developed for estimating parameters in an individual tree basal area growth model using a system of equations based on dbh rank classes. The estimation method developed is a compromise between an individual tree and a stand level basal area growth model that accounts for the correlation between trees within a plot by using seemingly unrelated regression (...

  1. Relation of snowpack Accumulation to Red Pine Stocking

    Treesearch

    Edward A. Hansen

    1969-01-01

    A snow accumulation study was conducted in a 33-year-old red pine plantation thinned to different stocking levels. Snowpack water content increased an average of 2 percent for each 10 square feet of basal area reduction, within the range of 60 to 180 square feet of basal area. Reducing plantation stocking from 180 to 60 square feet of basal area per acre would result...

  2. Functional Connectivity of Insula, Basal Ganglia, and Prefrontal Executive Control Networks during Hypoglycemia in Type 1 Diabetes

    PubMed Central

    Simonson, Donald C.; Nickerson, Lisa D.; Flores, Veronica L.; Siracusa, Tamar; Hager, Brandon; Lyoo, In Kyoon; Renshaw, Perry F.; Jacobson, Alan M.

    2015-01-01

    Human brain networks mediating interoceptive, behavioral, and cognitive aspects of glycemic control are not well studied. Using group independent component analysis with dual-regression approach of functional magnetic resonance imaging data, we examined the functional connectivity changes of large-scale resting state networks during sequential euglycemic–hypoglycemic clamp studies in patients with type 1 diabetes and nondiabetic controls and how these changes during hypoglycemia were related to symptoms of hypoglycemia awareness and to concurrent glycosylated hemoglobin (HbA1c) levels. During hypoglycemia, diabetic patients showed increased functional connectivity of the right anterior insula and the prefrontal cortex within the executive control network, which was associated with higher HbA1c. Controls showed decreased functional connectivity of the right anterior insula with the cerebellum/basal ganglia network and of temporal regions within the temporal pole network and increased functional connectivity in the default mode and sensorimotor networks. Functional connectivity reductions in the right basal ganglia were correlated with increases of self-reported hypoglycemic symptoms in controls but not in patients. Resting state networks that showed different group functional connectivity during hypoglycemia may be most sensitive to glycemic environment, and their connectivity patterns may have adapted to repeated glycemic excursions present in type 1 diabetes. Our results suggest that basal ganglia and insula mediation of interoceptive awareness during hypoglycemia is altered in type 1 diabetes. These changes could be neuroplastic adaptations to frequent hypoglycemic experiences. Functional connectivity changes in the insula and prefrontal cognitive networks could also reflect an adaptation to changes in brain metabolic pathways associated with chronic hyperglycemia. SIGNIFICANCE STATEMENT The major factor limiting improved glucose control in type 1 diabetes is the significant increase in hypoglycemia associated with insulin treatment. Repeated exposure to hypoglycemia alters patients' ability to recognize the autonomic and neuroglycopenic symptoms associated with low plasma glucose levels. We examined brain resting state networks during the induction of hypoglycemia in diabetic and control subjects and found differences in networks involved in sensorimotor function, cognition, and interoceptive awareness that were related to chronic levels of glycemic control. These findings identify brain regions that are sensitive to variations in plasma glucose levels and may also provide a basis for understanding the mechanisms underlying the increased incidence of cognitive impairment and affective disorders seen in patients with diabetes. PMID:26245963

  3. Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales—Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2

    PubMed Central

    Lindroos, Robert; Dorst, Matthijs C.; Du, Kai; Filipović, Marko; Keller, Daniel; Ketzef, Maya; Kozlov, Alexander K.; Kumar, Arvind; Lindahl, Mikael; Nair, Anu G.; Pérez-Fernández, Juan; Grillner, Sten; Silberberg, Gilad; Hellgren Kotaleski, Jeanette

    2018-01-01

    The basal ganglia are involved in the motivational and habitual control of motor and cognitive behaviors. Striatum, the largest basal ganglia input stage, integrates cortical and thalamic inputs in functionally segregated cortico-basal ganglia-thalamic loops, and in addition the basal ganglia output nuclei control targets in the brainstem. Striatal function depends on the balance between the direct pathway medium spiny neurons (D1-MSNs) that express D1 dopamine receptors and the indirect pathway MSNs that express D2 dopamine receptors. The striatal microstructure is also divided into striosomes and matrix compartments, based on the differential expression of several proteins. Dopaminergic afferents from the midbrain and local cholinergic interneurons play crucial roles for basal ganglia function, and striatal signaling via the striosomes in turn regulates the midbrain dopaminergic system directly and via the lateral habenula. Consequently, abnormal functions of the basal ganglia neuromodulatory system underlie many neurological and psychiatric disorders. Neuromodulation acts on multiple structural levels, ranging from the subcellular level to behavior, both in health and disease. For example, neuromodulation affects membrane excitability and controls synaptic plasticity and thus learning in the basal ganglia. However, it is not clear on what time scales these different effects are implemented. Phosphorylation of ion channels and the resulting membrane effects are typically studied over minutes while it has been shown that neuromodulation can affect behavior within a few hundred milliseconds. So how do these seemingly contradictory effects fit together? Here we first briefly review neuromodulation of the basal ganglia, with a focus on dopamine. We furthermore use biophysically detailed multi-compartmental models to integrate experimental data regarding dopaminergic effects on individual membrane conductances with the aim to explain the resulting cellular level dopaminergic effects. In particular we predict dopaminergic effects on Kv4.2 in D1-MSNs. Finally, we also explore dynamical aspects of the onset of neuromodulation effects in multi-scale computational models combining biochemical signaling cascades and multi-compartmental neuron models. PMID:29467627

  4. Trophic structure of mesopelagic fishes in the western Mediterranean based on stable isotopes of carbon and nitrogen

    NASA Astrophysics Data System (ADS)

    Valls, M.; Olivar, M. P.; Fernández de Puelles, M. L.; Molí, B.; Bernal, A.; Sweeting, C. J.

    2014-10-01

    Mesopelagic fishes play an important role in the transfer of organic material in the photic zone to depth although the trophodynamic partitioning amongst co-existing and presumably competing species is unclear. This study employs combined carbon and nitrogen stable isotope analyses (δ13C and δ15N) of the 18 most abundant western Mediterranean mesopelagic fishes to explore niche partitioning in this group. Sampling was conducted along the water column from the shelf and slope grounds of the Balearic Islands in two contrasting periods (late autumn and summer). Trophodynamics were explored at assemblage level and at inter- and intra-species resolutions respectively using Bayesian diet mixing models and size specific behaviour respectively. Seasonal δ13C differences in near basal particulate organic matter (POM) and zooplankton fractions were almost directly replicated in higher fauna suggesting strong isotopic coupling between mesopelagic fishes and planktonic production. Despite reliance on similar basal production, species were segregated by trophic position with a graduation from 2.9 for the small Gonostomatidae Cyclothone braueri to 4.0 for the Myctophidae Lobianchia dofleini. Mixing model data reflected basic trophic position estimates with higher contributions of small fish and zooplankton/POM in higher and lower trophic level species respectively. Species could be categorized as showing preference for i) mesozooplankton/POM as for C. braueri, (in the lower TrL), ii) euphausiids and fish prey as for L. dofleini and the near bottom Lampanyctus crocodilus (in the upper TrL) and iii) mesozooplankton/euphausiids as Ceratoscopelus maderensis, Lampanyctus pusillus or the migrating L. crocodilus. There was little evidence of size based inter-population trophodynamics, with size-isotope trends explained by co-varying lipid content.

  5. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  6. Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

    PubMed

    Eriksson, C J P; Etelälahti, T J; Apter, S J

    2017-06-01

    A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational stress than to intrinsic factors. In further studies, it should be investigated, whether the present results also apply to stress and human alcohol drinking. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Uptake, Distribution, and Metabolism of 1-Naphthaleneacetic Acid and Indole-3-Acetic Acid During Callus Initiation From Actinidia deliciosa Tissues.

    PubMed

    Centeno; Fernández; Feito; Rodríguez

    1999-10-01

    1-Naphthaleneacetic acid (NAA) and 6-benzyladenine (BA) were required for in vitro callus formation at the basal edge of kiwifruit (Actinidia deliciosa [A. Chev] Liang and Ferguson, cv. Hayward) petioles. The uptake, metabolism, and concentration of NAA and indole-3-acetic acid (IAA) content were examined in the explants during the callus initiation period. After 1, 6, 12, 24, 48, and 96 h of culture in the presence of [H(3)]NAA, petioles were divided into apical, middle, and basal portions and analyzed. Except for a high IAA level measured at 12 h, IAA content decreased in tissues during a culture period of 96 h. NAA uptake was higher in petiolar edges than in the middle portion, and NAA was rapidly conjugated with sugars and aspartic acid inside the tissues. The amide conjugation was triggered in apical and basal portions from 12 h and in the middle part from 48 h, with alpha-naphthylacetylaspartic acid being the major metabolite. Free-NAA concentration in cultured petioles achieved an equilibrium with the exogenously applied NAA (0.27 µm) from 12 h, and it remained constant thereafter. The relationships between the role attributed to NAA and BA in the initiation and the maintenance of disorganized growth of callus in kiwifruit cultures are discussed.

  8. An autocrine ATP release mechanism regulates basal ciliary activity in airway epithelium.

    PubMed

    Droguett, Karla; Rios, Mariana; Carreño, Daniela V; Navarrete, Camilo; Fuentes, Christian; Villalón, Manuel; Barrera, Nelson P

    2017-07-15

    Extracellular ATP, in association with [Ca 2+ ] i regulation, is required to maintain basal ciliary beat frequency. Increasing extracellular ATP levels increases ciliary beating in airway epithelial cells, maintaining a sustained response by inducing the release of additional ATP. Extracellular ATP levels in the millimolar range, previously associated with pathophysiological conditions of the airway epithelium, produce a transient arrest of ciliary activity. The regulation of ciliary beat frequency is dependent on ATP release by hemichannels (connexin/pannexin) and P2X receptor activation, the blockage of which may even stop ciliary movement. The force exerted by cilia, measured by atomic force microscopy, is reduced following extracellular ATP hydrolysis. This result complements the current understanding of the ciliary beating regulatory mechanism, with special relevance to inflammatory diseases of the airway epithelium that affect mucociliary clearance. Extracellular nucleotides, including ATP, are locally released by the airway epithelium and stimulate ciliary activity in a [Ca 2+ ] i -dependent manner after mechanical stimulation of ciliated cells. However, it is unclear whether the ATP released is involved in regulating basal ciliary activity and mediating changes in ciliary activity in response to chemical stimulation. In the present study, we evaluated ciliary beat frequency (CBF) and ciliary beating forces in primary cultures from mouse tracheal epithelium, using videomicroscopy and atomic force microscopy (AFM), respectively. Extracellular ATP levels and [Ca 2+ ] i were measured by luminometric and fluorimetric assays, respectively. Uptake of ethidium bromide was measured to evaluate hemichannel functionality. We show that hydrolysis of constitutive extracellular ATP levels with apyrase (50 U ml -1 ) reduced basal CBF by 45% and ciliary force by 67%. The apyrase effect on CBF was potentiated by carbenoxolone, a hemichannel inhibitor, and oxidized ATP, an antagonist used to block P2X7 receptors, which reduced basal CBF by 85%. Additionally, increasing extracellular ATP levels (0.1-100 μm) increased CBF, maintaining a sustained response that was suppressed in the presence of carbenoxolone. We also show that high levels of ATP (1 mm), associated with inflammatory conditions, lowered basal CBF by reducing [Ca 2+ ] i and hemichannel functionality. In summary, we provide evidence indicating that airway epithelium ATP release is the molecular autocrine mechanism regulating basal ciliary activity and is also the mediator of the ciliary response to chemical stimulation. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  9. Relationship between endogenous auxin and cytokinin levels and morphogenic responses inActinidia deliciosa tissue cultures.

    PubMed

    Centeno, M L; Rodríguez, A; Feito, I; Fernández, B

    1996-11-01

    Thein vitro culture ofActinidia deliciosa petioles results in a decline of cytokinin content and an increase of auxin levels. The addition of plant growth regulators (PGRs) to the medium lead to recovery of the initial auxin content, and callus induction occurs at the basal end of the explants. Endogenous auxin/cytokinin ratio was higher at this side than in the apical one, due to unequal distribution of endogenous PGRs in the cultured petioles. Some of the induced calluses showed shoot formation when they were transferred to proliferation medium. Most important differences found in hormonal content between organogenic and non-organogenic callus concerned benzyladenine levels. In this paper the relationships between explant behaviour and their hormonal content is discussed.

  10. Effects of Zinc Glycinate on Productive and Reproductive Performance, Zinc Concentration and Antioxidant Status in Broiler Breeders.

    PubMed

    Zhang, Ling; Wang, Yong-Xia; Xiao, Xue; Wang, Jiang-Shui; Wang, Qian; Li, Kai-Xuan; Guo, Tian-Yu; Zhan, Xiu-An

    2017-08-01

    An experiment was conducted to investigate the effects of zinc glycinate (Zn-Gly) supplementation as an alternative for zinc sulphate (ZnSO 4 ) on productive and reproductive performance, zinc (Zn) concentration and antioxidant status in broiler breeders. Six hundred 39-week-old Lingnan Yellow broiler breeders were randomly assigned to 6 groups consisting of 4 replicates with 25 birds each. Breeders were fed a basal diet (control group, 24 mg Zn/kg diet), basal diet supplemented with 80 mg Zn/kg diet from ZnSO 4 or basal diet supplemented with 20, 40, 60 and 80 mg Zn/kg diet from Zn-Gly. The experiment lasted for 8 weeks after a 4-week pre-test with the basal diet, respectively. Results showed that Zn supplementation, regardless of sources, improved (P < 0.05) the feed conversion ratio (kilogram of feed/kilogram of egg) and decreased broken egg rate, and elevated (P < 0.05) the qualified chick rate. Compared with the ZnSO 4 group, the 80 mg Zn/kg Zn-Gly group significantly increased (P < 0.05) average egg weight, fertility, hatchability and qualified chick rate, whereas it decreased (P < 0.05) broken egg rate. The Zn concentrations in liver and muscle were significantly higher (P < 0.05) in 80 mg Zn/kg Zn-Gly group than that in ZnSO 4 group. Compared with ZnSO 4 group, 80 mg Zn/kg Zn-Gly group significantly elevated (P < 0.05) the mRNA abundances of metallothionein (MT) and copper-zinc superoxide (Cu-Zn SOD), as well as the Cu-Zn SOD activity and MT concentration in liver. Moreover, the 80 mg Zn/kg Zn-Gly group had higher (P < 0.05) serum T-SOD and Cu-Zn SOD activities than that in the ZnSO 4 group. This study indicated that supplementation of Zn in basal diet improved productive and reproductive performance, Zn concentration and antioxidant status in broiler breeders, and the 80 mg Zn/kg from Zn-Gly was the optimum choice for broiler breeders compared with other levels of Zn from Zn-Gly and 80 mg/kg Zn from ZnSO 4 .

  11. Primary hypothyroidism in dogs is associated with elevated GH release.

    PubMed

    Lee, W M; Diaz-Espineira, M; Mol, J A; Rijnberk, A; Kooistra, H S

    2001-01-01

    The pulsatile secretion patterns of GH were investigated in seven beagle bitches by collecting blood samples every 10 min for 6 h during euthyroidism and 1.5 years after induction of primary hypothyroidism. Hypothyroidism was induced by surgical removal of the thyroid gland and subsequent destruction of any remnant thyroid tissue by oral administration of sodium [(131)I]iodide. Some of the physical changes observed in the dogs with primary hypothyroidism mimicked those of acromegaly. During both euthyroidism and hypothyroidism GH was secreted in a pulsatile fashion. The mean (+/-s.e.m. ) basal plasma GH concentration was significantly higher (P=0.003) in the hypothyroid state (4.1+/-1.6 microg/l) than in the euthyroid state (1.2+/-0.4 microg/l). Likewise, the mean area under the curve (AUC) for GH above the zero-level during hypothyroidism (27.0+/-10.0 microg/lx6 h) was significantly higher (P=0.004) than that during euthyroidism (11.7+/-2.0 microg/l x 6 h). The mean AUC for GH above the baseline was significantly lower (P=0.008) during hypothyroidism (2.4+/-0.8 microg/l x 6 h) than during euthyroidism (4.5+/-1.8 microg/lx6 h), whereas there was no significant difference in GH pulse frequency. The mean plasma IGF-I level was significantly higher (P<0.01) in the hypothyroid state (169+/-45 microg/l) than in the euthyroid (97+/-15 microg/l). The results of this study demonstrate that primary hypothyroidism in dogs is associated with elevated basal GH secretion and less GH secreted in pulses. This elevated GH secretion has endocrine significance as illustrated by elevated plasma IGF-I levels and some physical changes mimicking acromegaly. It is discussed that the increased GH release in hypothyroid dogs may be the result of the absence of a response element for thyroid hormone within the canine pituitary GH gene and alterations in supra-pituitary regulation.

  12. Increased GABA Levels in Medial Prefrontal Cortex of Young Adults with Narcolepsy

    PubMed Central

    Kim, Seog Ju; Lyoo, In Kyoon; Lee, Yujin S.; Sung, Young Hoon; Kim, Hengjun J.; Kim, Jihyun H.; Kim, Kye Hyun; Jeong, Do-Un

    2008-01-01

    Study Objectives: To explore absolute concentrations of brain metabolites including gamma amino-butyric acid (GABA) in the medial prefrontal cortex and basal ganglia of young adults with narcolepsy. Design: Proton magnetic resonance (MR) spectroscopy centered on the medial prefrontal cortex and the basal ganglia was acquired. The absolute concentrations of brain metabolites including GABA and glutamate were assessed and compared between narcoleptic patients and healthy comparison subjects. Setting: Sleep and Chronobiology Center at Seoul National University Hospital; A high strength 3.0 Tesla MR scanner in the Department of Radiology at Seoul National University Hospital. Patients or Participants: Seventeen young adults with a sole diagnosis of HLA DQB1 0602 positive narcolepsy with cataplexy (25.1 ± 4.6 years old) and 17 healthy comparison subjects (26.8 ± 4.8 years old). Interventions: N/A. Measurements and Results: Relative to comparison subjects, narcoleptic patients had higher GABA concentration in the medial prefrontal cortex (t = 4.10, P <0.001). Narcoleptic patients with nocturnal sleep disturbance had higher GABA concentration in the medial prefrontal cortex than those without nocturnal sleep disturbance (t = 2.45, P= 0.03), but had lower GABA concentration than comparison subjects (t = 2.30, P = 0.03). Conclusions: The current study reports that young adults with narcolepsy had a higher GABA concentration in the medial prefrontal cortex, which was more prominent in patients without nocturnal sleep disturbance. Our findings suggest that the medial prefrontal GABA level may be increased in narcolepsy, and the increased medial prefrontal GABA might be a compensatory mechanism to reduce nocturnal sleep disturbances in narcolepsy. Citation: Kim SJ; Lyoo IK; Lee YS; Sung YH; Kim HJ; Kim JH; Kim KH; Jeong DU. Increased GABA levels in medial prefrontal cortex of young adults with narcolepsy. SLEEP 2008;31(3):342-347. PMID:18363310

  13. A Comparison of Difficulty Levels of Vocabulary in First Grade Basal Readers for Preschool Dual Language Learners and Monolingual English Learners

    ERIC Educational Resources Information Center

    Leung, Cynthia B.; Silverman, Rebecca; Nandakumar, Ratna; Qian, Xiaoyu; Hines, Sara

    2011-01-01

    The present study investigated preschoolers' knowledge of vocabulary that appears in first grade basal readers by applying Rasch modeling to data from a researcher-developed receptive picture vocabulary assessment administered to 238 children. Levels of word difficulty for dual language learners (DLLs) and monolingual English learners (MELs) were…

  14. Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    PubMed

    Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

    2016-03-15

    Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. © 2015 UICC.

  15. High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

    PubMed

    Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

    2014-05-01

    Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

  16. Social approach and avoidance behaviour for negative emotions is modulated by endogenous oxytocin and paranoia in schizophrenia.

    PubMed

    Brown, Elliot C; Tas, Cumhur; Kuzu, Duygu; Esen-Danaci, Aysen; Roelofs, Karin; Brüne, Martin

    2014-11-30

    Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Hepatoprotective efficacy of Spirulina platensis against lead-induced oxidative stress and genotoxicity in catfish; Clarias gariepinus.

    PubMed

    Sayed, Alaa El-Din H; El-Sayed, Yasser S; El-Far, Ali H

    2017-09-01

    Lead (Pb) is a toxic environmental pollutant that induces a broad range of biochemical and physiological hazards in living organisms. We investigated the possible hepatoprotective effects of Spirulina platensis (SP) in counteracting the Pb-induced oxidative damage. Ninety-six adult African catfish were allocated into four equal groups. The 1st group (control) fed basal diet while the 2nd group (Pb-treated) fed on basal diet and exposed to 1mg Pb(NO 3 ) 2 /L. The 3rd and 4th groups fed SP-supplemented basal diets at levels of 0.25% and 0.5%, respectively and exposed to Pb. Serum samples were used to analyze hepatic function biomarkers, electrolytes, and oxidant and antioxidant status. Lipid peroxidation and DNA fragmentation were determined in the liver tissues. Pb exposure induced hepatic dysfunction, electrolytes (Na + , K + , Ca +2 , and Cl - ) imbalance, as well a significant decrease in GSH content, and LDH, AChE, SOD, CAT and GST enzymes activity. SP supplementation reverted these biochemical and genetic alterations close to control levels. This amelioration was higher with 0.5% SP and at the 4th week of exposure, showing concentration- and time-dependency. Thus, the current study suggests that SP could protect the catfish liver against lead-induced injury by scavenging ROS, sustaining the antioxidant status and diminishing DNA oxidative damage. The dietary inclusion of SP can be used as a promising protective agent to counteract oxidative stress-mediated diseases and toxicities. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis.

    PubMed

    Stagi, Stefano; di Tommaso, Mariarosaria; Scalini, Perla; Lapi, Elisabetta; Losi, Stefania; Bencini, Erica; Masoni, Fabrizio; Dosa, Laura; Becciani, Sabrina; de Martino, Maurizio

    2016-06-01

    To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Seasonal changes in testosterone and corticosterone levels in four social classes of a desert dwelling sociable rodent.

    PubMed

    Schradin, Carsten

    2008-04-01

    Animals have to adjust their physiology to seasonal changes, in response to variation in food availability, social tactics and reproduction. I compared basal corticosterone and testosterone levels in free ranging striped mouse from a desert habitat, comparing between the sexes, breeding and philopatric non-breeding individuals, and between the breeding and the non-breeding season. I expected differences between breeders and non-breeders and between seasons with high and low food availability. Basal serum corticosterone was measured from 132 different individuals and serum testosterone from 176 different individuals of free living striped mice. Corticosterone and testosterone levels were independent of age, body weight and not influenced by carrying a transmitter. The levels of corticosterone and testosterone declined by approximately 50% from the breeding to the non-breeding season in breeding females as well as non-breeding males and females. In contrast, breeding males showed much lower corticosterone levels during the breeding season than all other classes, and were the only class that showed an increase of corticosterone from the breeding to the non-breeding season. As a result, breeding males had similar corticosterone levels as other social classes during the non-breeding season. During the breeding season, breeding males had much higher testosterone levels than other classes, which decreased significantly from the breeding to the non-breeding season. My results support the prediction that corticosterone decreases during periods of low food abundance. Variation in the pattern of hormonal secretion in striped mice might assist them to cope with seasonal changes in energy demand in a desert habitat.

  20. Yield and size of oyster mushroom grown on rice/wheat straw basal substrate supplemented with cotton seed hull.

    PubMed

    Yang, Wenjie; Guo, Fengling; Wan, Zhengjie

    2013-10-01

    Oyster mushroom (Pleurotus ostreatus) was cultivated on rice straw basal substrate, wheat straw basal substrate, cotton seed hull basal substrate, and wheat straw or rice straw supplemented with different proportions (15%, 30%, and 45% in rice straw substrate, 20%, 30%, and 40% in wheat straw substrate) of cotton seed hull to find a cost effective substrate. The effect of autoclaved sterilized and non-sterilized substrate on growth and yield of oyster mushroom was also examined. Results indicated that for both sterilized substrate and non-sterilized substrate, oyster mushroom on rice straw and wheat basal substrate have faster mycelial growth rate, comparatively poor surface mycelial density, shorter total colonization period and days from bag opening to primordia formation, lower yield and biological efficiency, lower mushroom weight, longer stipe length and smaller cap diameter than that on cotton seed hull basal substrate. The addition of cotton seed hull to rice straw and wheat straw substrate slowed spawn running, primordial development and fruit body formation. However, increasing the amount of cotton seed hull can increase the uniformity and white of mycelium, yield and biological efficiency, and increase mushroom weight, enlarge cap diameter and shorten stipe length. Compared to the sterilized substrate, the non-sterilized substrate had comparatively higher mycelial growth rate, shorter total colonization period and days from bag opening to primordia formation. However, the non-sterilized substrate did not gave significantly higher mushroom yield and biological efficiency than the sterilized substrate, but some undesirable characteristics, i.e. smaller mushroom cap diameter and relatively long stipe length.

  1. Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

    PubMed

    Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

    2016-08-01

    Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

  2. Neonatal nociception elevated baseline blood pressure and attenuated cardiovascular responsiveness to noxious stress in adult rats.

    PubMed

    Chu, Ya-Chun; Yang, Cheryl C H; Lin, Ho-Tien; Chen, Pin-Tarng; Chang, Kuang-Yi; Yang, Shun-Chin; Kuo, Terry B J

    2012-10-01

    Neonatal nociception has significant long-term effects on sensory perception in adult animals. Although neonatal adverse experience affect future responsiveness to stressors is documented, little is known about the involvement of early nociceptive experiences in the susceptibility to subsequent nociceptive stress exposure during adulthood. The aim of this study is to explore the developmental change in cardiovascular regulating activity in adult rats that had been subjected to neonatal nociceptive insults. To address this question, we treated neonatal rats with an intraplantar injection of saline (control) or carrageenan at postnatal day 1. The carrageenan-treated rats exhibited generalized hypoalgesia at basal state, and localized hyperalgesia after re-nociceptive challenge induced by intraplantar injections of complete Freund's adjuvant (CFA) as adults. Then we recorded baseline cardiovascular variables and 24-h responsiveness to an injection of CFA in the free-moving adult rats with telemetric technique. The carrageenan-treated rats showed significantly higher basal blood pressures (110.3±3.16 vs. control 97.0±4.28 mmHg). In control animals, baroreceptor reflex sensitivity (BRS) decreased, sympathetic vasomotor activity increased, and parasympathetic activity was inhibited after CFA injection. Blood pressure elevation was evident (107.0±2.75 vs. pre-injection 97.0±4.28 mmHg). Comparatively, the carrageenan-treated rats showed a higher BRS (BrrLF 1.03±0.09 vs. control 0.70±0.06 ms/mmHg) and higher parasympathetic activity [0.93±0.17 vs. control 0.32±0.02 ln(ms²)] after CFA injection. The change in blood pressure is negligible (111.9±4.05 vs. pre-injection 110.3±3.16 mmHg). Our research has shown that neonatal nociception alters future pain sensation, raises basal blood pressure level, and attenuates cardiovascular responsiveness to nociceptive stress in adult rats. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

  3. Comparison of dynamic change of egg selenium deposition after feeding sodium selenite or selenium-enriched yeast.

    PubMed

    Lu, J; Qu, L; Shen, M M; Hu, Y P; Guo, J; Dou, T C; Wang, K H

    2018-05-19

    The aim of this study was to compare the dynamic change of egg selenium (Se) deposition after sodium selenite (SS) or selenium-enriched yeast (SY) supplementation for 1, 3, 5, 7, 14, 21, 28, 56, and 84 d. A total of 576 32-wk-old Hy-Line Brown laying hens were randomly assigned to 3 groups (192 laying hens per group) with 6 replicates, and fed a basal diet (without Se supplementation) or basal diets with 0.3 mg/kg of Se from SS or 0.3 mg/kg of Se from SY, respectively. The results showed that the Se concentrations in the eggs from hens fed a SY-supplemented diet were significantly higher (P < 0.001) than those from hens fed a SS-supplemented diet or a basal diet after 3 d. And the Se concentrations in the eggs from hens fed a SS-supplemented diet were significantly higher (P < 0.001) than those from hens fed a basal diet after 14 d. There was a positive linear and quadratic correlation between Se concentrations in the eggs from hens fed a SY-supplemented diet (r2 = 0.782, P < 0.001; r2 = 0.837, P < 0.001) or SS-supplemented diet (r2 = 0.355, P < 0.001; r2 = 0.413, P < 0.001) and number of feeding days. The Se concentrations in the breasts from hens fed a SY-supplemented diet were 126.98% higher (P < 0.001) than those from hens fed a SS-supplemented diet, and were 299.44% higher (P < 0.001) than those from hens fed a basal diet after the 84-d feeding period. In conclusion, the dietary Se was gradually transferred into eggs with the extension of the experimental duration. The deposition rate of Se in the eggs from hens fed a SY-supplemented diet was much more rapid than that from hens fed a SS-supplemented diet, and the organic Se from SY had higher bioavailability as compared to inorganic Se from SS.

  4. Clinical aspects of leptin.

    PubMed

    Sinha, M K; Caro, J F

    1998-01-01

    Hyperleptinemia is an essential feature of human obesity. Total body fat mass > % body fat > BMI are the best predictors of circulating leptin levels. Although ob gene is differentially expressed in different fat compartments, apart from total body fat, upper or lower body adiposity or visceral fat does not influence basal leptin levels. Similarly, age, basal glucose levels, and ethnicity do not influence circulating leptin levels. Only in insulin-sensitive individuals do basal levels of insulin and leptin correlate positively even after factoring in body fat. Diabetes does not influence leptin secretion in both lean and obese subjects per se. Independent of adiposity, leptin levels are higher in women than in men. This sexual dimorphism is also present in adolescent children. In eating disorders anorexia nervosa and bulimea nervosa, leptin levels are not upregulated but simply reflect BMI and probably body fat. In spite of strong correlation between body fat and leptin levels, there is great heterogeneity in leptin levels at any given index of body fat. About 5% of obese populations can be regarded as "relatively" leptin deficient which could benefit from leptin therapy. Leptin has dual regulation in human physiology. During the periods of weight maintenance, when energy intake and energy output are equal, leptin levels reflect total bodyfat mass. However, in conditions of negative (weight-loss programs) and positive (weight-gain programs) energy balances, the changes in leptin levels function as a sensor of energy imbalance. This latter phenomenon is best illustrated by short-term fasting and overfeeding experiments. Within 24 h of fasting leptin levels decline to approximately 30% of initial basal values. Massive overfeeding over a 12-h period increases leptin levels by approximately 50% of initial basal values. Meal ingestion does not acutely regulate serum leptin levels. A few studies have shown a modest increase in leptin secretion at supraphysiological insulin concentrations 4-6 h following insulin infusion. Under in vitro conditions, insulin stimulates leptin production only after four days in primary cultures of human adipocytes, which is apparently due to its trophic effects and an increased fat-cell size. Similar to other hormones, leptin secretion shows circadian rhythm and oscillatory pattern. The nocturnal rise of leptin secretion is entrained to mealtime probably due to cumulative hyperinsulinemia of the entire day. Like other growth factors and cytokines, leptin binding proteins including soluble leptin receptor are present in human serum. In lean subjects, the majority of leptin circulates in the bound form whereas in obese subjects, the majority of leptin is present in the free form. When free-leptin levels are compared between lean and obese subjects, even more pronounced hyperleptinemia in obesity is observed than that reported by measuring total leptin levels. During short-term fasting, free-leptin levels in lean subjects decrease in much greater proportion than those in obese subjects. In lean subjects with a relatively small energy store and particularly during food deprivation, leptin circulating predominantly in the bound form could be the mechanism to restrict its availability to hypothalamic leptin receptors for inhibiting leptin's effect on food intake and/or energy metabolism. Unlike marked changes in serum leptin, CSF leptin is only modestly increased in obese subjects and the CSF leptin/serum leptin ratio decreases logarithmically with increasing BMI. If CSF leptin levels are any indication of brain interstitial fluid levels, then hypothalami of obese subjects are not exposed to abnormally elevated leptin concentrations. In the presence of normal leptin receptor (functional long form, i.e., OB-Rb) mRNA expression and in the absence of leptin receptor gene mutations, it is logical to assume defective leptin signaling and/or impaired affector system(s) are the likely causes of leptin resistance in

  5. Correlates of elemental-isotopic composition of stream fishes: the importance of land-use, species identity and body size.

    PubMed

    Montaña, C G; Schalk, C M

    2018-04-01

    The isotopic (δ 13 C and δ 15 N) and stoichiometric (C:N:P) compositions of four fish species (Family Centrarchidae: Lepomis auritus, Lepomis cyanellus; Family Cyprinidae: Nocomis leptocephalus, Semotilus atromaculatus) were examined across four North Carolina Piedmont streams arrayed along an urbanization gradient. Both isotopic and stoichiometric composition of fishes appeared to track changes occurring in basal resource availability. Values of δ 13 C of basal resources and consumers were more enriched at the most urbanized streams. Similarly, basal resources and consumers were δ 15 N-enriched at more urbanized streams. Basal resource stoichiometry varied across streams, with periphyton being the most variable. Primary consumers stoichiometry also differed across streams. Intraspecific variation in fish stoichiometry correlated with the degree of urbanization, as the two cyprinids had higher N content and L. cyanellus had higher P content in more urbanized streams, probably due to enrichment of basal resources. Intrinsic factors, specifically species identity and body size also affected stoichiometric variation. Phosphorus (P) content increased significantly with body size in centrarchids, but not in cyprinids. These results suggest that although species identity and body size are important predictors of elemental stoichiometry, the complex nature of altered urban streams may yield imbalances in the elemental composition of consumers via their food resources. © 2018 The Fisheries Society of the British Isles.

  6. Detection of basal acetylcholine release in the microdialysis of rat frontal cortex by high-performance liquid chromatography using a horseradish peroxidase-osmium redox polymer electrode with pre-enzyme reactor.

    PubMed

    Kato, T; Liu, J K; Yamamoto, K; Osborne, P G; Niwa, O

    1996-06-28

    To determine the basal acetylcholine level in the dialysate of rat frontal cortex, a horseradish peroxidase-osmium redox polymer-modified glassy carbon electrode (HRP-GCE) was employed instead of the conventional platinum electrode used in high-performance liquid chromatography-electrochemical detection (HPLC-ED). In initial experiments, an oxidizable unknown compound interfered with the detection of basal acetylcholine release on HPLC-HRP-GCE. An immobilized peroxidase-choline oxidase precolumn (pre-reactor) was included in the HPLC system, to eliminate the interference from the unknown compound. This combination could detect less than 10 fmol of standard acetylcholine and basal acetylcholine levels in the dialysate from a conventional concentric design microdialysis probe, without the use of cholinesterase inhibitor, and may facilitate physiological investigation of cholinergic neuronal activity in the central nervous system.

  7. Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels.

    PubMed

    Haley, R W; Fleckenstein, J L; Marshall, W W; McDonald, G G; Kramer, G L; Petty, F

    2000-09-01

    Many complaints of Gulf War veterans are compatible with a neurologic illness involving the basal ganglia. In 12 veterans with Haley Gulf War syndrome 2 and in 15 healthy control veterans of similar age, sex, and educational level, we assessed functioning neuronal mass in both basal ganglia by measuring the ratio of N-acetyl-aspartate to creatine with proton magnetic resonance spectroscopy. Central dopamine activity was assessed by measuring the ratio of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenlyglycol (MHPG). The logarithm of the age-standardized HVA/MHPG ratio was inversely associated with functioning neuronal mass in the left basal ganglia (R(2) = 0.56; F(1,27) = 33.82; P<.001) but not with that in the right (R(2) = 0. 04; F(1,26) = 1.09; P =.30). Controlling for age, renal clearances of creatinine and weak organic anions, handedness, and smoking did not substantially alter the associations. The reduction in functioning neuronal mass in the left basal ganglia of these veterans with Gulf War syndrome seems to have altered central dopamine production in a lateralized pattern. This finding supports the theory that Gulf War syndrome is a neurologic illness, in part related to injury to dopaminergic neurons in the basal ganglia.

  8. Temperature-induced physiological stress and reproductive characteristics of the migratory seahorse Hippocampus erectus during a thermal stress simulation.

    PubMed

    Qin, Geng; Johnson, Cara; Zhang, Yuan; Zhang, Huixian; Yin, Jianping; Miller, Glen; Turingan, Ralph G; Guisbert, Eric; Lin, Qiang

    2018-05-15

    Inshore-offshore migration occurs frequently in seahorse species either because of prey opportunities or because it is driven by reproduction, and variations in water temperature may dramatically change migratory seahorse behavior and physiology. The present study investigated the behavioral and physiological responses of the lined seahorse Hippocampus erectus under thermal stress and evaluated the potential effects of different temperatures on its reproduction. The results showed that the thermal tolerance of the seahorses was time dependent. Acute thermal stress (30°C, 2-10 hours) increased the basal metabolic rate (breathing rate) and the expression of stress response genes ( Hsp genes) significantly and further stimulated seahorse appetite. Chronic thermal treatment (30°C, 4 weeks) led to a persistently higher basal metabolic rate, higher stress response gene expression, and higher mortality, indicating that the seahorses could not acclimate to chronic thermal stress and might experience massive mortality due to excessive basal metabolic rates and stress damage. Additionally, no significant negative effects on gonad development or reproductive endocrine regulation genes were observed in response to chronic thermal stress, suggesting that seahorse reproductive behavior could adapt to higher-temperature conditions during migration and within seahorse breeding grounds. In conclusion, this simulation experiment indicated that temperature variations during inshore-offshore migration have no effect on reproduction but promote basal metabolic rates and stress responses significantly. Therefore, we suggest that the high observed tolerance of seahorse reproduction was in line with the inshore-offshore reproductive migration pattern of lined seahorse. © 2018. Published by The Company of Biologists Ltd.

  9. Effect of long term high altitude exposure on cardiovascular autonomic adjustment during rest and post-exercise recovery.

    PubMed

    Bhattarai, Prem; Paudel, Bishnu H; Thakur, Dilip; Bhattarai, Balkrishna; Subedi, Bijay; Khadka, Rita

    2018-01-01

    Despite the successful adaptation to high altitude, some differences do occur due to long term exposure to the hypoxic environment. The effect of long term high altitude exposure on cardiac autonomic adjustment during basal and post-exercise recovery is less known. Thus we aimed to study the differences in basal cardiac autonomic adjustment and its response to exercise in highlanders and to compare it with lowlanders. The study was conducted on 29 healthy highlander males who were born and brought up at altitude of 3000 m and above from the sea level, their cardiac autonomic adjustment was compared with age, sex, physical activity and ethnicity-matched 29 healthy lowlanders using Heart Rate Variability (HRV) during rest and recovery from sub-maximal exercise (3 m step test). Intergroup comparison between the highlanders and lowlanders and intragroup comparison between the rest and the postexercise recovery conditions were done. Resting heart rate and HRV during rest was comparable between the groups. However, heart rate recovery after 3 min step test was faster in highlanders ( p  < 0.05) along with significantly higher LF power and total power during the recovery phase. Intragroup comparison of highlanders showed higher SDNN ( p  < 0.05) and lower LF/HF ratio ( p  < 0.05) during recovery phase compared to rest which was not significantly different in two phases in lowlanders. Further highlander showed complete recovery of RMSSD, NN50, pNN50 and HF power back to resting level within five minutes, whereas, these parameters failed to return back to resting level in lowlanders within the same time frame. Highlanders completely recovered back to their resting state within five minutes from cessation of step test with parasympathetic reactivation; however, recovery in lowlanders was delayed.

  10. Differential regulation of lipid and protein metabolism in obese vs. lean subjects before and after a 72-h fast.

    PubMed

    Bak, Ann Mosegaard; Møller, Andreas Buch; Vendelbo, Mikkel Holm; Nielsen, Thomas Svava; Viggers, Rikke; Rungby, Jørgen; Pedersen, Steen Bønløkke; Jørgensen, Jens Otto Lunde; Jessen, Niels; Møller, Niels

    2016-07-01

    Increased availability of lipids may conserve muscle protein during catabolic stress. Our study was designed to define 1) intracellular mechanisms leading to increased lipolysis and 2) whether this scenario is associated with decreased amino acid and urea fluxes, and decreased muscle amino acid release in obese subjects under basal and fasting conditions. We therefore studied nine lean and nine obese subjects twice, after 12 and 72 h of fasting, using measurements of mRNA and protein expression and phosphorylation of lipolytic and protein metabolic signaling molecules in fat and muscle together with whole body and forearm tracer techniques. Obese subjects displayed increased whole body lipolysis, decreased urea production rates, and decreased forearm muscle protein breakdown per 100 ml of forearm tissue, differences that persisted after 72 h of fasting. Lipolysis per fat mass unit was reduced in obese subjects and, correspondingly, adipose tissue hormone-sensitive lipase (HSL) phosphorylation and mRNA and protein levels of the adipose triglyceride lipase (ATGL) coactivator CGI58 were decreased. Fasting resulted in higher HSL phosphorylations and lower protein levels of the ATGL inhibitor G0S2. Muscle protein expressions of mammalian target of rapamycin (mTOR) and 4EBP1 were lower in obese subjects, and MuRf1 mRNA was higher with fasting in lean but not obese subjects. Phosphorylation and signaling of mTOR decreased with fasting in both groups, whereas ULK1 protein and mRNA levels increased. In summary, obese subjects exhibit increased lipolysis due to a large fat mass with blunted prolipolytic signaling, together with decreased urea and amino acid fluxes both in the basal and 72-h fasted state; this is compatible with preservation of muscle and whole body protein. Copyright © 2016 the American Physiological Society.

  11. The benefits of ω-3 supplementation depend on adiponectin basal level and adiponectin increase after the supplementation: A randomized clinical trial.

    PubMed

    Barbosa, Milena Maria de Araújo Lima; Melo, Alexandra Lorenzzi Trinanes Raposo de; Damasceno, Nágila Raquel Teixeira

    2017-02-01

    The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes. In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin). After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both). Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. External pancreatic secretion after bombesin infusion in man.

    PubMed

    Basso, N; Giri, S; Improta, G; Lezoche, E; Melchiorri, P; Percoco, M; Speranza, V

    1975-12-01

    The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon.

  13. External pancreatic secretion after bombesin infusion in man.

    PubMed Central

    Basso, N; Giri, S; Improta, G; Lezoche, E; Melchiorri, P; Percoco, M; Speranza, V

    1975-01-01

    The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon. PMID:1218823

  14. Parkinson's disease as a system-level disorder.

    PubMed

    Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

    2016-01-01

    Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson's disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson's disease as caused by the dysfunction of the entire basal ganglia-cortex-cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson's disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed.

  15. Effect of dietary vitamin C on the growth performance and innate immunity of juvenile cobia (Rachycentron canadum).

    PubMed

    Zhou, Qicun; Wang, Ligai; Wang, Hualang; Xie, Fengjun; Wang, Tuo

    2012-06-01

    This study was conducted to evaluate the effects of dietary vitamin C on growth performance, hematologic parameters and innate immune responses in juvenile cobia, Rachycentron canadum. Seven practical diets were formulated to contain 0.0 (as the basal diet), 13.6, 27.2, 54.4, 96.6, 193.4 and 386.5 mg ascorbic acid equivalent kg(-1) diet. Each diet was fed to triplicate groups of juvenile cobia with initial body weight of 5.5 g in 500-L cylindrical fiberglass tank. The results of 8 weeks feeding trial showed that typical vitamin C-deficient signs such as spinal deformation and body nigrescence were observed in the fish fed the basal diet. Fish fed the basal diet had significantly lower weight gain, specific growth rate (SGR), protein efficiency ratio (PER) and feed efficiency (FE) than those fed the diets supplemented with vitamin C, but no significant differences were observed among diets supplemented with vitamin C. However, survival rate was significantly affected by the dietary vitamin C levels, fish fed the basal diet had lower survival rate than those fed the diets supplemented with vitamin C. The ascorbic acid concentration in liver was correlated positively with the dietary vitamin C levels, however, the thiobarbituric acid reactive substances (TBARS) concentrations in liver was not significantly affected by the dietary vitamin C levels, although, fish fed the basal diet had the highest TBARS values among all treatments. The activities of serum lysozyme, superoxide dismutase (SOD), alkaline phophatase (AKP) and total immunoglobulin (Ig) were significantly influenced by the dietary vitamin C levels, fish fed the basal diet had lower lysozyme, SOD, AKP and total Ig than those fed diets supplemented with vitamin C. The serum glucose and triglyceride concentrations were significantly affected by the dietary vitamin C levels. Fish fed the basal diet had lower red blood cell and hemoglobin values than those fed the vitamin C supplemented diets. The challenge experiment with Vibrio harveyi showed that lower cumulative survival was in fish fed the unsupplemented diet, the cumulative survival were significantly increased with increase of the dietary ascorbic acid levels from 13.6 to 96.6 mg kg(-1), while the cumulative survival reached plateau when dietary ascorbic acid levels increased from 96.6 to 386.5 mg kg(-1). These results indicated that dietary vitamin C did significantly influence on growth performance and immune response of juvenile cobia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Changes of free, soluble conjugated and bound polyamine titers of jojoba explants under sodium chloride salinity in vitro.

    PubMed

    Roussos, Peter A; Pontikis, Constantine A

    2007-07-01

    Jojoba (Simmondsia chinensis L.) single node explants were cultured in a basal medium supplemented with 17.8 microM 6-benzyladenine and four levels of sodium chloride concentration (0, 56.41, 112.82 and 169.23 mM). The free, the soluble conjugated and the insoluble bound forms of polyamines (PAs) (putrescine (Put), spermidine (Spd) and spermine (Spm)) were determined monthly during a 3-month proliferation stage. Free Put and Spd were found in higher levels in the control treatment, while Spm content was higher in the salt treatments. All soluble conjugated PAs were found to be in lower concentrations in explants growing on medium supplemented with salt, while the opposite was true for the insoluble bound PAs. It appeared that certain PAs and PAs forms could play a significant role in the adaptation mechanism of jojoba under saline conditions.

  17. Bifurcation phenomena in an impulsive model of non-basal testosterone regulation

    NASA Astrophysics Data System (ADS)

    Zhusubaliyev, Zhanybai T.; Churilov, Alexander N.; Medvedev, Alexander

    2012-03-01

    Complex nonlinear dynamics in a recent mathematical model of non-basal testosterone regulation are investigated. In agreement with biological evidence, the pulsatile (non-basal) secretion of testosterone is modeled by frequency and amplitude modulated feedback. It is shown that, in addition to already known periodic motions with one and two pulses in the least period of a closed-loop system solution, cycles of higher periodicity and chaos are present in the model in hand. The broad range of exhibited dynamic behaviors makes the model highly promising in model-based signal processing of hormone data.

  18. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes.

    PubMed

    Zana, Marianna; Szécsényi, Anita; Czibula, Agnes; Bjelik, Annamária; Juhász, Anna; Rimanóczy, Agnes; Szabó, Krisztina; Vetró, Agnes; Szucs, Péter; Várkonyi, Agnes; Pákáski, Magdolna; Boda, Krisztina; Raskó, István; Janka, Zoltán; Kálmán, János

    2006-06-30

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n=7) and adults (n=18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

  19. PI3K is required for both basal and LPA-induced DNA synthesis in oral carcinoma cells.

    PubMed

    Aasrum, Monica; Tjomsland, Vegard; Thoresen, G Hege; De Angelis, Paula M; Christoffersen, Thoralf; Brusevold, Ingvild J

    2016-07-01

    The glycerophospholipid lysophosphatidic acid (LPA), which is present in most tissues and in high concentrations in saliva, may exert profound effects on oral cancer cells. We have investigated mitogenic signalling induced by LPA in the two oral carcinoma cell lines, D2 and E10, focusing on the role of EGFR transactivation and downstream pathways. Two oral squamous carcinoma cell lines, D2 and E10, were analysed for effects of LPA on signalling pathways and induction of DNA synthesis. Pathway activation was investigated by examining phosphorylation of signalling proteins and by the use of specific pathway inhibitors. The D2 cells had higher levels of activated signalling proteins and higher DNA synthesis activity in the basal condition than E10 cells. EGF did not induce proliferation in D2 cells, whereas LPA induced proliferation in both cell lines, by mechanisms depending on EGFR transactivation. Release of EGFR ligands was involved in basal and LPA-induced proliferation in both D2 and E10 cells. The proliferation in D2 cells was dependent on the PI3K/Akt pathway, but not the MEK/ERK pathway. In E10 cells, the PI3K/Akt, MEK/ERK and p38 pathways were all involved in the proliferation. Transactivation of EGFR is required for LPA-induced DNA synthesis in D2 and E10 cells. Our results also show that although proliferation of oral carcinoma cells is regulated by several pathways, and differentially in E10 and D2 cells, the PI3K pathway has a crucial role in both cell lines. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

    PubMed

    Okajima, Fumitaka; Nakamura, Yuko; Yamaguchi, Yuji; Shuto, Yuki; Kato, Katsuhito; Sugihara, Hitoshi; Emoto, Naoya

    2018-04-04

    Although reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported. Forty patients with type 2 diabetes who were admitted for glycemic control with basal-bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100-120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge. In the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033). In type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100. UMIN clinical trials registry (UMIN000023360).

  1. Polychlorinated Biphenyl-Xenobiotic Nuclear Receptor Interactions Regulate Energy Metabolism, Behavior, and Inflammation in Non-alcoholic-Steatohepatitis.

    PubMed

    Wahlang, Banrida; Prough, Russell A; Falkner, K Cameron; Hardesty, Josiah E; Song, Ming; Clair, Heather B; Clark, Barbara J; States, J Christopher; Arteel, Gavin E; Cave, Matthew C

    2016-02-01

    Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis and activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate PCB interactions with the pregnane-xenobiotic receptor (Pxr: Nr1i2) and constitutive androstane receptor (Car: Nr1i3) in NASH. Wild type C57Bl/6 (WT), Pxr(-/-) and Car(-/-) mice were fed the high fat diet (42% milk fat) and exposed to a single dose of Aroclor 1260 (20 mg/kg) in this 12-week study. Metabolic phenotyping and analysis of serum, liver, and adipose was performed. Steatohepatitis was pathologically similar in all Aroclor-exposed groups, while Pxr(-/-) mice displayed higher basal pro-inflammatory cytokine levels. Pxr repressed Car expression as evident by increased basal Car/Cyp2b10 expression in Pxr(-/-) mice. Both Pxr(-/-) and Car(-/-) mice showed decreased basal respiratory exchange rate (RER) consistent with preferential lipid metabolism. Aroclor increased RER and carbohydrate metabolism, associated with increased light cycle activity in both knockouts, and decreased food consumption in the Car(-/-) mice. Aroclor exposure improved insulin sensitivity in WT mice but not glucose tolerance. The Aroclor-exposed, Pxr(-/-) mice displayed increased gluconeogenic gene expression. Lipid-oxidative gene expression was higher in WT and Pxr(-/-) mice although RER was not changed, suggesting PCB-mediated mitochondrial dysfunction. Therefore, Pxr and Car regulated inflammation, behavior, and energy metabolism in PCB-mediated NASH. Future studies should address the 'off-target' effects of PCBs in steatohepatitis. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

  2. The Whole Language Approach versus the Basal Reading Approach and the Effects on Reading Achievement Scores.

    ERIC Educational Resources Information Center

    Puorro, Michelle

    A study examined two first-grade classrooms implementing the whole language approach and two utilizing the basal reading approach to determine the differences, if any, between the treatments. The hypothesis was that the whole language reading approach when combined with a phonics program would not result in higher test scores on a standardized…

  3. Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients.

    PubMed

    Bhukal, Ishwar; Thimmarayan, Gokul; Bala, Indu; Solanki, Sohan Lal; Samra, Tanvir

    2014-11-01

    Significant increase in serum triglyceride (ST) concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT). Though, medium chain triglyceride-LCT (MCT-LCT) propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol. A total of 40 children were randomized into two groups of 20 each; Group I were induced with 1% LCT propofol (3 mg/kg) and Group II with 1% medium and LCT propofol and maintained with descalating dose of 20.15 and 10 mg/kg/h at 10 min intervals. Blood samples for ST concentration were obtained before induction of anesthesia, at the end of propofol infusion and 4 h after terminating propofol infusion. ST levels were raised significantly above the basal values in both the groups but the rise was significantly higher in Group I (P < 0.05). Four hours after stopping propofol infusion the triglyceride levels were similar to the basal values in Group II, whereas in Group I the values were significantly greater than the baseline (P < 0.05) as well as those of Group II (P < 0.05). No clinically significant adverse effect of hypertriglyceridemia was observed. Even short term anesthesia with LCT and MCT-LCT propofol (1%) leads to elevated ST levels. The increase in ST levels is less with MCT-LCT propofol and elimination of triglyceride is also rapid after terminating MCT-LCT propofol infusion.

  4. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome

    PubMed Central

    Arbib, Michael A.; Baldassarre, Gianluca

    2017-01-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area. PMID:28358814

  5. Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome.

    PubMed

    Caligiore, Daniele; Mannella, Francesco; Arbib, Michael A; Baldassarre, Gianluca

    2017-03-01

    Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated. These predictions could be important in identifying new brain target areas for future therapies. Finally, the model represents the first computational attempt to study the role of the recently discovered basal ganglia-cerebellar anatomical links. Studying this non-cortex-mediated basal ganglia-cerebellar interaction could radically change our perspective about how these areas interact with each other and with the cortex. Overall, the model also shows the utility of casting Tourette syndrome within a system-level perspective rather than viewing it as related to the dysfunction of a single brain area.

  6. K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes.

    PubMed

    Tigges, G A; Philibert, R A; Dutton, G R

    1990-10-30

    Hypothalamic astrocytes in culture released taurine, a suspected inhibitory amino acid neurotransmitter/neuromodulator/osmoregulator, in response to isoosmotically increasing extracellular K+ in a dose-dependent fashion. In the absence of added Ca2+, basal release levels rose to approach those obtained after exposure to 60 mM K+ in the presence of 2.5 mM Ca2+, and were only partially lowered by the addition of 10 mM Mg2+. Stimulation with K+ (60 mM) did not further increase taurine efflux above the high basal levels seen in the absence of Ca2+. Under standard conditions complete replacement of Na+ with choline Cl had little effect on basal taurine release, but reduced K(+)-evoked (60 mM) efflux by 60%. The temperature dependence of the basal levels of taurine released from hypothalamic astrocytes was similar to that seen for cultured cerebellar astrocytes and neurons over the range 5-50 degrees C. Taurine release increased from 5 to 15 degrees C, remained constant between 15 and 33 degrees C, decreased between 33 and 37 degrees C and increased thereafter. The infection point of increased basal taurine release seen around 37 degrees C (most prominent in astrocytes), may be of physiological significance. Results presented also show that the ion (Na+, Ca2+ and K+) sensitivities of taurine efflux for cultured hypothalamic astrocytes are similar to those previously reported for cultured astrocytes from the cerebellum.

  7. Basal and dynamic relationships between implicit power motivation and estradiol in women.

    PubMed

    Stanton, Steven J; Schultheiss, Oliver C

    2007-12-01

    This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

  8. Striatal cell signaling in chronically food-restricted rats under basal conditions and in response to brief handling.

    PubMed

    Pan, Yan; Siregar, Ermanda; Carr, Kenneth D

    2006-01-30

    Chronic food restriction increases exploratory behavior, cognitive function, and the rewarding effects of abused drugs. Recently, striatal neuroadaptations that may be involved in these effects were observed. Specifically, D-1 dopamine (DA) receptor agonist challenge produced stronger activation of extracellular signal-regulated kinase (ERK), calcium-calmodulin-dependent kinase II (CaMKII), and the nuclear transcription factor cAMP response element binding protein (CREB) in nucleus accumbens (NAc) of food-restricted (FR) relative to ad libitum fed (AL) rats. Further, when FR rats were injected intracerebroventricularly (i.c.v.) with vehicle (saline) they displayed stronger activation of c-Jun N-terminal protein kinase (JNK), ERK and CaMKII than did AL rats. It is not known to what extent the latter effects represent the basal state of FR rats or an amplified response to the brief handling involved in the i.c.v. injection procedure. Using Western blotting it was found that basal phospho-JNK is higher in caudate-putamen (CPu) and NAc of FR relative to AL rats. Interestingly, brief handling decreased phospho-JNK levels in FR subjects. Basal phospho-ERK1/2 also tended to be elevated in CPu and NAc of FR rats but the elevation was not significant. However, phospho-MEK--the activated kinase upstream of ERK1/2--was significantly elevated in NAc of FR rats. Neither ERK1/2 nor MEK were activated by brief handling. CaMKII was selectively activated by handling in NAc of FR rats, suggesting a state-dependent response to a salient event. Given the established involvement of mitogen-activated protein kinase (MAPK) and CaMKII in synaptic plasticity, learning and memory, the increase in basal phospho-MEK and hyperresponsiveness of CaMKII in NAc may represent adaptive cellular responses to persistent negative energy balance that facilitate associative learning in connection with food-seeking.

  9. Gentamicin concentration gradients in scala tympani perilymph following systemic applications

    PubMed Central

    Hahn, Hartmut; Salt, Alec N.; Schumacher, Ulrike; Plontke, Stefan K.

    2013-01-01

    In prior studies it was shown that round window membrane (RWM) application of gentamicin produced a robust baso-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Meniere’s disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications. Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg/bw over a period of three hours or as a 300 mg/kg/bw subcutaneous bolus injection. Three and five hours after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively. Ten sequential 1 μL-perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay. In contrast to local RWM delivery, systemic application of gentamicin resulted in highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with amount of drug applied and time before sampling. While the basal-apical gradient measured after local drug applications to the RW niche is likely the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of scala tympani relative to endolymph in the apical turns. PMID:24192668

  10. Impairment of the proximal to distal tonic gradient in the human diabetic stomach.

    PubMed

    Min, Y W; Hong, Y S; Ko, E-J; Lee, J Y; Min, B-H; Sohn, T S; Kim, J J; Rhee, P-L

    2014-02-01

    Little has been known about the contractile characteristics of diabetic stomach. We investigated spontaneous contractions and responses to acetylcholine in the gastric muscle in diabetic patients and non-diabetic control subjects according to the region of stomach. Gastric specimens were obtained from 26 diabetics and 55 controls who underwent gastrectomy at Samsung Medical Center between February 2008 and November 2011. Isometric force measurements were performed using circular muscle strips from the different regions of stomach under basal condition and in response to acetylcholine. Basal tone of control was higher in the proximal stomach than in the distal (0.63 g vs 0.46 g, p = 0.027). However, in diabetics, basal tone was not significantly different between the proximal and distal stomach (0.75 g vs 0.62 g, p = 0.32). The distal stomach of diabetics had higher basal tone and lower frequency than that of control (0.62 g vs 0.46 g, p = 0.049 and 4.0/min vs 4.9/min, p = 0.049, respectively). After exposure to acetylcholine, dose-dependent increases of basal tone, peak, and area under the curve (AUC) were noticed in both proximal and distal stomach of the two groups. In the proximal stomach, however, the dose-dependent increase of basal tone and AUC was less prominent in diabetics than in control. On the contrary to control, the proximal to distal tonic gradient was not observed in diabetic stomach. Diabetic stomach also had lower frequency of spontaneous contraction in the distal stomach and less acetylcholine-induced positive inotropic effect in the proximal stomach than control. © 2013 John Wiley & Sons Ltd.

  11. Influence of basal-plane dislocation structures on expansion of single Shockley-type stacking faults in forward-current degradation of 4H-SiC p-i-n diodes

    NASA Astrophysics Data System (ADS)

    Hayashi, Shohei; Yamashita, Tamotsu; Senzaki, Junji; Miyazato, Masaki; Ryo, Mina; Miyajima, Masaaki; Kato, Tomohisa; Yonezawa, Yoshiyuki; Kojima, Kazutoshi; Okumura, Hajime

    2018-04-01

    The origin of expanded single Shockley-type stacking faults in forward-current degradation of 4H-SiC p-i-n diodes was investigated by the stress-current test. At a stress-current density lower than 25 A cm-2, triangular stacking faults were formed from basal-plane dislocations in the epitaxial layer. At a stress-current density higher than 350 A cm-2, both triangular and long-zone-shaped stacking faults were formed from basal-plane dislocations that converted into threading edge dislocations near the interface between the epitaxial layer and the substrate. In addition, the conversion depth of basal-plane dislocations that expanded into the stacking fault was inside the substrate deeper than the interface. These results indicate that the conversion depth of basal-plane dislocations strongly affects the threshold stress-current density at which the expansion of stacking faults occurs.

  12. Invasive pathogen threatens bird-pine mutualism: implications for sustaining a high-elevation ecosystem.

    PubMed

    McKinney, Shawn T; Fiedler, Carl E; Tomback, Diana F

    2009-04-01

    Human-caused disruptions to seed-dispersal mutualisms increase the extinction risk for both plant and animal species. Large-seeded plants can be particularly vulnerable due to highly specialized dispersal systems and no compensatory regeneration mechanisms. Whitebark pine (Pinus albicaulis), a keystone subalpine species, obligately depends upon the Clark's Nutcracker (Nucifraga columbiana) for dispersal of its large, wingless seeds. Clark's Nutcracker, a facultative mutualist with whitebark pine, is sensitive to rates of energy gain, and emigrates from subalpine forests during periods of cone shortages. The invasive fungal pathogen Cronartium ribicola, which causes white pine blister rust, reduces whitebark pine cone production by killing cone-bearing branches and trees. Mortality from blister rust reaches 90% or higher in some whitebark pine forests in the Northern Rocky Mountains, USA, and the rust now occurs nearly rangewide in whitebark pine. Our objectives were to identify the minimum level of cone production necessary to elicit seed dispersal by nutcrackers and to determine how cone production is influenced by forest structure and health. We quantified forest conditions and ecological interactions between nutcrackers and whitebark pine in three Rocky Mountain ecosystems that differ in levels of rust infection and mortality. Both the frequency of nutcracker occurrence and probability of seed dispersal were strongly related to annual whitebark pine cone production, which had a positive linear association with live whitebark pine basal area, and negative linear association with whitebark pine tree mortality and rust infection. From our data, we estimated that a threshold level of approximately 1000 cones/ha is needed for a high likelihood of seed dispersal by nutcrackers (probability > or = 0.7), and that this level of cone production can be met by forests with live whitebark pine basal area > 5.0 m2/ha. The risk of mutualism disruption is greatest in northern most Montana (USA), where three-year mean cone production and live basal area fell below predicted threshold levels. There, nutcracker occurrence, seed dispersal, and whitebark pine regeneration were the lowest of the three ecosystems. Managers can use these threshold values to differentiate between restoration sites requiring planting of rust-resistant seedlings and sites where nutcracker seed dispersal can be expected.

  13. Basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality.

    PubMed

    Devkota, Bhuminand; Takahashi, Ken-Ichi; Matsuzaki, Shigenori; Matsui, Motozumi; Miyamoto, Akio; Yamagishi, Norio; Osawa, Takeshi; Hashizume, Tsutomu; Izaike, Yoshiaki; Miyake, Yoh-Ichi

    2011-06-01

    The present study investigated the basal levels and GnRH-induced responses of peripheral testosterone and estrogen in Holstein bulls with poor semen quality. On the basis of semen parameters, bulls (n=5) having poor semen quality were selected as experimental bulls, and good semen quality bulls (n=4) were used as control bulls. Both groups were treated intramuscularly once with GnRH (250 µg of fertirelin acetate). Blood samples were collected at -1 day (d), -30 min and 0 h (treatment) followed by every 30 min for 5 h and 1, 3 and 5 d post-GnRH treatment (PGT), and LH, testosterone and estradiol-17β (E(2)) concentrations were measured. The pretreatment concentrations were used as basal levels. The percentage increments based on the 0-h levels were calculated per bull for each sampling time until 5 h PGT, and differences were compared between the experimental and control groups. The PGT concentrations of testosterone and basal and PGT concentrations of E(2) were significantly lower in the experimental group. The testosterone increment in the experimental group was delayed and significantly lower from 1 to 5 h PGT than those in the control group. It can be suggested that bulls with poor semen quality have delayed and lower GnRH-induced testosterone response and may also have lower estrogen levels.

  14. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

    PubMed

    Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

  15. Application of Control Method on a West Antarctic Glacier

    NASA Astrophysics Data System (ADS)

    Schmeltz, M.; Rignot, E. J.; Macayeal, D. R.

    2002-12-01

    We use surface velocity inferred with Interferometric synthetic-aperture radar and a control method to estimate unknown basal characteristics of a fast-moving glacier in West Antarctica, Pine Island Glacier. Previous modelling experiments on Pine Island Glacier have shown that using a coupled ice-stream/ice-shelf flow model in a forward approach (trial and error method) we were able to reproduce fairly well the surface velocity. Some discrepancies remained, however, that are partly due to uncertainties in the thickness map and incertainty in our chosen basal stress distribution (because of the non-unicity of the solution). The control method allow us to take the basal stress (or basal friction, since they are related through the velocity), as an unknown parameter. Results given by the control method should provide better reliable inputs for further modelling experiments. We investigate the results' sensitivity to the initial value of the basal stress. The inferred ratio basal drag/driving stress seems to be always low upstream, 60 to 80 km upstream of the grounding line, as if the ice stream was behaving like an ice shelf, and also reveals the presence of a snake shape channel of low ratio basal drag/driving stress, surrounded by a higher ratio, in the main flow of increasing velocity, from 20 to 40 km upstream of the grounding line.

  16. Histamine and thrombin modulate endothelial focal adhesion through centripetal and centrifugal forces.

    PubMed Central

    Moy, A B; Van Engelenhoven, J; Bodmer, J; Kamath, J; Keese, C; Giaever, I; Shasby, S; Shasby, D M

    1996-01-01

    We examined the contribution of actin-myosin contraction to the modulation of human umbilical vein endothelial cell focal adhesion caused by histamine and thrombin. Focal adhesion was measured as the electrical resistance across a cultured monolayer grown on a microelectrode. Actin-myosin contraction was measured as isometric tension of cultured monolayers grown on a collagen gel. Histamine immediately decreased electrical resistance but returned to basal levels within 3-5 min. Histamine did not increase isometric tension. Thrombin also immediately decreased electrical resistance, but, however, resistance did not return to basal levels for 40-60 min. Thrombin also increased isometric tension, ML-7, an inhibitor of myosin light chain kinase, prevented increases in myosin light chain phosphorylation and increases in tension development in cells exposed to thrombin. ML-7 did not prevent a decline in electrical resistance in cells exposed to thrombin. Instead, ML-7 restored the electrical resistance to basal levels in a shorter period of time (20 min) than cells exposed to thrombin alone. Also, histamine subsequently increased electrical resistance to above basal levels, and thrombin initiated an increase in resistance during the time of peak tension development. Hence, histamine and thrombin modulate endothelial cell focal adhesion through centripetal and centrifugal forces. PMID:8613524

  17. Isostasy as a Driver of Paleo Retreat of the Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Robinson, A.; Tabone, I.; Alvarez-Solas, J.; Montoya, M.

    2016-12-01

    During glacial times, the Greenland ice sheet (GrIS) extended onto the continental shelf, and thus was much more directly affected by changing ocean temperatures through basal melt of the marine ice margins than it is today. The larger glacial ice sheet also induced lithospheric depression of several hundred meters in regions that are near sea level today. As the ice sheet retreated inland under interglacial climatic forcing, the regions significantly affected by local isostatic changes in elevation were exposed to much higher basal melt rates than they would have been given the present-day topography. Here we explore this effect using a hybrid ice sheet model that represents both grounded and floating ice, as well as local isostatic effects, and is driven by both atmospheric and oceanic temperature anomalies. We find that when transient oceanic forcing is included in the model, isostasy plays an important role in allowing oceanic melting to drive GrIS retreat in some regions. During the last interglacial, for example, this effect can account for a significant additional sea-level contribution, as well as an increase in the rate of sea-level rise. Our results highlight the importance of accounting for ice-ocean-lithosphere interactions in the past, in order to be able to properly reconstruct the evolution of the ice sheet, and for estimating its sensitivity to potential changes in climate in the future.

  18. Angiopoietin-like protein 8/betatrophin as a new determinant of type 2 diabetes remission after bariatric surgery.

    PubMed

    Ejarque, Miriam; Borlaug, Marianne; Vilarrasa, Nuria; Martinez-Perez, Bruno; Llauradó, Gemma; Megía, Ana; Helland, Thomas; Gutierrez, Cristina; Serena, Carolina; Folkestad, Oddry; Nuñez-Roa, Catalina; Roche, Kelly; Casajoana, Ana; Fradera, Rosa; González-Clemente, José Miguel; López, Miguel; Mohn, Arne C; Nedrebø, Bjørn G; Nogueiras, Ruben; Mellgren, Gunnar; Fernø, Johan; Fernández-Veledo, Sonia; Vendrell, Joan

    2017-06-01

    This work aimed to explore the link between angiopoietin-like protein 8 (ANGPTL8) and weight loss after metabolic surgery. In the cross-sectional study (n = 100), circulating ANGPTL8 concentrations were significantly lower in morbidly obese than in lean subjects, and strikingly lower in morbidly obese patients with type 2 diabetes mellitus (T2DM). Conversely, ANGPTL8 expression in subcutaneous adipose tissue (SAT) was higher in morbidly obese patients, particularly in those with T2DM, whereas its expression in visceral adipose tissue was unchanged. The main predictors for circulating levels of ANGPTL8 were BMI and T2DM, whereas ANGPTL8 expression in SAT was determined by the presence of T2DM. The prospective cohort studies before and 1 year after bariatric surgery in morbidly obese patients with (n = 45) and without (n = 30) T2DM, revealed a significant increase of circulating ANGPTL8 levels 1 year after the bariatric surgery. Intriguingly, this increment, which was predicted by basal ANGPTL8 concentrations, appeared as a determinant of T2DM remission. In conclusion, circulating ANGPTL8 levels have an inverse relationship with SAT expression. Low basal levels of ANGPTL8 rebound after bariatric surgery. The increment in ANGPTL8 concentrations at 1 month of follow-up after weight loss emerged as a significant predictor of the T2DM remission at 1 year of follow-up. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Effect of inorganic N enrichment on basal pelagic production in boreal unproductive lakes along a gradient of DOC concentration - results after 1 year of fertilization

    NASA Astrophysics Data System (ADS)

    Deininger, Anne; Bergström, Ann-Kristin

    2013-04-01

    Input of inorganic nitrogen (N) in boreal unproductive lakes is steadily increasing due to anthropogenic deposition and usage of artificial fertilizers. N enrichment is predicted to have a major impact on the ecosystem productivity and food web structure in unproductive clear-water and humic lakes. For a long time, pelagic primary production (PP) has been mainly regarded as being phosphorus (P) limited. However, recent studies have shown that this is not true for unproductive lakes in northern Sweden, where phytoplankton is mainly N limited. Addition of inorganic N should therefore increase phytoplankton growth in these lake ecosystems. Bacterial production (BP) in the pelagic habitat, on the other hand, is usually limited by P. Nevertheless, elevated N could have a stimulating effect on BP through enhanced leakage of dissolved organic carbon (DOC) from phytoplankton following enhanced N availability and higher PP. Further, unproductive lakes vary naturally in their DOC content which affects overall nutrient- (N and P), energy- and carbon availability (light, C) for the basal producers (phytoplankton, bacteria). It is still not clear how higher inorganic N availability affects primary- and bacterial production in the pelagic in lakes with varying DOC content. We subsequently assessed this question by conducting whole-lake fertilization experiments with inorganic N additions in 6 lakes with varying DOC concentrations (2 low DOC; 2 medium DOC; 2 high DOC). For each DOC level one lake functioned as a reference and one was fertilized with N. Year 2011 was a reference year (all lakes) and 2012 was the first year of fertilization (i.e. in 3 lakes). Measurements included basal productivity such as primary production and bacteria production, lake water chemistry and physical parameters (i.e. light, temperature). The results of this study will help to develop a conceptual understanding of how increased inorganic N availability (through land use such as forestry and/or enhanced N deposition) affects basal productivity in boreal lakes which can have consequences for overall whole lake-ecosystem productivity and functioning.

  20. Children's Literature in the Basals.

    ERIC Educational Resources Information Center

    O'Brien, Maureen A.

    Three basal reading series, levels kindergarten through grade three, were studied to categorize the types of literature each contained. The following series were analyzed: "The Headway Program" (Open Court Publishing Company), "Series r Macmillan Reading," and "Basics in Reading" (Scott, Foresman and Company). It was…

  1. Effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion in humans.

    PubMed

    Lam, W F; Masclee, A A; Muller, E S; Souverijn, J H; Lamers, C B

    1998-08-01

    This study was undertaken to investigate the effect of acute hyperglycemia on basal and bombesin-stimulated pancreaticobiliary secretion. Seven healthy subjects participated in two experiments performed in random order during normoglycemia and hyperglycemic clamping at 15 mM. Duodenal outputs of bilirubin, trypsin, amylase, and bicarbonate were measured by aspiration with a recovery marker under basal conditions for 60 min and during continuous infusion of bombesin (1 ng/kg x min) for 60 min. Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were determined at regular intervals. Compared to normoglycemia, during hyperglycemia basal outputs of bilirubin (17 +/- 3 vs. 0.9 +/- 0.4 micromol/60 min), trypsin (24 +/- 4 vs. 4 +/- 1 U/60 min), amylase (12 +/- 1 vs. 3 +/- 1 kU/60 min), and bicarbonate (2.9 +/- 0.5 vs. 1.2 +/- 0.2 mmol/60 min) were significantly p < 0.05) reduced. Bombesin significantly (p < 0.05) increased pancreaticobiliary output during both normo- and hyperglycemia. During hyperglycemia bombesin-stimulated 60-min outputs of bilirubin, trypsin, amylase, and bicarbonate were not significantly different compared to those during normoglycemia. Basal and bombesin-stimulated plasma PP concentrations were significantly (p < 0.05) reduced during hyperglycemia, but plasma CCK levels were not significantly different. It is concluded that acute hyperglycemia reduces basal but does not affect bombesin-induced pancreaticobiliary secretion.

  2. The difficulty with correlations: Energy expenditure and brain mass in bats.

    PubMed

    McNab, Brian K; Köhler, Meike

    2017-10-01

    Brain mass has been suggested to determine a mammal's energy expenditure. This potential dependence is examined in 48 species of bats. A correlation between characters may be direct or derived from shared correlations with intervening factors without a direct interaction. Basal rate of metabolism in these bats increases with brain mass: large brains are more expensive than small brains, and both brain mass and basal rate increase with body mass. Basal rate and brain mass also correlate with food habits in bats. Mass-independent basal rate weakly correlates with mass-independent brain mass, the correlation only accounting for 12% of the variation in basal rate, which disappears when the combined effects of body mass and food habits are deleted. The correlation between basal rate and brain mass seen in this and other studies usually accounts for <10% of the variation in basal rate and often <4%, even when statistically significant, a minimalist explanation for the level the basal rate. This correlation probably reflects the intermediacy of secondary factors, as occurred with food habits in bats. Most biological correlations are complicated and must be examined in detail before assurance can be given as to their bases. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Ca2+-regulated-cAMP/PKA signaling in cardiac pacemaker cells links ATP supply to demand.

    PubMed

    Yaniv, Yael; Juhaszova, Magdalena; Lyashkov, Alexey E; Spurgeon, Harold A; Sollott, Steven J; Lakatta, Edward G

    2011-11-01

    In sinoatrial node cells (SANC), Ca(2+) activates adenylate cyclase (AC) to generate a high basal level of cAMP-mediated/protein kinase A (PKA)-dependent phosphorylation of Ca(2+) cycling proteins. These result in spontaneous sarcoplasmic-reticulum (SR) generated rhythmic Ca(2+) oscillations during diastolic depolarization, that not only trigger the surface membrane to generate rhythmic action potentials (APs), but, in a feed-forward manner, also activate AC/PKA signaling. ATP is consumed to pump Ca(2+) to the SR, to produce cAMP, to support contraction and to maintain cell ionic homeostasis. Since feedback mechanisms link ATP-demand to ATP production, we hypothesized that (1) both basal ATP supply and demand in SANC would be Ca(2+)-cAMP/PKA dependent; and (2) due to its feed-forward nature, a decrease in flux through the Ca(2+)-cAMP/PKA signaling axis will reduce the basal ATP production rate. O(2) consumption in spontaneous beating SANC was comparable to ventricular myocytes (VM) stimulated at 3 Hz. Graded reduction of basal Ca(2+)-cAMP/PKA signaling to reduce ATP demand in rabbit SANC produced graded ATP depletion (r(2)=0.96), and reduced O(2) consumption and flavoprotein fluorescence. Neither inhibition of glycolysis, selectively blocking contraction nor specific inhibition of mitochondrial Ca(2+) flux reduced the ATP level. Feed-forward basal Ca(2+)-cAMP/PKA signaling both consumes ATP to drive spontaneous APs in SANC and is tightly linked to mitochondrial ATP production. Interfering with Ca(2+)-cAMP/PKA signaling not only slows the firing rate and reduces ATP consumption, but also appears to reduce ATP production so that ATP levels fall. This distinctly differs from VM, which lack this feed-forward basal cAMP/PKA signaling, and in which ATP level remains constant when the demand changes. Published by Elsevier Ltd.

  4. Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat

    PubMed Central

    Sharott, Andrew; Magill, Peter J; Bolam, J Paul; Brown, Peter

    2005-01-01

    Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ‘global activation’. During SWA, there was coherence at ∼1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ∼1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15–60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change. PMID:15550466

  5. Short children with familial short stature show enhancement of somatotroph secretion but normal IGF-I levels.

    PubMed

    Bellone, S; Corneli, G; Bellone, J; Baffoni, C; Rovere, S; de Sanctis, C; Bona, G; Ghigo, E; Aimaretti, G

    2002-05-01

    The aim of the present study was to evaluate the GH status in children with familial, idiopathic short stature (FSS). To this goal we evaluated the GH response to GHRH (1 microg/kg iv) + arginine (ARG) (0.5 g/kg iv) test which is one of the most potent and reproducible provocative tests of somatotroph secretion, in 67 children with FSS [50 boys and 17 girls, age 10.8+/-0.4 yr, pubertal stages I-III, height between -3.6 and -1.6 standard deviation score (SDS), target height <10 degrees centile, normality of both spontaneous and stimulated GH secretion as well as of IGF-I levels]. The results in FSS were compared with those in groups of children of normal height (NHC) (42 NHC, 35 boys and 7 girls, age 12.0+/-0.5 yr, pubertal stages I-III, height between -1.3 and 1.4 SDS, height velocity standard deviation score (HVSDS)>25 degrees centile, GH peak >20 microg/l after GHRH+ARG test, mean GH concentration [mGHc]>3 microg/l) and children with organic GH deficiency (GHD) (38 GHD, 29 boys and 9 girls, age 11.2+/-3.7 yr, pubertal stages I-III, height between -5.7 and -1.3 SDS, GH peak <20 microg/l after GHRH +ARG test, mGHc <3 mg/l). Basal IGF-I levels and mGHc were also evaluated in each group over 8 nocturnal hours. IGF-I levels in FSS (209.2+/-15.6 microg/l) were similar to those in NHC (237.2+/-17.2 microg/l) and both were higher (p<0.0001) than those in GHD (72.0+/-4.0 microg/l). The GH response to GHRH +ARG test in FSS (peak: 66.4+/-5.6 microg/l) was very marked and higher (p<0.01) than that in NHC (53.3+/-4.5 microg/l) which, in turn, was higher (p<0.01) than in GHD (8.2+/-0.8 microg/l). Similarly, the mGHc in FSS was higher than in NHC (6.7+/-0.5 microg/l vs 5.1+/-0.7 microg/l, p<0.05) which, in turn, was higher than in GHD (1.5+/-0.2 microg/l, p<0.0001). In conclusion, our present study demonstrates that short children with FSS show enhancement of both basal and stimulated GH secretion but normal IGF-I levels. These findings suggest that increased somatotroph function would be devoted to maintain normal IGF-I levels thus reflecting a slight impairment of peripheral GH sensitivity in FSS.

  6. Effect of feeding different levels of Azolla pinnata on blood biochemicals, hematology and immunocompetence traits of Chabro chicken

    PubMed Central

    Mishra, Deepesh Bharat; Roy, Debashis; Kumar, Vinod; Bhattacharyya, Amitav; Kumar, Muneendra; Kushwaha, Raju; Vaswani, Shalini

    2016-01-01

    Aim: The present study was conducted to see the effect of feeding different levels of Azolla meal on blood biochemicals, hematology and immunocompetence traits of Chabro chicken. Materials and Methods: The study was conducted on 160 Chabro chicks, which were randomly divided into four treatment groups each with four replicates of 10 birds. The first treatment (T1) served as a control in which basal diets was offered without Azolla supplementation while in T2, T3, and T4 groups, basal diet was replaced with Azolla meal at 5%, 7.5%, and 10% levels, respectively. A feeding trial was conducted upto 8 weeks. At the last week of trial, blood samples were collected randomly from one bird of each replicate and plasma was separated to estimate certain biochemical parameters, some blood metabolites, minerals and enzymes like alanine aminotransferase and aspartate aminotransferase (AST). Hematological parameters such as hemoglobin, packed cell volume, total leukocytes count and differential leukocytes count were estimated in fresh blood just after collection. The humoral immune response was measured against sheep red blood cells,and cell-mediated immune response was measured against phyto hemagglutinin lectin from Phaseolus vulgaris (PHA-P). Results: The study showed that hematological profile of the Chabro bird was not affected by any treatment except heterophil and lymphocyte which was found higher in T2 and T3 groups and eosinophil was found higher in a T3 group than control. Blood glucose, creatinine, cholesterol, total protein, albumin, uric acid, and triglycerides were found similar in all the groups and within the normal values for broiler chicken. Liver enzymes and macro mineral content in blood were found similar in all the treatment groups and within normal physiological range. Although AST was found higher in 10% replacement group than control, the value was within normal range for broiler chicken. Although antibody titer was found similar in all the experimental groups in the present study, cell-mediate immune response (response to PHA-P) was found higher in 5%, 7.5%, and 10% replacement groups than control(p<0.05). Conclusion: Similar blood biochemical parameters and higher cell-mediated immune response in Azolla replacement group indicated immune-modulatory effect of Azolla meal without any toxicity. PMID:27051207

  7. Effect of feeding different levels of Azolla pinnata on blood biochemicals, hematology and immunocompetence traits of Chabro chicken.

    PubMed

    Mishra, Deepesh Bharat; Roy, Debashis; Kumar, Vinod; Bhattacharyya, Amitav; Kumar, Muneendra; Kushwaha, Raju; Vaswani, Shalini

    2016-02-01

    The present study was conducted to see the effect of feeding different levels of Azolla meal on blood biochemicals, hematology and immunocompetence traits of Chabro chicken. The study was conducted on 160 Chabro chicks, which were randomly divided into four treatment groups each with four replicates of 10 birds. The first treatment (T1) served as a control in which basal diets was offered without Azolla supplementation while in T2, T3, and T4 groups, basal diet was replaced with Azolla meal at 5%, 7.5%, and 10% levels, respectively. A feeding trial was conducted upto 8 weeks. At the last week of trial, blood samples were collected randomly from one bird of each replicate and plasma was separated to estimate certain biochemical parameters, some blood metabolites, minerals and enzymes like alanine aminotransferase and aspartate aminotransferase (AST). Hematological parameters such as hemoglobin, packed cell volume, total leukocytes count and differential leukocytes count were estimated in fresh blood just after collection. The humoral immune response was measured against sheep red blood cells,and cell-mediated immune response was measured against phyto hemagglutinin lectin from Phaseolus vulgaris (PHA-P). The study showed that hematological profile of the Chabro bird was not affected by any treatment except heterophil and lymphocyte which was found higher in T2 and T3 groups and eosinophil was found higher in a T3 group than control. Blood glucose, creatinine, cholesterol, total protein, albumin, uric acid, and triglycerides were found similar in all the groups and within the normal values for broiler chicken. Liver enzymes and macro mineral content in blood were found similar in all the treatment groups and within normal physiological range. Although AST was found higher in 10% replacement group than control, the value was within normal range for broiler chicken. Although antibody titer was found similar in all the experimental groups in the present study, cell-mediate immune response (response to PHA-P) was found higher in 5%, 7.5%, and 10% replacement groups than control(p<0.05). Similar blood biochemical parameters and higher cell-mediated immune response in Azolla replacement group indicated immune-modulatory effect of Azolla meal without any toxicity.

  8. EBSD analysis of subgrain boundaries and dislocation slip systems in Antarctic and Greenland ice

    NASA Astrophysics Data System (ADS)

    Weikusat, Ilka; Kuiper, Ernst-Jan N.; Pennock, Gill M.; Kipfstuhl, Sepp; Drury, Martyn R.

    2017-09-01

    Ice has a very high plastic anisotropy with easy dislocation glide on basal planes, while glide on non-basal planes is much harder. Basal glide involves dislocations with the Burgers vector b = 〈a〉, while glide on non-basal planes can involve dislocations with b = 〈a〉, b = [c], and b = 〈c + a〉. During the natural ductile flow of polar ice sheets, most of the deformation is expected to occur by basal slip accommodated by other processes, including non-basal slip and grain boundary processes. However, the importance of different accommodating processes is controversial. The recent application of micro-diffraction analysis methods to ice, such as X-ray Laue diffraction and electron backscattered diffraction (EBSD), has demonstrated that subgrain boundaries indicative of non-basal slip are present in naturally deformed ice, although so far the available data sets are limited. In this study we present an analysis of a large number of subgrain boundaries in ice core samples from one depth level from two deep ice cores from Antarctica (EPICA-DML deep ice core at 656 m of depth) and Greenland (NEEM deep ice core at 719 m of depth). EBSD provides information for the characterization of subgrain boundary types and on the dislocations that are likely to be present along the boundary. EBSD analyses, in combination with light microscopy measurements, are presented and interpreted in terms of the dislocation slip systems. The most common subgrain boundaries are indicative of basal 〈a〉 slip with an almost equal occurrence of subgrain boundaries indicative of prism [c] or 〈c + a〉 slip on prism and/or pyramidal planes. A few subgrain boundaries are indicative of prism 〈a〉 slip or slip of 〈a〉 screw dislocations on the basal plane. In addition to these classical polygonization processes that involve the recovery of dislocations into boundaries, alternative mechanisms are discussed for the formation of subgrain boundaries that are not related to the crystallography of the host grain.The finding that subgrain boundaries indicative of non-basal slip are as frequent as those indicating basal slip is surprising. Our evidence of frequent non-basal slip in naturally deformed polar ice core samples has important implications for discussions on ice about plasticity descriptions, rate-controlling processes which accommodate basal glide, and anisotropic ice flow descriptions of large ice masses with the wider perspective of sea level evolution.

  9. Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

    PubMed

    Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

    2012-11-01

    To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; P<0.01). CIR has diurnal variance and is estimated from the formula CIR=300/TDD at breakfast or CIR=400/TDD at lunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

  10. Nicergoline increases serum substance P levels in patients with an ischaemic stroke.

    PubMed

    Nishiyama, Yasuhiro; Abe, Arata; Ueda, Masayuki; Katsura, Ken-ichiro; Katayama, Yasuo

    2010-01-01

    Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. At entry to the study, mean concentration of substance P was significantly (p < 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. (c) 2009 S. Karger AG, Basel.

  11. One year follow-up of post-partum-onset depression: the role of depressive symptom severity and personality disorders.

    PubMed

    Uguz, Faruk; Akman, Cemal; Sahingoz, Mine; Kaya, Nazmiye; Kucur, Rahim

    2009-06-01

    Long-term follow-up and risk factors of persistent post-partum depression (PPD) are fairly unknown compared with its prevalence in the developing countries. In this study, we did a follow-up measure of PPD and examined the factors, which were associated with PPD 1-year post-partum. Our sample comprised of 34 women. Depressive symptoms were assessed by the Edinburgh post-natal depression scale (EPDS) 6 weeks post-partum, and women with scores >12 on this scale was categorised as depressed. Personality disorders were determined at the same occasion by means of the Structured Clinical Interview for DSM-III-R personality disorders (SCID-II). One year post-partum EPDS was completed. The rate of PPD 1-year post-partum was 32.4%, and it was unrelated to age at assessment, primiparity, number of children, employment status, economical status and educational level. Women depressed 1-year post-partum had significantly higher basal scores of EPDS and more often also a diagnosis of any axis II disorder; and specifically dependent and obsessive-compulsive personality disorders. In our sample, the predictors of 1-year post-partum PPD were having higher basal score of EPDS and the existence of a personality disorder. This study suggests that women with PPD, scoring high in the EPDS scale 6 weeks post-partum and having a personality disorder, run a higher risk for depression at 1-year follow-up.

  12. Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load.

    PubMed

    Katre, P; Joshi, S; Bhat, D S; Deshmukh, M; Gurav, N; Pandit, S; Lubree, H; Marczewski, S; Bennett, C; Gruca, L; Kalyanaraman, K; Naik, S S; Yajnik, C S; Kalhan, S C

    2016-06-01

    Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies.

  13. Parkinson’s disease as a system-level disorder

    PubMed Central

    Caligiore, Daniele; Helmich, Rick C; Hallett, Mark; Moustafa, Ahmed A; Timmermann, Lars; Toni, Ivan; Baldassarre, Gianluca

    2016-01-01

    Traditionally, the basal ganglia have been considered the main brain region implicated in Parkinson’s disease. This single area perspective gives a restricted clinical picture and limits therapeutic approaches because it ignores the influence of altered interactions between the basal ganglia and other cerebral components on Parkinsonian symptoms. In particular, the basal ganglia work closely in concert with cortex and cerebellum to support motor and cognitive functions. This article proposes a theoretical framework for understanding Parkinson’s disease as caused by the dysfunction of the entire basal ganglia–cortex–cerebellum system rather than by the basal ganglia in isolation. In particular, building on recent evidence, we propose that the three key symptoms of tremor, freezing, and impairments in action sequencing may be explained by considering partially overlapping neural circuits including basal ganglia, cortical and cerebellar areas. Studying the involvement of this system in Parkinson’s disease is a crucial step for devising innovative therapeutic approaches targeting it rather than only the basal ganglia. Possible future therapies based on this different view of the disease are discussed. PMID:28725705

  14. Association Analysis of Grain-setting Rates in Apical and Basal Spikelets in Bread Wheat (Triticum aestivum L.).

    PubMed

    Guo, Jie; Zhang, Yong; Shi, Weiping; Zhang, Boqiao; Zhang, Jingjuan; Xu, Yanhao; Cheng, Xiaoming; Cheng, Kai; Zhang, Xueyong; Hao, Chenyang; Cheng, Shunhe

    2015-01-01

    The rates of grain-setting in apical and basal spikelets in wheat directly affect the kernel number per spike (KNPS). In this study, 220 wheat lines from 18 Chinese provinces and five foreign countries were used as a natural population. Phenotypic analysis showed differences in grain-setting rates between apical and basal spikelets. The broad-sense heritability of grain-setting rate in apical spikelets (18.7-21.0%) was higher than that for basal spikelets (9.4-16.4%). Significant correlations were found between KNPS and grain numbers in apical (R (2) = 0.40-0.45, P < 0.01) and basal (R (2) = 0.41-0.56, P < 0.01) spikelets. Seventy two of 106 SSR markers were associated with grain setting, 32 for apical spikelets, and 34 for basal spikelets. The SSR loci were located on 17 chromosomes, except 3A, 3D, 4A, and 7D, and explained 3.7-22.9% of the phenotypic variance. Four markers, Xcfa2153-1A 202 , Xgwm186-5A 118 , Xgwm156-3B 319 , and Xgwm537-7B 210 , showed the largest effects on grain numbers in apical and basal spikelets. High grain numbers in apical and basal spikelets were associated with elite alleles. Ningmai 9, Ning 0569, and Yangmai 18 with high grain-setting rates carried larger numbers of favorable alleles. Comparison of grain numbers in basal and apical spikelets of 35 Yangmai and Ningmai lines indicated that the Ningmai lines had better grain-setting rates (mean 21.4) than the Yangmai lines (16.5).

  15. Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis.

    PubMed

    Iyer, Sapna; Park, Min-Jung; Moons, David; Kwan, Raymond; Liao, Jian; Liu, Li; Omary, M Bishr

    2017-01-22

    Acute pancreatitis has several underlying etiologies, and results in consequences ranging from mild to complex multi-organ failure. The wide range of pathology suggests a genetic predisposition for progression. We compared the susceptibility to acute pancreatitis in BALB/c and FVB/N mice, coupled with proteomic analysis, in order to identify potential protein associations with pancreatitis progression. Pancreatitis was induced in BALB/c and FVB/N mice by administration of cerulein or feeding a choline-deficient, ethionine-supplemented (CDE) diet. Histology and changes in serum amylase were examined. Proteome profiling in cerulein-treated mice was performed using 2-dimensional differential in gel electrophoresis (2D-DIGE) followed by mass spectrometry analysis and biochemical validation. Male and female FVB/N mice manifested more severe cerulein-induced pancreatitis as compared with BALB/c mice, but both strains were similarly susceptible to CDE-induced pancreatitis. Few of the 2D-DIGE alterations were validated by immunoblotting. Clusterin was markedly up-regulated after cerulein-induced pancreatitis in FVB/N but less-so in BALB/c mice. Pyrroline-5-carboxylate reductase (Pycr1), an enzyme involved in proline biosynthesis, had higher basal levels in FVB/N male and female mouse pancreata compared with BALB/c pancreata, and was relatively more resistant to degradation in FVB/N pancreata. However, serum and pancreas tissue proline levels were similar in the two strains. FVB/N is more susceptible than BALB/c mice to cerulein-induced but not CDE-induced pancreatitis. Most of the 2D-DIGE alterations in the two strains likely relate to posttranslational modifications rather than protein level differences. Clusterin levels increase dramatically in association with pancreatitis severity, while Pycr1 is higher in FVB/N versus BALB/c pancreata basally and after induction of pancreatitis. Changes in proline metabolism may represent a novel potential genetic modifier in the context of pancreatitis. Published by Elsevier Inc.

  16. Induction of chemokine receptor CXCR4 expression by transforming growth factor-β1 in human basal cell carcinoma cells.

    PubMed

    Chu, Chia-Yu; Sheen, Yi-Shuan; Cha, Shih-Ting; Hu, Yeh-Fang; Tan, Ching-Ting; Chiu, Hsien-Ching; Chang, Cheng-Chi; Chen, Min-Wei; Kuo, Min-Liang; Jee, Shiou-Hwa

    2013-11-01

    Higher CXCR4 expression enhances basal cell carcinoma (BCC) invasion and angiogenesis. The underlying mechanism of increased CXCR4 expression in invasive BCC is still not well understood. To investigate the mechanisms involved in the regulation of CXCR4 expression in invasive BCC. We used qRT-PCR, RT-PCR, Western blot, and flow cytometric analyses to examine different CXCR4 levels among the clinical samples, co-cultured BCC cells and BCC cells treated with recombinant transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF). Immunohistochemical studies were used to demonstrate the correlation between TGF-β1 and CXCR4 expressions. The signal transduction pathway and transcriptional regulation were confirmed by treatments with chemical inhibitors, neutralizing antibodies, or short interfering RNAs, as well as luciferase reporter activity. Invasive BCC has higher TGF-β1 and CTGF levels compared to non-invasive BCC. Non-contact dermal fibroblasts co-culture with human BCC cells also increases the expression of CXCR4 in BCC cells. Treatment with recombinant human TGF-β1, but not CTGF, enhanced the CXCR4 levels in time- and dose-dependent manners. The protein level and surface expression of CXCR4 in human BCC cells was increased by TGF-β1 treatment. TGF-β1 was intensely expressed in the surrounding fibroblasts of invasive BCC and was positively correlated with the CXCR4 expression of BCC cells. The transcriptional regulation of CXCR4 by TGF-β1 is mediated by its binding to the TGF-β receptor II and phosphorylation of the extracellular signal-related kinase 1/2 (ERK1/2)-ETS-1 pathway. TGF-β1 induces upregulation of CXCR4 in human BCC cells by phosphorylation of ERK1/2-ETS-1 pathway. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Seated saline suppression testing for the diagnosis of primary aldosteronism: a preliminary study.

    PubMed

    Ahmed, Ashraf H; Cowley, Diane; Wolley, Martin; Gordon, Richard D; Xu, Shengxin; Taylor, Paul J; Stowasser, Michael

    2014-08-01

    Failure of aldosterone suppression by sodium loading during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). We previously found recumbent SST (RSST) to lack sensitivity. Aldosterone levels can be higher upright (e.g. seated) than recumbent in patients with PA and upright levels are used during FST. We therefore hypothesized that seated SST (SSST) is more sensitive than RSST, especially for posture-responsive PA. Of 66 patients who underwent FST (upright plasma aldosterone levels measured at 10am basally and after 4 days fludrocortisone 0.1 mg 6-hourly and oral salt loading), 31 underwent SST (aldosterone levels measured basally at 8am and after infusion of 2 L normal saline over 4h) both recumbent and seated in randomized order and at least 2 weeks apart. FST confirmed PA in 23 of 31 patients (day 4 upright aldosterone level >165 pmol/L), excluded PA in three and was originally "inconclusive" in five. However, one with "inconclusive" FST had PA confirmed by lateralizing AVS and was reclassified "unilateral PA". Of 24 with confirmed PA (eight unilateral, 11 bilateral, and five undetermined subtype), 23 (96%) tested positive by SSST (4-h aldosterone level >165 pmol/L) compared with 8 (33%) by RSST (4-h plasma aldosterone level >140 pmol/L) (P < .001). RSST missed one unilateral, all bilateral, and four with as-yet undetermined subtype. RSST was positive in 7 of 10 (70%) posture-unresponsive vs one of 14 (7.1%) posture-responsive patients (P < .005). These preliminary results suggest that seated SST may be superior to recumbent SST in terms of sensitivity for detecting PA, especially posture-responsive forms, and may represent a reliable alternative to FST.

  18. Preserved cardiorespiratory function and NT-proBNP levels before and during exercise in patients with recent onset of rheumatoid arthritis: the clinical challenge of stratifying the patient cardiovascular risks.

    PubMed

    Zoli, A; Bosello, S; Comerci, G; Galiano, N; Forni, A; Loperfido, F; Ferraccioli, G F

    2017-01-01

    Rheumatoid arthritis (RA) is associated with an increased risk of myocardial infarction and congestive heart failure. In RA patients, elevated NT-proBNP levels have been reported to be a prognostic marker of left ventricular dysfunction. In this study, we evaluated cardiorespiratory functional capacity and NT-proBNP levels before and during cardiopulmonary exercise test in early RA (ERA) patients. Twenty ERA patients and 10 healthy controls were studied by color Doppler echocardiography to evaluate ventricular systolic and diastolic function. Arterial stiffness and wave reflections were quantified non-invasively using applanation tonometry of the radial artery. Cardiopulmonary treadmill test was performed to measure peak VO 2 and VE/VCO 2 parameters. NT-proBNP plasma levels were measured before and at the exercise peak during cardiopulmonary exercise. The peak oxygen uptake [VO 2 (ml/min/kg)], the ventilatory equivalents for carbon dioxide (EqCO 2 ), respiratory exchange ratio and arterial stiffness were similar between patients and controls during cardiopulmonary exercise test. Basal and peak cardiopulmonary exercise NT-proBNP plasma levels were comparable in ERA patients with respect to healthy controls. When we analyzed patients according to disease characteristics and cardiovascular risk factors, ERA patients with high disease activity, BMI > 25 kg/m 2 and ACPA positivity presented significantly higher baseline and exercise peak NT-proBNP levels. Cardiorespiratory function is preserved in patients with recent onset of rheumatoid arthritis. The increased basal and exercise peak NT-proBNP plasma levels in patients with negative disease prognostic factors represent a possible marker to stratify the cardiovascular risk in patients with early rheumatoid arthritis.

  19. Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

    PubMed

    Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

    2013-02-01

    Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

    PubMed

    Sömjen, D; Weisman, Y; Mor, Z; Harell, A; Kaye, A M

    1991-01-01

    We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.

  1. Effect of zinc imprinting and replacing inorganic zinc with organic zinc on early performance of broiler chicks

    PubMed Central

    Timmons, J.; Ao, T.; Paul, M.; Macalintal, L.; Pescatore, A.; Cantor, A.; Ford, M.; Dawson, K. A.

    2017-01-01

    Abstract The goal of this study was to determine the effects of feeding a zinc (Zn) deficient diet to broiler chicks for 96 h post-hatch followed by feeding diets with different Zn sources and supplemental levels (5 to 21 d) on the growth performance, tissue, and excreta Zn content. At the start of the study, four hundred 20-day-old male broiler chicks were divided into two groups. One group was fed a corn soybean meal based diet containing 25 mg of Zn/kg (imprinting diet, ID). The second group was fed the basal diet supplemented with 40 mg of Zn/kg from Zn oxide (ZnO) (non-imprinting diet, NID). Both groups were fed these diets for 96 h. At d 5, chicks from each group were randomly assigned to the dietary treatments consisting of the basal diet alone or the basal diet supplemented with 8 or 40 mg/kg Zn as ZnO or Zn proteinate. Main effects of post-hatch Zn ID were observed on feed intake and G:F. ID decreased (P < 0.05) feed intake and improved (P < 0.05) the gain to feed ratio (G:F) of 14 and 21 d old chicks compared to G:F of chicks fed NID. Additionally, G:F for 14 and 21 d was improved (P < 0.05) by interaction of Zn source × level. Furthermore, at d 21 chicks fed the ID had a lower (P < 0.05) Zn content in the tibia ash and excreta, and a higher (P < 0.05) Zn content in the pancreas tissue compared to chicks fed NID. These results suggest that Zn imprinting can affect body Zn stores and early performance. PMID:27664197

  2. Maintenance of basal levels of autophagy in Huntington's disease mouse models displaying metabolic dysfunction.

    PubMed

    Baldo, Barbara; Soylu, Rana; Petersén, Asa

    2013-01-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin protein. Neuropathology in the basal ganglia and in the cerebral cortex has been linked to the motor and cognitive symptoms whereas recent work has suggested that the hypothalamus might be involved in the metabolic dysfunction. Several mouse models of HD that display metabolic dysfunction have hypothalamic pathology, and expression of mutant huntingtin in the hypothalamus has been causally linked to the development of metabolic dysfunction in mice. Although the pathogenic mechanisms by which mutant huntingtin exerts its toxic functions in the HD brain are not fully known, several studies have implicated a role for the lysososomal degradation pathway of autophagy. Interestingly, changes in autophagy in the hypothalamus have been associated with the development of metabolic dysfunction in wild-type mice. We hypothesized that expression of mutant huntingtin might lead to changes in the autophagy pathway in the hypothalamus in mice with metabolic dysfunction. We therefore investigated whether there were changes in basal levels of autophagy in a mouse model expressing a fragment of 853 amino acids of mutant huntingtin selectively in the hypothalamus using a recombinant adeno-associate viral vector approach as well as in the transgenic BACHD mice. We performed qRT-PCR and Western blot to investigate the mRNA and protein expression levels of selected autophagy markers. Our results show that basal levels of autophagy are maintained in the hypothalamus despite the presence of metabolic dysfunction in both mouse models. Furthermore, although there were no major changes in autophagy in the striatum and cortex of BACHD mice, we detected modest, but significant differences in levels of some markers in mice at 12 months of age. Taken together, our results indicate that overexpression of mutant huntingtin in mice do not significantly perturb basal levels of autophagy.

  3. Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

    PubMed

    Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

    2018-06-01

    Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

  4. Expression profile of desiccation tolerance factors in intertidal seaweed species during the tidal cycle.

    PubMed

    Fierro, Camila; López-Cristoffanini, Camilo; Meynard, Andrés; Lovazzano, Carlos; Castañeda, Francisco; Guajardo, Eduardo; Contreras-Porcia, Loretto

    2017-06-01

    The transcriptional modulation of desiccation tolerance factors in P. orbicularis explains its successful recuperation after water deficit. Differential responses to air exposure clarify seaweed distribution along intertidal rocky zones. Desiccation-tolerant seaweed species, such as Pyropia orbicularis, can tolerate near 96% water loss during air exposure. To understand the phenotypic plasticity of P. orbicularis to desiccation, several tolerance factors were assessed by RT-qPCR, Western-blot analysis, and enzymatic assays during the natural desiccation-rehydration cycle. Comparative enzymatic analyses were used to evidence differential responses between P. orbicularis and desiccation-sensitive species. The results showed that during desiccation, the relative mRNA levels of genes associated with basal metabolism [trehalose phosphate synthase (tps) and pyruvate dehydrogenase (pdh)] were overexpressed in P. orbicularis. Transcript levels related to antioxidant metabolism [peroxiredoxin (prx); thioredoxin (trx); catalase (cat); lipoxygenase (lox); ferredoxin (fnr); glutathione S-transferase (gst)], cellular detoxification [ABC transporter (abc) and ubiquitin (ubq)], and signal transduction [calmodulin (cam)] increased approximately 15- to 20-fold, with the majority returning to basal levels during the final hours of rehydration. In contrast, actin (act) and transcription factor 1 (tf1) transcripts were down-regulated. ABC transporter protein levels increased in P. orbicularis during desiccation, whereas PRX transcripts decreased. The antioxidant enzymes showed higher specific activity in P. orbicularis under desiccation, and sensitive species exhibited enzymatic inactivation and scarce ABC and PRX protein detection following prolonged desiccation. In conclusion, the reported findings contribute towards understanding the ecological distribution of intertidal seaweeds at the molecular and functional levels.

  5. Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

    PubMed

    Lin, Joanne C; Jan, Reem K; Kydd, Rob R; Russell, Bruce R

    2015-04-01

    Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

    PubMed

    Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

    2017-04-01

    We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  7. Transient hypogonadotropic hypogonadism in an amateur kickboxer after head trauma.

    PubMed

    Tanriverdi, F; Unluhizarci, K; Selcuklu, A; Casanueva, F F; Kelestimur, F

    2007-02-01

    Traumatic brain injury (TBI) is a frequent health problem and increased prevalence of neurendocrine dysfunction in patients with TBI has been reported. Sports injuries and particularly boxing may result in pituitary dysfunction. However, transient hypogonadotropic hypogonadism after an acute head trauma due to boxing and/or kickboxing has not been defined yet. We describe the case of a 20-yr-old male amateur kickboxer who was admitted to hospital complaining of decreased libido and impotence 2 weeks after an intensive bout. Basal hormone levels were compatible with mild hyperprolactinemia and hypogonadotpopic hypogonadism. GH axis was evaluated by GHRH+GHRP-6 test and peak GH level was within normal reference range. Three months later his complaints improved and abnormalities in basal hormone levels normalized. He was also re-evaluated 9 months after the first evaluation; basal hormone levels were within normal ranges and he had no complaints. In conclusion acute head trauma due to kickboxing may cause transient gonadotropin deficiency. Therefore, screening the pituitary functions of sportsmen dealing with combative sports is crucial.

  8. Hypothalamic stimulation and baroceptor reflex interaction on renal nerve activity.

    NASA Technical Reports Server (NTRS)

    Wilson, M. F.; Ninomiya, I.; Franz, G. N.; Judy, W. V.

    1971-01-01

    The basal level of mean renal nerve activity (MRNA-0) measured in anesthetized cats was found to be modified by the additive interaction of hypothalamic and baroceptor reflex influences. Data were collected with the four major baroceptor nerves either intact or cut, and with mean aortic pressure (MAP) either clamped with a reservoir or raised with l-epinephrine. With intact baroceptor nerves, MRNA stayed essentially constant at level MRNA-0 for MAP below an initial pressure P1, and fell approximately linearly to zero as MAP was raised to P2. Cutting the baroceptor nerves kept MRNA at MRNA-0 (assumed to represent basal central neural output) independent of MAP. The addition of hypothalamic stimulation produced nearly constant increments in MRNA for all pressure levels up to P2, with complete inhibition at some level above P2. The increments in MRNA depended on frequency and location of the stimulus. A piecewise linear model describes MRNA as a linear combination of hypothalamic, basal central neural, and baroceptor reflex activity.

  9. Effects of dietary betaine on growth performance, fat deposition and serum lipids in broilers subjected to chronic heat stress.

    PubMed

    He, Shaojun; Zhao, Shujing; Dai, Sifa; Liu, Deyi; Bokhari, Shehla Gul

    2015-10-01

    We evaluated the effects of supplementing betaine on growth performance, fat deposition and lipid metabolism status in broilers kept under chronic heat stress. Five hundred and forty chicks were randomly divided into six groups and the two normal temperature groups were held at normal ambient temperature and fed the basal diet (CONT) and basal diet plus 0.1% betaine, respectively. Heat stressed (HS) broilers were held at 32 ± 1°C from days 22 to 42 and fed the basal diet containing variable levels of betaine. Broilers were examined at days 28, 35 and 42 for body weight, feed consumption, fat deposition and serum lipids. The CONT and betaine-supplemented groups showed higher (P < 0.01 or P < 0.05) feed consumption, body weight gain, and lower feed : gain ratio compared with the HS-CONT group. Meanwhile, heat stress increased abdominal, intermuscular and subcutaneous fat deposition, whereas the supplemental betaine significantly decreased those compared with the HS-CONT group. Additionally, betaine supplementation significantly decreased triglyceride, free fatty acids, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol compared with HS-CONT. Chronic HS reduces broiler production performance. However, betaine can reverse these negative effects partially and thus improve carcass composition by changing lipid metabolism. © 2015 Japanese Society of Animal Science.

  10. Effect of Forsythia suspensa extract and chito-oligosaccharide alone or in combination on performance, intestinal barrier function, antioxidant capacity and immune characteristics of weaned piglets.

    PubMed

    Zhao, Panfeng; Piao, Xiangshu; Zeng, Zhikai; Li, Ping; Xu, Xiao; Wang, Hongliang

    2017-06-01

    We investigated the effects of Forsythia suspensa extract (FSE) and chito-oligosaccharide (COS), alone or together, on performance and health status of weaned piglets. The treatments included a basal diet and three diets with 160 mg/kg COS, 100 mg/kg FSE, or 100 mg/kg FSE and 160 mg/kg COS. Supplementation with COS or FSE alone improved (P < 0.01) average daily gain and feed conversion ratio compared with the basal diet in the first 2 weeks. On day 14, COS or FSE supplementation separately produced stronger (P < 0.01) serum total antioxidant capacity and glutathione peroxidase activities and lower serum endotoxin (P < 0.05) and malondialdehyde (P < 0.01) concentrations, generated higher (P < 0.01) serum complement 4 concentration, peripheral blood lymphocyte proliferation and serum-specific ovalbumin antibody level than the basal diet. No differences in oxidative injury and immunity indices were detected on day 28. The combined FSE and COS produced similar results compared with FSE or COS when given alone. These data indicate FSE or COS can increase performance by modulating intestinal permeability, antioxidant status and immune function in younger pigs. There appears to be similar advantage in feeding the additives in combination over those obtained from feeding them separately. © 2016 Japanese Society of Animal Science.

  11. Physiologic and Metabolic Benefits of Formulated Diets and Mangifera indica in Fluoride Toxicity.

    PubMed

    Karn, Sanjay S; Narasimhacharya, A V R L

    2015-06-01

    Fluorosis is a major health problem affecting normal physiological and metabolic functions in people living in endemic fluoride areas. The present work was aimed at investigating the role of basal, high carbohydrate low protein (HCLP) and high protein low carbohydrate (HPLC) diets and Mangifera indica fruit powder as a food supplement in fluoride-induced metabolic toxicity. Exposure to fluoride resulted in elevation of plasma glucose levels, ACP, ALP, SGPT, SGOT, and hepatic G-6-Pase activities, plasma and hepatic lipid profiles with decreased plasma protein, HDL-C, hepatic glycogen content and hexokinase activity in basal, HCLP and HPLC diet fed albino rats. However among the three diets tested, HPLC diet was found to be relatively, a better metabolic regulator. All the three formulated diets (basal, HCLP and HPLC) supplemented with mango fruit powder (5 and 10 g), decreased plasma glucose content, ACP, ALP, SGPT, SGOT and hepatic G-6-Pase activities and plasma as well as hepatic lipid profiles. These diets also elevated the hepatic glycogen content and hexokinase activities. These effects however, were prominent with the HPLC diet supplemented with mango fruit powder and, among the two doses of mango fruit powder, the higher dose (10 g) yielded more promising results. It is surmised that the micronutrients and phytochemicals present in the diets and the mango fruit could be responsible for attenuation of fluoride-induced metabolic toxicity.

  12. Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin

    PubMed Central

    Xie, Lin; Pan, Chunshen; Wang, Yuexi; Vaidya, Neel; Ye, Fen; Preblick, Ronald; Meneghini, Luigi

    2018-01-01

    This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla‐100) or insulin detemir (DET) with ≥1 A1C measurement during 12‐month baseline and 18‐month follow‐up periods were included. Patients with a refill gap of >90 days were considered non‐persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow‐up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non‐persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C. PMID:29278460

  13. Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress–mediated apoptosis: possible implication in asthma

    PubMed Central

    Merendino, Anna M.; Paul, Catherine; Vignola, Antonio M.; Costa, Maria A.; Melis, Mario; Chiappara, Giuseppina; Izzo, V.; Bousquet, J.; Arrigo, André-Patrick

    2002-01-01

    Inflammation of the human bronchial epithelium, as observed in asthmatics, is characterized by the selective death of the columnar epithelial cells, which desquamate from the basal cells. Tissue repair initiates from basal cells that resist inflammation. Here, we have evaluated the extent of apoptosis as well as the Hsp27 level of expression in epithelial cells from bronchial biopsy samples taken from normal and asthmatic subjects. Hsp27 is a chaperone whose expression protects against oxidative stress. We report that in asthmatic subjects the basal epithelium cells express a high level of Hsp27 but no apoptotic morphology. In contrast, apoptotic columnar cells are devoid of Hsp27 expression. Moreover, we observed a decreased resistance to hydrogen peroxide–induced apoptosis in human bronchial epithelial 16–HBE cells when they were genetically modified to express reduced levels of Hsp27. PMID:12482203

  14. Tropical Rain Forest Structure, Tree Growth and Dynamics along a 2700-m Elevational Transect in Costa Rica

    PubMed Central

    Clark, David B.; Hurtado, Johanna; Saatchi, Sassan S.

    2015-01-01

    Rapid biological changes are expected to occur on tropical elevational gradients as species migrate upslope or go extinct in the face of global warming. We established a series of 9 1-ha plots in old-growth tropical rainforest in Costa Rica along a 2700 m relief elevational gradient to carry out long-term monitoring of tropical rain forest structure, dynamics and tree growth. Within each plot we mapped, identified, and annually measured diameter for all woody individuals with stem diameters >10 cm for periods of 3-10 years. Wood species diversity peaked at 400-600 m and decreased substantially at higher elevations. Basal area and stem number varied by less than two-fold, with the exception of the 2800 m cloud forest summit, where basal area and stem number were approximately double that of lower sites. Canopy gaps extending to the forest floor accounted for <3% of microsites at all elevations. Height of highest crowns and the coefficient of variation of crown height both decreased with increasing elevation. Rates of turnover of individuals and of stand basal area decreased with elevation, but rates of diameter growth and stand basal area showed no simple relation to elevation. We discuss issues encountered in the design and implementation of this network of plots, including biased sampling, missing key meteorological and biomass data, and strategies for improving species-level research. Taking full advantage of the major research potential of tropical forest elevational transects will require sustaining and extending ground based studies, incorporation of new remotely-sensed data and data-acquisition platforms, and new funding models to support decadal research on these rapidly-changing systems. PMID:25856163

  15. The Oncogenic Role of RhoGAPs in Basal-Like Breast Cancer

    DTIC Science & Technology

    2015-02-01

    cell lines, and mouse models . c) In vivo tumorigenesis and metastasis assays. Milestones: Identify whether ArhGAP11A and RacGAP1 can promote tumor growth...also upregulated in basal (C3(I)-Tag) but not luminal (MMTV-Neu) genetically- engineered mouse models (Fig. 1B). At the protein level, RacGAP1 was...hypothesis that these RhoGAPs are indeed playing an oncogenic role in these cells. Human Tumors Mouse Model Tumors Normal Luminal A Basal-like Normal

  16. House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

    PubMed

    Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

    2012-01-01

    Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal expression of FOXP3. Copyright © 2012 S. Karger AG, Basel.

  17. Patterned basal seismicity shows sub-ice stream bedforms

    NASA Astrophysics Data System (ADS)

    Barcheck, C. G.; Tulaczyk, S. M.; Schwartz, S. Y.

    2017-12-01

    Patterns in seismicity emanating from the bottom of fast-moving ice streams and glaciers may indicate localized patches of higher basal resistance— sometimes called 'sticky spots', or otherwise varying basal properties. These seismogenic basal areas resist an unknown portion of the total driving stress of the Whillans Ice Plain (WIP), in West Antarctica, but may play an important role in the WIP stick-slip cycle and ice stream slowdown. To better understand the mechanism and importance of basal seismicity beneath the WIP, we analyze seismic data collected by a small aperture (< 3km) network of 8 surface and 5 borehole seismometers installed in the main central sticky spot of the WIP. We use a network beamforming technique to detect and roughly locate thousands of small (magnitude < 0), local basal micro-earthquakes in Dec 2014, and we compare the resulting map of seismicity to ice bottom depth measured by airborne radar. The number of basal earthquakes per area within the network is spatially heterogeneous, but a pattern of two 400m wide streaks of high seismicity rates is evident, with >50-500 earthquakes detected per 50x50m grid cell in 2 weeks. These seismically active streaks are elongated approximately in the ice flow direction with a spacing of 750m. Independent airborne radar measurements of ice bottom depth from Jan 2013 show a low-amplitude ( 5m) undulation in the basal topography superposed on a regional gradient in ice bottom depth. The flow-perpendicular wavelength of these low-amplitude undulations is comparable to the spacing of the high seismicity bands, and the streaks of high seismicity intersect local lows in the undulating basal topography. We interpret these seismic and radar observations as showing seismically active sub-ice stream bedforms that are low amplitude and elongated in the direction of ice flow, comparable to the morphology of mega scale glacial lineations (MSGLs), with high basal seismicity rates observed in the MSGL troughs. These results have implications for understanding the formation mechanism of MSGLS and well as understanding the interplay between basal topographic roughness, spatially varying basal till and hydrologic properties, basal resistance to fast ice flow, and ice stream stick-slip.

  18. Serologic control against hepatitis B virus among dental students of the University of Granada, Spain.

    PubMed

    Arias-Moliz, M-T; Rojas, L; Liébana-Cabanillas, F; Bernal, C; Castillo, F; Rodríguez-Archilla, A; Castillo, A; Liébana, J

    2015-09-01

    To evaluate the immunological situation against hepatitis B virus (HBV) of a cohort of dentistry students, to analyze the behavior of the levels of hepatitis B surface antigen (anti-HBs) after the administration of one or three vaccine doses, and to determine the influence of age and sex on the immune response. This retrospective cohort study included students attending the School of Dentistry of the institution where the study was performed from 2005 to 2012 who had completed the public health vaccination calendar for HBV at the age of 12-13. Data on age, sex, basal anti-HBs levels, post-vaccination anti-HBs results and final anti-HBs levels were collected. Comparisons of the basal and final levels, as well as associations regarding age and sex, were performed by means of the Student t and Chi-square tests. Of the 359 students, 97 (27.02%) had basal antibody concentrations <10 mIU/ml, whereas in 262 the levels of anti-HBs were ≥10 mIU/ml (72.98%). Of the 288 participating students who completed the School's protocol for immunization, 287 (99.65%) attained a level of protection ≥10 mIU/ml. Globally, there were statistically significant differences between the basal antibody levels and those achieved after administration of the vaccine and booster, but no association with age or sex was observed. About 70% of dental students vaccinated as pre-adolescents had serologic evidence of protection against HBV. Administering a booster is associated with the presence of an excellent immune memory. There is clearly a need to reinforce control of the antibody levels in groups at risk, such as Dentistry students.

  19. Effect of vitamin E supplementation and diet on fatty acid composition and on meat colour and lipid oxidation of lamb leg steaks displayed in modified atmosphere packs.

    PubMed

    Kasapidou, E; Wood, J D; Richardson, R I; Sinclair, L A; Wilkinson, R G; Enser, M

    2012-04-01

    Groups of 8 lambs were allocated to one of five concentrate diets supplemented with all-rac-α-tocopheryl acetate containing 30 (C30), 60 (C60), 120 (C120), 250 (C250) and 500 (C500) mg/kg dry matter. Two other groups were fed grass silage and 400 g/day concentrate with 60 (S60) or 500 (S500) mg α-tocopheryl acetate/kg dry matter. Within diet, vitamin E level did not affect growth performance or carcass characteristics. Basal diet did not affect final live weight, conformation and fatness scores. M. semimembranosus from S lambs contained more α-tocopherol than that of C lambs on the same intake and by day 6 in MAP (75%O2/25%CO2) chroma and a* were below acceptable levels in C30 lambs. TBARS were higher in C30 and C60 muscle than in other treatments (P<0.001) after 3 and 6 days display. Muscle fatty acid composition varied with basal diet but lipid oxidation depended more on vitamin E concentration with an initial concentration of 1.9 μg/g muscle preventing significant lipid oxidation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Modulation of antioxidant defense and immune response in zebra fish (Danio rerio) using dietary sodium propionate.

    PubMed

    Safari, Roghieh; Hoseinifar, Seyed Hossein; Kavandi, Morteza

    2016-12-01

    The present study explores the effect of dietary sodium propionate on mucosal immune response and expression of antioxidant enzyme genes in zebra fish (Danio rerio). Six hundred healthy zebra fish (0.42 ± 0.06 g) supplied, randomly stocked in 12 aquariums and fed on basal diets supplemented with different levels of sodium propionate [0 (control), 5, 10 and 20 g kg -1 ] for 8 weeks. At the end of the feeding trial, mucosal immune parameters (TNF-α, IL-1β, Lyz), antioxidant enzyme (SOD, CAT) as well as heat shock protein 70 (HSP70) gene expression were measured. The results revealed feeding on sodium propionate significantly up-regulated inflammatory response genes (TNF-α, IL-1β, Lyz) in a dose-dependent manner (P < 0.05). However, antioxidant enzyme genes significantly down-regulated in the treated group compared with control (P < 0.05). Also, HSP70 gene expression was higher in the liver of fish fed the basal diet and deceased with elevation of sodium propionate levels in the diet. These results showed beneficial effects of dietary sodium propionate on mucosal immune response as well as the antioxidant defense of zebra fish.

  1. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  2. Bacterial overgrowth and methane production in children with encopresis.

    PubMed

    Leiby, Alycia; Mehta, Devendra; Gopalareddy, Vani; Jackson-Walker, Susan; Horvath, Karoly

    2010-05-01

    To assess the prevalence of small intestinal bacterial overgrowth (SIBO) and methane production in children with encopresis. Radiographic fecal impaction (FI) scores were assessed in children with secondary, retentive encopresis and compared with the breath test results. Breath tests with hypoosmotic lactulose solution were performed in both the study patients (n = 50) and gastrointestinal control subjects (n = 39) groups. The FI scores were significantly higher in the patients with encopresis who were methane producers (P < .01). SIBO was diagnosed in 21 of 50 (42%) patients with encopresis and 9 of 39 (23%) of control subjects (P = .06). Methane was produced in 56% of the patients with encopresis versus 23.1% of the control subjects in the gastrointestinal group (P < .01). Fasting methane level was elevated in 48% versus 10.3 %, respectively (P < .01). Children with FI and encopresis had a higher prevalence of SIBO, elevated basal methane levels, and higher methane production. Methane production was associated with more severe colonic impaction. Further study is needed to determine whether methane production is a primary or secondary factor in the pathogenesis of SIBO and encopresis.

  3. Institution of basal-bolus therapy at diagnosis for children with type 1 diabetes mellitus.

    PubMed

    Adhikari, Soumya; Adams-Huet, Beverley; Wang, Yu-Chi A; Marks, James F; White, Perrin C

    2009-04-01

    We studied whether the institution of basal-bolus therapy immediately after diagnosis improved glycemic control in the first year after diagnosis for children with newly diagnosed type 1 diabetes mellitus. We reviewed the charts of 459 children > or =6 years of age who were diagnosed as having type 1 diabetes between July 1, 2002, and June 30, 2006 (212 treated with basal-bolus therapy and 247 treated with a more-conventional neutral protamine Hagedorn regimen). We abstracted data obtained at diagnosis and at quarterly clinic visits and compared groups by using repeated-measures, mixed-linear model analysis. We also reviewed the records of 198 children with preexisting type 1 diabetes mellitus of >1-year duration who changed from the neutral protamine Hagedorn regimen to a basal-bolus regimen during the review period. Glargine-treated subjects with newly diagnosed diabetes had lower hemoglobin A1c levels at 3, 6, 9, and 12 months after diagnosis than did neutral protamine Hagedorn-treated subjects (average hemoglobin A1c levels of 7.05% with glargine and 7.63% with neutral protamine Hagedorn, estimated across months 3, 6, 9, and 12, according to repeated-measures models adjusted for age at diagnosis and baseline hemoglobin A1c levels; treatment difference: 0.58%). Children with long-standing diabetes had no clinically important changes in their hemoglobin A1c levels in the first year after changing regimens. The institution of basal-bolus therapy with insulin glargine at the time of diagnosis of type 1 diabetes was associated with improved glycemic control, in comparison with more-conventional neutral protamine Hagedorn regimens, during the first year after diagnosis.

  4. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations

    PubMed Central

    Vinciati, Federica

    2017-01-01

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical–basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on “direct pathway” SPNs (dSPNs) and “indirect pathway” SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15–30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine from the striatum, a part of the basal ganglia, causes some symptoms of Parkinson's disease. Here, we elucidate how dopamine depletion alters striatal neuron firing in vivo, with an emphasis on defining whether and how spiny projection neurons (SPNs) engage in the synchronized beta-frequency (15–30 Hz) oscillations that become pathologically exaggerated throughout basal ganglia circuits in parkinsonism. We discovered that a select population of so-called “indirect pathway” SPNs not only fire at abnormally high rates, but are also particularly prone to being recruited to exaggerated beta oscillations. Our results provide an important link between two complementary theories that explain the presentation of disease symptoms on the basis of changes in firing rate or firing synchronization/rhythmicity. PMID:28847810

  5. Determination of dietary iron requirements by full expression of iron-containing cytochrome c oxidase in the heart of broilers from 22 to 42 d of age.

    PubMed

    Liao, Xiudong; Ma, Chunyan; Lu, Lin; Zhang, Liyang; Luo, Xugang

    2017-10-01

    The present study was carried out to determine dietary Fe requirements for the full expression of Fe-containing enzyme in broilers chicks from 22 to 42 d of age. At 22 d of age, 288 Arbor Acres male chicks were randomly assigned to one of six treatments with six replicates and fed a basal maize-soyabean-meal diet (control, containing 47·0 mg Fe/kg) or the basal diet supplemented with 20, 40, 60, 80 or 100 mg Fe/kg from FeSO4.7H2O for 21 d. Regression analysis was performed to estimate the optimal dietary Fe level using quadratic models. Liver cytochrome c oxidase (Cox), heart Cox and kidney succinate dehydrogenase mRNA levels as well as heart COX activity were affected (P<0·08) by dietary Fe level, and COX mRNA level and activity in heart of broilers increased quadratically (P<0·03) as dietary Fe level increased. The estimates of dietary Fe requirements were 110 and 104 mg/kg for the full expression of Cox mRNA and for its activity in the heart of broilers, respectively. The results from this study indicate that COX mRNA level and activity in the heart are new and sensitive criteria to evaluate the dietary Fe requirements of broilers, and the dietary Fe requirements would be 104-110 mg/kg to support the full expression of COX in the heart of broiler chicks from 22 to 42 d of age, which are higher than the current National Research Council Fe requirement (80 mg/kg) of broiler chicks from 1 to 21 d or 22 to 42 d of age.

  6. The edge- and basal-plane-specific electrochemistry of a single-layer graphene sheet

    PubMed Central

    Yuan, Wenjing; Zhou, Yu; Li, Yingru; Li, Chun; Peng, Hailin; Zhang, Jin; Liu, Zhongfan; Dai, Liming; Shi, Gaoquan

    2013-01-01

    Graphene has a unique atom-thick two-dimensional structure and excellent properties, making it attractive for a variety of electrochemical applications, including electrosynthesis, electrochemical sensors or electrocatalysis, and energy conversion and storage. However, the electrochemistry of single-layer graphene has not yet been well understood, possibly due to the technical difficulties in handling individual graphene sheet. Here, we report the electrochemical behavior at single-layer graphene-based electrodes, comparing the basal plane of graphene to its edge. The graphene edge showed 4 orders of magnitude higher specific capacitance, much faster electron transfer rate and stronger electrocatalytic activity than those of graphene basal plane. A convergent diffusion effect was observed at the sub-nanometer thick graphene edge-electrode to accelerate the electrochemical reactions. Coupling with the high conductivity of a high-quality graphene basal plane, graphene edge is an ideal electrode for electrocatalysis and for the storage of capacitive charges. PMID:23896697

  7. Effect of heat stress on the expression profile of Hsp90 among Sahiwal (Bos indicus) and Frieswal (Bos indicus × Bos taurus) breed of cattle: a comparative study.

    PubMed

    Deb, Rajib; Sajjanar, Basavaraj; Singh, Umesh; Kumar, Sushil; Singh, Rani; Sengar, G; Sharma, Arjava

    2014-02-25

    We evaluated the effect of thermal challenge on the expression profile of heat shock protein 90 (Hsp90) among Sahiwal (Bos indicus) and Frieswal (Bos indicus × Bos taurus) breeds of cattle. The present investigation was focused on the comparative studies on Hsp90 expression among Frieswal and Sahiwal under in vitro and environmental heat stress. Measured immediately after the in vitro heat shock to the peripheral blood mononuclear cells (PBMCs), the relative expression of Hsp90 mRNA was significantly (P<0.05) higher in Sahiwal compared to those in Frieswal. In later intervals of time, the differences in the expression levels between the two breeds become negligible coming down towards the basal level. A similar pattern was observed in the protein concentration showing significantly (P<0.05) higher levels in Sahiwal compared to those in Frieswal. The second sets of experiments were undertaken during summer months (March to May) when temperature peaked from 37 to 45 °C. During these months, Frieswal cows consistently recorded higher rectal temperatures than the Sahiwal breed. Further during this peak summer stress, Sahiwal showed significantly higher levels of mRNA transcripts as well as protein concentration compared to the Frieswal breed. Our findings also interestingly showed that, the cell viability of PBMC are significantly higher among the Sahiwal than Frieswal. Taken together, the experiments of both induced in vitro and environmental stress conditions indicate that, Sahiwal may express higher levels of Hsp90 then Frieswal to regulate their body temperature and increase cell survivality under heat stressed conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Analysis of space-time projection of differential and Michelson-type speckle-interferometer output signal for cardiovibration measurement

    NASA Astrophysics Data System (ADS)

    Ulyanov, Sergey S.; Tuchin, Valery V.

    1993-06-01

    The sex differences in cardiovascular system responses to a mild noise stress are established using the physiological and the dynamic systems theory methods. Lower levels of basal systolic arterial pressure and higher rates of its dropping and normalization under influence and after its cessation are typical for women. There are no hypertensive responses to stresses in women in contrast to men. The normalized entropy of the ECG signal, describing the physiological variability, increases in women and decreases in men. The advantages of female cardiovascular system response to mild stresses are discussed.

  9. Relationship between Increase in Astrocytic GLT-1 Glutamate Transport and Late-LTP

    ERIC Educational Resources Information Center

    Pita-Almenar, Juan D.; Zou, Shengwei; Colbert, Costa M.; Eskin, Arnold

    2012-01-01

    Na[superscript +]-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early…

  10. Gap junctions and other mechanisms of cell-cell communication regulate basal insulin secretion in the pancreatic islet.

    PubMed

    Benninger, R K P; Head, W Steven; Zhang, Min; Satin, Leslie S; Piston, David W

    2011-11-15

    Cell-cell communication in the islet of Langerhans is important for the regulation of insulin secretion. Gap-junctions coordinate oscillations in intracellular free-calcium ([Ca(2+)](i)) and insulin secretion in the islet following elevated glucose. Gap-junctions can also ensure that oscillatory [Ca(2+)](i) ceases when glucose is at a basal levels. We determine the roles of gap-junctions and other cell-cell communication pathways in the suppression of insulin secretion under basal conditions. Metabolic, electrical and insulin secretion levels were measured from islets lacking gap-junction coupling following deletion of connexion36 (Cx36(-/-)), and these results were compared to those obtained using fully isolated β-cells. K(ATP) loss-of-function islets provide a further experimental model to specifically study gap-junction mediated suppression of electrical activity. In isolated β-cells or Cx36(-/-) islets, elevations in [Ca(2+)](i) persisted in a subset of cells even at basal glucose. Isolated β-cells showed elevated insulin secretion at basal glucose; however, insulin secretion from Cx36(-/-) islets was minimally altered. [Ca(2+)](i) was further elevated under basal conditions, but insulin release still suppressed in K(ATP) loss-of-function islets. Forced elevation of cAMP led to PKA-mediated increases in insulin secretion from islets lacking gap-junctions, but not from islets expressing Cx36 gap junctions. We conclude there is a redundancy in how cell-cell communication in the islet suppresses insulin release. Gap junctions suppress cellular heterogeneity and spontaneous [Ca(2+)](i) signals, while other juxtacrine mechanisms, regulated by PKA and glucose, suppress more distal steps in exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still suppress basal insulin secretion.

  11. Effect of exposure to polycyclic aromatic hydrocarbons on basal ganglia and attention-deficit hyperactivity disorder symptoms in primary school children.

    PubMed

    Mortamais, Marion; Pujol, Jesus; van Drooge, Barend L; Macià, Didac; Martínez-Vilavella, Gerard; Reynes, Christelle; Sabatier, Robert; Rivas, Ioar; Grimalt, Joan; Forns, Joan; Alvarez-Pedrerol, Mar; Querol, Xavier; Sunyer, Jordi

    2017-08-01

    Polycyclic aromatic hydrocarbons (PAHs) have been proposed as environmental risk factors for attention deficit hyperactivity disorder (ADHD). The effects of these pollutants on brain structures potentially involved in the pathophysiology of ADHD are unknown. The aim of this study was to investigate the effects of PAHs on basal ganglia volumes and ADHD symptoms in school children. We conducted an imaging study in 242 children aged 8-12years, recruited through a set of representative schools of the city of Barcelona, Spain. Indoor and outdoor PAHs and benzo[a]pyrene (BPA) levels were assessed in the school environment, one year before the MRI assessment. Whole-brain volumes and basal ganglia volumes (caudate nucleus, globus pallidus, putamen) were derived from structural MRI scans using automated tissue segmentation. ADHD symptoms (ADHD/DSM-IV Scales, American Psychiatric Association 2002) were reported by teachers, and inattentiveness was evaluated with standard error of hit reaction time in the attention network computer-based test. Total PAHs and BPA were associated with caudate nucleus volume (CNV) (i.e., an interquartile range increase in BPA outdoor level (67pg/m 3 ) and indoor level (76pg/m 3 ) was significantly linked to a decrease in CNV (mm 3 ) (β=-150.6, 95% CI [-259.1, -42.1], p=0.007, and β=-122.4, 95% CI [-232.9, -11.8], p=0.030 respectively) independently of intracranial volume, age, sex, maternal education and socioeconomic vulnerability index at home). ADHD symptoms and inattentiveness increased in children with higher exposure to BPA, but these associations were not statistically significant. Exposure to PAHs, and in particular to BPA, is associated with subclinical changes on the caudate nucleus, even below the legislated annual target levels established in the European Union. The behavioral consequences of this induced brain change were not identified in this study, but given the caudate nucleus involvement in many crucial cognitive and behavior processes, this volume reduction is concerning for the children's neurodevelopment. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Organoclay nanocomposites of post-industrial waste poly(butylene terephthalate) from automotive parts.

    PubMed

    Quispe, Noe B; Fernandes, Elizabeth G; Zanata, Fernanda; Bartoli, Julio R; Souza, Diego H S; Ito, Edson N

    2015-10-01

    Polymeric nanocomposites are novel materials of huge interest owing to their favourable cost/performance ratio with low amount of nanofillers, improved thermal resistance, flame retardancy and mechanical properties in relation to their matrices. In this work, composites based on post-industrial waste or primary recycled poly(butylene terephthalate) and 5 wt.% of organic modified montmorillonite clays were melt compounded using a twin-screw extruder. A 2(2) factorial experimental design was used to study the compounding and processing variables: Organic modified montmorillonite with one or two hydrogenated tallow (initial basal spacing) and screw speed of the extruder. X-ray diffraction and transmission electron microscopy suggest that a partial exfoliation of the organoclay in the recycled poly(butylene terephthalate) matrix was achieved for organic modified montmorillonite with lower initial basal spacing. On the other hand, formulations containing organic modified montmorillonite with higher initial basal spacing showed only intercalated structure. The recycled poly(butylene terephthalate)-organic modified montmorillonite nanocomposites did not drip flaming material during burning tests. Storage of dynamic-mechanical, tensile and flexural moduli of the recycled poly(butylene terephthalate)-organic modified montmorillonite were improved when compared with both virgin and recycled poly(butylene terephthalate)s, mainly for nanocomposites formulated at a lower initial basal spacing organoclay. This could be related to a better diffusion of polymer into organic modified montmorillonite layers compared with the higher initial basal spacing organoclay. The improvements on the physical properties of recycled poly(butylene terephthalate) showed the feasibility to add value to primary recycled engineering thermoplastics with a very small amount of organic modified montmorillonite. © The Author(s) 2015.

  13. ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis.

    PubMed

    Cecchini, Nicolás M; Jung, Ho Won; Engle, Nancy L; Tschaplinski, Timothy J; Greenberg, Jean T

    2015-04-01

    Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively.

  14. Effects of irradiated Ergosan on the growth performance and mucus biological components of rainbow trout Oncorhynchus mykiss

    NASA Astrophysics Data System (ADS)

    Sheikhzadeh, Najmeh; Chehrara, Fatemeh; Heidarieh, Marzieh; Nofouzi, Katayoon; Baradaran, Behzad

    2016-01-01

    Effects of irradiated and non-irradiated Ergosan extract (alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish (128.03±9.4 g) were randomly divided into four equal groups, given the basal diet either unsupplemented with Ergosan (control group) or supplemented with crude Ergosan (5 g/kg), ethanol-extracted Ergosan (0.33 g/kg) or irradiated Ergosan (0.33 g/kg) according to this protocol: basal diet for 15 days, treatment diet for 15 days, basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan ( P <0.05). Dietary administration of different Ergosan types did not cause any changes in mucus protein level, but improved alkaline phosphatase level and hemagglutination titer compared with the control (basal diet without Ergosan) on day 55 of feeding trial ( P <0.05). Furthermore, the highest value of lysozyme activity was observed in gamma-irradiated Ergosan on day 55. In conclusion, gamma-irradiated Ergosan at 0.33 g/kg was found to improve growth performance and mucus biological components significantly in comparison with the control group (basal diet without Ergosan).

  15. SLC20A2 DEFICIENCY IN MICE LEADS TO ELEVATED PHOSPHATE LEVELS IN CEREBROSPINAL FLUID AND GLYMPHATIC PATHWAY-ASSOCIATED ARTERIOLAR CALCIFICATION, AND RECAPITULATES HUMAN IDIOPATHIC BASAL GANGLIA CALCIFICATION

    PubMed Central

    Wallingford, MC; Chia, J; Leaf, EM; Borgeia, S; Chavkin, NW; Sawangmake, C; Marro, K; Cox, TC; Speer, MY; Giachelli, CM

    2016-01-01

    Idiopathic basal ganglia calcification is a brain calcification disorder that has been genetically linked to autosomal dominant mutations in the sodium-dependent phosphate co-transporter, SLC20A2. The mechanisms whereby deficiency of Slc20a2 leads to basal ganglion calcification are unknown. In the mouse brain, we found that Slc20a2 was expressed in tissues that produce and/or regulate cerebrospinal fluid, including choroid plexus, ependyma and arteriolar smooth muscle cells. Haploinsufficient Slc20a2 +/− mice developed age-dependent basal ganglia calcification that formed in glymphatic pathway-associated arterioles. Slc20a2 deficiency uncovered phosphate homeostasis dysregulation characterized by abnormally high cerebrospinal fluid phosphate levels and hydrocephalus, in addition to basal ganglia calcification. Slc20a2 siRNA knockdown in smooth muscle cells revealed increased susceptibility to high phosphate-induced calcification. These data suggested that loss of Slc20a2 led to dysregulated phosphate homeostasis and enhanced susceptibility of arteriolar smooth muscle cells to elevated phosphate-induced calcification. Together, dysregulated cerebrospinal fluid phosphate and enhanced smooth muscle cell susceptibility may predispose to glymphatic pathway-associated arteriolar calcification. PMID:26822507

  16. Repression of endogenous Smad7 by Ski.

    PubMed

    Denissova, Natalia G; Liu, Fang

    2004-07-02

    The Ski protein has been proposed to serve as a corepressor for Smad4 to maintain a transforming growth factor-beta (TGF-beta)-responsive promoter at a repressed, basal level. However, there have been no reports so far that it indeed acts on a natural promoter. We have previously cloned the human Smad7 promoter and shown that it contains the 8-base pair palindromic Smad-binding element (SBE) necessary for TGF-beta induction. In this report, we have characterized the negative regulation of Smad7 promoter basal activity by Ski. We show that Ski inhibits the Smad7 promoter basal activity in a SBE-dependent manner. Mutation of the SBE abrogates the inhibitory effect of Ski on the Smad7 promoter. Moreover, mutation of the SBE increases the Smad7 promoter basal activity. Using the chromatin immunoprecipitation assay, we further show that Ski together with Smad4 binds to the endogenous Smad7 promoter. Finally, we show that RNAi knockdown of Ski increases Smad7 reporter gene activity in transient transfection assays as well as elevating the endogenous level of Smad7 mRNA. Taken together, our results provide the first evidence that Ski is indeed a corepressor for Smad4, which can inhibit a natural TGF-beta responsive gene at the basal state.

  17. The effect of extra virgin olive oil and soybean on DNA, cytogenicity and some antioxidant enzymes in rats.

    PubMed

    El-Kholy, Thanaa A; Abu Hilal, Mohammad; Al-Abbadi, Hatim Ali; Serafi, Abdulhalim Salim; Al-Ghamdi, Ahmad K; Sobhy, Hanan M; Richardson, John R C

    2014-06-23

    We investigated the effect of extra virgin (EV) olive oil and genetically modified (GM) soybean on DNA, cytogenicity and some antioxidant enzymes in rodents. Forty adult male albino rats were used in this study and divided into four groups. The control group of rodents was fed basal ration only. The second group was given basal ration mixed with EV olive oil (30%). The third group was fed basal ration mixed with GM (15%), and the fourth group survived on a combination of EV olive oil, GM and the basal ration for 65 consecutive days. On day 65, blood samples were collected from each rat for antioxidant enzyme analysis. In the group fed on basal ration mixed with GM soyabean (15%), there was a significant increase in serum level of lipid peroxidation, while glutathione transferase decreased significantly. Interestingly, GM soyabean increased not only the percentage of micronucleated polychromatic erythrocytes (MPCE), but also the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PEC/NEC); however, the amount of DNA and NCE were significantly decreased. Importantly, the combination of EV olive oil and GM soyabean significantly altered the tested parameters towards normal levels. This may suggest an important role for EV olive oil on rodents' organs and warrants further investigation in humans.

  18. Essential basal cytonemes take up Hedgehog in the Drosophila wing imaginal disc.

    PubMed

    Chen, Weitao; Huang, Hai; Hatori, Ryo; Kornberg, Thomas B

    2017-09-01

    Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression, and analyzed the movement and colocalization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes. Hh:GFP moved to basal subcellular locations prior to release from posterior compartment cells that express it, and was taken up by basal cytonemes that extend to the source cells. Hh and Ptc were present in puncta that moved along the basal cytonemes and formed characteristic apical-basal distributions in the anterior compartment cells. The basal cytonemes required diaphanous , SCAR , N euroglian and S ynaptobrevin , and both the Hh gradient and Hh signaling declined under conditions in which the cytonemes were compromised. These findings show that in the wing disc, Hh distributions and signaling are dependent upon basal release and uptake, and on cytoneme-mediated movement. No evidence for apical dispersion was obtained. © 2017. Published by The Company of Biologists Ltd.

  19. Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid leukemia

    PubMed Central

    Folkerts, Hendrik; Hilgendorf, Susan; Wierenga, Albertus T J; Jaques, Jennifer; Mulder, André B; Coffer, Paul J; Schuringa, Jan Jacob; Vellenga, Edo

    2017-01-01

    Here we have explored whether inhibition of autophagy can be used as a treatment strategy for acute myeloid leukemia (AML). Steady-state autophagy was measured in leukemic cell lines and primary human CD34+ AML cells with a large variability in basal autophagy between AMLs observed. The autophagy flux was higher in AMLs classified as poor risk, which are frequently associated with TP53 mutations (TP53mut), compared with favorable- and intermediate-risk AMLs. In addition, the higher flux was associated with a higher expression level of several autophagy genes, but was not affected by alterations in p53 expression by knocking down p53 or overexpression of wild-type p53 or p53R273H. AML CD34+ cells were more sensitive to the autophagy inhibitor hydroxychloroquine (HCQ) than normal bone marrow CD34+ cells. Similar, inhibition of autophagy by knockdown of ATG5 or ATG7 triggered apoptosis, which coincided with increased expression of p53. In contrast to wild-type p53 AML (TP53wt), HCQ treatment did not trigger a BAX and PUMA-dependent apoptotic response in AMLs harboring TP53mut. To further characterize autophagy in the leukemic stem cell-enriched cell fraction AML CD34+ cells were separated into ROSlow and ROShigh subfractions. The immature AML CD34+-enriched ROSlow cells maintained higher basal autophagy and showed reduced survival upon HCQ treatment compared with ROShigh cells. Finally, knockdown of ATG5 inhibits in vivo maintenance of AML CD34+ cells in NSG mice. These results indicate that targeting autophagy might provide new therapeutic options for treatment of AML since it affects the immature AML subfraction. PMID:28703806

  20. Visceral predictors of cardiovascular deconditioning in late middle-aged men

    NASA Technical Reports Server (NTRS)

    Goldwater, D. J.; De Roshia, C.; Natelson, B. H.; Levin, B. E.

    1985-01-01

    A number of visceral and behavioral factors connected with cardiovascular deconditioning were investigated, in order to identify a method for predicting the degree of orthostatic intolerance to spaceflight in several late-middle-aged men (55-65 years). Preliminary measurements were made of: mean arterial blood pressure plasma cortisol levels; and norepinephrine levels. Measurements of core temperature; plasma epinephrine level and subjective arousal from sleep were also obtained. Pairwise correlations were found for each of the variables and the time-to-blackout due centrifugal acceleration of up to +3 Gz. It is shown that the men with relatively low resting blood pressure were at greater risk of developing the clinical signs of cardiovascular deconditioning than were the men with higher basal blood pressure. Some applications of the experimental results to the development of selection criteria for Shuttle crews are discussed.

  1. Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

    PubMed

    Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

    2017-07-01

    This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

  2. Allostasis and Allostatic Load in the Context of Poverty in Early Childhood

    PubMed Central

    Blair, Clancy; Raver, Cybele; Granger, Douglas; Mills-Koonce, Roger; Hibel, Leah

    2014-01-01

    This paper examined the relation of early environmental adversity associated with poverty to child resting or basal level of cortisol in a prospective longitudinal sample of 1,135 children seen at 7, 15, 24, 35, and 48 months of age. We found main effects for length of time in poverty, poor housing quality, African American ethnicity, and low positive caregiving behavior in which each was uniquely associated with an overall higher level of cortisol from age 7 months to 48 months. We also found that two aspects of the early environment in the context of poverty, adult exits from the home and perceived economic insufficiency, were related to salivary cortisol in a time dependent manner. The effect for the first of these, exits from the home, was consistent with the principle of allostatic load in which the effects of adversity on stress physiology accumulate over time. The effect for perceived economic insufficiency was one in which insufficiency was associated with higher levels of cortisol in infancy but with a typical but steeper decline in cortisol with age at subsequent time points. PMID:21756436

  3. Real-world clinical responses in patients with type 2 diabetes mellitus adding exenatide BID (EBID) or mealtime insulin to basal insulin: a retrospective study using electronic medical record data.

    PubMed

    Lang, Kathleen; Nguyen, Hiep; Huang, Huan; Bauer, Elise; Levin, Philip

    2018-06-01

    Exenatide twice daily (EBID) and mealtime insulin are effective add-on therapies to basal insulin for type 2 diabetes patients in clinical trials. This study used electronic medical record (EMR) data to evaluate analogous real-world clinical responses. Adult patients initiating EBID or mealtime insulin as add-on to basal insulin during January 2008-March 2013 were identified in a US EMR database. EBID patients were propensity score matched 1:1 to mealtime insulin patients. Cohorts were followed for 12 months before (baseline) and 6 months after the index. A1C, hypoglycemic events, change in weight, and other clinical measures were evaluated by A1C attainment level (<6.5, < 7, < 7.5, <8, <9%) and baseline A1C. In total, 1249 EBID patients were matched to 1249 mealtime insulin patients. During follow-up, the percentage reaching A1C levels was similar for EBID vs mealtime insulin cohorts for all attainment levels (<7%: 27.8% vs 24.2%; < 9%: 79.7% vs 79.2%; p = NS). The percentage reaching A1C < 7% was similar for both cohorts with different baseline A1C. EBID patients had less hypoglycemia at all attainment levels (3.1% vs 11.1% [<6.5%]; 2.5% vs 4.7% [<9%]; all p < .03) and more weight loss (-9.0 vs -3.2 lb [<6.5%]; -3.4 vs +0.8 lb [<9%]; all p < .01). EBID added to basal insulin was as effective in a real-world setting as mealtime insulin added to basal insulin in reducing A1C, with less weight gain and less hypoglycemia for a wide range of A1C attainment levels and baseline values.

  4. Relationship between analytic values and canine obesity.

    PubMed

    Peña, C; Suárez, L; Bautista, I; Montoya, J A; Juste, M C

    2008-06-01

    The objective of this study was to assess the relationship between canine body condition and metabolic parameters like serum lipids, blood glucose and alanine aminotransferase (ALT) concentrations. We selected 127 dogs (42 males and 85 females) that were taken to our veterinary medicine service during routine visits. The mean age was 6.67 +/- 5.24 years. Body condition (BC) was measured by Laflamme scale and dogs were considered as obese when BC score was over 6. The following variables were collected: total cholesterol, high-density lipoprotein cholesterol, triglycerides, basal glucose and ALT. 66.1% of the dog cohort were obese. Total cholesterol and triglycerides were found to be higher (p < 0.05) in obese dogs with respect to normal weight dogs. In conclusion, obesity in dogs is associated with higher serum lipid levels.

  5. Correlates of basal insulin persistence among insulin-naïve people with type 2 diabetes: results from a multinational survey.

    PubMed

    Peyrot, Mark; Perez-Nieves, Magaly; Ivanova, Jasmina; Cao, Dachuang; Schmerold, Luke; Kalirai, Samaneh; Hadjiyianni, Irene

    2017-10-01

    People with T2DM who initiate basal insulin therapy often stop therapy temporarily or permanently soon after initiation. This study analyzes the reasons for and correlates of stopping and restarting basal insulin therapy among people with T2DM. An online survey was completed by 942 insulin-naïve adults with self-reported T2DM from Brazil, France, Germany, Japan, Spain, UK, and US. Respondents had initiated basal insulin therapy within the 3-24 months before survey participation and met criteria for one of three persistence groups: continuers had no gaps of ≥7 days in basal insulin treatment; interrupters had at least one gap in insulin therapy of ≥7 days within the first 6 months after initiation and had since restarted basal insulin; and discontinuers stopped using basal insulin within the first 6 months after initiation and had not restarted. Physician recommendations and cost were strongly implicated in patients stopping and not resuming insulin therapy. Continuous persistence was lower for patients with more worries about insulin initiation, greater difficulties and weight gain while using insulin, and higher for those using pens and perceiving their diabetes as severe. Repeated interruption of insulin therapy was associated with hyperglycemia and treatment burden while using insulin. Resumption and perceived likelihood of resumption were associated with hyperglycemia upon insulin cessation. Perceived likelihood of resumption among discontinuers was associated with perceived benefits of insulin. Better understanding of the risk factors for patient cessation and resumption of basal insulin therapy may help healthcare providers improve persistence with therapy.

  6. Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

    PubMed

    Debelić, Vladimir; Drnovšek Olup, Brigita; Žižek, Bogomir; Skitek, Milan; Jerin, Aleš

    2016-10-31

    To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. Patients with T1D had significantly higher levels of blood glucose (P<0.001), fructosamine (P<0.001), and 8-OHdG (P<0.001), but there were no significant differences in triglycerides (P=0.108), cholesterol (P=0.531), and LDL (P=0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11±0.15 vs 1.24±0.23; P=0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r=0.58; P<0.001), fructosamine (r=0.46; P=0.003), 8-OHdG (r=0.48; P=0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2=0.38, P<0.001). Higher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

  7. Evaluating the influence of National Research Council levels of copper, iron, manganese, and zinc using organic (Bioplex) minerals on resulting tissue mineral concentrations, metallothionein, and liver antioxidant enzymes in grower-finisher swine diets.

    PubMed

    Gowanlock, D W; Mahan, D C; Jolliff, J S; Hill, G M

    2015-03-01

    Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( < 0.05) as dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( < 0.05) to the 50% NRC treatment level. Liver Zn (relative and total) increased ( < 0.05) as dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The activities of liver enzymes containing graded levels of Zn were not affected by dietary microminerals at 115 kg BW. These results indicate that the supplemental levels of Cu, Fe, and Mn were not necessary for grower-finisher pigs and that these innate microminerals in a corn-soybean meal diet were adequate, whereas a need for supplemental Zn was demonstrated.

  8. Evaluation of various extracted vegetable oils, roasted soybeans, medium-chain triglyceride and an animal-vegetable fat blend for postweaning swine.

    PubMed

    Cera, K R; Mahan, D C; Reinhart, G A

    1990-09-01

    A total of 280 crossbred pigs weaned at 21 d of age and weighing approximately 6 kg were utilized in five replicates to evaluate pig growth responses when fed a basal diet or one of several dietary lipid sources during a 4-wk postweaning period. A basal corn-soybean meal-corn starch-dried whey diet was compared with diets supplemented at a 7.75% level with one of the following lipid sources: corn oil, coconut oil, soybean oil, medium-chain triglyceride (MCT) or an animal-vegetable blend. A sixth treatment evaluated a roasted soybean diet formulated to an energy:lysine level equivalent to that of the fat-supplemented diets. In Exp. II, 36 crossbred weanling barrows were used to determine apparent fat and N digestibilities when soybean oil, roasted soybean, coconut oil or the MCT-supplemented diets were fed. Although pigs fed coconut oil grew somewhat faster, fat inclusion generally did not increase pig growth rate or result in lowered feed intake during the initial weeks postweaning; during the latter portion of the starter phase the addition of dietary fat resulted in a higher growth rate but feed intake was unaffected, resulting in an overall improvement in feed-to-gain ratio (P less than .05) for all but the roasted soybean diet. Pigs fed coconut oil had higher serum triglyceride and lower serum urea concentrations than did pigs fed diets containing most other lipid sources. Pigs fed MCT and coconut oil diets had a higher (P less than .01) apparent fat digestibility during the initial 2 wk postweaning than pigs fed soybean oil or roasted soybean diets. Pigs fed MCT and roasted soybeans had poorest growth rates; apparent fat and N digestibilities were lowest (P less than .05) for the roasted soybean diet.

  9. Effect of N Fertilization Pattern on Rice Yield, N Use Efficiency and Fertilizer–N Fate in the Yangtze River Basin, China

    PubMed Central

    Liu, Xiaowei; Wang, Huoyan; Zhou, Jianmin; Hu, Fengqin; Zhu, Dejin; Chen, Zhaoming; Liu, Yongzhe

    2016-01-01

    High N loss and low N use efficiency (NUE), caused by high N fertilizer inputs and inappropriate fertilization patterns, have become important issues in the rice (Oryza sativa L.) growing regions of southern China. Changing current farmer fertilizer practice (FFP, 225 kg ha–1 N as three applications, 40% as basal fertilizer, 30% as tillering fertilizer and 30% as jointing fertilizer) to one—time root—zone fertilization (RZF, 225 kg ha–1 N applied once into 10 cm deep holes positioned 5 cm from the rice root as basal fertilizer) will address this problem. A two—year field experiment covering two rice growing regions was conducted to investigate the effect of urea one—time RZF on rice growth, nutrient uptake, and NUE. The highest NH4+–N content for RZF at fertilizer point at 30 d and 60 d after fertilization were 861.8 and 369.9 mg kg–1 higher than FFP, respectively. Rice yield and total N accumulation of RZF increased by 4.3–44.9% and 12.7–111.2% compared to FFP, respectively. RZF reduced fertilizer—N loss by 56.3–81.9% compared to FFP. The NUEs following RZF (mean of 65.8% for the difference method and 43.7% for the labelled method) were significantly higher than FFP (mean of 35.7% for the difference method and 14.4% for the labelled method). In conclusion, RZF maintained substantial levels of fertilizer—N in the root—zone, which led to enhanced rice biomass and N uptake during the early growth stages, increased fertilizer—N residual levels and reduced fertilizer—N loss at harvest. RZF produced a higher yield increment and showed an increased capacity to resist environmental threats than FFP in sandy soils. Therefore, adopting suitable fertilizer patterns plays a key role in enhancing agricultural benefits. PMID:27861491

  10. The GIP receptor displays higher basal activity than the GLP-1 receptor but does not recruit GRK2 or arrestin3 effectively.

    PubMed

    Al-Sabah, Suleiman; Al-Fulaij, Munya; Shaaban, Ghina; Ahmed, Hanadi A; Mann, Rosalind J; Donnelly, Dan; Bünemann, Moritz; Krasel, Cornelius

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important regulators of insulin secretion, and their functional loss is an early characteristic of type 2 diabetes mellitus (T2DM). Pharmacological levels of GLP-1, but not GIP, can overcome this loss. GLP-1 and GIP exert their insulinotropic effects through their respective receptors expressed on pancreatic β-cells. Both the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR) are members of the secretin family of G protein-coupled receptors (GPCRs) and couple positively to adenylate cyclase. We compared the signalling properties of these two receptors to gain further insight into why GLP-1, but not GIP, remains insulinotropic in T2DM patients. GLP-1R and GIPR were transiently expressed in HEK-293 cells, and basal and ligand-induced cAMP production were investigated using a cAMP-responsive luciferase reporter gene assay. Arrestin3 (Arr3) recruitment to the two receptors was investigated using enzyme fragment complementation, confocal microscopy and fluorescence resonance energy transfer (FRET). GIPR displayed significantly higher (P<0.05) ligand-independent activity than GLP-1R. Arr3 displayed a robust translocation to agonist-stimulated GLP-1R but not to GIPR. These observations were confirmed in FRET experiments, in which GLP-1 stimulated the recruitment of both GPCR kinase 2 (GRK2) and Arr3 to GLP-1R. These interactions were not reversed upon agonist washout. In contrast, GIP did not stimulate recruitment of either GRK2 or Arr3 to its receptor. Interestingly, arrestin remained at the plasma membrane even after prolonged (30 min) stimulation with GLP-1. Although the GLP-1R/arrestin interaction could not be reversed by agonist washout, GLP-1R and arrestin did not co-internalise, suggesting that GLP-1R is a class A receptor with regard to arrestin binding. GIPR displays higher basal activity than GLP-1R but does not effectively recruit GRK2 or Arr3.

  11. Effects of chestnut tannins on the meat quality, welfare, and antioxidant status of heat-stressed lambs.

    PubMed

    Liu, Huawei; Li, Ke; Mingbin, Lv; Zhao, Jinshan; Xiong, Benhai

    2016-06-01

    A study was conducted to evaluate the effects of chestnut tannins (CT) on the meat quality, welfare and antioxidant status of heat-stressed lambs. Lambs in one group were raised at 20°C and fed a basal diet (N), and three other groups (32°C) were fed a basal diet with 0 (CT0), 5 (CT5), and 10 g (CT10) of CT/kg. Addition of CT increased the b* and L* values of meat and superoxide dismutase and glutathione peroxidase activity in the serum and liver of heat-stressed lambs. The malondialdehyde concentration in meat, serum, and liver of heat-stressed lambs was decreased by dietary CT supplementation. Lambs in the CT0 group had higher cortisol, T3, and T4 levels, creatine kinase activity, white blood cell count, neutrophil count, neutrophil:lymphocyte ratio and a lower lymphocyte count than that in the N and CT10 groups. In conclusion, the addition of CT improved meat quality, certain stress parameters, and the antioxidant status of heat-stressed lambs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Itoh, Masahiko; Nelson, Celeste M.; Myers, Connie A.

    Maintenance of apico-basal polarity in normal breast epithelial acini requires a balance between cell proliferation, cell death, and proper cell-cell and cell-extracellular matrix signaling. Aberrations in any of these processes can disrupt tissue architecture and initiate tumor formation. Here we show that the small GTPase Rap1 is a crucial element in organizing acinar structure and inducing lumen formation. Rap1 activity in malignant HMT-3522 T4-2 cells is appreciably higher than in S1 cells, their non-malignant counterparts. Expression of dominant-negative Rap1 resulted in phenotypic reversion of T4-2 cells, led to formation of acinar structures with correct apico-basal polarity, and dramatically reduced tumormore » incidence despite the persistence of genomic abnormalities. The resulting acini contained prominent central lumina not observed when other reverting agents were used. Conversely, expression of dominant-active Rap1 in T4-2 cells inhibited phenotypic reversion and led to increased invasiveness and tumorigenicity. Thus, Rap1 acts as a central regulator of breast architecture, with normal levels of activation instructing apical polarity during acinar morphogenesis, and increased activation inducing tumor formation and progression to malignancy.« less

  13. Differential metallothionein expression in oral lichen planus and amalgam-associated oral lichenoid lesions

    PubMed Central

    Mendes, Gabriela-Geraldo; Servato, João-Paulo-Silva; Borges, Fabiana-Custódio; Rosa, Roberta-Rezende; Siqueira, Carla-Silva; de Faria, Paulo-Rogério; Loyola, Adriano-Mota

    2018-01-01

    Background Oral lichen planus (OLP) is a chronic inflammatory disease mediated by T cells, which manifests as reticular (white) or erosive (red) lesions, that are eventually painful. Oral lichenoid lesion (OLL) are distinguished from OLP by the presence of precipitating factors. The aim of this study was to evaluate whether the presence of metallothionein, which is involved in anti-apoptotic pathways and the anti-oxidative response, could serve as a differential diagnostic for OLP and OLL. Material and Methods We evaluated the expression of metallothionein in 40 cases of OLP and 20 cases of OLL using immunohistochemistry. Results and Conclusions White OLP has higher concentrations of metallothionein than red OLP in basal and parabasal layers. Moreover, metallothionein was more frequently observed in the cytoplasm and nuclei of basal cells in OLP patients compared to the same regions of OLL cases. Metallothionein levels are related to OLP severity and may contribute to a differential diagnosis between OLP and OLL. Key words:Oral lichen planus, oral lichenoid lesions, autoimmune disorders, metallothionein, immunohistochemistry. PMID:29680841

  14. Choline acetyltransferase and TrkA expression, as well as the improvement in cognition produced by E2 and P4 in ovariectomized rats, are blocked by ICI 182 780 and RU486.

    PubMed

    Espinosa-Raya, Judith; Cruz-Raya, Ulises; López-Martínez, Margarita; Picazo, Ofir

    2018-01-09

    Treatment with 17-β estradiol and progesterone improves the performance of ovariectomized rats in an autoshaping learning task, representing cognitive improvement. To test whether this is attributable to genomic mechanisms, the antiestrogen ICI 182 780 or antiprogesterone RU486 was injected into ovariectomized animals primed previously with estrogen or progesterone, respectively. Compared with the vehicle control, each hormone administered alone produced an elevated expression of choline acetyltransferase and TrkA, along with an improvement in performance on the behavioral test. E2+ICI reverted the increase in these two proteins. However, RU alone elicited higher ChAT expression. With this exception, there was a clear linear regression between the number of conditioned responses and the level of ChAT and TrkA in the basal forebrain. The results suggest that TrkA may be more important than ChAT for regulating autoshaping learning tasks, and that genomic mechanisms in the basal forebrain could possibly underlie hormonal improvement of cognition.

  15. Serum prolidase activity and oxidative status in patients with bronchial asthma.

    PubMed

    Cakmak, Alpay; Zeyrek, Dost; Atas, Ali; Celik, Hakim; Aksoy, Nurten; Erel, Ozcan

    2009-01-01

    Asthma is a disease where there is an accumulation of collagen in the reticular basal membrane of the airway leading to chronic inflammation. The enzyme prolidase plays an important role in the breakdown of collagen and the breakdown of intracellular protein especially in the final stage when peptides and dipeptides contain a high level of proline. To evaluate the relationship between prolidase activity and oxidative status in asthma patients. Comparison was made between 42 patients diagnosed with bronchial asthma and 32 healthy children of similar age and gender. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity (TAC) and total oxidant status (TOS) measurement. The prolidase activity of the asthma patient group was statistically significant compared with the control group (P< or =0.001). TAC and TOS levels in the asthma patient group were higher than the control group (P< or =0.001, P< or =0.002, respectively). No correlation was found between the prolidase and oxidative levels of the two groups. A positive correlation was determined between the prolidase activity and TAC in the asthma patient group (P< or =0.001, r=0.501). The prolidase enzyme activity, which plays a role in the collagen turnover, was low in the asthma patients; therefore, their collagen metabolism had undergone a change and this indicates that there may be an effect on the accumulation of collagen in the reticular basal membrane. Moreover, the high level of TOS indicates that these patients were exposed to severe oxidative stress with an increased TAC response. (c) 2009 Wiley-Liss, Inc.

  16. Increase in interleukin-8 production from circulating neutrophils upon antibiotic therapy in cystic fibrosis patients.

    PubMed

    Montemurro, Pasqualina; Mariggiò, Maria A; Barbuti, Giovanna; Cassano, Amalia; Vincenti, Alessandra; Serio, Gabriella; Guerra, Lorenzo; Diana, Anna; Santostasi, Teresa; Polizzi, Angela; Fumarulo, Ruggiero; Casavola, Valeria; Manca, Antonio; Conese, Massimo

    2012-12-01

    It is not known whether antibiotic therapy for lung disease in cystic fibrosis (CF) has an influence on circulating polymorphonuclear neutrophil (PMN) function and apoptosis. Blood PMNs were obtained from 14 CF patients before and after antibiotic treatment for an acute exacerbation, and from 10 healthy controls. PMNs were evaluated for production of reactive oxygen species (ROS) by spectrophotometry, of cytokines in the conditioned medium by ELISA, and apoptotic response by cytofluorimetry. ROS and interleukin (IL)-8 were produced at higher levels by CF PMNs pre-therapy than control PMNs under basal conditions. IL-8 levels further increased after therapy. Early apoptotic response was higher in CF PMNs pre-therapy than in control PMNs, and this pattern did not change after antibiotic treatment. Circulating PMNs are primed in CF acute patients. Further studies are needed to consider PMN-produced IL-8 as a biomarker to evaluate response to antibiotic therapy in CF patients. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  17. Measurement of Lactate Content and Amide Proton Transfer Values in the Basal Ganglia of a Neonatal Piglet Hypoxic-Ischemic Brain Injury Model Using MRI.

    PubMed

    Zheng, Y; Wang, X-M

    2017-04-01

    As amide proton transfer imaging is sensitive to protein content and intracellular pH, it has been widely used in the nervous system, including brain tumors and stroke. This work aimed to measure the lactate content and amide proton transfer values in the basal ganglia of a neonatal piglet hypoxic-ischemic brain injury model by using MR spectroscopy and amide proton transfer imaging. From 58 healthy neonatal piglets (3-5 days after birth; weight, 1-1.5 kg) selected initially, 9 piglets remained in the control group and 43 piglets, in the hypoxic-ischemic brain injury group. Single-section amide proton transfer imaging was performed at the coronal level of the basal ganglia. Amide proton transfer values of the bilateral basal ganglia were measured in all piglets. The ROI of MR spectroscopy imaging was the right basal ganglia, and the postprocessing was completed with LCModel software. After hypoxic-ischemic insult, the amide proton transfer values immediately decreased, and at 0-2 hours, they remained at their lowest level. Thereafter, they gradually increased and finally exceeded those of the control group at 48-72 hours. After hypoxic-ischemic insult, the lactate content increased immediately, was maximal at 2-6 hours, and then gradually decreased to the level of the control group. The amide proton transfer values were negatively correlated with lactate content ( r = -0.79, P < .05). This observation suggests that after hypoxic-ischemic insult, the recovery of pH was faster than that of lactate homeostasis. © 2017 by American Journal of Neuroradiology.

  18. Does systemic steroid deficiency affect inner ear functions?

    PubMed

    Dogan, Remzi; Merıc, Ayşenur; Gedık, Ozge; Tugrul, Selahattin; Eren, Sabri Baki; Ozturan, Orhan

    2015-01-01

    Today corticosteroids are employed for the treatment of various inner ear disorders. In this study we have investigated probable changes in hearing functions resulting from a deficiency of systemic steroid secretions. Twenty four healthy female rats were used in our study, allocated into three groups (medical adrenalectomy, medical adrenalectomy+dexamethasone, no treatment). Audiological evaluations were conducted at the beginning of the study and on days 7, 14 and 21. Blood samples were taken at the beginning and at the end of the study and blood corticosterone levels were determined. While there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values of group 1, their ABR threshold values showed significant increases. In group 2, there were no significant differences between the basal, 7th, 14th and 21st day DPOAE values. ABR thresholds of group 2 showed significant increases on days 7 and 14 as compared to their basal values, but there were no significant differences between the 21st day and basal ABR threshold values. There were no significant differences between the basal cortisol levels of the three groups. The mean cortisol level of group 1 on day 21 was found to be significantly lower than those of groups 2 and 3. The results of the study demonstrated that there were no significant changes in DPOAE values with the cessation of cortisol secretion, while there was a progressive increase in ABR thresholds, which could be overcome with cortisone replacement. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Decellularized bone extracellular matrix and human dental pulp stem cells as a construct for bone regeneration.

    PubMed

    Paduano, Francesco; Marrelli, Massimo; Alom, Noura; Amer, Mahetab; White, Lisa J; Shakesheff, Kevin M; Tatullo, Marco

    2017-06-01

    Dental pulp tissue represents a source of mesenchymal stem cells that have a strong differentiation potential towards the osteogenic lineage. The objective of the current study was to examine in vitro osteogenic induction of dental pulp stem cells (DPSCs) cultured on hydrogel scaffolds derived from decellularized bone extracellular matrix (bECM) compared to collagen type I (Col-I), the major component of bone matrix. DPSCs in combination with bECM hydrogels were cultured under three different conditions: basal medium, osteogenic medium and medium supplemented with growth factors (GFs) and cell growth, mineral deposition, gene and protein expression were investigated. The DPSCs/bECM hydrogel constructs cultured in basal medium showed that cells were viable after three weeks and that the expression of runt-related transcription factor 2 (RUNX-2) and bone sialoprotein (BSP) were significantly upregulated in the absence of extra osteogenic inducers compared to Col-I hydrogel scaffolds. In addition, the protein expression levels of BSP and osteocalcin were higher on bECM with respect to Col-I hydrogel scaffolds. Furthermore, DPSCs/bECM hydrogels cultured with osteogenic or GFs supplemented medium displayed a higher upregulation of the osteo-specific markers compared to Col-I hydrogels in identical media. Collectively, our results demonstrate that bECM hydrogels might be considered as suitable scaffolds to support osteogenic differentiation of DPSCs.

  20. Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.

    PubMed

    Caligiore, Daniele; Pezzulo, Giovanni; Baldassarre, Gianluca; Bostan, Andreea C; Strick, Peter L; Doya, Kenji; Helmich, Rick C; Dirkx, Michiel; Houk, James; Jörntell, Henrik; Lago-Rodriguez, Angel; Galea, Joseph M; Miall, R Chris; Popa, Traian; Kishore, Asha; Verschure, Paul F M J; Zucca, Riccardo; Herreros, Ivan

    2017-02-01

    Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

  1. Changes in gene expression in PBMCs profiles of PPARα target genes in obese and non-obese individuals during fasting.

    PubMed

    Felicidade, Ingrid; Marcarini, Juliana Cristina; Carreira, Clísia Mara; Amarante, Marla Karine; Afman, Lydia A; Mantovani, Mário Sérgio; Ribeiro, Lúcia Regina

    2015-01-01

    The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Q-PCR was utilized to assess the mRNA expression levels of target genes. In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel.

  2. Effect of long-term stress on H3Ser10 histone phosphorylation in neuronal nuclei of the sensorimotor cortex and midbrain reticular formation in rats with different nervous system excitability.

    PubMed

    Pavlova, M B; Dyuzhikova, N A; Shiryaeva, N V; Savenko, Yu N; Vaido, A I

    2013-07-01

    The effects of long-term mental and pain stress on H3Ser10 histone phosphorylation in neurons of the the sensorimotor corex and midbrain reticular formation were studied 24 h, 2 weeks, and 2 months after exposure of rats differing by the nervous system excitability. Rats with high excitability threshold exhibited higher basal level of H3Ser10 histone phosphorylation in the midbrain reticular formation neurons than rats with low excitability threshold. The sensorimotor cortical neurons of the two strains did not differ by this parameter. Stress led to a significant increase in the counts of immunopositive neuronal nuclei in rats with low excitability threshold: the parameter increased significantly in the sensorimotor cortex 24 h after exposure and normalized in 2 weeks after neurotization. In the midbrain reticular formation of this rat strain stress stimulated H3Ser10 histone phosphorylation after 24 h and after 2 weeks; the parameter normalized after neurotization in 2 months. Hence, genetically determined level of the nervous system excitability was essential for the basal level of neuron phosphorylation and for the time course of this process after long-term exposure to mental and pain stress, depending on the brain structure. A probable relationship between H3Ser10 histone phosphorylation process and liability to obsessive compulsive mental disorders in humans was discussed.

  3. Interaction of basal foliage removal and late season fungicide applications in management of Hop powdery mildew

    USDA-ARS?s Scientific Manuscript database

    Experiments were conducted over three years to evaluate whether fungicide applications could be ceased after the most susceptible stages of cone development (late July) without unduly affecting crop yield and quality when disease pressure was moderated with varying levels of basal foliage removal. I...

  4. Marital satisfaction, recovery from work, and diurnal cortisol among men and women.

    PubMed

    Saxbe, Darby E; Repetti, Rena L; Nishina, Adrienne

    2008-01-01

    Multilevel modeling was used to model relationships between salivary cortisol, daily diary ratings of work experiences, and Marital Adjustment Test scores (Locke & Wallace, 1959), in a sample of 60 adults who sampled saliva 4 times per day over 3 days. Among women but not men, marital satisfaction was significantly associated with a stronger basal cortisol cycle, with higher morning values and a steeper decline across the day. For women but not men, marital satisfaction moderated the within-subjects association between afternoon and evening cortisol level, such that marital quality appeared to bolster women's physiological recovery from work. For both men and women, evening cortisol was lower than usual on higher-workload days, and marital satisfaction augmented this association among women. Men showed higher evening cortisol after more distressing social experiences at work, an association that was strongest among men with higher marital satisfaction. This work has implications for the study of physiological recovery from work, and also suggests a pathway by which marital satisfaction influences allostatic load and physical health.

  5. Influence of exercise on serum levels of myoglobin measured by radioimmunoassay.

    PubMed

    Sabriá, M; Ruibal, A; Rey, C; Foz, M; Domenech, F M

    1983-01-01

    To determine the influence of exercise on serum levels of myoglobin, serum levels of this protein were determined by RIA in 90 healthy men, divided as follows: (1) Basal control (no exercise) 25 cases; (2) Moderate exercise (after subject had been working for 12 h in Medicine Emergency Service) 19 cases, and (3) Intensive exercise: (a) football professional (45-min match) 10 cases; (b) football amateur (45-min match) 10 cases; (c) basketball professional (45-min match) 10 cases, and (d) basketball professional (90-min training) 16 cases. Our results led us to the following conclusions. (1) Moderate exercise, such as the usual daily work, does not modify myoglobin levels; (2) Myoglobin serum levels after exercise increase in nearly all individuals. They are higher in untrained people; (3) There seems to be a correlation between exercise intensity and increase of myoglobin serum levels, and (4) The detection of serum myoglobin by RIA may have a wide field of application for sport medicine.

  6. Salt Marsh Formation in the Lower Hudson River Estuary

    NASA Technical Reports Server (NTRS)

    Merley, Michael; Peteet, Dorothy; Hansen, James E. (Technical Monitor)

    2001-01-01

    Salt marshes are constant depositional environments and as a result contain accurate indicators of past relative sea level rise and salinity. The Hudson River marshes are at least twice as deep when compared to coastal marshes on either side of the mouth of the Hudson. The reason for this difference in sedimentation is unclear. This study uses macrofossil data as well as sediment stratigraphy in order to understand the formation and evolution of these marshes. The composition of seeds, roots, shoots and foraminifera, are used to indicate past sea levels. The four sites involved in this study are, from south to north, the Arthur Kill Marsh in Staten Island (40 36 N, 74 77W), Piermont marsh (N 4100; 73 55W) Croton Point (41 14 N; 73 50W) and Iona Island (41 18N, 73 58W). These are all tidally influenced but with increasing distances from the New York Bight, which gives a good spectrum of tidal influence. AMS-C14 dates on basal macrofossils will document the time of each marsh formation. Basal material from Arthur Kill (8 m) includes freshwater seeds such as Viola, Potomageton and Alnus along with Salix buds. Basal material from Croton Point (10 m) includes fibrous woody material, foraminifera and Zanichellia seeds and other brackish vegetational components. The basal material from Piermont (13.77 m) is lacking any identifiable macrofossils between 150 and 500 microns. The basal material from Iona Island (10 m) has vegetation such as Scirpus and Cyperus seeds, probably implying a brackish environment. The freshwater origin of the Arthur Kill marsh in Staten Island is significant because it predates either sea level rise or the western channel incision. Additional implications for this study include evidence for changes in river channel geomorphology. Reasons for the relatively deeper river marshes include possible basal clay compaction, high production due to river and marine nutrients as well as tectonic activity. This study provides the groundwork for more high-resolution studies of these marshes to understand the fluctuations in salinity caused by relative sea level rise, tectonic faulting and/or changes in precipitation/evaporation.

  7. Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

    PubMed

    Botticelli, G; Bacchi Modena, A; Bresciani, D; Villa, P; Aguzzoli, L; Florio, P; Nappi, R E; Petraglia, F; Genazzani, A R

    1992-12-01

    The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Associations of coagulation factors IX and XI levels with incident coronary heart disease and ischemic stroke: the REGARDS study.

    PubMed

    Olson, N C; Cushman, M; Judd, S E; Kissela, B M; Safford, M M; Howard, G; Zakai, N A

    2017-06-01

    Essentials Coagulation factors (F) IX and XI have been implicated in cardiovascular disease (CVD) risk. We studied associations of FIX and FXI with incident coronary heart disease (CHD) and stroke. Higher FIX antigen was associated with incident CHD risk in blacks but not whites. Higher levels of FIX antigen may be a CHD risk factor among blacks. Background Recent studies have suggested the importance of coagulation factor IX and FXI in cardiovascular disease (CVD) risk. Objectives To determine whether basal levels of FIX or FXI antigen were associated with the risk of incident coronary heart disease (CHD) or ischemic stroke. Patients/Methods The REasons for Geographic And Racial Differences in Stroke (REGARDS) study recruited 30 239 participants across the contiguous USA between 2003 and 2007. In a case-cohort study within REGARDS, FIX and FXI antigen were measured in participants with incident CHD (n = 609), in participants with incident ischemic stroke (n = 538), and in a cohort random sample (n = 1038). Hazard ratios (HRs) for CHD and ischemic stroke risk were estimated with Cox models per standard deviation higher FIX or FXI level, adjusted for CVD risk factors. Results In models adjusting for CHD risk factors, higher FIX levels were associated with incident CHD risk (HR 1.19; 95% confidence interval [CI] 1.01-1.40) and the relationship of higher FXI levels was slightly weaker (HR 1.15; 95% CI 0.97-1.36). When stratified by race, the HR of FIX was higher in blacks (HR 1.39; 95% CI 1.10-1.75) than in whites (HR 1.06; 95% CI 0.86-1.31). After adjustment for stroke risk factors, there was no longer an association of FIX levels with ischemic stroke, whereas the association of FXI levels with ischemic stroke was slightly attenuated. Conclusions Higher FIX antigen levels were associated with incident CHD in blacks but not in whites. FIX levels may increase CHD risk among blacks. © 2017 International Society on Thrombosis and Haemostasis.

  9. [Calcitonin physiologically regulates the postmenopausal bone loss and possibly inhibits the bone loss in fast losers].

    PubMed

    Chen, J T; Shiraki, M; Katase, K; Kato, T; Hirai, Y; Hasumi, K

    1994-10-01

    To study the correlation between the basal serum calcitonin level and L2-4 bone mineral density (BMD), a cross sectional study of 384 healthy subjects (106 premenopausal, 88 perimenopausal and 109 postmenopausal subjects) and a longitudinal study of 42 oophorectomized subjects were conducted. A positive correlation was found in perimenopause (r = 0.219, p = 0.040) but not in premenopause (r = 0.069, p = 0.4898) and postmenopause (r = 0.141, p = 0.0554) in a cross sectional study. The percent reduction in L2-4BMD compared to the baseline also correlated with preoperative calcitonin levels at 6 months after oophorectomy (r = 0.333, p = 0.0442), but not significantly at 12 months (r = 0.224, p = 0.27). These data suggest that the basal calcitonin level correlates to L2-4BMD only at perimenopause or in the early postoophorectomized period when bone turnover is accelerated and bone resorption seems to be faster than bone formation. In addition the premenopausal basal calcitonin level may be an indicator of the fast loser after menopause.

  10. Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study.

    PubMed

    Sekine, Yoshimoto; Minabe, Yoshio; Kawai, Masayoshi; Suzuki, Katsuaki; Iyo, Masaomi; Isoda, Haruo; Sakahara, Harumi; Ashby, Charles R; Takei, Nori; Mori, Norio

    2002-09-01

    Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

  11. Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hattangadi-Gluth, Jona A.; Wo, Jennifer Y.; Nguyen, Paul L.

    2012-03-01

    Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ ormore » PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal breast cancers, such as increased boost doses, concomitant radiation and chemotherapy, or targeted therapy agents, should be explored.« less

  12. Farmers develop more aggressive histologic subtypes of basal cell carcinoma. Experience from a Tertiary Hospital in Northern Greece.

    PubMed

    Apalla, Z; Lallas, A; Sotiriou, E; Lazaridou, E; Vakirlis, E; Trakatelli, M; Kyrgidis, A; Ioannides, D

    2016-04-01

    Ultraviolet radiation plays an important role in the pathogenesis of non-melanoma skin cancer. Outdoor workers, including farmers, experience higher exposure levels compared to the general population. Available literature data suggest that occupational ultraviolet exposure represents an independent risk factor for squamous cell carcinoma; whereas for basal cell carcinoma (BCC) this association still remains unclarified. To analyse the epidemiological, clinical and histological data of patients diagnosed with BCC, and correlate them with outdoor occupation in farmers. Individuals with histologically diagnosed BCCs, between September 2013 and September 2015, were included in the study. Their medical data, including epidemiological, clinical and histological characteristics, were recorded and analysed in conjunction with the occupation. Farmers were identified based on their specific public health insurance. Three hundred and forty patients, with 542 BCCs were included in the study. One hundred and twenty (35.3%) were farmers. Mean age of farmers was lower than non-farmers (66.0 ± 9.1 years vs. 75 ± 6.6 years, Mann-Whitney U-test, P < 0.001). Farmers had a sixfold higher probability for exhibiting photodamaged skin (OR = 6.02, 95% CI: 3.66-9.90, P < 0.001). Farmer workers were more likely to exhibit infiltrative or morpheaform BCC, but less likely to develop superficial BCC. Our results indicate a higher risk of earlier development of more aggressive histological subtypes of BCCs in farmers. Photodamage was also more common in this group. Primary and secondary prevention strategies focusing on outdoor workers, including farmers, are mandatory. © 2016 European Academy of Dermatology and Venereology.

  13. Pregnane X Receptor-Humanized Mice Recapitulate Gender Differences in Ethanol Metabolism but Not Hepatotoxicity.

    PubMed

    Spruiell, Krisstonia; Gyamfi, Afua A; Yeyeodu, Susan T; Richardson, Ricardo M; Gonzalez, Frank J; Gyamfi, Maxwell A

    2015-09-01

    Both human and rodent females are more susceptible to developing alcoholic liver disease following chronic ethanol (EtOH) ingestion. However, little is known about the relative effects of acute EtOH exposure on hepatotoxicity in female versus male mice. The nuclear receptor pregnane X receptor (PXR; NR1I2) is a broad-specificity sensor with species-specific responses to toxic agents. To examine the effects of the human PXR on acute EtOH toxicity, the responses of male and female PXR-humanized (hPXR) transgenic mice administered oral binge EtOH (4.5 g/kg) were analyzed. Basal differences were observed between hPXR males and females in which females expressed higher levels of two principal enzymes responsible for EtOH metabolism, alcohol dehydrogenase 1 and aldehyde dehydrogenase 2, and two key mediators of hepatocyte replication and repair, cyclin D1 and proliferating cell nuclear antigen. EtOH ingestion upregulated hepatic estrogen receptor α, cyclin D1, and CYP2E1 in both genders, but differentially altered lipid and EtOH metabolism. Consistent with higher basal levels of EtOH-metabolizing enzymes, blood EtOH was more rapidly cleared in hPXR females. These factors combined to provide greater protection against EtOH-induced liver injury in female hPXR mice, as revealed by markers for liver damage, lipid peroxidation, and endoplasmic reticulum stress. These results indicate that female hPXR mice are less susceptible to acute binge EtOH-induced hepatotoxicity than their male counterparts, due at least in part to the relative suppression of cellular stress and enhanced expression of enzymes involved in both EtOH metabolism and hepatocyte proliferation and repair in hPXR females. U.S. Government work not protected by U.S. copyright.

  14. Efflux Pump Gene Expression in Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates

    PubMed Central

    Jiang, Yi; Wei, Jianhao; Zhao, Li-li; Zhao, Xiuqin; Lu, Jianxin; Wan, Kanglin

    2015-01-01

    Isoniazid (INH) and rifampicin (RIF) are the two most effective drugs in tuberculosis therapy. Understanding the molecular mechanisms of resistance to these two drugs is essential to quickly diagnose multidrug-resistant (MDR) tuberculosis and extensive drug-resistant tuberculosis. Nine clinical Mycobacterium tuberculosis isolates resistant to only INH and RIF and 10 clinical pan-sensitive isolates were included to evaluate the expression of 20 putative drug efflux pump genes and sequence mutations in rpoB (RIF), katG (INH), the inhA promoter (INH), and oxyR-ahpC (INH). Nine and three MDR isolates were induced to overexpress efflux pump genes by INH and RIF, respectively. Eight and two efflux pump genes were induced to overexpress by INH and RIF in MDR isolates, respectively. drrA, drrB, efpA, jefA (Rv2459), mmr, Rv0849, Rv1634, and Rv1250 were overexpressed under INH or RIF stress. Most efflux pump genes were overexpressed under INH stress in a MDR isolates that carried the wild-type katG, inhA, and oxyR-ahpC associated with INH resistance than in those that carried mutations. The expression levels of 11 genes (efpA, Rv0849, Rv1250, P55 (Rv1410c), Rv1634, Rv2994, stp, Rv2459, pstB, drrA, and drrB) without drug inducement were significantly higher (P < 0.05) in nine MDR isolates than in 10 pan-sensitive isolates. In conclusion, efflux pumps may play an important role in INH acquired resistance in MDR M. tuberculosis, especially in those strains having no mutations in genes associated with INH resistance; basal expression levels of some efflux pump genes are higher in MDR isolates than in pan-sensitive isolates and the basal expressional differences may be helpful to diagnose and treat resistant tuberculosis. PMID:25695504

  15. HSP70 in human polymorphonuclear and mononuclear leukocytes: comparison of the protein content and transcriptional activity of HSPA genes.

    PubMed

    Boyko, Anna A; Azhikina, Tatyana L; Streltsova, Maria A; Sapozhnikov, Alexander M; Kovalenko, Elena I

    2017-01-01

    Cell-type specific variations are typical for the expression of different members of the HSP70 family. In circulating immune cells, HSP70 proteins interact with units of signaling pathways involved in the immune responses and may promote cell survival in sites of inflammation. In this work, we compared basal HSP70 expression and stress-induced HSP70 response in polymorphonuclear and mononuclear human leukocytes. The intracellular content of inducible and constitutive forms of HSP70 was analyzed in relation to the transcriptional activity of HSPA genes. Hyperthermia was used as the stress model for induction of HSP70 synthesis in the cells. Our results demonstrated that granulocytes (mainly neutrophils) and mononuclear cells differ significantly by both basal HSP70 expression and levels of HSP70 induction under hyperthermia. The differences were observed at the levels of HSPA gene transcription and intracellular HSP70 content. The expression of constitutive Hsс70 protein was much higher in mononuclear cells consisting of monocytes and lymphocytes than in granulocytes. At the same time, intact neutrophils showed increased expression of inducible Hsp70 protein compared to mononuclear cells. Heat treatment induced additional expression of HSPA genes in leukocytes. The most pronounced increase in the expression was observed in polymorphonuclear and mononuclear leukocytes for HSPA1A/B. However, in granulocytes, the induction of the transcription of the HSPA8 gene encoding the Hsc70 protein was significantly higher than in mononuclear cells. These variations in transcriptional activity of HSPA genes and intracellular HSP70 content in different populations of leukocytes may reflect specified requirements for the chaperone activity in the cells with a distinct functional role in the immune system.

  16. Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

    PubMed

    Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

    2016-04-01

    Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. A Mid-Holocene Relative Sea-Level Stack, New Jersey, USA

    NASA Astrophysics Data System (ADS)

    Horton, B.; Walker, J. S.; Kemp, A.; Shaw, T. J.; Kopp, R. E.

    2017-12-01

    Most high resolution (decimeter- and decadal-scale) relative sea-level (RSL) records using salt-marsh microfossils as a proxy only extend through the Common Era, limiting our understanding of driving mechanisms of RSL change and how sea-level is influenced by changing climate. Records beyond the Common Era are limited by the depth of continuous sequences of salt-marsh peat suitable for high resolution reconstructions, as well as contamination by local processes such as sediment compaction. In contrast, sequences of basal peats have produced compaction-free RSL records through the Holocene, but at a low resolution (meter- and centennial-scale). We devise a new Multi-Proxy Presence/Absence Method (MP2AM) to develop a mid-Holocene RSL stack. We stack a series of 1 m basal peat cores that overlap along a uniform elevational gradient above an incompressible basal sand. We analyzed three sea-level indicators from 14 cores: foraminifera, testate amoebae, and stable carbon isotope geochemistry. To reconstruct RSL, this multi-proxy approach uses the timesaving presence/absence of forams and testates to determine the elevation of the highest occurrence of forams and the lowest occurrence of testates in each basal core. We use stable carbon isotope geochemistry to determine the C3/C4 vegetation boundary in each core. We develop age-depth models for each core using a series of radiocarbon dates. The RSL records from each 1 m basal core are combined to create a stack or, in effect, one long core of salt-marsh material. This method removes the issue of compaction to create a continuous RSL record to address temporal changes and periods of climate and sea-level variability. We reconstruct a southern NJ mid-Holocene RSL record from Edwin B. Forsythe National Wildlife Refuge, where Kemp et al. (2013) completed a 2500 yr RSL record using a foraminifera-based transfer function approach. Preliminary radiocarbon dates suggest the basal sequence is at least 4246-4408 cal yrs BP. Presence/absence of forams and testates and the transition of C3/C4 vegetation is identified in each core and constrained with radiocarbon dating. A short core with full counts of forams and testates is used to test the new method and compare with the traditional foraminifera-based transfer function approach and the local tide gauge record.

  18. Effect of guava leaves on growth and the non-specific immune response of Penaeus monodon.

    PubMed

    Yin, Xiao-Li; Li, Zhuo-Jia; Yang, Keng; Lin, Hei-Zhao; Guo, Zhi-Xun

    2014-09-01

    Guava (Psidium guajava L.) leaf extracts have antiviral and antibacterial activity against shrimp pathogens such as yellow-head virus (YHV), white spot syndrome virus (WSSV), and Vibrio harveyi, which make it a potential water disinfectant for use in shrimp culture. In this study, the safety of guava leaf supplementation in shrimp was evaluated by studying its influence on growth and the non-specific immune response of Penaeus monodon. Six diets containing different levels of guava leaves (0% [basal diet], 0.025% [G1], 0.05% [G2], 0.1% [G3], 0.2% [G4], and 0.4% [G5]) were fed to groups of shrimp (1.576 ± 0.011 g body weight) in triplicate for 56 days. Growth performance (final body weight, WG, PWG, SGR) of shrimp fed guava leaf diets was significantly higher (P < 0.05) than that of shrimp fed on the basal diet. The G1 diet resulted in the highest body weight gain (308.44%), followed by the G2 (295.45%), G3 (283.05%), G5 (281.29%), G4 (276.11%), and finally the basal diet (214.58%). Survival of shrimp in the G1 diet group was higher than that of shrimp in the control and the other experimental groups; however, no statistical differences (P > 0.05) were found. Dietary supplementation with guava leaf improved the activities of prophenoloxidase (PO) and nitric oxide synthase (NOS) in serum, and of superoxide dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LSZ) both in serum and hepatopancreas of shrimp. In the experimental groups, the activities of these enzymes followed a similar pattern of change; they increased initially at low levels of dietary supplementation and then decreased with increasing concentrations of dietary guava leaf. Serum PO and SOD activities in shrimp fed the G1 diet reached 7.50 U ml(-1) and 178.33 U ml(-1), respectively, with PO activity being significantly higher than in controls. In shrimp fed the G1 diet, SOD, ACP, and AKP activities in hepatopancreas were significantly higher than in the controls, reaching 57.32 U g(-1), 23.28 U g(-1), and 19.35 U g(-1) protein, respectively. The highest activities of serum ACP, AKP, LSZ, and of hepatopancreas LSZ, were observed in the G3 diet group. Total nitric oxide synthase (TNOS) activity was highest (64.80 U ml(-1)) in the G4 diet group, which was significantly higher than that observed in the control group. These results suggest that dietary guava leaf supplementation could enhance the growth performance and non-specific immune response of P. monodon. Therefore, guava leaf is considered safe for use as a water disinfectant in shrimp culture. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Cytokine modulation in response to acute and chronic aquatic therapy intervention in Parkinson disease individuals: A pilot study.

    PubMed

    Pochmann, Daniela; Peccin, Pâmela Krause; da Silva, Ivy Reichert Vital; Dorneles, Gilson Pires; Peres, Alessandra; Nique, Simone; Striebel, Vera; Elsner, Viviane Rostirola

    2018-05-01

    The study aimed to compare the basal plasma levels of inflammatory markers (MCP-1, IL-1ra and IL-1β) in Parkinson Disease group (PDG) with control healthy subjects (control group, CG), as well to investigate the acute and chronic effects of an aquatic physiotherapy program on these biomarkers in PDG. Firstly, a rest blood sampling was taken from antecubital vein of the PD and CG. After, the PD individuals were submitted to a supervisioned aquatic physiotherapy program during 1 month, twice a week (60 min/session). In order to evaluate the acute and chronic effects of the intervention on the biomarkers, blood samples were in 4 times: before the exercise program (pre), immediately after the first session, 48 h after the exercise session and 1 month after the intervention. It was observed higher levels of the pro-inflammatory cytokines IL-1β and MCP-1 and reduced levels IL-1ra in PDG compared to the CG. Regarding the intervention effects in PDG, a remarkable reduction on IL-1β and MCP-1 levels at 48 h when compared to the basal were found. Furthermore, after 1 month, it was observed diminished levels of MCP-1 in combination to an increase on IL-1ra. Our data support the idea that an inflammatory status is linked to PD and that MCP-1 and IL-1ra could be taken as promising biomarkers in this condition. We also demonstrated that an aquatic physiotherapy program may offer a potential intervention able to attenuate immune responses in PD individuals in a short and long-term perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.

    PubMed

    Duvic, Madeleine; Ni, Xiao; Talpur, Rakhashandra; Herne, Kelly; Schulz, Claudia; Sui, Dawen; Ward, Staci; Joseph, Aaron; Hazarika, Parul

    2003-10-01

    Basal cell carcinomas are the most common form of skin cancer. Tazarotene is a retinoic acid receptor selective retinoid that upregulates a tumor suppressor, tazarotene-induced gene 3 (TIG-3), in keratinocytes and psoriasis. Expression of TIG-3 in basal cell carcinomas was studied in an opened-label pilot biomarker study of 22 patients with basal cell carcinomas who applied tazarotene 0.1% gel for up to 12 wk prior to excision. Nineteen paired baseline and treated specimens were compared using immunohistochemistry and in situ hybridization. Compared to overlying normal epidermis, TIG-3 protein and mRNA were decreased in 14 and 18 of 19 basal cell carcinomas (74% and 95%), respectively (p < 0.001). Tazarotene treatment was associated with increased TIG-3 protein and mRNA expression in basal cell carcinomas compared to baseline levels (p < or = 0.001 and p = 0.028, respectively). Sixty percent of basal cell carcinomas treated with tazarotene decreased in size by at least 25%. Ten of 19 lesions improved histologically, including three complete responses. There was a correlation between the increased expression of TIG-3 protein and histologic improvement (p = 0.020), suggesting that suppression of TIG-3 may underlie the development of basal cell carcinomas. This association suggests that reversal of TIG-3 expression may help to explain the mechanism of retinoid action in epidermal differentiation and chemoprevention.

  1. Postnatal handling does not normalize hypothalamic corticotropin-releasing factor mRNA levels in animals prenatally exposed to ethanol.

    PubMed

    Gabriel, Kara I; Glavas, Maria M; Ellis, Linda; Weinberg, Joanne

    2005-06-09

    Postnatal handling has been shown to attenuate some of the deficits in developmental outcome observed following prenatal ethanol exposure (E) although it appears to be ineffective at ameliorating the hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stressors that has been observed in adult E animals. However, the effects of postnatal handling on central regulation of HPA activity in E animals, particularly with regard to alterations in steady-state hypothalamic corticotropin-releasing factor (CRF) activity, have not been examined. In the present study, offspring from E, pair-fed (PF), and ad-libitum-fed control (C) groups were exposed to daily handling during the first 2 weeks of life (H) or were left entirely undisturbed until weaning (NH). Basal CRF and arginine vasopressin (AVP) mRNA in the parvocellular portion of the paraventricular nucleus (pPVN) of the hypothalamus were assessed at 90-110 days of age. Prenatal ethanol exposure resulted in elevated basal pPVN CRF mRNA levels compared to those in ad-libitum-fed controls. Handling altered CRF mRNA levels in a sex-specific and prenatal treatment-specific manner. Females showed no significant effects of handling. In contrast, handling decreased CRF mRNA levels in PF and C but not E males compared to their NH counterparts. There were no effects of prenatal ethanol or postnatal handling on AVP mRNA levels. These findings indicate that prenatal ethanol exposure results in elevated basal CRF mRNA levels in adulthood and that handling appears to be ineffective in normalizing those elevations, supporting the suggestion that altered basal HPA regulation in E animals may, at least in part, underlie their HPA hyperresponsiveness to stressors.

  2. Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study.

    PubMed

    Murillo-Rodriguez, Eric; Blanco-Centurion, Carlos; Sanchez, Cristina; Piomelli, Daniele; Shiromani, Priyattam J

    2003-12-15

    The principal component of marijuana, delta-9-tetrahydrocannabinol increases sleep in humans. Endogenous cannabinoids, such as N-arachidonoylethanolamine (anandamide), also increase sleep. However, the mechanism by which these molecules promote sleep is not known but might involve a sleep-inducing molecule such as adenosine. Microdialysis samples were collected from the basal forebrain in order to detect levels of adenosine before and after injection of anandamide. Rats were implanted for sleep studies, and a cannula was placed in the basal forebrain to collect microdialysis samples. Samples were analyzed using high-performance liquid chromatography. Basic neuroscience research laboratory. Three-month-old male F344 rats. At the start of the lights-on period, animals received systemic injections of dimethyl sulfoxide (vehicle), anandamide, SR141716A (cannabinoid receptor 1 [CB1] antagonist), or SR141716A and anandamide. One hour after injections, microdialysis samples were collected (5 microL) from the basal forebrain every hour over a 20-minute period for 5 hours. The samples were immediately analyzed via high-performance liquid chromatography for adenosine levels. Sleep was also recorded continuously over the same period. Anandamide increased adenosine levels compared to vehicle controls with the peak levels being reached during the third hour after drug injection. There was a significant increase in slow-wave sleep during the third hour. The induction in sleep and the rise in adenosine were blocked by the CB1-receptor antagonist, SR141716A. Anandamide increased adenosine levels in the basal forebrain and also increased sleep. The soporific effects of anandamide were mediated by the CB1 receptor, since the effects were blocked by the CB1-receptor antagonist. These findings identify a potential therapeutic use of endocannabinoids to induce sleep in conditions where sleep may be severely attenuated.

  3. Noninvasive assessment of myocardial mechanics of the left ventricle in rabbits using velocity vector imaging.

    PubMed

    Zhou, Jia; Pu, Da-Rong; Tian, Lei-Qi; Tong, Hai; Liu, Hong-Yu; Tang, Yan; Zhou, Qi-Chang

    2015-05-28

    Our study aimed to investigate the feasibility of velocity vector imaging (VVI) to analyze left ventricular (LV) myocardial mechanics in rabbits at basal state. The animals used in this study were 30 New Zealand white rabbits. All rabbits underwent routine echocardiography under VVI-mode at basal state. The 2-dimensional (2-D) echocardiography images acquired included parasternal left long-axis views and short-axis views at the level of LV mitral valve, papillary muscles, and apex. Images were analyzed by VVI software. At basal state, longitudinal LV velocity decreased from the basal to the apical segment (P<0.05). In the short axis direction, the highest peak myocardial velocity was found between the anterior septum and anterior wall for each segment at the same level; the peak strains and strain rates (SR) were the highest in the anterior and lateral wall compared to other segments (all P<0.05). During systole, LV base rotated in a clockwise direction and LV apex rotated in a counter-clockwise direction, while during diastole, both LV base and apex rotated in the direction opposite to systole. The rotation angle, rotation velocity and unwinding velocity in the apical segment were greater than the basal segment (P<0.05). VVI is a reliable tool for evaluating LV myocardial mechanics in rabbits at basal state, and the LV long-axis short-axis and torsional motions reflect the normal regular patterns. Our study lays the foundation for future experimental approaches in rabbit models and for other applications related to the study of human myocardial mechanics.

  4. Evaluation of Physical Examination Tests for Thumb Basal Joint Osteoarthritis

    PubMed Central

    Model, Zina; Liu, Andrew Y.; Kang, Lana; Wolfe, Scott W.; Burket, Jayme C.; Lee, Steve K.

    2016-01-01

    Background: We compare the ability of 3 diagnostic tests to reproduce the pain of basilar joint arthritis (BJA): the grind test, the lever test (grasping the first metacarpal just distal to the basal joint and shucking back and forth in radial and ulnar directions), and the metacarpophalangeal extension test. Methods: Sixty-two patients with thumb BJA were enrolled. The 3 tests were performed in a random order on both hands of each patient. Prior to testing, patients reported their typical pain level and subsequently rated their pain after each test on a 0 to 10 scale, also specifying the extent to which the test reproduced their thumb pain (fully, partially, not at all). All patients had radiographs that displayed basal joint arthritis. A test was defined as positive for BJA if pain produced was greater than 0. Sensitivity and specificity for each test were calculated using the patients’ history of pain localized to the basal joint and BJA diagnosis on radiographs as the gold standard. Results: The lever test produced the greatest level of pain and best reproduced the presenting pain. The lever test also had the highest sensitivity, high specificity, and the lowest false-negative rate. The grind test had the lowest sensitivity, highest specificity, and highest false-negative rate. Conclusions: The lever test was the diagnostic test that best reproduced the pain caused by thumb basal joint osteoarthritis. We recommend using the lever physical examination test when evaluating the patient with suspected basal joint osteoarthritis. The often-quoted grind test is of limited diagnostic value. PMID:27418899

  5. Individual differences in brainstem and basal ganglia structure predict postural control and balance loss in young and older adults.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; Chalavi, Sima; van Ruitenbeek, Peter; Leunissen, Inge; Levin, Oron; Nieuwboer, Alice; Swinnen, Stephan P

    2017-02-01

    It remains unclear which specific brain regions are the most critical for human postural control and balance, and whether they mediate the effect of age. Here, associations between postural performance and corticosubcortical brain regions were examined in young and older adults using multiple structural imaging and linear mixed models. Results showed that of the regions involved in posture, the brainstem was the strongest predictor of postural control and balance: lower brainstem volume predicted larger center of pressure deviation and higher odds of balance loss. Analyses of white and gray matter in the brainstem showed that the pedunculopontine nucleus area appeared to be critical for postural control in both young and older adults. In addition, the brainstem mediated the effect of age on postural control, underscoring the brainstem's fundamental role in aging. Conversely, lower basal ganglia volume predicted better postural performance, suggesting an association between greater neural resources in the basal ganglia and greater movement vigor, resulting in exaggerated postural adjustments. Finally, results showed that practice, shorter height and heavier weight (i.e., higher body mass index), higher total physical activity, and larger ankle active (but not passive) range of motion were predictive of more stable posture, irrespective of age. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  7. Field Assessment of Gopher Tortoise Habitat at Camp Shelby, MS. Phase II: Overstory and Combined Assessments

    DTIC Science & Technology

    2010-10-17

    conditions between active, recently active and randomly selected non-burrow locations at this site. Field surveys were completed in three study areas ...at the installation. On average, burrow sites had a much higher overall occurrence of longleaf pine and significantly lower total basal area as...East Area burrow and non-burrow locations, Camp Shelby, MS 2007 .................. 10 2 Mean basal area per acre for pine and hardwood on T-44, Mars

  8. Breed- and age-related differences in canine mammary tumors

    PubMed Central

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-01-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

  9. The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

    PubMed

    Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

    2018-03-06

    This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Modeling and Theories of Pathophysiology and Physiology of the Basal Ganglia–Thalamic–Cortical System: Critical Analysis

    PubMed Central

    Montgomery Jr., Erwin B.

    2016-01-01

    Theories impact the movement disorders clinic, not only affecting the development of new therapies but determining how current therapies are used. Models are theories that are procedural rather than declarative. Theories and models are important because, as argued by Kant, one cannot know the thing-in-itself (das Ding an sich) and only a model is knowable. Further, biological variability forces higher level abstraction relevant for all variants. It is that abstraction that is raison d’être of theories and models. Theories “connect the dots” to move from correlation to causation. The necessity of theory makes theories helpful or counterproductive. Theories and models of the pathophysiology and physiology of the basal ganglia–thalamic–cortical system do not spontaneously arise but have a history and consequently are legacies. Over the last 40 years, numerous theories and models of the basal ganglia have been proposed only to be forgotten or dismissed, rarely critiqued. It is not harsh to say that current popular theories positing increased neuronal activities in the Globus Pallidus Interna (GPi), excessive beta oscillations and increased synchronization not only fail to provide an adequate explication but are inconsistent with many observations. It is likely that their shared intellectual and epistemic inheritance plays a factor in their shared failures. These issues are critically examined. How one is to derive theories and models and have hope these will be better is explored as well. PMID:27708569

  11. Effects of a protected inclusion of organic acids and essential oils as antibiotic growth promoter alternative on growth performance, intestinal morphology and gut microflora in broilers.

    PubMed

    Liu, Yanli; Yang, Xin; Xin, Hongliang; Chen, Si; Yang, Chengbo; Duan, Yulan; Yang, Xiaojun

    2017-09-01

    This experiment was conducted to investigate the effects of protected essential oils and organic acids mixture on poultry feeding. A total of 450 1-day-old Cobb 500 chicks were randomly allotted into three treatments with six replicates. Birds were offered a basal diet (C), basal diet with 0.15 g/kg enramycin premix (A) and basal diet with 0.30 g/kg protected essential oils and organic acids mixture product (P). The results showed that protected essential oils and organic acids mixture supplementation reduced average daily feed intake and ratio of feed to gain (F/G) at 22-42 days of age, and F/G during 1-42 days of age also declined (P < 0.05). Product supplementation improved spleen index, villus height and crypt depth of the jejunum at 42 days when compared with the control (P < 0.05). In addition, secretory immunoglobulin A level of ileal mucosa and trypsin and chymotrypsin activities of intestinal tract were higher in the P treatment. Bacterial sequence analysis of the intestinal tract revealed that protected essential oils and organic acids mixture supplementation changed gut microflora mainly in Lactobacillus. These data suggested that dietary mixture of organic acids and essential oils addition could be used in the poultry industry as an antibiotic growth promoter alternative. © 2017 Japanese Society of Animal Science.

  12. Carbon Source Requirements for Exopolysaccharide Production by Lactobacillus casei CG11 and Partial Structure Analysis of the Polymer

    PubMed Central

    Cerning, J.; Renard, C. M. G. C.; Thibault, J. F.; Bouillanne, C.; Landon, M.; Desmazeaud, M.; Topisirovic, L.

    1994-01-01

    Exopolysaccharide production by Lactobacillus casei CG11 was studied in basal minimum medium containing various carbon sources (galactose, glucose, lactose, sucrose, maltose, melibiose) at concentrations of 2, 5, 10, and 20 g/liter. L. casei CG11 produced exopolysaccharides in basal minimum medium containing each of the sugars tested; lactose and galactose were the poorest carbon sources, and glucose was by far the most efficient carbon source. Sugar concentrations had a marked effect on polymer yield. Plasmid-cured Muc- derivatives grew better in the presence of glucose and attained slightly higher populations than the wild-type strain. The values obtained with lactose were considerably lower for both growth and exopolysaccharide yield. The level of specific polymer production per cell obtained with glucose was distinctively lower for Muc- derivatives than for the Muc+ strain. The polymer produced by L. casei CG11 in the presence of glucose was different from that formed in the presence of lactose. The polysaccharide produced by L. casei CG11 in basal minimum medium containing 20 g of glucose per liter had an intrinsic viscosity of 1.13 dl/g. It was rich in glucose (76%), which was present mostly as 2- or 3-linked residues along with some 2,3 doubly substituted glucose units, and in rhamnose (21%), which was present as 2-linked or terminal rhamnose; traces of mannose and galactose were also present. PMID:16349427

  13. The cholinergic basal forebrain in the ferret and its inputs to the auditory cortex

    PubMed Central

    Bajo, Victoria M; Leach, Nicholas D; Cordery, Patricia M; Nodal, Fernando R; King, Andrew J

    2014-01-01

    Cholinergic inputs to the auditory cortex can modulate sensory processing and regulate stimulus-specific plasticity according to the behavioural state of the subject. In order to understand how acetylcholine achieves this, it is essential to elucidate the circuitry by which cholinergic inputs influence the cortex. In this study, we described the distribution of cholinergic neurons in the basal forebrain and their inputs to the auditory cortex of the ferret, a species used increasingly in studies of auditory learning and plasticity. Cholinergic neurons in the basal forebrain, visualized by choline acetyltransferase and p75 neurotrophin receptor immunocytochemistry, were distributed through the medial septum, diagonal band of Broca, and nucleus basalis magnocellularis. Epipial tracer deposits and injections of the immunotoxin ME20.4-SAP (monoclonal antibody specific for the p75 neurotrophin receptor conjugated to saporin) in the auditory cortex showed that cholinergic inputs originate almost exclusively in the ipsilateral nucleus basalis. Moreover, tracer injections in the nucleus basalis revealed a pattern of labelled fibres and terminal fields that resembled acetylcholinesterase fibre staining in the auditory cortex, with the heaviest labelling in layers II/III and in the infragranular layers. Labelled fibres with small en-passant varicosities and simple terminal swellings were observed throughout all auditory cortical regions. The widespread distribution of cholinergic inputs from the nucleus basalis to both primary and higher level areas of the auditory cortex suggests that acetylcholine is likely to be involved in modulating many aspects of auditory processing. PMID:24945075

  14. Glutamine alleviates heat stress-induced impairment of intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers.

    PubMed

    Wu, Q J; Liu, N; Wu, X H; Wang, G Y; Lin, L

    2018-05-17

    The aim of this study was to investigate the protective effect of glutamine (Gln) on the intestinal morphology, intestinal inflammatory response, and barrier integrity in broilers exposed to high ambient temperature. Three-hundred-sixty 21-d-old Arbor Acres broilers (half male and half female) were randomly allocated to 4 treatment groups in a completely randomized design, each of which included 6 replicates with 15 birds per replicate, for 21 d. The 4 treatment groups were as follows: the control group, in which birds were kept in a thermoneutral room at 22 ± 1°C (no stress, NS; fed a basal diet); the heat stress group (36 ± 1°C for 10 h/d from 08:00 to 18:00 h and 22 ± 1°C for the remaining time, heat stress (HT); fed a basal diet); and heat stress + Gln group (0.5 and 1.0% Gln, respectively). Compared to the NS group, broilers in the HT group had lower villus height (P < 0.05), higher crypt depth (P < 0.05), higher D-lactic acid and diamine oxidase (DAO) activity (P < 0.05), higher soluble intercellular adhesion molecule-1 (sICAM-1) concentration (P < 0.05), higher tumor necrosis factor (TNF)-α/interleukin (IL)-10 (P < 0.05), and lower tight junction protein expression levels (P < 0.05). Compared with birds in the HT, birds in the HT + Gln group exhibited increased villus height (P < 0.05), decreased D-lactate and DAO activity (P < 0.05), decreased sICAM-1 concentration (P < 0.05), and mediate the secretion of cytokines (P < 0.05), as well as increased zonula occludens-1 (ZO-1), claudin-1, and occludin mRNA expression levels (P < 0.05). In conclusion, these results indicate that supplementation with Gln was effective in partially ameliorating the adverse effects of heat stress on intestinal barrier function in broilers by promoting epithelial cell proliferation and renewal, modifying the function of the intestinal mucosa barrier, and regulating the secretion of cytokines.

  15. Efficacy of a basal bolus insulin protocol to treat prednisolone-induced hyperglycaemia in hospitalised patients.

    PubMed

    Burt, M G; Drake, S M; Aguilar-Loza, N R; Esterman, A; Stranks, S N; Roberts, G W

    2015-03-01

    Few studies have specifically investigated treatment of prednisolone-induced hyperglycaemia. To determine if a basal bolus insulin (BBI) protocol for inpatient hyperglycaemia is effective in patients prescribed acute prednisolone for an inflammatory disease. In a cross-sectional study, 66 patients with type 2 diabetes admitted to a general medical ward and treated with BBI for up to 5 days were studied. Twenty-four patients were taking prednisolone ≥10 mg/day to treat an acute inflammatory disease. The remaining 42 patients were a control group. The primary outcome was mean daily blood glucose level. There were no significant differences in glycosylated haemoglobin (8.1 ± 1.0 vs 8.1 ± 1.6%, P = 0.88), age (77 ± 11 vs 75 ± 14 years, P = 0.57), male sex (63 vs 60%, P = 0.81) or body mass index (30.0 ± 5.3 vs 30.2 ± 11.5 kg/m(2) , P = 0.90) between patients taking prednisolone and controls. Mean daily glucose concentration was higher in patients taking prednisolone than in controls (12.2 ± 0.3 vs 10.0 ± 0.1 mmol/L, P < 0.001). Blood glucose level was higher in patients on prednisolone at 1700 h (14.6 ± 0.6 vs 10.3 ± 0.3 mmol/L, P < 0.001) and 2100 h (14.5 ± 0.6 vs 10.5 ± 0.3 mmol/L, P < 0.001), with no significant differences at 0700 h and 1200 h. These findings occurred despite patients taking prednisolone receiving a higher daily insulin dose than controls (0.67-0.70 vs 0.61-0.65 U/kg, P = 0.001) because of higher doses of ultra-rapid-acting insulin at 1200 h and 1700 h. Hospitalised patients taking prednisolone had substantial afternoon and evening hyperglycaemia despite receiving BBI via a protocol for inpatient hyperglycaemia. Specific insulin regimens for prednisolone-induced hyperglycaemia are needed that recommend more insulin during this time period. © 2015 Royal Australasian College of Physicians.

  16. Antidepressants differentially affect striatal amphetamine-stimulated dopamine and serotonin release in rats with high and low novelty-oriented behaviour.

    PubMed

    O'Leary, Aet; Kõiv, Kadri; Raudkivi, Karita; Harro, Jaanus

    2016-11-01

    In the studies of depression pathogenesis and antidepressant action, the monoaminergic hypothesis of depression has mainly focused on the serotonergic and noradrenergic mechanisms. However, dopaminergic neurotransmission is also linked to both depressive symptomatology as well as antidepressant effects. We have previously shown that persistent inter-individual differences in the rat behavioural activity in novel environments is associated with differences in the striatal extracellular levels of dopamine and serotonin, depressive-like behaviour and the expression of several depression-related genes. The aim of the current study was to investigate the relative potency of the tricyclic antidepressant imipramine, the selective serotonin re-uptake inhibitor fluoxetine, and the selective noradrenaline re-uptake inhibitor reboxetine (all drugs administered in the dose of 10mg/kg, i.p.) to enhance amphetamine-stimulated dopamine and serotonin release in the striatum using in vivo microdialysis in awake, freely-moving rats, categorized into high explorers (HE) and low explorers (LE) based on their spontaneous novelty-oriented behaviour. The basal extracellular dopamine and serotonin concentration in the striatum did not differ between the LE- and HE-rats. None of the antidepressants alone were able to modify baseline striatal dopamine levels, but the amphetamine-stimulated dopamine release was significantly higher in the HE-rats after acute and chronic imipramine (but not fluoxetine or reboxetine). Acute imipramine and fluoxetine, but not reboxetine, increased both the basal and amphetamine-stimulated levels of serotonin in the striatum. Again, the HE-rats had higher amphetamine-stimulated serotonin release after fluoxetine administration. These findings suggest that rats with depressive-like phenotype are less sensitive to the neurochemical effects of antidepressants in the striatum. These results may have relevance in understanding the neurobiological bases for inter-individual differences in antidepressant treatment response in humans and development of novel medicines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Inhibition of human lung cancer cell proliferation and survival by wine

    PubMed Central

    2014-01-01

    Background Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events. Methods Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53. Results In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells. Conclusions Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further systematic investigation in animal models of lung cancer. PMID:24456610

  18. Sex Hormones, Sleep, and Core Body Temperature in Older Postmenopausal Women

    PubMed Central

    Murphy, Patricia J.; Campbell, Scott S.

    2007-01-01

    Study Objectives: Assessment of relationships between polysomnographic sleep, sex hormones, and core body temperature in postmenopausal women. Design and Participants: Ten women aged 57 to 71 years, at least 5 years past menopause. Setting: Laboratory of Human Chronobiology at Weill Cornell Medical College. Interventions: N/A. Measurements and Results: Lower estradiol (E2) and higher luteinizing hormone (LH) levels were significantly correlated with indices of poor sleep quality. Relationships between LH and polysomnographic variables were more robust than those for E2. Significant increases from basal LH levels (i.e., LH pulses) occurred more frequently after sleep onset than prior to sleep onset, and 30 of 32 of these LH pulses occurred prior to long awakenings from sleep. In addition, higher body core temperature prior to and during sleep was significantly correlated with poorer sleep efficiency and higher LH levels. Conclusions: Most investigations of relationships between sleep, sex hormones, and body temperature have focused on perimenopausal women, menopausal phenomena such as hot flashes, the role of declining estrogen, and treatment with exogenous estrogen. The current results suggest that altered levels of both sex steroids and gonadotropins may contribute to sleep disturbance in older women and confirm the results of previous studies indicating that higher body core temperature is associated with poorer sleep quality, even in women without vasomotor symptoms. The findings also raise the possibility of alternate treatment avenues for menopause- and age-related sleep disturbance that focus on altering LH levels. Citation: Murphy PJ; Campbell SS. Sex hormones, sleep, and core body temperature in older postmenopausal women. SLEEP 2007;30(12):1788-1794. PMID:18246988

  19. Structural and elastic properties of La{sub 2}Mg{sub 17} from first-principles calculations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Luo, Tao-Peng; Ma, Li; Pan, Rong-Kai

    2013-10-15

    Structural and elastic properties of La{sub 2}Mg{sub 17} with layer structure have been investigated within framework of the density functional theory. Different from the general layer-structured materials, the obtained c/a is less than unity. The calculated elastic constants C{sub 33} is larger than C{sub 11}, being novel in comparison with other alloys with layer structure. The calculated bulk, shear and Young’s modulus of La{sub 2}Mg{sub 17} are higher than other Mg–La alloys with higher La content, implying the stronger covalent bonding. Moreover, the elastic isotropies of La{sub 2}Mg{sub 17} are more excellent. The electronic structure within basal plane is highlymore » symmetric, and the electronic interaction within basal plane is slightly weaker than one between basal planes, which reveal the underlying mechanism for the structural and elastic properties of La{sub 2}Mg{sub 17}. - Graphical abstract: The crystal structure (a) and the atomic positions for (b) (0 0 0 2), (c) (0 0 0 4) and (d) (1 2{sup ¯} 1 0) plane of La{sub 2}Mg{sub 17}. Display Omitted - Highlights: • The c/a of La{sub 2}Mg{sub 17} is anomalously less than unity. • It is novel that for La{sub 2}Mg{sub 17} the elastic constants C{sub 33} is larger than C{sub 11}. • The elastic modulus of La{sub 2}Mg{sub 17} is higher than other Mg–La alloys. • The elastic isotropy of La{sub 2}Mg{sub 17} is excellent. • The electronic structure within basal plane is highly symmetric.« less

  20. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity.

    PubMed

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-02-23

    The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer-methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  1. Large-scale patterns of turnover and Basal area change in Andean forests.

    PubMed

    Báez, Selene; Malizia, Agustina; Carilla, Julieta; Blundo, Cecilia; Aguilar, Manuel; Aguirre, Nikolay; Aquirre, Zhofre; Álvarez, Esteban; Cuesta, Francisco; Duque, Álvaro; Farfán-Ríos, William; García-Cabrera, Karina; Grau, Ricardo; Homeier, Jürgen; Linares-Palomino, Reynaldo; Malizia, Lucio R; Cruz, Omar Melo; Osinaga, Oriana; Phillips, Oliver L; Reynel, Carlos; Silman, Miles R; Feeley, Kenneth J

    2015-01-01

    General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century.

  2. Large-Scale Patterns of Turnover and Basal Area Change in Andean Forests

    PubMed Central

    Blundo, Cecilia; Aguilar, Manuel; Aguirre, Nikolay; Aquirre, Zhofre; Álvarez, Esteban; Cuesta, Francisco; Farfán-Ríos, William; García-Cabrera, Karina; Grau, Ricardo; Linares-Palomino, Reynaldo; Malizia, Lucio R.; Cruz, Omar Melo; Osinaga, Oriana; Reynel, Carlos; Silman, Miles R.

    2015-01-01

    General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century. PMID:25973977

  3. Effects of chronic ammonium sulfate treatment on the forest at the Bear Brook Watershed in Maine.

    PubMed

    Elvir, Jose Alexander; Wiersma, G Bruce; Bethers, Suzanne; Kenlan, Peter

    2010-12-01

    At the Bear Brook Watershed in Maine (BBWM), the forest tree composition was characterized and the effects of the chronic ammonium sulfate ((NH(4))(2)SO(4)) treatment on basal area growth, foliar chemistry, and gas exchange were investigated on forest species. The BBWM is a paired watershed forest ecosystem study with one watershed, West Bear (WB), treated since 1989 with 26.6 kg N ha(-1) year(-1) and 30 kg S ha(-1) year(-1)applied bimonthly as (NH(4))(2)SO(4), while the other watershed, East Bear (EB), serves as a reference. Tree species richness, density, and mortality were found to be similar between watersheds. Basal area increment was estimated from red spruce and sugar maple, showing that, for the first 7 years of treatment, it was significantly higher for sugar maple growing in WB compared to EB, but no differences were observed for red spruce between watersheds. However, the initial higher sugar maple basal area growth in WB subsequently decreased after 8 years of treatment. Foliar chemical analysis performed in trees, saplings, and ground flora showed higher N concentrations in the treated WB compared to the reference EB. But, foliar cation concentrations, especially Ca and Mg, were significantly lower for most of the species growing in WB compared with those growing in EB. For sugar maple, foliar N was higher on WB, but there were no differences in foliar Ca and Mg concentrations between treated and reference watersheds. In addition, only sugar maple trees in the treated WB showed significantly higher photosynthetic rates compared to reference EB trees.

  4. Lipid metabolism and body composition in Gclm(-/-) mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kendig, Eric L.; Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267; Chen, Ying

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipidmore » for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial oxygen consumption. Black-Right-Pointing-Pointer Expression of lipid metabolizing genes is extremely low in Gclm(-/-) mice.« less

  5. Association between serum levels of caspase-cleaved cytokeratin-18 and early mortality in patients with severe spontaneous intracerebral hemorrhage.

    PubMed

    Lorente, Leonardo; Martín, María M; Pérez-Cejas, Antonia; Ramos, Luis; Argueso, Mónica; Solé-Violán, Jordi; Cáceres, Juan J; Jiménez, Alejandro; García-Marín, Victor

    2018-04-16

    Apoptotic changes after cerebral hemorrhage in brain samples of humans have been found. Caspase-cleaved cytokeratin (CCCK)-18 could be detected in the bloodstream during apoptosis. Higher circulating CCCK-18 levels have been associated with 6-month mortality in patients with basal ganglia hemorrhage. The aim of our study was to determine whether there is an association between serum CCCK-18 levels and early mortality of spontaneous intracerebral hemorrhage (SIH) patients. We performed an observational, prospective and multicentre study. There were included patients with severe SIH defined as Glasgow Coma Scale (GCS) lower than 9. We determined serum CCCK-18 levels at the severe SIH diagnosis moment. We found that non-surviving SIH patients (n = 46) showed lower GCS, and higher serum CCCK-18 levels and APACHE-II score than survivor ones (n = 54). In ROC analysis was found that the area under the curve of serum CCCK-18 levels for 30-day mortality prediction was 90% (95% CI 82-95%; p < 0.001). In the multiple logistic regression analysis, we found an association between serum CCCK-18 levels and 30-day mortality (OR 1.034; 95% CI 1.013-1.055; p = 0.002). The novel finding of our study was that there is an association between high serum CCCK-18 levels and 30-day mortality in severe SIH patients.

  6. Geothermal flux and basal melt rate in the Dome C region inferred from radar reflectivity and heat modelling

    NASA Astrophysics Data System (ADS)

    Passalacqua, Olivier; Ritz, Catherine; Parrenin, Frédéric; Urbini, Stefano; Frezzotti, Massimo

    2017-09-01

    Basal melt rate is the most important physical quantity to be evaluated when looking for an old-ice drilling site, and it depends to a great extent on the geothermal flux (GF), which is poorly known under the East Antarctic ice sheet. Given that wet bedrock has higher reflectivity than dry bedrock, the wetness of the ice-bed interface can be assessed using radar echoes from the bedrock. But, since basal conditions depend on heat transfer forced by climate but lagged by the thick ice, the basal ice may currently be frozen whereas in the past it was generally melting. For that reason, the risk of bias between present and past conditions has to be evaluated. The objective of this study is to assess which locations in the Dome C area could have been protected from basal melting at any time in the past, which requires evaluating GF. We used an inverse approach to retrieve GF from radar-inferred distribution of wet and dry beds. A 1-D heat model is run over the last 800 ka to constrain the value of GF by assessing a critical ice thickness, i.e. the minimum ice thickness that would allow the present local distribution of basal melting. A regional map of the GF was then inferred over a 80 km × 130 km area, with a N-S gradient and with values ranging from 48 to 60 mW m-2. The forward model was then emulated by a polynomial function to compute a time-averaged value of the spatially variable basal melt rate over the region. Three main subregions appear to be free of basal melting, two because of a thin overlying ice and one, north of Dome C, because of a low GF.

  7. Effect of dietary taurine supplementation on growth, feed efficiency, and nutrient composition of juvenile sablefish (Anoplopoma fimbria)

    USDA-ARS?s Scientific Manuscript database

    Juvenile sablefish were fed a low taurine, basal feed with seven graded levels of supplemental taurine to determine taurine requirements for growth and feed efficiency. The basal feed was plant based, formulated primarily with soy and corn proteins with a minimal (9%) amount of fishmeal. The unsuppl...

  8. The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

    ERIC Educational Resources Information Center

    Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

    2013-01-01

    Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

  9. Increasing Dopamine Levels in the Brain Improves Feedback-Based Procedural Learning in Healthy Participants: An Artificial-Grammar-Learning Experiment

    ERIC Educational Resources Information Center

    de Vries, Meinou H.; Ulte, Catrin; Zwitserlood, Pienie; Szymanski, Barbara; Knecht, Stefan

    2010-01-01

    Recently, an increasing number of studies have suggested a role for the basal ganglia and related dopamine inputs in procedural learning, specifically when learning occurs through trial-by-trial feedback (Shohamy, Myers, Kalanithi, & Gluck. (2008). "Basal ganglia and dopamine contributions to probabilistic category learning." "Neuroscience and…

  10. Junior High Basals: Effective Hi/Lo Materials for Remedial High School Readers.

    ERIC Educational Resources Information Center

    Alvermann, Donna E.

    1981-01-01

    Discusses the results of an analysis of the appropriateness of eighth-grade basal reading materials for remedial instruction of ninth- and tenth-grade students who read two to three years below grade level. Readability, interest appeal, and representation of content areas are considered. Three data tables and a 14-item reference list are included.…

  11. Nonlinear mixed modeling of basal area growth for shortleaf pine

    Treesearch

    Chakra B. Budhathoki; Thomas B. Lynch; James M. Guldin

    2008-01-01

    Mixed model estimation methods were used to fit individual-tree basal area growth models to tree and stand-level measurements available from permanent plots established in naturally regenerated shortleaf pine (Pinus echinata Mill.) even-aged stands in western Arkansas and eastern Oklahoma in the USA. As a part of the development of a comprehensive...

  12. [Diagnostics of acute myocardial infarction in elderly patients].

    PubMed

    Bahrmann, P; Heppner, H J; Bahrmann, A; Christ, M; Bertsch, T; Sieber, C C

    2011-06-01

    The early diagnosis of an acute myocardial infarction (MI) is improved by the introduction of novel high-sensitivity troponin assays. These assays can measure low level myocardial injury not detectable by standard troponin assays. Especially in older patients who appear to have a higher basal troponin level, the results must always be judged in the context of the medical history, physical examination, electrocardiogram (ECG) and any further findings. Even small increases in high-sensitivity troponin indicate increased risk for death or MI during follow-up. In the case of MI an invasive strategy results in better survival rates compared with conservative therapy but at the expense of an increased risk of bleeding in elderly patients. This article provides an overview on the diagnosis of MI in elderly patients.

  13. Effect of dietary manganese on antioxidant status and expression levels of heat-shock proteins and factors in tissues of laying broiler breeders under normal and high environmental temperatures.

    PubMed

    Zhu, Yong-Wen; Lu, Lin; Li, Wen-Xiang; Zhang, Li-Yang; Ji, Cheng; Lin, Xi; Liu, Hsiao-Ching; Odle, Jack; Luo, Xu-Gang

    2015-12-28

    To investigate the effect of Mn on antioxidant status and expression levels of heat-shock proteins/factors in tissues of laying broiler breeders subjected to heat challenge, we used a completely randomised design (n 6) with a factorial arrangement of 2 environmental temperatures (normal, 21 (sem 1)°C and high, 32 (sem 1)°C)×3 dietary Mn treatments (an Mn-unsupplemented basal diet (CON), or a basal diet supplemented with 120 mg Mn/kg diet as inorganic Mn sulphate (iMn) or organic Mn proteinate (oMn)). There were no interactions (P>0·10) between environmental temperature and dietary Mn in all of the measured indices. High temperature decreased (P<0·003) Mn content, and also tended (P=0·07) to decrease copper zinc superoxide dismutase (CuZnSOD) activity in the liver and heart. However, an increased manganese superoxide dismutase (MnSOD) activity (P<0·05) and a slight increase of malondialdehyde level (P=0·06) were detected in breast muscle. Up-regulated (P<0·05) expression levels of heat-shock factor 1 (HSF1) and HSF3 mRNA and heat-shock protein 70 (HSP70) mRNA and protein were found in all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn content (P<0·0001), heart MnSOD and CuZnSOD activities (P<0·01) and breast muscle MnSOD protein levels (P<0·05), and lower (P<0·05) breast muscle HSP70 mRNA and protein levels than those fed CON. Broiler breeders fed oMn had higher (P<0·03) bone Mn content than those fed iMn. These results indicate that high temperature decreases Mn retention and increases HSP70 and HSF1, HSF3 expression levels in tissues of laying broiler breeders. Furthermore, dietary supplementation with Mn in either source may enhance heart antioxidant ability and inhibit the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be more available than inorganic Mn for bone in laying broiler breeders regardless of environmental temperatures.

  14. Basal-topographic control of stationary ponds on a continuously moving landslide

    USGS Publications Warehouse

    Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

    2009-01-01

    The Slumgullion landslide in the San Juan Mountains of southwestern Colorado has been moving for at least the last few hundred years and has multiple ponds on its surface. We have studied eight ponds during 30 trips to the landslide between July 1998 and July 2007. During each trip, we have made observations on the variability in pond locations and water levels, taken ground-based photographs to document pond water with respect to moving landslide material and vegetation, conducted Global Positioning System surveys of the elevations of water levels and mapped pond sediments on the landslide surface. Additionally, we have used stereo aerial photographs taken in October 1939, October 1940 and July 2000 to measure topographic profiles of the eight pond locations, as well as a longitudinal profile along the approximate centerline of the landslide, to examine topographic changes over a 60- to 61-year period of time. Results from field observations, analyses of photographs, mapping and measurements indicate that all pond locations have remained spatially stationary for 60-300 years while landslide material moves through these locations. Water levels during the observation period were sensitive to changes in the local, spring-fed, stream network, and to periodic filling of pond locations by sediment from floods, hyperconcentrated flows, mud flows and debris flows. For pond locations to remain stationary, the locations must mimic depressions along the basal surface of the landslide. The existence of such depressions indicates that the topography of the basal landslide surface is irregular. These results suggest that, for translational landslides that have moved distances larger than the dimensions of the largest basal topographic irregularities (about 200 m at Slumgullion), landslide surface morphology can be used as a guide to the morphology of the basal slip surface. Because basal slip surface morphology can affect landslide stability, kinematic models and stability analyses of translational landslides should attempt to incorporate irregular basal surface topography. Additional implications for moving landslides where basal topography controls surface morphology include the following: dateable sediments or organic material from basal layers of stationary ponds will yield ages that are younger than the date of landslide initiation, and it is probable that other landslide surface features such as faults, streams, springs and sinks are also controlled by basal topography. The longitudinal topographic profile indicated that the upper part of the Slumgullion landslide was depleted at a mean vertical lowering rate of 5.6 cm/yr between 1939 and 2000, while the toe advanced at an average rate of 1.5 m/yr during the same period. Therefore, during this 61-year period, neither the depletion of material at the head of the landslide nor continued growth of the landslide toe has decreased the overall movement rate of the landslide. Continued depletion of the upper part of the landslide, and growth of the toe, should eventually result in stabilization of the landslide. Copyright ?? 2008 John Wiley & Sons, Ltd.

  15. The Molecular Pathway Regulating Bergmann Glia and Folia Generation in the Cerebellum.

    PubMed

    Leung, Alan W; Li, James Y H

    2018-02-01

    Evolution of complex behaviors in higher vertebrates and primates require the development of sophisticated neuronal circuitry and the expansion of brain surface area to accommodate the vast number of neuronal and glial populations. To achieve these goals, the neocortex in primates and the cerebellum in amniotes have developed specialized types of basal progenitors to aid the folding of their cortices. In the cerebellum, Bergmann glia constitute such a basal progenitor population, having a distinctive morphology and playing a critical role in cerebellar corticogenesis. Here, we review recent studies on the induction of Bergmann glia and their crucial role in mediating folding of the cerebellar cortex. These studies uncover a key function of FGF-ERK-ETV signaling cascade in the transformation of Bergmann glia from radial glia in the ventricular zone. Remarkably, in the neocortex, the same signaling axis operates to facilitate the transformation of ventricular radial glia into basal radial glia, a Bergmann glia-like basal progenitor population, which have been implicated in the establishment of neocortical gyri. These new findings draw a striking similarity in the function and ontogeny of the two basal progenitor populations born in distinct brain compartments.

  16. Insulin appearance of subcutaneously infused insulin: influence of the basal rate pulse interval of the infusion pump.

    PubMed

    Birch, K; Hildebrandt, P; Jensen, B M; Kühl, C; Brange, J

    1985-05-01

    To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.

  17. Electrochemical generation of sulfur vacancies in the basal plane of MoS2 for hydrogen evolution

    PubMed Central

    Tsai, Charlie; Li, Hong; Park, Sangwook; Park, Joonsuk; Han, Hyun Soo; Nørskov, Jens K.; Zheng, Xiaolin; Abild-Pedersen, Frank

    2017-01-01

    Recently, sulfur (S)-vacancies created on the basal plane of 2H-molybdenum disulfide (MoS2) using argon plasma exposure exhibited higher intrinsic activity for the electrochemical hydrogen evolution reaction than the edge sites and metallic 1T-phase of MoS2 catalysts. However, a more industrially viable alternative to the argon plasma desulfurization process is needed. In this work, we introduce a scalable route towards generating S-vacancies on the MoS2 basal plane using electrochemical desulfurization. Even though sulfur atoms on the basal plane are known to be stable and inert, we find that they can be electrochemically reduced under accessible applied potentials. This can be done on various 2H-MoS2 nanostructures. By changing the applied desulfurization potential, the extent of desulfurization and the resulting activity can be varied. The resulting active sites are stable under extended desulfurization durations and show consistent HER activity. PMID:28429782

  18. Electrochemical generation of sulfur vacancies in the basal plane of MoS2 for hydrogen evolution

    DOE PAGES

    Tsai, Charlie; Li, Hong; Park, Sangwook; ...

    2017-04-21

    Recently, sulfur (S)-vacancies created on the basal plane of 2H-molybdenum disulfide (MoS 2) using argon plasma exposure exhibited higher intrinsic activity for the electrochemical hydrogen evolution reaction than the edge sites and metallic 1T-phase of MoS 2 catalysts. But, a more industrially viable alternative to the argon plasma desulfurization process is needed. In this work, we introduce a scalable route towards generating S-vacancies on the MoS 2 basal plane using electrochemical desulfurization. We found that they can be electrochemically reduced under accessible applied potentials, even though sulfur atoms on the basal plane are known to be stable and inert. Thismore » can be done on various 2H-MoS 2 nanostructures. Furthermore, by changing the applied desulfurization potential, the extent of desulfurization and the resulting activity can be varied. The resulting active sites are stable under extended desulfurization durations and show consistent HER activity.« less

  19. Basal and thermal control mechanisms of the Ragnhild glaciers, East Antarctica

    NASA Astrophysics Data System (ADS)

    Pattyn, Frank; de Brabander, Sang; Huyghe, Ann

    The Ragnhild glaciers are three enhanced-flow features situated between the Sør Rondane and Yamato Mountains in eastern Dronning Maud Land, Antarctica. We investigate the glaciological mechanisms controlling their existence and behavior, using a three-dimensional numerical thermomechanical ice-sheet model including higher-order stress gradients. This model is further extended with a steady-state model of subglacial water flow, based on the hydraulic potential gradient. Both static and dynamic simulations are capable of reproducing the enhanced ice-flow features. Although basal topography is responsible for the existence of the flow pattern, thermomechanical effects and basal sliding seem to locally soften and lubricate the ice in the main trunks. Lateral drag is a contributing factor in balancing the driving stress, as shear margins can be traced over a distance of hundreds of kilometers along west Ragnhild glacier. Different basal sliding scenarios show that central Ragnhild glacier stagnates as west Ragnhild glacier accelerates and progressively drains the whole catchment area by ice and water piracy.

  20. Neighborhood-Level Stress and Circadian Cortisol: A Systematic Review and Meta-Analysis.

    PubMed

    Hosseini, Fatemeh; Adha, Nikmatul; Zainol, Rosilawati; Isahak, Marzuki; Nemati, Nahid

    2014-10-01

    The main objective was to find association between basal cortisol and neighborhood-level stress. Systematic searches, including electronic and hand searches, were conducted. The most recent date of the search was July 26, 2013. Primary observational studies included if they considered stress related outcomes in the neighborhood context. Using the EndNote X7 advanced search option; the authors examined the abstracts and titles of the 18,092 articles to exclude obviously irrelevant studies, gray literature, discussion papers, reviews and, studies with no complete data. Two authors independently extracted data from the original reports into pre-designed data extraction forms based on the Data Extraction Template of the Cochrane Consumer and Communication Review Group (CCCRG). Ten studies with a total of 2,134 participants were synthesized and analyzed. Two studies out of ten received expanded meta-analysis. The overall effect size (95% CI) for cortisol level for residents in neighborhoods with lower stress compared to inhabitants from higher was 0.12 (0.01, 0.23). This review is demonstrating a link between psychosocial or physical stress and cortisol obtained from saliva. However, living in high disorder neighborhoods results in higher level of cortisol. This represents a biological indicator of psychosocial/physical stress exposure (i.e., neighborhood disorder) that reflects variances in stress exposure levels.

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