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Sample records for addition decreased levels

  1. Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

    PubMed

    Roth, Alena; Glaesener, Stephanie; Schütz, Katharina; Meyer-Bahlburg, Almut

    2016-01-01

    Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

  2. Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23

    PubMed Central

    Roth, Alena; Glaesener, Stephanie; Schütz, Katharina; Meyer-Bahlburg, Almut

    2016-01-01

    Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response. PMID:27031098

  3. Decreasing Cloudiness Over China: An Updated Analysis Examining Additional Variables

    SciTech Connect

    Kaiser, D.P.

    2000-01-14

    As preparation of the IPCC's Third Assessment Report takes place, one of the many observed climate variables of key interest is cloud amount. For several nations of the world, there exist records of surface-observed cloud amount dating back to the middle of the 20th Century or earlier, offering valuable information on variations and trends. Studies using such databases include Sun and Groisman (1999) and Kaiser and Razuvaev (1995) for the former Soviet Union, Angel1 et al. (1984) for the United States, Henderson-Sellers (1986) for Europe, Jones and Henderson-Sellers (1992) for Australia, and Kaiser (1998) for China. The findings of Kaiser (1998) differ from the other studies in that much of China appears to have experienced decreased cloudiness over recent decades (1954-1994), whereas the other land regions for the most part show evidence of increasing cloud cover. This paper expands on Kaiser (1998) by analyzing trends in additional meteorological variables for Chi na [station pressure (p), water vapor pressure (e), and relative humidity (rh)] and extending the total cloud amount (N) analysis an additional two years (through 1996).

  4. Decreased selenium levels in acute myocardial infarction

    SciTech Connect

    Kok, F.J.; Hofman, A.; Witteman, J.C.M.; de Bruijn, A.M.; Kruyssen, D.H.C.M.; de Bruin, M.; Valkenburg, H.A. )

    1989-02-24

    To study the association between selenium status and the risk of myocardial infarction, the authors compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls. Because toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

  5. Huggable communication medium decreases cortisol levels

    PubMed Central

    Sumioka, Hidenobu; Nakae, Aya; Kanai, Ryota; Ishiguro, Hiroshi

    2013-01-01

    Interpersonal touch is a fundamental component of social interactions because it can mitigate physical and psychological distress. To reproduce the psychological and physiological effects associated with interpersonal touch, interest is growing in introducing tactile sensations to communication devices. However, it remains unknown whether physical contact with such devices can produce objectively measurable endocrine effects like real interpersonal touching can. We directly tested this possibility by examining changes in stress hormone cortisol before and after a conversation with a huggable communication device. Participants had 15-minute conversations with a remote partner that was carried out either with a huggable human-shaped device or with a mobile phone. Our experiment revealed significant reduction in the cortisol levels for those who had conversations with the huggable device. Our approach to evaluate communication media with biological markers suggests new design directions for interpersonal communication media to improve social support systems in modern highly networked societies. PMID:24150186

  6. 47. MAIN WAREHOUSE SECOND LEVEL ADDITION Second level was ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    47. MAIN WAREHOUSE - SECOND LEVEL ADDITION Second level was added in 1941. Note the variety of building materials used in the wall: cement, bricks and finally cement blocks, with wood topping the entire wall. - Hovden Cannery, 886 Cannery Row, Monterey, Monterey County, CA

  7. [Is it possible to decrease cholesterol levels with dietary supplements?].

    PubMed

    Rodondi, Pierre-Yves; Degoumois, Florence; Marques-Vidal, Pedro; Rodondi, Nicolas

    2016-03-01

    Patients often use dietary supplements for cardiovascular prevention. An US study showed that 75% of patients with cardiovascular disease used dietary supplements. Red yeast rice, phytosterols and fibers can significantly decrease LDL. The level of monacolin in red yeast rice can vary between products and toxins can sometimes be found. Prospective studies showed that fibers could decrease cardiovascular risk. Others substances, like guggul, soy and artichoke leaf extracts, did not show a clear benefit for cardiovascular prevention. Measurements of cholesterol levels can help the physician to discuss with his patient about the effects of some dietary supplements.

  8. [Is it possible to decrease cholesterol levels with dietary supplements?].

    PubMed

    Rodondi, Pierre-Yves; Degoumois, Florence; Marques-Vidal, Pedro; Rodondi, Nicolas

    2016-03-01

    Patients often use dietary supplements for cardiovascular prevention. An US study showed that 75% of patients with cardiovascular disease used dietary supplements. Red yeast rice, phytosterols and fibers can significantly decrease LDL. The level of monacolin in red yeast rice can vary between products and toxins can sometimes be found. Prospective studies showed that fibers could decrease cardiovascular risk. Others substances, like guggul, soy and artichoke leaf extracts, did not show a clear benefit for cardiovascular prevention. Measurements of cholesterol levels can help the physician to discuss with his patient about the effects of some dietary supplements. PMID:27089602

  9. Decreasing brain natriuretic peptide levels after treatment for hyperthyroidism.

    PubMed

    Ertugrul, Derun Taner; Yavuz, Bunyamin; Ata, Naim; Yalcin, Ahmet Arif; Kucukazman, Metin; Algul, Beyza; Dal, Kursad; Akin, Kadir Okhan; Deveci, Onur Sinan; Canbolat, Nihat; Ure, Oznur Sari; Tutal, Emre

    2009-01-01

    BNP are produced in ventricular cardiomyocytes, and secreted in response to volume expansion or pressure overload. The purpose of this study was to assess BNP levels in patients with hyperthyroidism before specific treatment for hyperthyroidism and after euthyroidism was achieved. The study was performed in a prospective design. The study population consisted of 48 consecutive newly diagnosed untreated overt hyper-thyroid patients who had not been treated any anti-thyroid medications before. All subjects underwent transt-horacic echocardiography. Levels of fT3, fT4, TSH and BNP were measured before the onset of the treatment and after euthyroidism was achieved. A significant decrease in BNP (102.5 (6.7-1769) ng/L vs. 5.0 (0.1-87.0) ng/L p< 0.001) levels were observed, after euthyroidism was achieved. The decrease in BNP levels was posi-tively correlated with the decrease in fT3 (r=0.298; p=0.049) and fT4 (r=0.313; p=0.030). There was no cor-relation between BNP levels and TSH levels (p=NS). We conclude that hyperthyroidism may cause high BNP measurements which can lead to misdiagnosis of congestive heart failure. We suggest that thyroid hormones should be checked in patients with high levels of BNP.

  10. Decreased frontal lobe phosphocreatine levels in methamphetamine users

    PubMed Central

    Sung, Young-Hoon; Yurgelun-Todd, Deborah A.; Shi, Xian-Feng; Kondo, Douglas G.; Lundberg, Kelly J.; McGlade, Erin C.; Hellem, Tracy L.; Huber, Rebekah S.; Fiedler, Kristen K.; Harrell, Renee E.; Nickerson, Bethany R.; Kim, Seong-Eun; Jeong, Eun-Kee; Renshaw, Perry F.

    2012-01-01

    BACKGROUND Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with highenergy phosphate metabolism have not been investigated in METH users. Phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and β-nucleoside triphosphate (β-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=0.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=0.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0 gram) of METH use than males (1.4±1.7 gram), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=0.02). CONCLUSIONS The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels. PMID:23084413

  11. Bifurcated method and apparatus for floating point addition with decreased latency time

    DOEpatents

    Farmwald, Paul M.

    1987-01-01

    Apparatus for decreasing the latency time associated with floating point addition and subtraction in a computer, using a novel bifurcated, pre-normalization/post-normalization approach that distinguishes between differences of floating point exponents.

  12. Decreased IL-35 levels in patients with immune thrombocytopenia.

    PubMed

    Yang, Yanhui; Xuan, Min; Zhang, Xian; Zhang, Donglei; Fu, Rongfeng; Zhou, Fangfang; Ma, Li; Li, Huiyuan; Xue, Feng; Zhang, Lei; Yang, Renchi

    2014-08-01

    IL-35 is a novel heterodimeric anti-inflammatory cytokine consisting of Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. IL-35 has been shown to possess the potency of inhibiting the CD4+ effector T cells and alleviating autoimmune diseases. In the study we investigated the levels of IL-35 as well as its prospective role in immune thrombocytopenia (ITP).ELISA was adopted to measure plasma IL-35, TGF-β and IL-10 levels. The mRNA expression levels of P35 and EBI3 in peripheral blood mononuclear cells (PBMCs) were studied based on real-time quantitative PCR. The correlation between plasma cytokine levels and clinical parameters was analyzed. Significantly lower plasma IL-35 levels were found in active ITP patients compared with those in remission (p = 0.017) and the healthy controls (p < 0.001). In active ITP patients, the plasma IL-35 levels displayed a significantly positive correlation with platelet counts (r = 0.5335, p < 0.0008). Further, P35 mRNA expression levels were lower in patients with active ITP than patients in remission (p = 0.033) and normal controls (p = 0.016).Thus, for the first time, this research reported a dramatically decreased IL-35 levels in ITP patients, suggesting that IL-35 may be involved in the pathogenesis of ITP.

  13. Forearm muscle oxygenation decreases with low levels of voluntary contraction

    NASA Technical Reports Server (NTRS)

    Murthy, G.; Kahan, N. J.; Hargens, A. R.; Rempel, D. M.

    1997-01-01

    The purpose of our investigation was to determine if the near infrared spectroscopy technique was sensitive to changes in tissue oxygenation at low levels of isometric contraction in the extensor carpi radialis brevis muscle. Nine subjects were seated with the right arm abducted to 45 degrees, elbow flexed to 85 degrees, forearm pronated 45 degrees, and wrist and forearm supported on an armrest throughout the protocol. Altered tissue oxygenation was measured noninvasively with near infrared spectroscopy. The near infrared spectroscopy probe was placed over the extensor carpi radialis brevis of the subject's right forearm and secured with an elastic wrap. After 1 minute of baseline measurements taken with the muscle relaxed, four different loads were applied just proximal to the metacarpophalangeal joint such that the subjects isometrically contracted the extensor carpi radialis brevis at 5, 10, 15, and 50% of the maximum voluntary contraction for 1 minute each. A 3-minute recovery period followed each level of contraction. At the end of the protocol, with the probe still in place, a value for ischemic tissue oxygenation was obtained for each subject. This value was considered the physiological zero and hence 0% tissue oxygenation. Mean tissue oxygenation (+/-SE) decreased from resting baseline (100% tissue oxygenation) to 89 +/- 4, 81 +/- 8, 78 +/- 8, and 47 +/- 8% at 5, 10, 15, and 50% of the maximum voluntary contraction, respectively. Tissue oxygenation levels at 10, 15, and 50% of the maximum voluntary contraction were significantly lower (p < 0.05) than the baseline value. Our results indicate that tissue oxygenation significantly decreases during brief, low levels of static muscle contraction and that near infrared spectroscopy is a sensitive technique for detecting deoxygenation noninvasively at low levels of forearm muscle contraction. Our findings have important implications in occupational medicine because oxygen depletion induced by low levels of muscle

  14. Intralipid Decreases Apolipoprotein M Levels and Insulin Sensitivity in Rats

    PubMed Central

    Zheng, Lu; Feng, Yuehua; Shi, Yuanping; Zhang, Jun; Mu, Qinfeng; Qin, Li; Berggren-Söderlund, Maria; Nilsson-Ehle, Peter; Zhang, Xiaoying; Luo, Guanghua; Xu, Ning

    2014-01-01

    Background Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. Aims To assess the effects of increased free fatty acids (FFAs) levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. Methods Adult male Sprague-Dawley (SD) rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR) were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK) rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. Results Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8) was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. Conclusion These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes. PMID:25144649

  15. Decreased serum vitamin D levels in early spontaneous pregnancy loss

    PubMed Central

    Hou, W; Yan, X-t; Bai, C-m; Zhang, X-w; Hui, L-y; Yu, X-w

    2016-01-01

    Background/Objectives: Effects of vitamin D deficiency in pregnancy have been associated with some adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in childbearing aged women and pregnancy loss (PL) in the first trimester. Subjects/Methods: This is a cross-sectional study. Plasma was collected from 60 nulliparous women with singleton at 7–9 weeks of gestation (30 with viable gestation and 30 with PL) and 60 non-gravid childbearing aged women (30 with a successful pregnancy history, and 30 with one or more spontaneous first-trimester PL history). Quantitation of serum 25-hydroxyvitamin D (25(OH)D) and 25-hydroxyvitamin D-1 alpha hydroxylase (CYP27B1) was assayed. Results: By pregnancy/non-gravid, normal pregnant women had higher 25(OH)D (49.32 μg/l) and CYP27B1 (82.00 pg/ml) than PL women (34.49 μg/l and 37.87 pg/ml, both P<0.01); the non-gravid women with a successful pregnancy history also had higher 25(OH)D (39.56 μg/l) and CYP27B1 (39.04 pg/ml) than women with PL history (12.30 μg/l and 12.35 pg/ml, both P<0.01). The 96.7% of non-gravid women with PL history and 43.3% of PL women had serum 25(OH)D concentrations below 30 μg/l. There was a strong association between low vitamin D levels and PL (odds ratio 1.71; 95% confidence interval: 1.2–2.4, P<0.001). The regression analyses showed that PL was significantly inversely correlated with 25(OH)D (P<0.01) and CYP27B1 levels (P<0.01). Conclusions: Vitamin D deficiency associated with PL in the first trimester of pregnancy. Decreased serum vitamin D levels among childbearing aged women with the failed clinical pregnancies history may predispose to increased risk for PL. PMID:27222154

  16. Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum.

    PubMed

    Barca, Emanuele; Kleiner, Giulio; Tang, Guomei; Ziosi, Marcello; Tadesse, Saba; Masliah, Eliezer; Louis, Elan D; Faust, Phyllis; Kang, Un J; Torres, Jose; Cortes, Etty P; Vonsattel, Jean-Paul G; Kuo, Sheng-Han; Quinzii, Catarina M

    2016-07-01

    In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q10 (CoQ10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ10 biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ10 deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ10 To investigate whether CoQ10 deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ10 levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ10 deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ10 in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ10 deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ10 levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.

  17. Decreased energy levels can cause and sustain obesity.

    PubMed

    Wlodek, Danuta; Gonzales, Michael

    2003-11-01

    Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the "obese" change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This "obese" change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries. PMID:14559057

  18. Decreased Plasma BDNF Levels of Patients with Somatization Disorder

    PubMed Central

    Kang, Nam-In; Park, Jong-Il

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF), one of the most abundant and important neurotrophins, is known to be involved in the development, survival, maintenance, and plasticity of neurons in the nervous system. Some studies have suggested that BDNF may play a role in the pathophysiology of several psychiatric illnesses such as depression and schizophrenia. Similarly, it is likely that the alteration of BDNF may be associated with the neuro-modulation that contributes to the development of somatization disorder. Methods The purpose of this study was to determine whether there is an abnormality of plasma BDNF levels in patients with somatization disorder, and to analyze the nature of the alteration after pharmacotherapy using an enzyme-linked immunosorbent assay (ELISA). Results The plasma BDNF levels of the patients with a somatization disorder were significantly lower compared with those of the control volunteers (83.61±89.97 pg/mL vs. 771.36±562.14 pg/mL); moreover, the plasma BDNF levels of those patients who received an antidepressant were significantly increased after the treatment (118.13±91.45 pg/mL vs. 72.92±88.21 pg/mL). Conclusion These results suggest that BDNF may play a role in the pathophysiology of somatization disorder. PMID:27757131

  19. Nitrate but not tea saponin feed additives decreased enteric methane emissions in nonlactating cows.

    PubMed

    Guyader, J; Eugène, M; Doreau, M; Morgavi, D P; Gérard, C; Loncke, C; Martin, C

    2015-11-01

    Tea saponin is considered a promising natural compound for reducing enteric methane emissions in ruminants. A trial was conducted to study the effect of this plant extract fed alone or in combination with nitrate on methane emissions, total tract digestive processes, and ruminal characteristics in cattle. The experiment was conducted as a 2 × 2 factorial design with 4 ruminally cannulated nonlactating dairy cows. Feed offer was restricted to 90% of voluntary intake and diets consisted of (DM basis): 1) control (CON; 50% hay and 50% pelleted concentrates), 2) CON with 0.5% tea saponin (TEA), 3) CON with 2.3% nitrate (NIT), and 4) CON with 0.5% tea saponin and 2.3% nitrate (TEA+NIT). Tea saponin and nitrate were included in pelleted concentrates. Diets contained similar amounts of CP (12.2%), starch (26.0%), and NDF (40.1%). Experimental periods lasted 5 wk including 2 wk of measurement (wk 4 and 5), during which intake was measured daily. In wk 4, daily methane emissions were quantified for 4 d using open circuit respiratory chambers. In wk 5, total tract digestibility, N balance, and urinary excretion of purine derivatives were determined from total feces and urine collected separately for 6 d. Ruminal fermentation products and protozoa concentration were analyzed from samples taken after morning feeding for 2 nonconsecutive days in wk 5. Tea saponin and nitrate supplementation decreased feed intake ( < 0.05), with an additive effect when fed in combination. Compared with CON, tea saponin did not modify methane emissions (g/kg DMI; > 0.05), whereas nitrate-containing diets (NIT and TEA+NIT) decreased methanogenesis by 28%, on average ( < 0.001). Total tract digestibility, N balance, and urinary excretion of purine derivatives were similar among diets. Ruminal fermentation products were not affected by tea saponin, whereas nitrate-containing diets increased acetate proportion and decreased butyrate proportion and ammonia concentration ( < 0.05). Under the

  20. Decrease in phosphocreatine level in skeletal muscle of SIV-infected rhesus macaques correlates with decrease in intracellular glutathione.

    PubMed

    Hack, V; Gross, A; Böhme, A; Stahl-Hennig, C; Dröge, W

    1997-09-01

    Loss of skeletal muscle tissue (cachexia) is one of the hallmarks of HIV infection. It has been found (1) that creatine kinase, i.e., an enzyme of pivotal importance in muscular mitochondrial energy metabolism, is inhibited by oxidative glutathiolation, and (2) that reduced glutathione (GSH) is decreased in skeletal muscle of SIV-infected rhesus monkeys. We, therefore, have studied the phosphocreatine (P-Cr) levels. Muscle tissue from SIV-infected macaques showed significantly decreased P-Cr but normal creatine (Cr), ATP, and ADP when compared with uninfected macaques. Individual P-Cr levels were significantly correlated with GSH. Our findings may explain the dysregulation of energy metabolism in cachexia.

  1. A possible mechanism for the decrease in serum thyroxine level by phenobarbital in rodents

    SciTech Connect

    Kato, Yoshihisa; Suzuki, Hiroshi; Haraguchi, Koichi; Ikushiro, Shinichi; Ito, Yoshihiko; Uchida, Shinya; Yamada, Shizuo; Degawa, Masakuni

    2010-12-15

    Effects of phenobarbital (PB) on the levels of serum thyroid hormones such as total thyroxine (T{sub 4}) and triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs. One day after the final administration of PB (80 mg/kg, intraperitoneal, once daily for 4 days), significant decreases in the levels of the serum total T{sub 4} and free T{sub 4} occurred in mice, hamsters, and rats, while a significant decrease in the level of serum triiodothyronine was observed in hamsters and rats among the animals examined. In addition, a significant decrease in the level of serum thyroid-stimulating hormone was observed in only hamsters among the rodents examined. Significant increases in the level and activity of hepatic T{sub 4}-UDP-glucuronosyltransferase (UGT1A) after the PB administration occurred in mice, hamsters, and rats, while the increase in the amount of biliary [{sup 125}I]T{sub 4}-glucuronide after an intravenous injection of [{sup 125}I]T{sub 4} to the PB-pretreated animals occurred only in rats. In mice, rats, and hamsters, but not guinea pigs, PB pretreatment promoted the clearance of [{sup 125}I]T{sub 4} from the serum, led to a significant increase in the steady-state distribution volumes of [{sup 125}I]T{sub 4}, and raised the concentration ratio (Kp value) of the liver to serum and the liver distribution of [{sup 125}I]T{sub 4}. The present findings indicate that the PB-mediated decreases in the serum T{sub 4} level in mice, hamsters, and rats, but not guinea pigs, occur mainly through an increase in the accumulation level of T{sub 4} in the liver.

  2. Krill oil significantly decreases 2-arachidonoylglycerol plasma levels in obese subjects.

    PubMed

    Banni, Sebastiano; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Giordano, Elena; Sirigu, Anna Rita; Berge, Kjetil; Vik, Hogne; Maki, Kevin C; Di Marzo, Vincenzo; Griinari, Mikko

    2011-01-30

    We have previously shown that krill oil (KO), more efficiently than fish oil, was able to downregulate the endocannabinoid system in different tissues of obese zucker rats.We therefore aimed at investigating whether an intake of 2 g/d of either KO or menhaden oil (MO), which provides 309 mg/d of EPA/DHA 2:1 and 390 mg/d of EPA/DHA 1:1 respectively, or olive oil (OO) for four weeks, is able to modify plasma endocannabinoids in overweight and obese subjects.The results confirmed data in the literature describing increased levels of endocannabinoids in overweight and obese with respect to normo-weight subjects. KO, but not MO or OO, was able to significantly decrease 2-arachidonoylglycerol (2-AG), although only in obese subjects. In addition, the decrease of 2-AG was correlated to the plasma n-6/n-3 phospholipid long chain polyunsaturated fatty acid (LCPUFA) ratio. These data show for the first time in humans that relatively low doses of LCPUFA n-3 as KO can significantly decrease plasma 2-AG levels in obese subjects in relation to decrease of plasma phospholipid n-6/n-3 LCPUFA ratio. This effect is not linked to changes of metabolic syndrome parameters but is most likely due to a decrease of 2-AG biosynthesis caused by the replacement of 2-AG ultimate precursor, arachidonic acid, with n-3 PUFAs, as previously described in obese Zucker rats.

  3. Increased O-GlcNAc Levels Correlate with Decreased O-GlcNAcase Levels in Alzheimer Disease Brain

    PubMed Central

    Förster, Sarah; Welleford, Andrew S.; Triplett, Judy C.; Sultana, Rukhsana; Schmitz, Brigitte; Butterfield, D. Allan

    2014-01-01

    The potential role of the posttranslational modification of proteins with O-linked N-acetyl-β-D-glucosamine (O-GlcNAc) in the pathogenesis of Alzheimer disease (AD) has been studied extensively, yet the exact function of O-GlcNAc in AD remains elusive. O-GlcNAc cycling is facilitated by only two highly conserved enzymes: O-GlcNAc transferase (OGT) catalyzes the addition, while O-GlcNAcase (OGA) catalyzes the removal of GlcNAc from proteins. Studies analyzing global O-GlcNAc levels in AD brain have produced inconsistent results and the reasons for altered O-GlcNAcylation in AD are still poorly understood. In this study, we show a 1.2 fold increase in cytosolic protein O-GlcNAc modification in AD brain when compared to age-matched controls. Interestingly, O-GlcNAc changes seem to be attributable to differential modification of a few individual proteins. While our finding of augmented O-GlcNAcylation concurs with some reports, it is contrary to others demonstrating decreased O-GlcNAc levels in AD brain. These conflicting results emphasize the need for further studies providing conclusive evidence on the subject of O-GlcNAcylation in AD. We further demonstrate that, while OGT protein levels are unaffected in AD, OGA protein levels are significantly decreased to 75 % of those in control samples. In addition, augmented protein O-GlcNAc modification correlates to decreased OGA protein levels in AD subjects. While OGA inhibitors are already being tested for AD treatment, our results provide a strong indication that the general subject of O-GlcNAcylation and specifically its regulation by OGA and OGT in AD need further investigation to conclusively elucidate its potential role in AD pathogenesis and treatment. PMID:24859566

  4. Involvement of decreased neuroglobin protein level in cognitive dysfunction induced by 1-bromopropane in rats.

    PubMed

    Guo, Ying; Yuan, Hua; Jiang, Lulu; Yang, Junlin; Zeng, Tao; Xie, Keqin; Zhang, Cuili; Zhao, Xiulan

    2015-03-10

    1-Bromopropane (1-BP) is used as a substitute for ozone-depleting solvents (ODS) in industrial applications. 1-BP could display central nervous system (CNS) neurotoxicity manifested by cognitive dysfunction. Neuroglobin (Ngb) is an endogenous neuroprotectant and is predominantly expressed in the nervous system. The present study aimed to investigate Ngb involvement in CNS neurotoxicity induced by 1-BP in rats. Male Wistar rats were randomly divided into 5 groups (n=14) and treated with 0, 100, 200, 400 and 800 mg/kg bw 1-BP, respectively, by gavage for consecutive 12 days. Rats displayed cognitive dysfunction dose-dependently through Morris water maze (MWM) test. Significant neuron loss in layer 5 of the prelimbic cortex (PL) was observed. Moreover, 1-BP decreased Ngb protein level in cerebral cortex and Ngb decrease was significantly positively correlated with cognitive dysfunction. Glutathione (GSH) content, GSH/oxidized glutathione (GSSG) ratio and glutamate cysteine ligase (GCL) activity decreased in cerebral cortex, coupled with the increase in GSSG content. GSH and GSH/GSSG ratio decrease were significantly positively correlated with cortical Ngb decrease. Additionally, levels of N-epsilon-hexanoyl-lysine (HEL) and 4-hydroxy-2-nonenal (4-HNE) modified proteins in cerebral cortex of 1-BP-treated rats increased significantly. In conclusion, it was suggested that 1-BP resulted in decreased endogenous neuroprotectant Ngb in cerebral cortex, which might play an important role in CNS neurotoxicity induced by 1-BP and that 1-BP-induced oxidative stress in cerebral cortex might partly be responsible for Ngb decrease.

  5. 38. VIEW SOUTHWEST OF STREET LEVEL IN SHOWROOM ADDITION (NOW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. VIEW SOUTHWEST OF STREET LEVEL IN SHOWROOM ADDITION (NOW USED AS FINISHING ROOM) WITH FRESHLY PAINTED DORY BOATS ON DISPLAY. 2X4 STUD WALL AND ROOF FRAMING CAN BE SEEN. - Lowell's Boat Shop, 459 Main Street, Amesbury, Essex County, MA

  6. Decreasing curing temperature of spin-on dielectrics by using additives

    NASA Astrophysics Data System (ADS)

    Bae, Jin Hee; Han, Kwen Woo; Park, Eun Su; Yoon, Hui Chan; Na, Yoong Hee; Seo, Jin Woo; Lim, Wan Hee; Kim, Bo Sun; Jang, Jun Young; Cho, Younjin

    2014-03-01

    Spin-on dielectric (SOD) is widely used in semiconductor industry, to form insulating layers including shallow trench isolation (STI) or inter-layer dielectrics (ILD). SOD has several advantages over high density plasma chemical vapor deposition (HDP-CVD) for manufacturing process, such as less defect and higher throughput. However, both SOD and HDP-CVD have a drawback, which is a high temperature curing process required to make pure silicon oxide layers. High temperature curing could cause high stress and thermal distortion. These disadvantages are becoming more problematic as the semiconductor device shrinks. To resolve the problem, we tested several additives to moderate the curing temperature. It was found out that amine compounds were effective to convert SOD polymer into silicon oxide, therefore the curing process could be performed at a lower temperature. We also observed that the SOD films containing amine additives have higher etch resistance during a wet etch process. These results, as well as the lower curing temperature, are beneficial for manufacturing insulating layers. Further investigation is ongoing to characterize other film properties of the SOD with additives, and to optimize the formulation conditions according to the requirements of manufacturing processes.

  7. 113. Stage level floor structure. In addition to the movable ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    113. Stage level floor structure. In addition to the movable sections, there were hinged slots that could be opened in the stage floor (see sheet 4 of 9, note 4; sheet 5 of 9, note 2; and sheet 7 of 9, note 1). A remaining cast iron bracket is visible in the left foreground of the photograph. The actual structure for a hinged section is visible in the background, to the right of center. The hydraulic ram (type D) visible below the floor level is the south ram in the middle row; the view is facing north. - Auditorium Building, 430 South Michigan Avenue, Chicago, Cook County, IL

  8. 45. VIEW OF UPPER LEVEL CRUSHER ADDITION FROM CRUSHED OXIDIZED ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    45. VIEW OF UPPER LEVEL CRUSHER ADDITION FROM CRUSHED OXIDIZED ORE BIN. 18 INCH BELT CONVEYOR BIN FEED, LOWER CENTER, WITH STEPHENS-ADAMSON 25 TON/HR ELEVATOR SPLIT DISCHARGE (OXIDIZED/UNOXIDIZED) IN CENTER. CRUDE ORE BINS AND MACHINE SHOP BEYOND. NOTE TOP OF CRUSHED OXIDIZED ORE BIN IS BELOW TOP OF CRUDE ORE BINS. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  9. Brazilian propolis extract used as an additive to decrease methane emissions from the rumen microbial population in vitro.

    PubMed

    Santos, Nadine Woruby; Zeoula, Lucia Maria; Yoshimura, Emerson Henri; Machado, Erica; Macheboeuf, Didier; Cornu, Agnès

    2016-06-01

    Propolis is a product that is rich in phenolic compounds and can be utilized in animal nutrition as a dietary additive. In this study, the effects of a Brazilian green propolis extract on rumen fermentation and gas production were determined. The fate of propolis phenolic compounds in the rumen medium was also investigated. Fermentation was done in 24-h batches over three periods. Inoculates were obtained from cows fed on grassland hay and concentrate. Propolis extract in a hydroalcoholic solution was applied at increasing doses to the substrate (1 to 56 g/kg). The fermentation substrate consisted on a mixture of alfalfa hay, soybean meal, and wheat grain mixture in dry matter. After 24 h of fermentation, seven new compounds were observed in the medium in amounts that correlated to the propolis dose. The dose of propolis extract linearly decreased the pH of the medium and linearly increased propionate production, which reduced the acetate-to-propionate ratio and influenced the total production of short-chain fatty acids. Propolis also linearly reduced methane production and increased the carbon dioxide-to-methane ratio. Ammonia nitrogen levels and in vitro digestibility of organic matter were similar among the treatments. The combination of increased propionate production and decreased methane production suggests better energy utilization from the feed. PMID:27105625

  10. R-ETODOLAC DECREASES BETA-CATENIN LEVELS ALONG WITH SURVIVAL AND PROLIFERATION OF HEPATOMA CELLS

    PubMed Central

    Behari, Jaideep; Zeng, Gang; Otruba, Wade; Thompson, Michael; Muller, Peggy; Micsenyi, Amanda; Sekhon, Sandeep S.; Leoni, Lorenzo; Monga, Satdarshan P. S.

    2007-01-01

    Background Inhibition of hepatoma cells by cyclooxygenase (COX)-2 dependent and independent mechanisms has been shown previously. Here, we examine the effect of Celecoxib, a COX-2-inhibitor and R-Etodolac, an enantiomer of the nonsteroidal anti-inflammatory drug Etodolac, which lacks COX-inhibitory activity, on the Wnt/β-catenin pathway and human hepatoma cells. Methods Hep3B and HepG2 cell lines were treated with Celecoxib or R-Etodolac, and examined for viability, DNA synthesis, Wnt/β-catenin pathway components, and downstream target gene expression. Results Celecoxib at high doses affected β-catenin protein by inducing its degradation via GSK3β and APC along with diminished tumor cell proliferation and survival. R-Etodolac at physiological doses caused decrease in total and activated β-catenin protein secondary to decrease in its gene expression and post-translationally through GSK3β activation. In addition, increased β-catenin-E-cadherin was also observed at the membrane. An associated inhibition of β-catenin-dependent Tcf reporter activity, decreased levels of downstream target gene products glutamine synthetase and cyclin-D1, and decreased proliferation and survival of hepatoma cells was evident. Conclusion The antitumor effects of Celecoxib (at high concentrations) and R-Etodolac (at physiological doses) on HCC cells were accompanied by the down-regulation of β-catenin demonstrating a useful therapeutic strategy in hepatocellular cancer. PMID:17275129

  11. Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats.

    PubMed

    Valentini, Juliana; Vicentini, Juliana; Grotto, Denise; Tonello, Raquel; Garcia, Solange C; Barbosa, Fernando

    2010-02-01

    In this study, we examined the effects of low levels and sub-chronic exposure to methylmercury (MeHg) on butyrylcholinesterase (BuChE) activity in rats. Moreover, we examined the relationship between BuChE activity and oxidative stress biomarkers [delta-aminolevulinic acid dehydratase (delta-ALA-D) and malondialdehyde levels (MDA)] in the same animals. Rats were separated into three groups (eight animals per group): (Group I) received water by gavage; (Group II) received MeHg (30 microg/kg/day) by gavage; (Group III) received MeHg (100 microg/kg/day). The time of exposure was 90 days. BuChE and ALA-D activities were measured in serum and blood, respectively; whereas MDA levels were measured in plasma. We found BuChE and ALA-D activities decreased in groups II and III compared to the control group. Moreover, we found an interesting negative correlation between plasmatic BuChE activity and MDA (r = -0.85; p < 0.01) and a positive correlation between plasmatic BuChE activity and ALA-D activities (r = 0.78; p < 0.01), thus suggesting a possible relationship between oxidative damage promoted by MeHg exposure and the decrease of BuChE activity. In conclusion, long-term exposure to low doses of MeHg decreases plasmatic BuChE activity. Moreover, the decrease in the enzyme is strongly correlated with the oxidative stress promoted by the metal exposure. This preliminary finding highlights a possible mechanism for MeHg to reduce BuChE activity in plasma. Additionally, this enzyme could be an auxiliary biomarker on the evaluation of MeHg exposure.

  12. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: decreased CIMT, reduced plasma lipid levels, and decreased blood pressure

    PubMed Central

    Fogelman, Yacov; Gaitini, Diana; Carmeli, Eli

    2016-01-01

    Background Ethanolic extract of licorice root has been shown to reduce low-density lipoprotein (LDL) oxidation in atherosclerotic mice and in both hypercholesterolemic and normal lipidemic humans. Objective This study examined the effect of licorice-root extract on carotid intima-media thickness (CIMT) in individuals with hypercholesterolemia. Design Individuals with hypercholesterolemia (total cholesterol ≥6.18 mmol/L [240 mg/dL]) and without significant stenosis were randomly allocated to two groups: an experimental group that consumed 0.2 g/day of ethanolic extract of licorice root for 12 months, and a control group that received a placebo. Results Of 110 eligible participants, 94 (41–80 years old) completed the study. A significant CIMT decrease from 0.92±0.25 mm to 0.84±0.21 mm was observed in the experimental group compared with an increase from 0.85±0.17 mm to 0.88±0.19 mm in the control group. Mean plasma total cholesterol levels and LDL cholesterol decreased, at the range baseline to 1 year, from 284±32 mg/dl to 262±25 mg/dl and from 183±8.5 mg/dl to 174±9.1 mg/dl, respectively, for the experimental group (p<0.001) and from 291±35 to 289±31 mg/dl and from 177.6±10.7 to 179.3±9.6 (p=0.08), respectively, for the control group. Mean high-density lipoprotein (HDL) did not change significantly in either group. In the experimental group, systolic blood pressure decreased from 138±12 mmHg to 125±13 mmHg after 1 year (p=0.01) and increased from 136±15 mmHg to 137±13 mmHg in the control group. Diastolic blood pressure decreased from 92±9 mmHg to 84±10 mmHg (p=0.01) in the experimental group and increased from 89±11 mmHg to 90±8 mmHg in the control group. Conclusion Following 1 year of licorice consumption, mean CIMT, total cholesterol, LDL levels, and blood pressure were decreased. This suggests that licorice may attenuate the development of atherosclerosis and of related cardiovascular diseases. PMID:27113136

  13. Decreasing phosphorus runoff losses from land-applied poultry litter with dietary modifications and alum addition.

    PubMed

    Smith, Douglas R; Moore, P A; Miles, D M; Haggard, B E; Daniel, T C

    2004-01-01

    Phosphorus (P) losses from pastures fertilized with poultry litter contribute to the degradation of surface water quality in the United States. Dietary modification and manure amendments may reduce potential P runoff losses from pastures. In the current study, broilers were fed a normal diet, phytase diet, high available phosphorus (HAP) corn diet, or HAP corn + phytase diet. Litter treatments were untreated control and alum added at 10% by weight between flocks. Phytase and HAP corn diets reduced litter dissolved P content in poultry litter by 10 and 35%, respectively, compared with the normal diet (789 mg P kg(-1)). Alum treatment of poultry litter reduced the amount of dissolved P by 47%, while a 74% reduction was noted after alum treatment of litter from the HAP corn + phytase diet. The P concentrations in runoff water were highest from plots receiving poultry litter from the normal diet, whereas plots receiving poultry litter from phytase and HAP corn diets had reduced P concentrations. The addition of alum to the various poultry litters reduced P runoff by 52 to 69%; the greatest reduction occurred when alum was used in conjunction with HAP corn and phytase. This study demonstrates the potential added benefits of using dietary modification in conjunction with manure amendments in poultry operations. Integrators and producers should consider the use of phytase, HAP corn, and alum to reduce potential P losses associated with poultry litter application to pastures. PMID:15537944

  14. Decreasing phosphorus runoff losses from land-applied poultry litter with dietary modifications and alum addition.

    PubMed

    Smith, Douglas R; Moore, P A; Miles, D M; Haggard, B E; Daniel, T C

    2004-01-01

    Phosphorus (P) losses from pastures fertilized with poultry litter contribute to the degradation of surface water quality in the United States. Dietary modification and manure amendments may reduce potential P runoff losses from pastures. In the current study, broilers were fed a normal diet, phytase diet, high available phosphorus (HAP) corn diet, or HAP corn + phytase diet. Litter treatments were untreated control and alum added at 10% by weight between flocks. Phytase and HAP corn diets reduced litter dissolved P content in poultry litter by 10 and 35%, respectively, compared with the normal diet (789 mg P kg(-1)). Alum treatment of poultry litter reduced the amount of dissolved P by 47%, while a 74% reduction was noted after alum treatment of litter from the HAP corn + phytase diet. The P concentrations in runoff water were highest from plots receiving poultry litter from the normal diet, whereas plots receiving poultry litter from phytase and HAP corn diets had reduced P concentrations. The addition of alum to the various poultry litters reduced P runoff by 52 to 69%; the greatest reduction occurred when alum was used in conjunction with HAP corn and phytase. This study demonstrates the potential added benefits of using dietary modification in conjunction with manure amendments in poultry operations. Integrators and producers should consider the use of phytase, HAP corn, and alum to reduce potential P losses associated with poultry litter application to pastures.

  15. 41. VIEW NORTH OF UPPER LEVEL OF CRUSHER ADDITION. DINGS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    41. VIEW NORTH OF UPPER LEVEL OF CRUSHER ADDITION. DINGS MAGNETIC PULLEY AT CENTER. ALSO SHOWS 100-TON CRUSHED UNOXIDIZED ORE BIN (RIGHT), PULLEY FORM 18 INCH BELT CONVEYOR CRUSHED OXIDIZED ORE BIN FEED AND STEPHENSADAMSON 25 TON/HR BUCKET ELEVATOR (UPPER CENTER). THE UPPER PORTION OF THE SAMPLING ELEVATOR IS ABOVE THE MAGNETIC PULLEY (CENTER LEFT) WITH THE ROUTE OF THE 16 INCH BELT CONVEYOR FINES FEED TO CRUSHED OXIDIZED ORE BIN TO ITS LEFT. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  16. Serum estradiol but not gonadotropin levels decrease acutely after insulin-induced hypoglycemia in cycling women.

    PubMed

    Bing-You, R G; Spratt, D I

    1992-10-01

    Although corticotropin-releasing hormone (CRH) acutely suppresses gonadotropin-releasing hormone (GnRH) secretion in animal models, its effect on the hypothalamic-pituitary-gonadal axis in humans is not well defined. To further evaluate the acute effects of adrenal axis activation on the hypothalamic-pituitary-gonadal axis in humans, we employed a model of insulin-induced hypoglycemia to stimulate endogenous CRH secretion in eight cycling women. Serum samples were obtained immediately before and 15, 30, 45, 60, 75, 90, and 120 min following iv insulin (0.15 U/kg) or saline injection. To ensure that the degree of hypothalamic-pituitary-adrenal activation in our subjects was similar to that observed in severely ill patients with hypogonadotropism, serum cortisol (F) levels were also measured in a group of acutely ill patients selected to have hypogonadotropism. All women experienced symptomatic hypoglycemia after insulin injection. Differences between serum F levels in hypoglycemic vs. control sessions were evident at 30 min (P < 0.01) and maximum at 120 min (P < 0.0001) after insulin injection. Serum estradiol levels were significantly lower following hypoglycemia than during control sessions (P < 0.001). In contrast, serum LH and FSH levels were not significantly different between control and hypoglycemic sessions. Peak serum F levels in these hypoglycemic women were similar to F levels in critically ill patients with hypogonadotropism. These results demonstrate that stress and/or hypoglycemia can acutely decrease circulating estradiol levels. In addition, these data suggest that endogenous CRH does not play a major role in acute suppression of GnRH (over 2 h) in humans. Further studies are required to identify longer term effects of CRH on GnRH secretion which may be present in hypothalamic amenorrhea or hypogonadotropic hypogonadism of critical illness.

  17. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

    PubMed Central

    Brigandi, Sarah A.; Shao, Hong; Qian, Steven Y.; Shen, Yiping; Wu, Bai-Lin; Kang, Jing X.

    2015-01-01

    Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (p < 0.001). In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2) were higher in a subset of the autistic participants (n = 20) compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism. PMID:25946342

  18. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed Central

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T. S.; Janssens, Ivan A.; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including “all” papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  19. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T S; Janssens, Ivan A; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity.

  20. Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation.

    PubMed

    Sawada, Kazutaka; Kitagaki, Hiroshi

    2016-01-01

    Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation. PMID:26839744

  1. Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation

    PubMed Central

    Sawada, Kazutaka

    2016-01-01

    Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation. PMID:26839744

  2. Affinity proteomics discovers decreased levels of AMFR in plasma from Osteoporosis patients

    PubMed Central

    Qundos, Ulrika; Drobin, Kimi; Mattsson, Cecilia; Hong, Mun‐Gwan; Sjöberg, Ronald; Forsström, Björn; Solomon, David; Uhlén, Mathias; Nilsson, Peter; Michaëlsson, Karl

    2015-01-01

    Purpose Affinity proteomic approaches by antibody bead arrays enable multiplexed analysis of proteins in body fluids. In the presented study, we investigated blood plasma within osteoporosis to discovery differential protein profiles and to propose novel biomarkers candidates for subsequent studies. Experimental design Starting with 4608 antibodies and plasma samples from 22 women for an untargeted screening, a set of 72 proteins were suggested for further analysis. Complementing these with targets from literature and other studies, a targeted bead array of 180 antibodies was built to profile for 92 proteins in plasma samples of 180 women from two independent population‐based studies. Results Differential profiles between osteoporosis patients and matched controls were discovered for 12 proteins in at least one of the two study sets. Among these targets, the levels of autocrine motility factor receptor (AMFR) were concordantly lower in plasma of female osteoporosis patients. Subsequently, verification of anti‐AMFR antibody selectivity was conducted using high‐density peptide and protein arrays, and Western blotting. Conclusions and clinical relevance Further validation in additional study sets will be needed to determine the clinical value of the observed decrease in AMFR plasma levels in osteoporosis patients, but AMFR may aid our understanding of disease mechanisms and could support existing tools for diagnosis and monitoring of patient mobility within osteoporosis. PMID:25689831

  3. Neither testosterone levels nor aggression decrease when the male Mongolian gerbil (Meriones unguiculatus) displays paternal behavior.

    PubMed

    Juana, Luis; Bárbara, Vázquez-Gaytán; Martín, Martínez-Torres; Agustín, Carmona; Guillermo, Ramos-Blancas; Guadalupe, Ortíz

    2010-03-01

    The first studies that correlated mammalian paternal behavior and testosterone levels indicated that the concentration of this steroid hormone decreases when males exhibit paternal care. However, recent studies have also shown that testosterone levels do not decrease when males display paternal behavior. In this study, we measured testosterone levels in plasma throughout the reproductive cycle of the Mongolian gerbil. Testosterone concentrations were correlated with paternal care as well as aggression. We also examined whether there is a trade-off between paternal behavior and aggression in this mammal. Our results show that Mongolian gerbil testosterone levels do not decrease when the males give paternal care. Likewise, male Mongolian gerbils exhibit high levels of aggression while displaying paternal behavior, indicating that there is no trade-off between aggression and paternal behavior. More studies are needed to determine whether testosterone is involved in the regulation of paternal behavior in this rodent.

  4. YM155 reverses cisplatin resistance in head and neck cancer by decreasing cytoplasmic survivin levels

    PubMed Central

    Kumar, Bhavna; Yadav, Arti; Lang, James C.; Cipolla, Michael; Schmitt, Alessandra C.; Arradaza, Nicole; Teknos, Theodoros N.; Kumar, Pawan

    2013-01-01

    Cisplatin is one of the commonly used chemotherapeutic drugs for the treatment of head and neck squamous cell carcinoma (HNSCC). However, acquisition of cisplatin resistance is common in patients with HNSCC and it often leads to local and distant failure. In this study, we demonstrate that survivin expression is significantly upregulated in HNSCC primary tumors and cell lines. In addition, survivin levels were significantly higher in HPV negative patients that normally respond poorly to cisplatin treatment. Survivin expression was further increased in cisplatin resistant cells (CAL27-CisR) as compared to its parent cells (CAL27). Therefore, we hypothesize that targeting of survivin in HNSCC could reverse the resistant phenotype in tumor cells thereby enhancing the therapeutic efficacy of cisplatin. We used both in vitro and in vivo models to test the efficacy of YM155, a small molecule survivin inhibitor, either as a single agent or in combination with cisplatin. YM155 significantly decreased survivin levels and cell proliferation in a dose-dependent manner. In addition, YM155 pretreatment significantly reversed cisplatin resistance in cancer cells. Interestingly, YM155 treatment altered the dynamic localization of survivin in cells by inducing a rapid reduction in cytoplasmic survivin, which plays a critical role in its anti-apoptotic function. In a SCID mouse xenograft model, YM155 significantly enhanced the anti-tumor and anti-angiogenic effects of cisplatin with no added systemic toxicity. Taken together, our results suggest a potentially novel strategy to use YM155 to overcome the resistance in tumor cells thereby enhancing the effectiveness of the chemotherapy in HNSCC. PMID:22723337

  5. Verruculogen: a new substance for decreasing of GABA levels in CNS.

    PubMed

    Hotujac, L; Muftić, R H; Filipović, N

    1976-01-01

    In our previous work we examined the mechanism of action of the new tremorogenic substance verruculogen isolated by Cole and coworkers. Examining the effect of various substances with known mechanisms of action on verruculogen-induced tremor, we concluded that this tremor was probably related to decrease of GABA levels in CNS. In order to further define the mechanisms of action of verruculogen, we determined brain GABA levels in animals in which tremor was produced by verruculogen administration. Verruculogen administration produced a decrease in GABA levels in mouse CNS. This finding substantiates our earlier suggestion that verruculogen-induced tremor is mediated by a loss of inhibitory GABA function. PMID:935244

  6. Decreased aortic glutathione levels may contribute to impaired nitric oxide-induced relaxation in hypercholesterolaemia

    PubMed Central

    Adachi, Takeshi; Cohen, Richard A

    2000-01-01

    The aim of this study was to determine if the decrease in aortic total glutathione (GSH) levels in hypercholesterolaemia is related to the impairment of relaxation to acetylcholine (ACh) and exogenous nitric oxide (NO). Isometric tension and vascular GSH levels were measured in thoracic aortic rings from rabbits fed for 12 weeks with 0.5% cholesterol diet. Hypercholesterolaemia decreased aortic GSH levels and impaired relaxation to ACh and NO. To determine if GSH depletion impaired the response to NO, normal rabbit thoracic aorta was incubated with 1,3-bis [2-chloroethyl]-1-nitrosourea (BCNU; 0.2 mmol L−1), a GSH reductase inhibitor, or diazine-dicarboxylic acid bis [N, N dimethylamide] (diamide; 1 mmol L−1), a thiol oxidizing agent. BCNU or diamide decreased aortic GSH levels and impaired ACh and NO-induced relaxation. The effects of diamide on GSH levels and relaxation were partially prevented by co-incubation with GSH ester (GSE; 2 mmol L−1). Increasing GSH with GSE significantly enhanced NO-induced relaxation in aorta from both hypercholesterolaemic and normal rabbits, however relaxation of hypercholesterolaemic rabbit aorta was not restored to normal. These data suggest that other factors, perhaps related to the long-term decrease in GSH levels, are responsible for reduced NO bioactivity in hypercholesterolaemia. PMID:10696103

  7. Decreased cerebral spinal fluid neurotransmitter levels in Smith-Lemli-Opitz syndrome.

    PubMed

    Sparks, S E; Wassif, C A; Goodwin, H; Conley, S K; Lanham, D C; Kratz, L E; Hyland, K; Gropman, A; Tierney, E; Porter, F D

    2014-05-01

    Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3β-hydroxysterol Δ(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials.

  8. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration

    PubMed Central

    Douglas, Gavin M.; Wilson, Michael D.; Moses, Alan M.

    2016-01-01

    Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions. We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID:26882985

  9. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  10. In situ clinical evidence that zinc levels are decreased in breast invasive ductal carcinoma

    PubMed Central

    Zou, Jing; Franklin, Renty B.

    2016-01-01

    Purpose Altered zinc levels in malignant cells versus their normal cells have important implications in the development and progression of several cancers. Prostate, pancreatic, and hepatocellular carcinomas exhibit consistent marked zinc decrease in situ in the malignant cells, and other cancers (such as kidney, lung, and thyroid) also exhibit decreased tissue zinc levels. However, zinc levels are increased in breast cancer tissue compared to breast normal tissue, and the contemporary dominant view is that zinc is increased in invasive ductal carcinoma. This has important implications regarding the role and effects of zinc in breast malignancy compared to other cancers, which caused us to initiate this study to either confirm or challenge the contemporary view of an increased zinc level in the invasive ductal malignant cells. Methods We employed dithizone staining of breast tissue sections and tissue cores to determine the relative in situ cellular zinc levels specifically in the invasive ductal malignant cells as compared to normal ductal epithelium. This approach had not been employed in any of the reported breast studies. Results The results revealed that the zinc levels are consistently and markedly decreased in the ductal malignant cells as compared with higher prominent zinc levels in the normal ductal epithelium. Decreased zinc is evident in Grade 1 well-differentiated malignancy and in Grade 2 and Grade 3 carcinomas. Among the twenty-five cancer cases in this study, none exhibited increased zinc in the invasive ductal carcinoma compared to the zinc level in the normal ductal epithelium. Conclusions The decreased zinc levels in breast invasive ductal carcinoma is consistent with prostate, pancreatic, and liver carcinomas in which the decrease in zinc is a required event in the development of malignancy to prevent cytotoxicity that would result from the higher zinc levels in the normal cells. This new understanding requires a redirection in elucidating the

  11. Aspartame decreases evoked extracellular dopamine levels in the rat brain: an in vivo voltammetry study.

    PubMed

    Bergstrom, Brian P; Cummings, Deirdre R; Skaggs, Tricia A

    2007-12-01

    Conflicting reports exist concerning the effect aspartame (APM, l-aspartyl-l-phenylalanine methyl ester) has upon brain biogenic amines. In the following study, in vivo voltammetry was utilized to measure evoked extracellular dopamine (DA) levels in the striatum of rats in order to assess APM's effect. Time-course experiments revealed a significant decline in evoked extracellular DA levels within 1h of a single systemic dose (500mg/kg i.p.) when compared to vehicle-injected controls. The effect was frequency dependent and showed a significant decrease utilizing high frequency stimulation parameters (50 and 60Hz). In order to further determine APM's potential to alter evoked extracellular DA levels, extended stimulation periods were employed to deplete releasable stores both before and after APM administration in intact and 6-OHDA partially lesioned animals. The extended stimulation periods were applied at 60Hz for 2,5,10 and 20s durations. APM decreased DA levels under these conditions in both intact and 6-OHDA partially lesioned animals by an average of 34% and 51%, respectively. Kinetic analysis performed on frequency series indicated that the diminished DA levels corresponded to a significant reduction in DA release. These findings suggest that APM has a relatively potent effect of decreasing evoked extracellular DA levels when administered systemically under the conditions specified.

  12. Plasma levels on thyroid hormones in sockeye salmon (Oncorhynchus nerka) decrease before spawning.

    PubMed

    Biddiscombe, S; Idler, D R

    1983-12-01

    Blood samples were taken from mature sockeye salmon (Oncorhynchus nerka) at various stages in their upstream migration to spawn at Adam's River in British Columbia, Canada. Plasma T3 and T4 levels decreased significantly in both males and females between time of entry into fresh water and postspawning.

  13. Chronic social isolation decreases glutamate and glutamine levels and induces oxidative stress in the rat hippocampus.

    PubMed

    Shao, Yuan; Yan, Gen; Xuan, Yinghua; Peng, Hui; Huang, Qing-Jun; Wu, Renhua; Xu, Haiyun

    2015-04-01

    Social isolation (SI) rearing of rodents is a developmental manipulation, which is commonly compared with the psychological stressors in humans as it produces several behavioral outcomes similar to those observed in humans with early life stress. To explain the SI-induced behavioral outcomes, animal studies have been performed to examine the dopaminergic and glutamatergic systems in the brain. In this study, we measured possible changes in levels of glutamate and glutamine of SI-rats using proton magnetic resonance spectroscopy. We also assessed the oxidative stress parameters in certain brain regions to see if glutamate and/or glutamine changes, if any, are associated with oxidative stress. SI rearing for 8 weeks decreased the activities of antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, and the total antioxidant capacity, but increased levels of hydrogen peroxide, in certain brain regions, of which prefrontal cortex and hippocampus were most vulnerable. It also decreased levels of glutamate, glutamine, N-acetyl-l-aspartate (NAA), and phosphocreatine in the dorsal hippocampus, but not in the cerebral cortex. Decreased phosphocreatine and NAA indicate energy metabolism deficit in brain cells; the latter also suggests the neuronal viability was inhibited. Decreased glutamate and glutamine may suggest the neuron-glial integrity was implicated by chronic SI. These neurochemical and biochemical changes may contribute to the SI-induced behavioral abnormalities including a high level of anxiety, social interaction deficit, and impaired spatial working memory shown in this study.

  14. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  15. Decreased levels of serum oxytocin in pediatric patients with Attention Deficit/Hyperactivity Disorder.

    PubMed

    Sasaki, Tsuyoshi; Hashimoto, Kenji; Oda, Yasunori; Ishima, Tamaki; Kurata, Tsutomu; Takahashi, Junpei; Kamata, Yu; Kimura, Hiroshi; Niitsu, Tomihisa; Komatsu, Hideki; Ishikawa, Masatomo; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shiraishi, Tetsuya; Iyo, Masaomi

    2015-08-30

    Attention Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) are highly comorbid, and both disorders share executive function deficits. Accumulating evidence suggests that ASD patients have significantly lower peripheral oxytocin (OXT) levels compared with their normal counterparts, and that the repetitive behavior seen in ASD is related to abnormalities in the OXT system. In this study, we investigated whether serum levels of OXT are altered in pediatric patients with ADHD. We measured serum OXT levels: drug naive ADHD (n=23), medicated ADHD (n=13), and age- and sex- matched, neurotypical controls (n=22). Patients were evaluated using the ADHD-RS. Serum levels of OXT in total subjects with ADHD were significantly decreased compared with those of neurotypical controls, and serum levels of OXT in drug naive ADHD patients were significantly lower than those in medicated ADHD patients. Interestingly, there was a significant negative correlation between serum OXT levels and ADHD-RS total scores, as well as ADHD-RS inattentive scores in all ADHD patients. In conclusion, this study suggests that decreased levels of OXT may play a role in the pathophysiology of patients with ADHD and its inherent inattentiveness.

  16. Decreased levels of serum oxytocin in pediatric patients with Attention Deficit/Hyperactivity Disorder.

    PubMed

    Sasaki, Tsuyoshi; Hashimoto, Kenji; Oda, Yasunori; Ishima, Tamaki; Kurata, Tsutomu; Takahashi, Junpei; Kamata, Yu; Kimura, Hiroshi; Niitsu, Tomihisa; Komatsu, Hideki; Ishikawa, Masatomo; Hasegawa, Tadashi; Shiina, Akihiro; Hashimoto, Tasuku; Kanahara, Nobuhisa; Shiraishi, Tetsuya; Iyo, Masaomi

    2015-08-30

    Attention Deficit/Hyperactivity Disorder (ADHD) and autism spectrum disorder (ASD) are highly comorbid, and both disorders share executive function deficits. Accumulating evidence suggests that ASD patients have significantly lower peripheral oxytocin (OXT) levels compared with their normal counterparts, and that the repetitive behavior seen in ASD is related to abnormalities in the OXT system. In this study, we investigated whether serum levels of OXT are altered in pediatric patients with ADHD. We measured serum OXT levels: drug naive ADHD (n=23), medicated ADHD (n=13), and age- and sex- matched, neurotypical controls (n=22). Patients were evaluated using the ADHD-RS. Serum levels of OXT in total subjects with ADHD were significantly decreased compared with those of neurotypical controls, and serum levels of OXT in drug naive ADHD patients were significantly lower than those in medicated ADHD patients. Interestingly, there was a significant negative correlation between serum OXT levels and ADHD-RS total scores, as well as ADHD-RS inattentive scores in all ADHD patients. In conclusion, this study suggests that decreased levels of OXT may play a role in the pathophysiology of patients with ADHD and its inherent inattentiveness. PMID:26168929

  17. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

    PubMed

    Zhang, Yiting; Hodgson, Nathaniel W; Trivedi, Malav S; Abdolmaleky, Hamid M; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

  18. Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia

    PubMed Central

    Zhang, Yiting; Hodgson, Nathaniel W.; Trivedi, Malav S.; Abdolmaleky, Hamid M.; Fournier, Margot; Cuenod, Michel; Do, Kim Quang; Deth, Richard C.

    2016-01-01

    Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders. PMID:26799654

  19. Regular Exercise Training Increases the Number of Endothelial Progenitor Cells and Decreases Homocysteine Levels in Healthy Peripheral Blood

    PubMed Central

    Choi, Jeong Kyu; Moon, Ki Myung; Jung, Seok Yun; Kim, Ji Yong; Choi, Sung Hyun; Kim, Da Yeon; Kang, Songhwa; Chu, Chong Woo

    2014-01-01

    Endothelial progenitor cells (EPCs) are known to play an important role in the repair of damaged blood vessels. We used an endothelial progenitor cell colony-forming assay (EPC-CFA) to determine whether EPC numbers could be increased in healthy individuals through regular exercise training. The number of functional EPCs obtained from human peripheral blood-derived AC133 stem cells was measured after a 28-day regular exercise training program. The number of total endothelial progenitor cell colony-forming units (EPC-CFU) was significantly increased compared to that in the control group (p=0.02, n=5). In addition, we observed a significant decrease in homocysteine levels followed by an increase in the number of EPC-CFUs (p=0.04, n=5), indicating that the 28-day regular exercise training could increase the number of EPC colonies and decrease homocysteine levels. Moreover, an inverse correlation was observed between small-endothelial progenitor cell colony-forming units (small-EPC-CFUs) and plasma homocysteine levels in healthy men (r=-0.8125, p=0.047). We found that regular exercise training could increase the number of EPC-CFUs and decrease homocysteine levels, thus decreasing the cardiovascular disease risk in men. PMID:24757379

  20. Decreased plasma gonadotropin and testosterone levels in arthritic rats: are corticosteroids involved?

    PubMed

    Rivier, C

    1995-05-01

    Infectious and inflammatory diseases are often accompanied by abnormal reproductive functions, and the present working hypothesis is that proteins (called cytokines or interleukins, ILs) released by activated immune cells are at least in part responsible for these neuroendocrine changes. In order to test this hypothesis, we need paradigms of immune pathologies in which concentrations of cytokines are increased, and those of hormones of the hypothalamic-pituitary-gonadal (HPG) axis are blunted. We chose a rodent model of arthritis, adjuvant-induced arthritis (AIA), in which rats show elevated plasma IL-6 and decreased testosterone (T) concentrations. We describe here the first phase of our studies, in which we determined whether gonadotropin release was also altered, whether this change was responsible for the low T levels, and whether elevated corticosterone participated in the decreased activity of the HPG axis.AIA is induced by the intramuscular injection ofMycobacterium butyricum (MBB) into the tail base of the rat, with swelling of the limbs occurring 11-12 days later. We observed significant decreases in LH and FSH secretion of castrated AIA male rats, suggesting that altered gonadotropin output was independent of the gonads. The absence of significant alterations in GnRH gene expression in the hypothalamus of AIA rats, as well as only modest declines in pituitary responsiveness to GnRH, indicate that these mechanisms are not primarily responsible for the blunted gonadotropin concentrations. Intact AIA rats exhibited a dramatic decline in T levels, but no concimitant rise in LH concentrations. The observation that gonadotropin secretion does not increase despite significantly reduced T levels suggests the presence of an unidentified defect within the GnRH neuronal circuitry that prevents the gonadotrophs to respond to decreased steroid feedback. Testicular responsiveness to hCG was significantly blunted in AIA rats, and this decrease was not reversed by acute

  1. Serum level of vascular endothelial growth factor decreased in chronic ketamine abusers

    PubMed Central

    Fan, Ni; Zhang, Minling; Xu, Ke; Ke, Xiaoyin; Ding, Yi; Wang, Daping; Liu, Yuping; Ning, Yuping; Deng, Xuefeng; He, Hongbo

    2016-01-01

    Aims To evaluate the serum level of vascular endothelial growth factor (VEGF) in a group of chronic ketamine abusers in comparison to healthy controls. Methods Eighty-one ketamine abusers who were hospitalized for the treatment of ketamine dependence and 39 healthy controls were recruited. Serum VEGF level was measured by enzyme linked immunosorbent assay (ELISA). Psychopathological symptoms were assessed using Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results Serum level of VEGF was significantly lower in chronic ketamine abusers compared to healthy controls (64.6 ± 42.1 vs. 92.4 ± 59.4 pg/ml, F = 7.243, p = 0.008). Conclusions Serum level of VEGF decreased in chronic ketamine abusers compared to healthy controls. PMID:26003336

  2. Forearm Muscle Oxygenation Decreases During Low Levels of Brief, Isometric Contraction

    NASA Technical Reports Server (NTRS)

    Murthy Gita; Kahan, N. J.; Hargens, Alan R.; Rempel, D. M.; Hargens, Murthy G. (Technical Monitor)

    1997-01-01

    Regional muscle pain syndromes can be caused by repeated and sustained exertion of a specific muscle. Such exertion may elevate local tissue fluid pressure, reduce blood flow and tissue oxygenation (TO2), and cause fatigue, pain and functional deficits of the Involved muscle. Low levels (less than 20% maximum voluntary contraction (MVC)) of prolonged static contraction of the upper extremity are common In many occupational settings and May cause fatigue. The purpose of our Investigation was to determine whether TO2 decreases significantly at low levels of static contraction of the extensor carpi radialis brevis (ECRB).

  3. Decreased training volume and increased carbohydrate intake increases oxidized LDL levels.

    PubMed

    Välimäki, I A; Vuorimaa, T; Ahotupa, M; Kekkonen, R; Korpela, R; Vasankari, T

    2012-04-01

    We studied effects of probiotics and training volume on oxidized LDL lipids (ox-LDL), serum antioxidant potential (s-TRAP) and serum antioxidants (s-α-tocopherol, s-γ-tocopherol, s-retinol, s-β-carotene and s-ubiquinone-10) in marathon runners during 3-months training period, 6-days preparation period and marathon run. Runners (n=127) were recruited for a randomized, double-blind intervention during which they received either Lactobacillus rhamnosus GG (LGG, probiotic group) or placebo drink (placebo group) during whole study. During the preparation period, subjects decreased training and increased carbohydrate intake. Blood samples were taken at baseline, before 6-days preparation, before and immediately after the marathon. Probiotics did not have any effect on ox-LDL, s-TRAP or serum antioxidants levels during the study. Interestingly, ox-LDL increased by 28% and 33% during the preparation period and decreased by 16% and 19% during the marathon run in the placebo and probiotic groups, respectively (in all, P<0.001). No changes were seen in s-TRAP before marathon, but during run s-TRAP raised by 16% in both groups (both, P<0.001). The increase of ox-LDL level during the preparative period after several months' training suggests that aerobic training may reduce the concentration of ox-LDL and that decrease of training together with increased energy intake, mainly carbohydrate, before marathon is capable of increasing the level of ox-LDL.

  4. Decreased serum cholesterol level after snake bite (Vipera palaestinae) as a marker of severity of envenomation.

    PubMed

    Winkler, E; Chovers, M; Almog, S; Pri-Chen, S; Rotenberg, M; Tirosh, M; Ezra, D; Halkin, H

    1993-06-01

    In 44 patients bitten by snakes (Vipera palaestinae), admission serum cholesterol levels were negatively correlated with severity of envenomation (mean +/- SD, 175 +/- 49, 137 +/- 36, and 96 +/- 40 mg/dl, respectively, in cases with mild, moderate, and severe clinical manifestations [p < 0.0001]). Concomitant decreases in serum albumin were not significant. These findings were supported by experimental results in rabbits, in which low, medium, and high doses of purified V. palaestinae venom (all in the non-lethal range), led to dose-dependent decreases in serum cholesterol, at 180 minutes, of 9.5% +/- 8.9%, 18.6% +/- 10.1%, and 32.7% +/- 11.8%, respectively (p < 0.01). This rapid decrease in serum cholesterol level is only partially explained by transcapillary lipoprotein leakage and probably indicates changes in lipoprotein transport and metabolism caused by the phospholipase A2 component of V. palaestinae venom. Admission total serum cholesterol level may serve as an indicator of severity of envenomation in patients bitten by snakes of the Vipera genus before full development of the clinical syndrome. PMID:8505588

  5. CSF levels of the histamine metabolite tele-methylhistamine are only slightly decreased in Alzheimer's disease.

    PubMed

    Motawaj, Mouhammad; Peoc'h, Katell; Callebert, Jacques; Arrang, Jean-Michel

    2010-01-01

    Neuropathological studies have reported a strong neurofibrillary degeneration of the tuberomamillary nucleus, the region of origin of histamine neurons, in Alzheimer's disease (AD). Histaminergic neurons enhance cognition and memory, suggesting that their degeneration may contribute to the cognitive decline of AD. Besides neurons, the brain histaminergic system comprises mast cells and microglia that can also produce histamine. The level of activity of this histaminergic system in AD remained unknown. In the present study, we have measured the levels of the main histamine metabolite in brain, tele-methylhistamine (t-MeHA), an index of histaminergic system activity, in the cerebrospinal fluid (CSF) of 97 non-AD (controls) and 91 AD patients, males or females. t-MeHA levels in CSF of controls tended to be higher, although non-significantly, in females than in males. t-MeHA levels of controls and AD significantly increased with age (1.66 ± 0.13, 2.04 ± 0.12, and 2.76 ± 0.12 pmol/ml at 40, 60 and 80 years, respectively). In spite of the strong degeneration of histamine neurons in the disease, t-MeHA levels in CSF were only slightly decreased in AD compared to controls (2.14 ± 0.10 vs 2.76 ± 0.13 pmol/ml, -22%, p < 0.01). This decrease was similar whatever the age, and was slightly higher in females than in males. The increase observed with age, and the limited magnitude of the decrease in AD even at late stages may result from the compensatory activation of spared neurons, as well as the neuroinflammation-induced activation of microglia occurring in senescence and AD.

  6. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure.

    PubMed

    Huang, Ying; Lin, Yingzhong; Zhang, Shumin; Wang, Zhijian; Zhang, Jianwei; Chang, Chao; Liu, Ling; Ji, Qingwei; Liu, Xiaofei

    2016-01-01

    Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (R = -0.376, P = 0.005), C-reactive protein (CRP) (R = -0.320, P = 0.001), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (R = -0.365, P = 0.000) levels as well as left ventricular end-diastolic diameter (LVEDD) (R = -0.200, P = 0.046) but were positively correlated with left ventricular ejection fraction (LVEF) (R = 0.496, P = 0.000). Plasma adiponectin levels were positively correlated with CRP (R = 0.273, P = 0.006) and NT-proBNP (R = 0.329, P = 0.001) levels but were negatively correlated with fasting glucose (R = -0.218, P = 0.029) and LVEF (R = -0.615, P = 0.000) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; P = 0.008) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. PMID:27313334

  7. OKN-007 decreases free radical levels in a preclinical F98 rat glioma model.

    PubMed

    Coutinho de Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin; Ziegler, Jadith; Njoku, Charity; Lerner, Megan; Ehrenshaft, Marilyn; Mason, Ronald P; Meek, Bill; Plafker, Scott M; Saunders, Debra; Mamedova, Nadezda; Towner, Rheal A

    2015-10-01

    Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants. PMID:26119786

  8. Decreased levels of serum nitric oxide in different forms of dementia.

    PubMed

    Corzo, Lola; Zas, Raquel; Rodríguez, Susana; Fernández-Novoa, Lucía; Cacabelos, Ramón

    2007-06-15

    Nitric oxide is involved in normal physiological functions and also in pathological processes leading to tissue damage due, in part, to its free radical nature (oxidative stress). Oxidative stress and vascular dysfunction have been recognized as contributing factors in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VD). In order to study the possible links between these processes and dementia, we have analysed plasma amyloid-beta(1-42) levels (Abeta) and total nitric oxide (NOx), apolipoprotein E (ApoE), lipids, vitamin B12, and folate concentrations in the serum of 99 patients with dementia and 55 age-matched non-demented controls. Both nitrate and nitrite levels were measured by a colorimetric method using Griess Reagent and plasma Abeta levels were analysed by a hypersensitive ELISA method. Our data showed a significant decrease of serum NOx levels in dementia, especially in probable AD and VD patients, as compared with controls. We observed a weak correlation between serum NOx levels and cognitive deterioration in dementia; however, NOx levels were not associated with ApoE and Abeta levels. In dementia and controls, a similar correlation pattern between HDL-cholesterol versus NOx was found. No apparent association between NOx, Abeta and AD-related genes [APOE (apolipoprotein E), PSEN1 (Presenilin 1)] was observed. Our data suggest that NOx may contribute to the pathogenesis of dementia through a process mediated by HDL-cholesterol.

  9. Decrease in TSH levels after lactose restriction in Hashimoto's thyroiditis patients with lactose intolerance.

    PubMed

    Asik, Mehmet; Gunes, Fahri; Binnetoglu, Emine; Eroglu, Mustafa; Bozkurt, Neslihan; Sen, Hacer; Akbal, Erdem; Bakar, Coskum; Beyazit, Yavuz; Ukinc, Kubilay

    2014-06-01

    We aimed to evaluate the prevalence of lactose intolerance (LI) in patients with Hashimoto's thyroiditis(HT) and the effects of lactose restriction on thyroid function in these patients. Eighty-three HT patients taking L-thyroxine (LT4) were enrolled, and lactose tolerance tests were performed on all patients. Lactose intolerance was diagnosed in 75.9 % of the patients with HT. Thirty-eight patients with LI were started on a lactose-restricted diet for 8 weeks. Thirty-eight patients with LI (30 euthyroid and 8 with subclinical hypothyroidism), and 12 patients without LI were included in the final analysis. The level of TSH significantly decreased in the euthyroid and subclinical hypothyroid patients with LI [from 2.06 ± 1.02 to 1.51 ±1.1 IU/mL and from 5.45 ± 0.74 to 2.25 ± 1.88 IU/mL,respectively (both P<0.05)]. However, the level of TSH in patients without LI did not change significantly over the 8 weeks (P>0.05). Lactose intolerance occurs at a high frequency in HT patients. Lactose restriction leads to decreased levels of TSH, and LI should be considered in hypothyroid patients who require increasing LT4 doses,have irregular TSH levels and are resistant to LT4 treatment.

  10. Heterozygous Deficiency of Endoglin Decreases Insulin and Hepatic Triglyceride Levels during High Fat Diet

    PubMed Central

    Beiroa, Daniel; Romero-Picó, Amparo; Langa, Carmen; Bernabeu, Carmelo; López, Miguel; López-Novoa, José M.; Nogueiras, Ruben; Diéguez, Carlos

    2013-01-01

    Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism. PMID:23336009

  11. Decreased docosahexaenoic acid levels in retina and pigment epithelium of frogs fed crickets.

    PubMed

    Chen, H; Wiegand, R D; Anderson, R E

    1992-06-01

    Whole retina, rod outer segments, and retinal pigment epithelium of frogs (Rana pipiens) fed crickets for more than 1 year had significantly lower levels of docosahexaenoic acid (22: 6n-3) than the same tissues of frogs fed crickets for less than 1 month. Decreases in 22:6n-3 levels in these tissues were compensated for by increases in the n-6 polyunsaturated fatty acids (PUFAs), primarily 22:5n-6. There were no changes in the levels of saturated, monoenoic, or dienoic acids. Analysis of diacyl phospholipid molecular species (PLMS) revealed decreases in both the 22:6(n-3)-containing dipolyenoic molecular species in phosphatidylethanolamine and phosphatidylserine, and the monopolyenoic molecular species in phosphatidylcholine. These PLMS were replaced by species containing 22:5n-6 or other n-6 PUFAs. Examination of fatty acid methyl esters of total lipids extracted from crickets revealed that less than 1 mol% fatty acids were of the n-3 family, while more than 30 mol% were of the n-6 family. Thus, frogs raised on an n-3-deficient diet have reduced levels of n-3 PUFA in their retinas, rod outer segments, and retinal pigment epithelium. Although such changes have been reported for mammals, this is the first report of the effects of n-3 deficiency on the lipids of amphibians.

  12. Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis.

    PubMed

    Fernandes, Luis G V; Filho, Antonio F S; Souza, Gisele O; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2016-08-01

    Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure. PMID:27260249

  13. Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis.

    PubMed

    Fernandes, Luis G V; Filho, Antonio F S; Souza, Gisele O; Vasconcellos, Silvio A; Romero, Eliete C; Nascimento, Ana L T O

    2016-08-01

    Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure.

  14. The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

    PubMed

    Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2011-10-01

    In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

  15. Optimal intravenous infusion to decrease the haematocrit level in patient of DHF infection

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Saragih, R.; Wijaya, K. P.; Naiborhu, J.

    2014-02-01

    The optimal control of infusion model for Dengue Hemorrhagic Fever (DHF) infection is formulated here. The infusion model will be presented in form of haematocrit level. The input control aim to normalize the haematocrit level and is expressed as infusion volume on mL/day. The stability near the equilibrium points will be analyzed. Numerical simulation shows the dynamic of each infection compartments which gives a description of within-host dynamic of dengue virus. These results show particularly that infected compartments tend to be vanished in ±15days after the onset of the virus. In fact, without any control added, the haematocrit level will decrease but not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control. Control treatment for a fixed time using a control input can bring haematocrit level to normal range 42-47%. The optimal control in this paper is divided into three cases, i.e. fixed end point, constrained input, and tracking haematocrit state. Each case shows different infection condition in human body. However, all cases require that the haematocrit level to be in normal range in fixed final time.

  16. Decreasing arterial aging by controlling blood pressure levels and hypertension: a step forward.

    PubMed

    Scuteri, Angelo; Cunha, Pedro Guimarães

    2012-11-01

    Arterial aging, characterized by arterial stiffening that is clinically evaluable as aortic pulse wave velocity, is risky for CV events, disability, and loss of cognitive function. Today the only adopted strategy to decrease arterial aging/ arterial stiffness is represented by decreasing BP. Selective antihypertensive drug classes (calcium channel blockers, converting enzyme inhibitors, angiotensin type 1 receptor antagonists) showed a beneficial effect on the arterial wall and on both large and small arteries over and above the reduction in BP levels. Still, the lower the better paradigm seems only to expose older subjects to higher rate of side effects, that via hypotension result in even transient organ hypoperfusion. This vicious circle may be particularly detrimental for cerebral district and, thus, for cognitive impairment onset and progression until dementia.

  17. Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.

    PubMed

    Timby, Erika; Hedström, Helena; Bäckström, Torbjörn; Sundström-Poromaa, Inger; Nyberg, Sigrid; Bixo, Marie

    2011-12-01

    Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous gamma-aminobutyric acid A (GABA(A)) receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABA(A) receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), oestradiol, and progesterone. Serum-FSH decreased between 5 and 105 min after the allopregnanolone injection (F(16,144)=2.18, p=0.008). Serum-LH was reduced between 5 and 35 min following the allopregnanolone injection (F(16,144)=2.63, p=0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABA(A) receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolon.

  18. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

    PubMed Central

    Song, Guohua; Li, Min; Sang, Hui; Zhang, Liying; Li, Xiuhong; Yao, Shutong; Yu, Yang; Zong, Chuanlong; Xue, Yazhuo; Qin, Shucun

    2013-01-01

    We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9–1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum. In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome. PMID:23610159

  19. Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome.

    PubMed

    Song, Guohua; Li, Min; Sang, Hui; Zhang, Liying; Li, Xiuhong; Yao, Shutong; Yu, Yang; Zong, Chuanlong; Xue, Yazhuo; Qin, Shucun

    2013-07-01

    We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9-1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum. In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.

  20. Decreased Integrity, Content, and Increased Transcript Level of Mitochondrial DNA Are Associated with Keratoconus

    PubMed Central

    Hao, Xiao-Dan; Chen, Zhao-Li; Qu, Ming-Li; Zhao, Xiao-Wen; Li, Su-Xia; Chen, Peng

    2016-01-01

    Oxidative stress may play an important role in the pathogenesis of keratoconus (KC). Mitochondrial DNA (mtDNA) is involved in mitochondrial function, and the mtDNA content, integrity, and transcript level may affect the generation of reactive oxygen species (ROS) and be involved in the pathogenesis of KC. We designed a case-control study to research the relationship between KC and mtDNA integrity, content and transcription. One-hundred ninety-eight KC corneas and 106 normal corneas from Chinese patients were studied. Quantitative real-time PCR was used to measure the relative mtDNA content, transcript levels of mtDNA and related genes. Long-extension PCR was used to detect mtDNA damage. ROS, mitochondrial membrane potential and ATP were measured by respective assay kit, and Mito-Tracker Green was used to label the mitochondria. The relative mtDNA content of KC corneas was significantly lower than that of normal corneas (P = 9.19×10−24), possibly due to decreased expression of the mitochondrial transcription factor A (TFAM) gene (P = 3.26×10−3). In contrast, the transcript levels of mtDNA genes were significantly increased in KC corneas compared with normal corneas (NADH dehydrogenase subunit 1 [ND1]: P = 1.79×10−3; cytochrome c oxidase subunit 1 [COX1]: P = 1.54×10−3; NADH dehydrogenase subunit 1, [ND6]: P = 4.62×10−3). The latter may be the result of increased expression levels of mtDNA transcription-related genes mitochondrial RNA polymerase (POLRMT) (P = 2.55×10−4) and transcription factor B2 mitochondrial (TFB2M) (P = 7.88×10−5). KC corneas also had increased mtDNA damage (P = 3.63×10−10), higher ROS levels, and lower mitochondrial membrane potential and ATP levels compared with normal corneas. Decreased integrity, content and increased transcript level of mtDNA are associated with KC. These changes may affect the generation of ROS and play a role in the pathogenesis of KC. PMID:27783701

  1. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  2. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects.

    PubMed

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng

    2009-03-01

    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P < .001), and factor VIII (P < .001), suggesting that the plasma levels of the 3 coagulation factors continuously declined during intake; also, the extents of decrease were similar between groups. After 2 months of administration, fibrinogen, factor VII, and factor VIII decreased 9%, 14%, and 17%, respectively, for the Healthy Group; 7%, 13%, and 19%, respectively, for the Cardiovascular Group; and 10%, 7%, and 19%, respectively, for the Dialysis Group, whereas blood lipids were unaffected by nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  3. Decreased expression and DNA methylation levels of GATAD1 in preeclamptic placentas.

    PubMed

    Ma, Xiaoling; Li, Jinping; Brost, Brian; Cheng, Wenjun; Jiang, Shi-Wen

    2014-05-01

    Expression of syncytin-1, or the human endogenous retroviral family W member 1 (HERVWE1) in human placental trophoblasts is regulated by DNA methylation. Increased DNA methylation and decreased expression of syncytin-1 have been observed in preeclamptic placentas. The syncytin-1-mediated fusogenic as well as non-fusogenic activities, e.g., cell cycle promotion, anti-apoptosis, and immune suppression, are implicated in the pathogenic changes in preeclamptic placentas. It is noteworthy that in a close vicinity to syncytin-1 there are two genes, peroxisome biogenesis factor 1 (PEX1) and GATA zinc finger domain containing 1 (GATAD1), as well as multiple CpG islands around these genes. In this study we determined if these adjacent genes might, like syncytin-1, subject to epigenetic regulation in preeclamptic placentas. Data from quantitative real-time PCR and Western blotting indicated that while PEX1 expression remained stable, GATAD1 expression was significantly decreased in the third-trimester placentas associated with preeclampsia than those associated with normal pregnancy. Immunohistochemistry detected high GATAD1 expression in trophoblast linage, and confirmed its reduced levels in preeclamptic placentas. However, COBRA and bisulfate sequencing detected decreased DNA methylation in levels in the 3 [prime] region of GATAD1 gene in preeclamptic placentas. The positive correlation between 3 [prime] methylation and GATAD1 expression was confirmed by treatment of choriocarcinoma JAR cells with DNMT inhibitor. These data pointed to a potential role of GATAD1 for the syncytium deficiency often associated with preeclamptic placentas. The sharp contrast of the methylation alterations for the closely positioned GATAD1 and HERVWE1 may provide a useful model for studying the accurate control of DNA methylation as well as their positive and negative impact on gene expression in placental trophoblasts. PMID:24462704

  4. Early decrease in dietary protein:energy ratio by fat addition and ontogenetic changes in muscle growth mechanisms of rainbow trout: short- and long-term effects.

    PubMed

    Alami-Durante, Hélène; Cluzeaud, Marianne; Duval, Carine; Maunas, Patrick; Girod-David, Virginia; Médale, Françoise

    2014-09-14

    As the understanding of the nutritional regulation of muscle growth mechanisms in fish is fragmentary, the present study aimed to (1) characterise ontogenetic changes in muscle growth-related genes in parallel to changes in muscle cellularity; (2) determine whether an early decrease in dietary protein:energy ratio by fat addition affects the muscle growth mechanisms of rainbow trout (Oncorhynchus mykiss) alevins; and (3) determine whether this early feeding of a high-fat (HF) diet to alevins had a long-term effect on muscle growth processes in juveniles fed a commercial diet. Developmental regulation of hyperplasia and hypertrophy was evidenced at the molecular (expression of myogenic regulatory factors, proliferating cell nuclear antigen and myosin heavy chains (MHC)) and cellular (number and diameter of white muscle fibres) levels. An early decrease in dietary protein:energy ratio by fat addition stimulated the body growth of alevins but led to a fatty phenotype, with accumulation of lipids in the anterior part, and less caudal muscle when compared at similar body weights, due to a decrease in both the white muscle hyperplasia and maximum hypertrophy of white muscle fibres. These HF diet-induced cellular changes were preceded by a very rapid down-regulation of the expression of fast-MHC. The present study also demonstrated that early dietary composition had a long-term effect on the subsequent muscle growth processes of juveniles fed a commercial diet for 3 months. When compared at similar body weights, initially HF diet-fed juveniles indeed had a lower mean diameter of white muscle fibres, a smaller number of large white muscle fibres, and lower expression levels of MyoD1 and myogenin. These findings demonstrated the strong effect of early feed composition on the muscle growth mechanisms of trout alevins and juveniles.

  5. PPAR-α Agonist Fenofibrate Decreased RANTES Levels in Type 2 Diabetes Patients with Hypertriglyceridemia

    PubMed Central

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Xu, Yuan; Wang, Guang

    2016-01-01

    Background Regulated upon activation, normal T cells expressed and secreted (RANTES) is associated with inflammation and atherosclerosis. We investigated the effect of fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, on RANTES in type 2 diabetes mellitus (T2DM) patients with hypertriglyceridemia. Material/Methods This study evaluated cross-sectional and interventional studies of 25 T2DM patients with hypertriglyceridemia (group A) and 32 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum RANTES and clinical characteristics were examined. Results Serum RANTES was significantly higher in group A compared with group B (59.04±16.74 vs. 38.57±12.98 ng/ml, P<0.001) and correlated with triglycerides (TG) (r=0.535, P<0.001), fasting blood glucose (FBG) (r=0.485, P<0.001), glycosylated hemoglobin (HbA1c) (r=0.485, P<0.001), homocysteine (Hcy) (r=0.520, P<0.001), and high-sensitivity C-reactive protein (hsCRP) (r=0.701, P<0.001). In multiple regression analysis after controlling for confounders, increased hsCRP levels (β=7.430, P<0.001) and T2DM with hypertriglyceridemia (β=11.496, P=0.002) were independently related to high serum RANTES levels. After 8 weeks of fenofibrate treatment, serum RANTES significantly decreased in group A compared with baseline (52.75±17.41 vs. 59.04±16.74 ng/ml, P=0.018). Conclusions Fenofibrate decreased serum RANTES levels in T2DM patients with hypertriglyceridemia, indicating that PPAR-α agonists may play an important role in inhibiting inflammatory responses. PMID:26944934

  6. Zinc fortification decreases ZIP1 gene expression of some adolescent females with appropriate plasma zinc levels.

    PubMed

    Méndez, Rosa O; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B; de la Barca, Ana M Calderón; García, Hugo S

    2014-06-11

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1.

  7. Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

    PubMed Central

    Méndez, Rosa O.; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B.; de la Barca, Ana M. Calderón; García, Hugo S.

    2014-01-01

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1. PMID:24922175

  8. Vitellogenin-RNAi and ovariectomy each increase lifespan, increase protein storage, and decrease feeding, but are not additive in grasshoppers.

    PubMed

    Tetlak, Alicia G; Burnett, Jacob B; Hahn, Daniel A; Hatle, John D

    2015-12-01

    Reduced reproduction has been shown to increase lifespan in many animals, yet the mechanisms behind this trade-off are unclear. We addressed this question by combining two distinct, direct means of life-extension via reduced reproduction, to test whether they were additive. In the lubber grasshopper, Romalea microptera, ovariectomized (OVX) individuals had a ~20% increase in lifespan and a doubling of storage relative to controls (Sham operated). Similarly, young female grasshoppers treated with RNAi against vitellogenin (the precursor to egg yolk protein) had increased fat body mass and halted ovarian growth. In this study, we compared VgRNAi to two control groups that do not reduce reproduction, namely buffer injection (Buffer) and injection with RNAi against a hexameric storage protein (Hex90RNAi). Each injection treatment was tested with and without ovariectomy. Hence, we tested feeding, storage, and lifespans in six groups: OVX and Buffer, OVX and Hex90RNAi, OVX and VgRNAi, Sham and Buffer, Sham and Hex90RNAi, and Sham and VgRNAi. Ovariectomized grasshoppers and VgRNAi grasshoppers each had similar reductions in feeding (~40%), increases in protein storage in the hemolymph (150-300%), and extensions in lifespan (13-21%). Ovariectomized grasshoppers had higher vitellogenin protein levels than did VgRNAi grasshoppers. Last but not least, when ovariectomy and VgRNAi were applied together, there was no greater effect on feeding, protein storage, or longevity. Hence, feeding regulation, and protein storage in insects, may be conserved components of life-extension via reduced reproduction. PMID:26298568

  9. Hydrogen sulfide decreases adenosine triphosphate levels in aortic rings and leads to vasorelaxation via metabolic inhibition

    PubMed Central

    Kiss, Levente; Deitch, Edwin A; Szabó, Csaba

    2014-01-01

    Aims Hydrogen sulfide (H2S) at low concentrations serves as a physiological endogenous vasodilator molecule, while at higher concentrations it can trigger cytotoxic effects. The aim of our study was to elucidate the potential mechanisms responsible for the effects of H2S on vascular tone. Main methods We measured the vascular tone in vitro in precontracted rat thoracic aortic rings and we have tested the effect of different oxygen levels and a variety of inhibitors affecting known vasodilatory pathways. We have also compared the vascular effect of high concentrations of H2S to those of pharmacological inhibitors of oxidative phosphorylation. Furthermore, we measured adenosine triphosphate (ATP)-levels in the same vascular tissues. Key findings We have found that in rat aortic rings: (1) H2S decreases ATP levels; (2) relaxations to H2S depend on the ambient oxygen concentration; (3) prostaglandins do not take part in the H2S induced relaxations; (4) the 3':5'-cyclic guanosine monophosphate (cGMP) – nitric oxide (NO) pathway does not have a role in the relaxations (5) the role of KATP channels is limited, while Cl−/HCO3− channels have a role in the relaxations. (6): We have observed that high concentrations of H2S relax the aortic rings in a fashion similar to sodium cyanide, and both agents reduce cellular ATP levels to a comparable degree. Significance H2S, a new gasotransmitter of emerging importance, leads to relaxation via Cl−/HCO3− channels and metabolic inhibition and the interactions of these two factors depend on the oxygen levels of the tissue. PMID:18790700

  10. Elevated triglyceride and decreased high density lipoprotein level in carbon disulfide workers in Taiwan.

    PubMed

    Luo, Jiin-Chyuan John; Chang, Ho-Yuan; Chang, Shu-Ju; Chou, Tzu-Chieh; Chen, Chiou-Jong; Shih, Tung-Sheng; Huang, Chin-Chang

    2003-01-01

    Carbon disulfide (CS2) is a man-made product utilized primarily in the manufacture of viscose rayon. Overexposure to CS2 has been associated with an increase in coronary heart disease. The aims of this study were to examine the dose-response relationship of CS2 exposure and elevated lipid profile tests among CS2-exposed workers in Taiwan. A total of 132 workers were recruited from two viscose rayon plants. Air sampling was performed to determine the CS2 exposure of workers. Demographic data and work history were gathered by a standard self-administered questionnaire. Lipid profile tests were also performed by routine methods. The average CS2 exposure concentration was 50.6 +/- 25.6 ppm (range: 24-127 ppm) in the high-exposure group, 12.9 +/- 5 ppm (range: 5.2-22.3 ppm) in the mid-exposure group, and 3.5 +/- 1.2 ppm (range 0.97-5.2 ppm) in the low-exposure group. There were 21 out of 33 (63.7%) elevated triglyceride levels among high-CS2-exposure workers, 27 out of 64 (42.2%) among the middle-CS2-exposure, and 14 out of 35 (40%) among low-CS2-exposure workers, respectively. Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratios (and 95% confidence intervals) of the prevalence of elevated triglyceride value were 1.12 (0.5, 2.7) for middle-CS2-exposure workers, and 2.81 (1.02, 7.8) for high-CS2-exposure workers. There was a significant linear trend between CS2 exposure and the prevalence of elevated triglyceride value (P = 0.046) after adjusting for other factors. There was also a lower prevalence of elevated HDL level in high-CS2-exposure workers than low-CS2-exposure workers (15.2% versus 31.4%). Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratio (and 95% confidence intervals) of elevated HDL level were 0.34 (0.1, 1.18) for high-CS2-exposure workers, which was borderline significant. In conclusion, this study suggests that elevated triglyceride level and decreased HDL level are associated with CS2 exposure

  11. Phospholipase D1 decreases type I collagen levels in hepatic stellate cells via induction of autophagy.

    PubMed

    Seo, H-Y; Jang, B-K; Jung, Y-A; Lee, E-J; Kim, H-S; Jeon, J-H; Kim, J-G; Lee, I-K; Kim, M-K; Park, K-G

    2014-06-20

    Hepatic stellate cells (HSCs) are major players in liver fibrogenesis. Accumulating evidence shows that suppression of autophagy plays an important role in the development and progression of liver disease. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine to yield phosphatidic acid (PA) and choline, was recently shown to modulate autophagy. However, little is known about the effects of PLD1 on the production of type I collagen that characterizes liver fibrosis. Here, we examined whether PLD1 regulates type I collagen levels in HSCs through induction of autophagy. Adenovirus-mediated overexpression of PLD-1 (Ad-PLD1) reduced type I collagen levels in the activated human HSC lines, hTERT and LX2. Overexpression of PLD1 in HSCs led to induction of autophagy as demonstrated by increased LC3-II conversion and formation of LC3 puncta, and decreased p62 abundance. Moreover, inhibiting the induction of autophagy by treating cells with bafilomycin or a small interfering (si)RNA for ATG7 rescued Ad-PLD1-induced suppression of type I collagen accumulation in HSCs. The effects of PLD on type I collagen levels were not related to TGF-β/Smad signaling. Furthermore, treatment of cells with PA induced autophagy and inhibited type I collagen accumulation. The present study indicates that PLD1 plays a role in regulating type I collagen accumulation through induction of autophagy. PMID:24802400

  12. DECREASED LEVEL OF CORD BLOOD CIRCULATING ENDOTHELIAL COLONY-FORMING CELLS IN PREECLAMPSIA

    PubMed Central

    Muñoz-Hernandez, Rocio; Miranda, Maria L.; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M.; Dominguez-Simeon, Maria J.; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M.

    2014-01-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation and migration towards VEGF-A and FGF-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P = .04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events. PMID:24752434

  13. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia.

    PubMed

    Muñoz-Hernandez, Rocio; Miranda, Maria L; Stiefel, Pablo; Lin, Ruei-Zeng; Praena-Fernández, Juan M; Dominguez-Simeon, Maria J; Villar, Jose; Moreno-Luna, Rafael; Melero-Martin, Juan M

    2014-07-01

    Preeclampsia is a pregnancy-related disorder associated with increased cardiovascular risk for the offspring. Endothelial colony-forming cells (ECFCs) are a subset of circulating endothelial progenitor cells that participate in the formation of vasculature during development. However, the effect of preeclampsia on fetal levels of ECFCs is largely unknown. In this study, we sought to determine whether cord blood ECFC abundance and function are altered in preeclampsia. We conducted a prospective cohort study that included women with normal (n=35) and preeclamptic (n=15) pregnancies. We measured ECFC levels in the umbilical cord blood of neonates and characterized ECFC phenotype, cloning-forming ability, proliferation, and migration toward vascular endothelial growth factor-A and fibroblast growth factor-2, in vitro formation of capillary-like structures, and in vivo vasculogenic ability in immunodeficient mice. We found that the level of cord blood ECFCs was statistically lower in preeclampsia than in control pregnancies (P=0.04), a reduction that was independent of other obstetric factors. In addition, cord blood ECFCs from preeclamptic pregnancies required more time to emerge in culture than control ECFCs. However, once derived in culture, ECFC function was deemed normal and highly similar between preeclampsia and control, including the ability to form vascular networks in vivo. This study demonstrates that preeclampsia affects ECFC abundance in neonates. A reduced level of ECFCs during preeclamptic pregnancies may contribute to an increased risk of developing future cardiovascular events.

  14. Biomarker responses and decreasing contaminant levels in ringed seals (Pusa hispida) from Svalbard, Norway.

    PubMed

    Wolkers, Hans; Krafft, Bjørn A; van Bavel, Bert; Helgason, Lisa B; Lydersen, Christian; Kovacs, Kit M

    2008-01-01

    Blubber was analyzed for a wide range of contaminants from five sub-adult and eight adult male ringed seals sampled in 2004, namely, for polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), toxaphenes, chlordanes, dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenylethers (PBDEs). Contaminant levels were compared to previously sampled animals from the same area, as well as data from literature for other arctic wildlife species from a wide variety of locations. Ringed seals sampled in 2004 showed 50-90% lower levels of legacy contaminants such as PCBs and chlorinated pesticides compared to animals sampled in 1996 of similar age (14 sub-adults and 7 adult males), indicating that the decline of chlorinated contaminants observed during the 1990s in a variety of arctic wildlife species is continuing into the 21st century. The results also indicated that PBDE declined in ringed seals; levels in 2004 were about 70-80% lower than in animals sampled in 1998. This is one of the first observations of reduced exposure to these compounds and might be a first indication that restrictions of production and use of these contaminants have resulted in lower exposures in the Arctic. The PCB pattern shifted toward the less chlorinated (i.e., less persistent) PCBs, especially in adult ringed seals, possibly as a result of reduced overall contaminant exposures and a consequently lower cytochrome P-450 (CYP) induction, which results in a slower metabolism of less persistent PCBs. The overall effect would be relative increases in the lower chlorinated PCBs and a relative decreases in the higher chlorinated PCB. Possibly due to low exposure and consequent low induction levels, ethoxyresorufin O-deethylation (EROD) activity proved to be a poor biomarker for contaminant exposure in ringed seals in the present study. The close negative correlation (r(2) = 70.9%)between EROD activity and percent blubber indicates that CYP might respond to increased bioavailability of the

  15. HSP90 inhibitors decrease AID levels and activity in mice and in human cells.

    PubMed

    Montamat-Sicotte, Damien; Litzler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Müschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-08-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert noncanonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications.

  16. HSP90 inhibitors decrease AID levels and activity in mice and in human cells

    PubMed Central

    Montamat-Sicotte, Damien; Liztler, Ludivine C; Abreu, Cecilia; Safavi, Shiva; Zahn, Astrid; Orthwein, Alexandre; Muschen, Markus; Oppezzo, Pablo; Muñoz, Denise P; Di Noia, Javier M

    2015-01-01

    Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation and isotype switching. AID can also be pathogenic by contributing to autoimmune diseases and oncogenic mutations. Moreover, AID can exert non-canonical functions when aberrantly expressed in epithelial cells. The lack of specific inhibitors prevents therapeutic applications to modulate AID functions. Here, we have exploited our previous finding that the HSP90 molecular chaperoning pathway stabilizes AID in B cells, to test whether HSP90 inhibitors could target AID in vivo. We demonstrate that chronic administration of HSP90 inhibitors decreases AID protein levels and isotype switching in immunized mice. HSP90 inhibitors also reduce disease severity in a mouse model of acute B-cell lymphoblastic leukemia in which AID accelerates disease progression. We further show that human AID protein levels are sensitive to HSP90 inhibition in normal and leukemic B cells, and that HSP90 inhibition prevents AID-dependent epithelial to mesenchymal transition in a human breast cancer cell line in vitro. Thus, we provide proof-of-concept that HSP90 inhibitors indirectly target AID in vivo and that endogenous human AID is widely sensitive to them, which could have therapeutic applications. PMID:25912253

  17. Degradation of Malaysian peatlands decreases levels of phenolics in soil and in leaves of Macaranga pruinosa

    NASA Astrophysics Data System (ADS)

    Yule, Catherine; Lim, Yau; Lim, Tse

    2016-04-01

    Indo-Malaysian tropical peat swamp forests (PSF) sequester enormous stores of carbon in the form of phenolic compounds, particularly lignin as well as tannins. These phenolic compounds are crucial for ecosystem functioning in PSF through their inter-related roles in peat formation and plant defenses. Disturbance of PSF causes destruction of the peat substrate, but the specific impact of disturbance on phenolic compounds in peat and its associated vegetation has not previously been examined. A scale was developed to score peatland degradation based on the three major human impacts that affect tropical PSF - logging, drainage and fire. The objectives of this study were to compare the amount of phenolic compounds in Macaranga pruinosa, a common PSF tree, and in the peat substrate along a gradient of peatland degradation from pristine peat swamp forest to cleared, drained and burnt peatlands. We examined phenolic compounds in M. pruinosa and in peat and found that levels of total phenolic compounds and total tannins decrease in the leaves of M.pruinosa and also in the surface peat layers with an increase in peatland degradation. We conclude that waterlogged conditions preserve the concentration of phenolic compounds in peat, and that even PSF that has been previously logged but which has recovered a full canopy cover will have high levels of total phenolic content (TPC) in peat. High levels of TPC in peat and in the flora are vital for the inhibition of decomposition of organic matter and this is crucial for the accretion of peat and the sequestration of carbon. Thus regional PSF flourish despite the phenolic rich, toxic, waterlogged, nutrient poor, conditions, and reversal of such conditions is a sign of degradation.

  18. Degradation of Malaysian peatlands decreases levels of phenolics in soil and in leaves of Macaranga pruinosa

    NASA Astrophysics Data System (ADS)

    Yule, Catherine; Lim, Yau; Lim, Tse

    2016-04-01

    Indo-Malaysian tropical peat swamp forests (PSF) sequester enormous stores of carbon in the form of phenolic compounds, particularly lignin as well as tannins. These phenolic compounds are crucial for ecosystem functioning in PSF through their inter-related roles in peat formation and plant defenses. Disturbance of PSF causes destruction of the peat substrate, but the specific impact of disturbance on phenolic compounds in peat and its associated vegetation has not previously been examined. A scale was developed to score peatland degradation based on the three major human impacts that affect tropical PSF – logging, drainage and fire. The objectives of this study were to compare the amount of phenolic compounds in Macaranga pruinosa, a common PSF tree, and in the peat substrate along a gradient of peatland degradation from pristine peat swamp forest to cleared, drained and burnt peatlands. We examined phenolic compounds in M. pruinosa and in peat and found that levels of total phenolic compounds and total tannins decrease in the leaves of M.pruinosa and also in the surface peat layers with an increase in peatland degradation. We conclude that waterlogged conditions preserve the concentration of phenolic compounds in peat, and that even PSF that has been previously logged but which has recovered a full canopy cover will have high levels of total phenolic content (TPC) in peat. High levels of TPC in peat and in the flora are vital for the inhibition of decomposition of organic matter and this is crucial for the accretion of peat and the sequestration of carbon. Thus regional PSF flourish despite the phenolic rich, toxic, waterlogged, nutrient poor, conditions, and reversal of such conditions is a sign of degradation.

  19. Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

    PubMed

    Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

    2014-01-01

    Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

  20. Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study

    PubMed Central

    Cleto, Sérgio Aparecido; Rodrigues, Camila Eleutério; Malaque, Ceila Maria; Sztajnbok, Jaques; Seguro, Antônio Carlos; Andrade, Lúcia

    2016-01-01

    Background Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. Methods In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups—SLED (n = 19) and SLEDf (n = 20)—evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. Results During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential

  1. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane.

    PubMed

    Morrissey, Meghan A; Jayadev, Ranjay; Miley, Ginger R; Blebea, Catherine A; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R

    2016-02-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  2. Retinoic acid reverses the PTU related decrease in neurogranin level in mice brain.

    PubMed

    Enderlin, V; Vallortigara, J; Alfos, S; Féart, C; Pallet, V; Higueret, P

    2004-09-01

    Recent data have shown that fine regulation of retinoid mediated gene expression is fundamentally important for optimal brain functioning in aged mice. Nevertheless, alteration of the thyroid hormone signalling pathway may be a limiting factor, which impedes retinoic acid (RA) from exerting its modulating effect. Mild hypothyroidism is often described in the elderly. Thus, in the present study, it was of interest to determine if RA exerts its neurological modulating effect in mild hypothyroidism. To obtain further insight into this question, mice were submitted to a low propylthiouracyl (PTU) drink (0.05%) in order to slightly reduce the serum level of triiodothyronine (T3). A quantitative evaluation of RA nuclear receptors (RAR, RXR), T3 nuclear receptor (TR) and of neurogranin (RC3, a RA target gene which codes for a protein considered as a good marker of synaptic plasticity) in PTU treated mice injected with vehicle or RA or T3 was carried out. The PTU-related decrease in expression of RAR, RXR and RC3 was restored following RA or T3 administration, as observed in aged mice. The amount of TR mRNA, which was not affected in PTU treated mice, was increased only after T3 treatment as observed in overt hypothyroidism. These results suggest that neurobiological alterations observed in aged mice are probably related to RA and T3 signalling pathway modifications associated, in part, with mild changes in thyroid function.

  3. SPARC Promotes Cell Invasion In Vivo by Decreasing Type IV Collagen Levels in the Basement Membrane

    PubMed Central

    Morrissey, Meghan A.; Jayadev, Ranjay; Miley, Ginger R.; Blebea, Catherine A.; Chi, Qiuyi; Ihara, Shinji; Sherwood, David R.

    2016-01-01

    Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells. PMID:26926673

  4. Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.

    PubMed

    O'Keefe, Lena M; Doran, Sarah J; Mwilambwe-Tshilobo, Laetitia; Conti, Lisa H; Venna, Venugopal R; McCullough, Louise D

    2014-03-01

    Social isolation prior to stroke leads to poorer outcomes after an ischemic injury in both animal and human studies. However, the impact of social isolation following stroke, which may be more clinically relevant as a target for therapeutic intervention, has yet to be examined. In this study, we investigated both the sub-acute (2 weeks) and chronic (7 weeks) effects of social isolation on post-stroke functional and histological outcome. Worsened histological damage from ischemic injury and an increase in depressive-like behavior was observed in isolated mice as compared to pair-housed mice. Mice isolated immediately after stroke showed a decrease in the levels of brain-derived neurotrophic factor (BDNF). These changes, both histological and behavioral, suggest an overall negative effect of social isolation on stroke outcome, potentially contributing to post-stroke depression and anxiety. Therefore, it is important to identify patients who have perceived isolation post-stroke to hopefully prevent this exacerbation of histological damage and subsequent depression.

  5. Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

    PubMed Central

    Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

    2015-01-01

    Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

  6. Does low-level laser therapy decrease swelling and pain resulting from orthognathic surgery?

    PubMed

    Gasperini, G; Rodrigues de Siqueira, I C; Rezende Costa, L

    2014-07-01

    Low-level laser therapy (LLLT) could be an alternative for the treatment of swelling and pain after orthognathic surgery, but there is a paucity of data in the literature on the effects of its use. This study verified the efficacy of an LLLT protocol to reduce swelling and pain after orthognathic surgery. Ten healthy patients who underwent a bilateral sagittal split with Le Fort I osteotomy were randomly selected for this study. The LLLT protocol consisted of intraoral and extraoral application to one side of the face after surgery (irradiated side); application to the other side was simulated (non-irradiated side). The irradiated and non-irradiated sides were compared regarding the swelling coefficient and were assessed for pain using a visual analogue scale. There were no significant differences between the irradiated and non-irradiated sides regarding swelling and pain in the immediate postoperative assessment. Swelling decreased significantly on the irradiated side in the postoperative assessments on days 3, 7, 15, and 30. Self-reported pain was less intense on the irradiated side at the 24-h (1.2 vs. 3.4) and 3-day (0.6 vs. 2.1) assessments, but at 7 days after surgery neither side showed pain. This LLLT protocol can improve the tissue response and reduce the pain and swelling resulting from orthognathic surgery.

  7. Climate change affects low trophic level marine consumers: warming decreases copepod size and abundance.

    PubMed

    Garzke, Jessica; Ismar, Stefanie M H; Sommer, Ulrich

    2015-03-01

    Concern about climate change has re-ignited interest in universal ecological responses to temperature variations: (1) biogeographical shifts, (2) phenology changes, and (3) size shifts. In this study we used copepods as model organisms to study size responses to temperature because of their central role in the pelagic food web and because of the ontogenetic length constancy between molts, which facilitates the definition of size of distinct developmental stages. In order to test the expected temperature-induced shifts towards smaller body size and lower abundances under warming conditions, a mesocosm experiment using plankton from the Baltic Sea at three temperature levels (ambient, ambient +4 °C, ambient -4 °C) was performed in summer 2010. Overall copepod and copepodit abundances, copepod size at all life stages, and adult copepod size in particular, showed significant temperature effects. As expected, zooplankton peak abundance was lower in warm than in ambient treatments. Copepod size-at-immature stage significantly increased in cold treatments, while adult size significantly decreased in warm treatments.

  8. Novel thigmomorphogenetic responses in Carica papaya: touch decreases anthocyanin levels and stimulates petiole cork outgrowths

    PubMed Central

    Porter, Brad W.; Zhu, Yun J.; Webb, David T.; Christopher, David A.

    2009-01-01

    Background and Aims Because of its rapid growth rate, relative ease of transformation, sequenced genome and low gene number relative to Arabidopsis, the tropical fruit tree, Carica papaya, can serve as a complementary genetic model for complex traits. Here, new phenotypes and touch-regulated gene homologues have been identified that can be used to advance the understanding of thigmomorphogenesis, a multigenic response involving mechanoreception and morphological change. Methods Morphological alterations were quantified, and microscopy of tissue was conducted. Assays for hypocotyl anthocyanins, lignin and chlorophyll were performed, and predicted genes from C. papaya were compared with Arabidopsis touch-inducible (TCH) and Mechanosensitive channel of Small conductance-like genes (MscS-like or MSL). In addition, the expression of two papaya TCH1 homologues was characterized. Key Results On the abaxial side of petioles, treated plants were found to have novel, hypertrophic outgrowths associated with periderm and suberin. Touched plants also had higher lignin, dramatically less hypocotyl anthocyanins and chlorophyll, increased hypocotyl diameter, and decreased leaf width, stem length and root fresh weight. Papaya was found to have fewer MSL genes than Arabidopsis, and four touch-regulated genes in Arabidopsis had no counterparts in papaya. Water-spray treatment was found to enhance the expression of two papaya TCH1 homologues whereas induction following touch was only slightly correlated. Conclusions The novel petiole outgrowths caused by non-wounding, mechanical perturbation may be the result of hardening mechanisms, including added lignin, providing resistance against petiole movement. Inhibition of anthocyanin accumulation following touch, a new phenotypic association, may be caused by diversion of p-coumaroyl CoA away from chalcone synthase for lignin synthesis. The absence of MSL and touch-gene homologues indicates that papaya may have a smaller set of touch

  9. Decrease in Corneal Damage due to Benzalkonium Chloride by the Addition of Mannitol into Timolol Maleate Eye Drops.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Tanino, Tadatoshi; Ito, Yoshimasa; Okamoto, Norio; Shimomura, Yoshikazu

    2015-01-01

    We investigated the protective effects of mannitol on corneal damage caused by benzalkonium chloride (BAC), which is used as a preservative in commercially available timolol maleate eye drops, using rat debrided corneal epithelium and a human cornea epithelial cell line (HCE-T). Corneal wounds were monitored using a fundus camera TRC-50X equipped with a digital camera; eye drops were instilled into rat eyes five times a day after corneal epithelial abrasion. The viability of HCE-T cells was calculated by TetraColor One; and Escherichia coli (ATCC 8739) were used to measure antimicrobial activity. The reducing effects on transcorneal penetration and intraocular pressure (IOP) of the eye drops were determined using rabbits. The corneal wound healing rate and rate constant (kH), as well as cell viability, were higher following treatment with 0.005% BAC solution containing 0.5% mannitol than in the case BAC solution alone; the antimicrobial activity was approximately the same for BAC solutions with and without mannitol. In addition, the kH for rat eyes instilled with commercially available timolol maleate eye drops containing 0.5% mannitol was significantly higher than that for eyes instilled with timolol maleate eye drops without mannitol, and the addition of mannitol did not affect the corneal penetration or IOP reducing effect of the timolol maleate eye drops. A preservative system comprising BAC and mannitol may provide effective therapy for glaucoma patients requiring long-term treatment with anti-glaucoma agents.

  10. Decreasing Enterobacter sakazakii (Cronobacter spp.) food contamination level with bacteriophages: prospects and problems

    PubMed Central

    Zuber, Sophie; Boissin‐Delaporte, Catherine; Michot, Lise; Iversen, Carol; Diep, Benjamin; Brüssow, Harald; Breeuwer, Pieter

    2008-01-01

    Summary Enterobacter sakazakii (Cronobacter spp.) is an opportunistic pathogen, which can cause rare, but life‐threatening infections in neonates and infants through feeding of a contaminated milk formula. We isolated 67 phages from environmental samples and tested their lytic host range on a representative collection of 40 E. sakazakii strains. A cocktail of five phages prevented the outgrowth of 35 out of 40 test strains in artificially contaminated infant formula. Two E. sakazakii phages represented prolate head Myoviridae. Molecular tests identified them as close relatives of Escherichia coli phage T4. The remaining three phages represented isometric head Myoviridae with large genome size of 140 and 200 kb, respectively, which belonged to two different DNA hybridization groups. A high dose of 108 pfu ml−1 of phage could effectively sterilize a broth contaminated with both high and low pathogen counts (106 and 102 cfu ml−1). In contrast, broth inoculated with 104 phage and 102 bacteria per ml first showed normal bacterial growth until reaching a cell titre of 105 cfu ml−1. Only when crossing this threshold, phage replication started, but it could not reduce the contamination level below 100 cfu ml−1. Phages could be produced with titres of 1010 pfu ml−1 in broth culture, but they were not stable upon freeze‐drying. Addition of trehalose or milk formula stabilized the phage preparation, which then showed excellent storage stability even at elevated temperature. PMID:21261874

  11. Addition of aspirin to a fish oil-rich diet decreases inflammation and atherosclerosis in ApoE-null mice.

    PubMed

    Sorokin, Alexander V; Yang, Zhi-Hong; Vaisman, Boris L; Thacker, Seth; Yu, Zu-Xi; Sampson, Maureen; Serhan, Charles N; Remaley, Alan T

    2016-09-01

    Aspirin (ASA) is known to alter the production of potent inflammatory lipid mediators, but whether it interacts with omega-3 fatty acids (FAs) from fish oil to affect atherosclerosis has not been determined. The goal was to investigate the impact of a fish oil-enriched diet alone and in combination with ASA on the production of lipid mediators and atherosclerosis. ApoE(-/-) female mice were fed for 13weeks one of the four following diets: omega-3 FA deficient (OD), omega-3 FA rich (OR) (1.8g omega-3 FAs/kg·diet per day), omega-3 FA rich plus ASA (ORA) (0.1g ASA/kg·diet per day) or an omega-3 FA deficient plus ASA (ODA) with supplement levels equivalent to human doses. Plasma lipids, atherosclerosis, markers of inflammation, hepatic gene expression and aortic lipid mediators were determined. Hepatic omega-3 FAs were markedly higher in OR (9.9-fold) and ORA (7-fold) groups. Mice in both OR and ORA groups had 40% less plasma cholesterol in very low-density lipoprotein-cholesterol and low-density lipoprotein fractions, but aortic plaque area formation was only significantly lower in the ORA group (5.5%) compared to the OD group (2.5%). Plasma PCSK9 protein levels were approximately 70% lower in the OR and ORA groups. Proinflammatory aortic lipid mediators were 50%-70% lower in the ODA group than in the OD group and more than 50% lower in the ORA group. In summary, less aortic plaque lesions and aortic proinflammatory lipid mediators were observed in mice on the fish oil diet plus ASA vs. just the fish oil diet. PMID:27394692

  12. Elite sport is not an additional source of distress for adolescents with high stress levels.

    PubMed

    Gerber, Markus; Holsboer-Trachsler, Edith; Pühse, Uwe; Brand, Serge

    2011-04-01

    This study examined whether participation in elite sport interacts with stress in decreasing or increasing symptoms of depression and anxiety among adolescents, and further, whether the interplay between participation in high-performance sport and stress is related to the perceived quality of sleep. 434 adolescents (278 girls, 156 boys; age: M = 17.2 yr.) from 15 "Swiss Olympic Sport Classes" and 9 conventional classes answered a questionnaire and completed a 7-day sleep log. Analyses of covariance showed that heightened stress was related to more depressive symptoms and higher scores for trait-anxiety. Moreover, those classified as having poor sleep by a median split cutoff reported higher levels of depressive symptoms. No significant (multivariate) main effects were found for high-performance sport athletes. Similarly, no significant two- or three-way interaction effects were found. These results caution against exaggerated expectations concerning sport participation as a stress buffer. Nevertheless, participation in high-performance sport was not found to be an additional source of distress for adolescents who reported high stress levels despite prior research that has pointed toward such a relationship.

  13. Curcumin (Diferuloylmethane) Inhibits Cell Proliferation, Induces Apoptosis, and Decreases Hormone Levels and Secretion in Pituitary Tumor Cells

    PubMed Central

    Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

    2008-01-01

    Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas. PMID:18450960

  14. Curcumin (diferuloylmethane) inhibits cell proliferation, induces apoptosis, and decreases hormone levels and secretion in pituitary tumor cells.

    PubMed

    Miller, Matthew; Chen, Shenglin; Woodliff, Jeffrey; Kansra, Sanjay

    2008-08-01

    Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted. Curcumin, a commonly used food additive in South Asian cooking, inhibits proliferation of several tumor cell lines; however, its effect on pituitary tumor cell proliferation has not been determined. Our objectives were to: 1) determine whether curcumin inhibits proliferation of pituitary tumor cell lines; 2) identify the signaling intermediaries that mediate the effect of curcumin; 3) examine whether curcumin inhibited pituitary hormone production and release; and 4) examine whether curcumin could enhance the growth-inhibitory effect of bromocriptine. Using rat lactotroph cell lines, GH3 and MMQ cells, we report that curcumin had a robust dose and time-dependent inhibitory effect on GH3 and MMQ cell proliferation. Inhibitory effects of curcumin persisted, even on removal of curcumin, and curcumin also blocked colony formation ability of pituitary tumor cells. The growth-inhibitory effect of curcumin was accompanied by decreased expression of cyclin D3 and ser 780 phosphorylation of retinoblastoma protein. In addition, curcumin also induced apoptosis in both GH3 and MMQ cells. Furthermore, curcumin suppresses intracellular levels and release of both prolactin and GH. Finally, we show that low concentrations of curcumin enhanced the growth-inhibitory effect of bromocriptine on MMQ cell proliferation. Taken together we demonstrate that curcumin inhibits pituitary tumor cell proliferation, induces apoptosis, and decreases hormone production and release, and thus, we propose developing curcumin as a novel therapeutic tool in the management of prolactinomas.

  15. Serum soluble TWEAK levels are decreased in treatment naive noncirrhotic chronic hepatitis B patients.

    PubMed

    Asil, Mehmet; Dertli, Ramazan

    2016-09-01

    The mechanisms underlying hepatic inflammation and fibrogenesis in chronic hepatitis B (CHB) are complex and several cytokines are involved. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily which also acts as a cytokine. This study was conducted to evaluate serum soluble TWEAK (sTWEAK) levels in noncirrhotic CHB patients.Fifty-two treatment naive CHB patients and 30 healthy controls were included in the study and serum sTWEAK concentrations were measured using commercially available ELISA kits.Mean serum sTWEAK concentration was significantly lower in CHB group than healthy controls (189.6 ± 63.3 pg/mL in CHB group and 297.6 ± 61.5 pg/mL in control group, P < 0.001). According to the degree of necroinflammation in liver biopsies mean sTWEAK concentrations were found to be 168.14 ± 51.51, 206.96 ± 58.51, and 223.62 ± 78.88 pg/mL in patients with mild, moderate, and severe inflammation, respectively, and the difference between groups was statistically significant (P = 0.022). sTWEAK concentration was also found to be significantly higher in patients with advanced fibrosis in liver biopsy samples (169.59 ± 52.02 and 211.17 ± 68.22 pg/mL in patients with mild and advanced fibrosis, respectively, P = 0.016). Receiver operating characteristic (ROC) curves were obtained in CHB group to differentiate patients with advanced fibrosis from patients with mild fibrosis. Area under curve (AUC) was 0.676 (95% Cl; 0.526-0.825) for sTWEAK and for the specified cut-off value of 213.67 pg/mL sensitivity and specificity were 60% and 81.4%, respectively. ROC curve for sTWEAK to differentiate patients with severe inflammation revealed an AUC of 0.664 (95% Cl; 0.450-0.878). A cut-off value of 243.27 pg/mL yielded 54.5% sensitivity and 82.9% specificity.Serum sTWEAK concentration is decreased in treatment naive CHB patients. Further studies with simultaneous

  16. Decreased glycogen synthase kinase 3-beta levels and related physiological changes in Bacillus anthracis lethal toxin-treated macrophages.

    PubMed

    Tucker, Amy E; Salles, Isabelle I; Voth, Daniel E; Ortiz-Leduc, William; Wang, Han; Dozmorov, Igor; Centola, Michael; Ballard, Jimmy D

    2003-08-01

    The lethal factor (LF) component of Bacillus anthracis lethal toxin (LeTx) cleaves mitogen activated protein kinase kinases (MAPKKs) in a variety of different cell types, yet only macrophages are rapidly killed by this toxin. The reason for this selective killing is unclear, but suggests other factors may also be involved in LeTx intoxication. In the current study, DNA membrane arrays were used to identify broad changes in macrophage physiology after treatment with LeTx. Expression of genes regulated by MAPKK activity did not change significantly, yet a series of genes under glycogen synthase kinase-3-beta (GSK-3beta) regulation changed expression following LeTx treatment. Correlating with these transcriptional changes GSK-3beta was found to be below detectable levels in toxin-treated cells and an inhibitor of GSK-3beta, LiCl, sensitized resistant IC-21 macrophages to LeTx. In addition, zebrafish embryos treated with LeTx showed signs of delayed pigmentation and cardiac hypertrophy; both processes are subject to regulation by GSK-3beta. A putative compensatory response to loss of GSK-3beta was indicated by differential expression of three motor proteins following toxin treatment and Kif1C, a motor protein involved in sensitivity to LeTx, increased expression in toxin-sensitive cells yet decreased in resistant cells following toxin treatment. Differential expression of microtubule-associating proteins and a decrease in the level of cellular tubulin were detected in LeTx-treated cells, both of which can result from loss of GSK-3beta activity. These data provide new information on LeTx's overall influence on macrophage physiology and suggest loss of GSK-3beta contributes to cytotoxicity. PMID:12864812

  17. The potential effectiveness of mercury minerals in decreasing the level of iodine-129 in a nuclear fuel waste disposal vault

    SciTech Connect

    Oscarson, D.W.; Miller, H.G.; Watson, R.L.

    1986-01-01

    Mercury forms sparingly soluble phases with I under certain conditions. Therefore, Hg minerals have been suggested as potential additives to a clay-based buffer material in nuclear fuel waste disposal vault for the selective removal of /sup 129/I from solution. In oxidizing systems containing HgS, clay (bentonite or kaolinite), and either a synthetic groundwater solution (SGW) or deionized, distilled water, it was found that Hg lowers the concentration of I/sup -/ in solution to approx. =10/sup -6/ mol/L. X-ray diffraction analysis indicated that Hg/sub 2/I/sub 2/(s) is formed in these systems and is the phase controlling the level of I/sup -/ in solution. At levels below approx. = 10/sup -6/ mol/L, all the I/sup -/ is consumed in the formation of HgI/sup 0//sub 2/(aq) and no solid Hg-I phase can form. Bentonite has only a minor effect on the Hg/I system, and kaolinite has little or no effect. Theoretical calculations of the Hg system indicate that, under oxidizing conditions and when the levels of C1/sup -/ or Br/sup -/ are approx. =1 and 0.01 mol/L, respectively (values typical for deep groundwaters in the Canadian Shield), Hg/sub 2/I/sub 2/(s) is not able to decrease the I/sup -/ activity below approx. = 10/sup -5/ mol/L, because of the greater stability of Hg/sub 2/Cl/sup 2/(s) and Hg/sub 2/Br/sub 2/(s) phases (in the experimental study, Hg/sub 2/I/sub 2/(s) is able to lower the level of I/sup -/ below 10/sup -5/ mol/L because the Cl/sup -/ concentration in the SGW was lower (0.18 mol/L) and there was no Br/sup -/ in the system). Further, Hg-I minerals are not stable under reducing to mildly oxidizing conditions. The maximum level of /sup 129/I in disposal vault in Canada is likely to be much less than 10/sup -3.5/ mol/L. Therefore, Hg can in solution. The results of this study indicate the Hg minerals would not be effective additives to a buffer material in a disposal vault in the Canadian shield for the removal of /sup 129/I from solution.

  18. Argon laser trabeculoplasty as a means of decreasing intraocular pressure from ''normal'' levels in glaucomatous eyes

    SciTech Connect

    Sharpe, E.D.; Simmons, R.J.

    1985-06-15

    The authors conducted a retrospective study of 67 patients (85 eyes) with severe glaucoma to determine whether argon laser trabeculoplasty could reduce intraocular pressures below the ''normal'' range. All patients had initial intraocular pressures of less than or equal to 19 mm Hg. Success was defined as a decrease in intraocular pressure of at least 20%, no increase in medications, stable visual field, and no subsequent glaucoma surgery. After an average follow-up period of 30 months, treatment was successful in 31 cases. One half of the failures occurred by six months and 11 failures (30%) occurred after 12 months. Sixteen patients were able to decrease their medications. Two patients achieved intraocular pressures between 6 and 9 mm Hg and 20 between 10 and 12 mm Hg.

  19. Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging.

    PubMed

    Kuo, Ivana Y; Duong, Sophie L; Nguyen, Lily; Ehrlich, Barbara E

    2016-01-01

    Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement. PMID:27081851

  20. Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing androgen receptor levels in prostate cancer cells.

    PubMed

    Khurana, Namrata; Talwar, Sudha; Chandra, Partha K; Sharma, Pankaj; Abdel-Mageed, Asim B; Mondal, Debasis; Sikka, Suresh C

    2016-10-01

    Prostate cancer (PCa) cells utilize androgen for their growth. Hence, androgen deprivation therapy (ADT) using anti-androgens, e.g. bicalutamide (BIC) and enzalutamide (ENZ), is a mainstay of treatment. However, the outgrowth of castration resistant PCa (CRPC) cells remains a significant problem. These CRPC cells express androgen receptor (AR) and utilize the intratumoral androgen towards their continued growth and invasion. Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, can decrease AR protein levels. In the present study, we tested the combined efficacy of anti-androgens and SFN in suppressing PCa cell growth, motility and clonogenic ability. Both androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells were used to monitor the effects of BIC and ENZ, alone and in combination with SFN. Co-exposure to SFN significantly (p<0.005) enhanced the anti-proliferative effects of anti-androgens and downregulated expression of the AR-responsive gene, prostate specific antigen (PSA) (p<0.05). Exposure to SFN decreased AR protein levels in a time- and dose-dependent manner with almost no AR detected at 24 h with 15 µM SFN (p<0.005). This rapid and potent AR suppression by SFN occurred by both AR protein degradation, as suggested by cycloheximide (CHX) co-exposure studies, and by suppression of AR gene expression, as evident from quantitative RT-PCR experiments. Pre-exposure to SFN also reduced R1881-stimulated nuclear localization of AR, and combined treatment with SFN and anti-androgens abrogated the mitogenic effects of this AR-agonist (p<0.005). Wound-healing assays revealed that co-exposure to SFN and anti-androgens can significantly (p<0.005) reduce PCa cell migration. In addition, long-term exposures (14 days) to much lower concentrations of these agents, SFN (0.2 µM), BIC (1 µM) and/or ENZ (0.4 µM) significantly (p<0.005) decreased the number of colony forming units (CFUs). These findings clearly suggest that

  1. Vacuum cleaning decreases the levels of mite allergens in house dust.

    PubMed

    Munir, A K; Einarsson, R; Dreborg, S K

    1993-08-01

    To investigate the capacity of chemical treatment of surfaces and the difference in capacity among common vacuum cleaners to reduce mite allergen content in house dust, we recruited 52 families with allergic children. Ten families used their central vacuum cleaners. Forty-two families were randomly divided into four groups with 10 or 11 families in each. These families used either new vacuum cleaners with either HEPA (High Efficiency Particulate Air) or micro-filters, or their own vacuum cleaners with either tannic acid or placebo. Dust samples were collected from carpets and upholstered furniture in the living rooms and from the mattresses of the children at Days 0, 7, 21, and 35. Der pI and Der fI allergens were determined by sandwich ELISA. After one week, tannic acid reduced the concentration of mite allergens/g of dust and the total amount/sampling area by 30% and 34%, respectively (p < 0.05), but there was no significant decrease in relation to placebo. After 5 weeks, central, HEPA- and micro-filter vacuum cleaners decreased the mite allergen concentration by 10-50% (p < 0.05) and the total amount of mite allergen from the investigated areas by 50-85% (p < 0.01). In relation to the placebo group the decrease was significant for HEPA- and micro-filter vacuums (p < 0.05). The total amount of mite allergens/sampling area was more significantly (p < 0.05) reduced than the concentration/g of dust. We conclude, that tannic acid reduces mite allergen concentrations in dust and total amount/sampling area for a short period of time.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Oxidative stress and decreased thiol level in patients with migraine: cross-sectional study.

    PubMed

    Eren, Yasemin; Dirik, Ebru; Neşelioğlu, Salim; Erel, Özcan

    2015-12-01

    Although migraine is a neurological disorder known since long, its physiopathology remains unclear. Recent studies suggest that migraine is associated with oxidative stress; however, they report divergent results. The aim of the present study was to evaluate total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and serum thiol level in migraine patients with or without aura. The study group consisted of 141 migraine patients. The control group included 70 healthy subjects. TAS, TOS, OSI were evaluated using a method developed by Erel. Serum thiol level was measured using the Hu method. No difference was found in TAS, TOS, OSI between the patients and controls. The level of thiol was significantly lower in patients than in controls. Negative correlations were detected between thiol level and Migraine Disability Assessment score in patients. Although TAS, TOS, and OSI were similar to those of the control group, serum thiol level, an important marker of antioxidant capacity, was significantly lower in migraines compared with controls, and caused more serious disability. Novel treatment approaches may be developed based on these data, and compounds containing thiol, such as alpha lipoic acid and N-acetyl cysteine, may be used in prophylaxis.

  3. Birdsong decreases protein levels of FoxP2, a molecule required for human speech.

    PubMed

    Miller, Julie E; Spiteri, Elizabeth; Condro, Michael C; Dosumu-Johnson, Ryan T; Geschwind, Daniel H; White, Stephanie A

    2008-10-01

    Cognitive and motor deficits associated with language and speech are seen in humans harboring FOXP2 mutations. The neural bases for FOXP2 mutation-related deficits are thought to reside in structural abnormalities distributed across systems important for language and motor learning including the cerebral cortex, basal ganglia, and cerebellum. In these brain regions, our prior research showed that FoxP2 mRNA expression patterns are strikingly similar between developing humans and songbirds. Within the songbird brain, this pattern persists throughout life and includes the striatal subregion, Area X, that is dedicated to song development and maintenance. The persistent mRNA expression suggests a role for FoxP2 that extends beyond the formation of vocal learning circuits to their ongoing use. Because FoxP2 is a transcription factor, a role in shaping circuits likely depends on FoxP2 protein levels which might not always parallel mRNA levels. Indeed our current study shows that FoxP2 protein, like its mRNA, is acutely downregulated in mature Area X when adult males sing with some differences. Total corticosterone levels associated with the different behavioral contexts did not vary, indicating that differences in FoxP2 levels are not likely attributable to stress. Our data, together with recent reports on FoxP2's target genes, suggest that lowered FoxP2 levels may allow for expression of genes important for circuit modification and thus vocal variability.

  4. Daily walking decreases casual glucose level among pregnant women in the second trimester.

    PubMed

    Hayashi, Ayako; Matsuzaki, Masayo; Kusaka, Momoko; Shiraishi, Mie; Haruna, Megumi

    2016-01-01

    The objective of this study was to explore the relationship between carbohydrate metabolism and the number of steps walked daily, as evaluated by accelerometer, among Japanese women in the second trimester of pregnancy. This longitudinal study was conducted at a university hospital in Tokyo, Japan, from August 2012 to January 2013. Healthy pregnant women at 14 to 18 gestational weeks were recruited. Participants wore accelerometers on the waist for 4 weeks. Casual glucose and hemoglobin A1c (HbA1c) levels were compared between two groups based on whether participants habitually walked ≥ 6,000 steps/day or < 6,000 steps/day. Fifty-one pregnant women were included in the present study; data from 35 were analyzed. There were 22 women in the group that habitually walked ≥ 6,000 steps/day and 13 in the group habitually walking < 6,000 steps/day. Although the median serum casual glucose level at the end of the investigation was 90.0 mg/dL in the group walking < 6,000 steps/day, the level in the group walking ≥ 6000 steps/day was 83.5 mg/dL (p = 0.01). HbA1c levels were not significantly different between the two groups. Our results suggest that walking as a daily habitual physical activity is effective for controlling casual glucose levels in the second trimester of pregnancy. PMID:27594297

  5. Elevated venous glutamate levels in (pre)catabolic conditions result at least partly from a decreased glutamate transport activity.

    PubMed

    Hack, V; Stütz, O; Kinscherf, R; Schykowski, M; Kellerer, M; Holm, E; Dröge, W

    1996-06-01

    Abnormally high postabsorptive venous plasma glutamate levels have been reported for several diseases that are associated with a loss of body cell mass including cancer, human/simian immunodeficiency virus infection, and amyotrophic lateral sclerosis. Studies on exchange rates in well-nourished cancer patients now show that high venous plasma glutamate levels may serve as a bona fide indicator for a decreased uptake of glutamate by the peripheral muscle tissue in the postabsorptive period and may be indicative for a precachectic state. High glutamate levels are also moderately correlated with a decreased uptake of glucose and ketone bodies. Relatively high venous glutamate levels have also been found in non-insulin-dependent diabetes mellitus and to some extent also in the cubital vein of normal elderly subjects, i.e., in conditions commonly associated with a decreased glucose tolerance and progressive loss of body cell mass.

  6. Therapeutic Plasma Exchange Decreases Levels of Routinely Used Cardiac and Inflammatory Biomarkers

    PubMed Central

    Beutel, Gernot; Bauersachs, Johann; David, Sascha; Schmidt, Bernhard M. W.; Lichtinghagen, Ralf; Kielstein, Jan T.

    2012-01-01

    Background Therapeutic plasma exchange (TPE) plays a key role in the management of various diseases, from thrombotic thrombocytopenic purpura and Goodpasture's syndrome to cardiac allograft rejection. In many of these disease states cardiac and inflammatory involvement is common and biomarkers are routinely used for diagnosis or assessment of therapeutic success. The effect of TPE on biomarkers used in the clinical routine has not been investigated. Methods TPE was initiated for established clinical conditions in 21 patients. Troponin T, NT-proBNP, C-reactive protein, procalcitonin and routine chemistry were drawn before and after TPE, as well as before and after the 2nd TPE. The total amount of these markers in the waste bag was also analyzed. Results In 21 patients 42 TPEs were performed. The procedure reduced plasma levels of the examined biomarkers: 23% for NT-proBNP (pre vs. post: 4637±10234 ng/l to 3565±8295 ng/l, p<0.001), 64% for CRP (21.9±47.0 mg/l vs. 7.8±15.8 mg/l, p<0.001) and 31% for procalcitonin (0.39±1.1 µg/l vs. 0.27±0.72 µg/l, p=0.004). TPE also tended to reduce plasma levels of troponin T by about 14% (60.7±175.5 ng/l vs. 52.2±141.3 ng/l), however this difference was not statistical significant (p=0.95). There was a significant correlation between the difference of pre TPE levels to post TPE levels of all examined biomarkers and the total amount of the removed biomarker in the collected removed plasma. Conclusions TPE significantly reduces plasma levels of inflammatory and cardiac biomarkers. Therefore, post TPE levels of cardiac and inflammatory biomarkers should be viewed with caution. PMID:22685586

  7. Decreased levels of procoagulant phospholipids in bleeding patients treated by vitamin K antagonists.

    PubMed

    Mathieu, Emmanuel; Van Dreden, Patrick; Aulagnier, Jérôme; Grusse, Matthieu; Dreyfus, Jean-François; François, Dominique; Vasse, Marc

    2016-01-01

    International Normalized Ratio (INR) is currently used to monitor vitamin K antagonist therapy, and the bleeding incidence becomes exponential for INR>4.5. Inversely, more than 50% of patients with a supratherapeutic INR are asymptomatic. Therefore it could be of interest to identify patients with a higher bleeding risk. Microparticles derived from different cell types express procoagulant phospholipids (PPL) which can be evaluated by a chronometric coagulation assay where a shortening of the clotting times is associated with increased levels of PPL. In a series of 174 consecutive patients referred to our Emergency Department with an INR>5, median level of PPL was significantly (p=0.004) lower (38.2s) in the 119 asymptomatic patients than in patients with nonmajor (43.6s, n=35) or major bleeding (46.6s, n=19), indicating higher levels of procoagulant phospholipids in asymptomatic patients. By receiver operating characteristic curve analysis, a cut-off of 43.5s discriminated patients with higher haemorrhagic risk (area under the curve=0.648). In contrast, thrombomodulin levels, quantified either by immunological or functional assays were not significantly different between both groups. In conclusion, evaluation of PPL could be of interest to define the haemorrhagic risk of VKA- treated patients. PMID:26632514

  8. Intervening to Decrease Alcohol Abuse at University Parties: Differential Reinforcement of Intoxication Level

    ERIC Educational Resources Information Center

    Fournier, Angela K.; Ehrhart, Ian J.; Glindemann, Kent E.; Geller, E. Scott

    2004-01-01

    This quasi-experimental field study assessed whether an incentive/reward intervention can change the drinking behavior and the subsequent levels of intoxication among college students attending fraternity parties. A total of 356 blood alcohol concentration (BAC) assessments, using hand-held breathalyzers, were obtained at two baseline and at two…

  9. Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman.

    PubMed

    Hodgson, Nathaniel W; Waly, Mostafa I; Al-Farsi, Yahya M; Al-Sharbati, Marwan M; Al-Farsi, Omar; Ali, Amanat; Ouhtit, Allal; Zang, Tianzhu; Zhou, Zhaohui Sunny; Deth, Richard C

    2014-06-01

    Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B₁₂. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury.

  10. Anomalous low level of cosmic ray intensity decreases observed during 1980

    NASA Technical Reports Server (NTRS)

    Jain, A. K.; Pandey, P. K.; Agrawal, S. P.

    1985-01-01

    Past studies have revealed solar cycle changes in the sunspot activity, as well as in many other solar parameters, such as, solar flares and solar coronal holes. These solar features in turn produce the observed cyclic variations in the interplanetary plasma and fields. Both the cosmic ray intensity as well as the intensity of geomagnetic disturbances are affected by the interplanetary changes and produce 11/22 year periodicity. An anomalous situation has been noticed during the year 1980 (period of high sunspot activity), when both the geomagnetic disturbance index Ap, as well as the magnitude and number of Forbush decreases as small. Such an anomaly occurs, in spite of the fact that both the sunspot numbers and the energetic solar flares are almost maximum during the present solar cycle.

  11. PPAR-α Agonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia.

    PubMed

    Feng, Xiaomeng; Gao, Xia; Jia, Yumei; Zhang, Heng; Pan, Qingrong; Yao, Zhi; Yang, Ning; Liu, Jia; Xu, Yuan; Wang, Guang; Yang, Xinchun

    2015-01-01

    Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the effect of fenofibrate, a PPAR-α agonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15 ± 10.48 versus 35.38 ± 9.97 ng/ml, P < 0.001) and correlated with body mass index (r = 0.314, P = 0.011), fasting blood glucose (r = 0.399, P = 0.001), total cholesterol (r = 0.256, P = 0.040), and high-density lipoprotein cholesterol (r = 0.247, P = 0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β = 5.615, P < 0.001) and high-density lipoprotein cholesterol (β = 19.483, P < 0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15 ± 10.48 versus 38.74 ± 12.54 ng/ml, P = 0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-α agonists may protect against metabolic disorders by improving irisin resistance. PMID:26693220

  12. Bancroftian filariasis: circulating B-1 cells decreased in microfilaria carriers and correlate with immunoglobulin M levels.

    PubMed

    Mishra, R; Sahoo, P K; Mishra, S; Achary, K G; Dwibedi, B; Kar, S K; Satapathy, A K

    2014-05-01

    B-1 cells play an important role in the outcome of infection in schistosomiasis, pneumonia and experimental filariasis. However, no information exists regarding status of B-1 cells in clinical manifestations of human filariasis. We investigated the levels of B-1 cells from the total B cells by flow cytometry. Significantly low levels of B-1 cells and IgM antibodies were detected against a wide variety of autoantigens in microfilariae carriers as compared to endemic controls and patients with chronic pathology. A positive correlation was found between IgM antibodies to actin and ss-DNA. Absorption of plasma with soluble actin, myosin and lipopolysaccharides (LPS) resulted in significant removal of antifilarial antibodies. Affinity-purified anti-ss-DNA antibodies were found to be reactive to filarial antigens and various autoantigens. Further, a positive correlation was found between polyreactive antibodies and B-1 cells in filarial-infected human subjects. After antifilarial treatment, levels of IgM antibodies to ss-DNA, actin, LPS and filarial antigen increased significantly indicating a role of polyreactive naturally occurring antibodies in filarial infection. Our findings add to the existing evidence that the B-cell defect in BALB.Xid mice account for susceptibility to murine filarial infection and indicate an important role for these antibodies in providing host protection against filarial infection.

  13. Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.

    PubMed

    Silaste, Marja-Leena; Alfthan, Georg; Aro, Antti; Kesäniemi, Y Antero; Hörkkö, Sohvi

    2007-12-01

    High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0.56, P = 0.009; r 0.60, P = 0.004, total and LDL, respectively), beta-carotene (r 0.58, P = 0.005; r 0.70, P < 0.001) and gamma-carotene concentrations (r 0.64, P = 0.002; r 0.64, P = 0.002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P = 0.02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, beta-carotene and gamma-carotene levels. PMID:17617941

  14. Selenium supplementation restores the decreased albumin level of peripheral blood mononuclear cells in streptozotocin-induced diabetic mice

    PubMed Central

    AHN, Taeho; BAE, Chun-Sik; YUN, Chul-Ho

    2016-01-01

    Previously, it has been suggested that the phenotypic level of albumin in peripheral blood mononuclear cells (PBMC) decreased in streptozotocin (STZ)-induced diabetic rats. Concomitantly, the production of oxidative stresses was also elevated in the diabetic PBMC compared to that of normal control. These results suggest the close relationship between PBMC-albumin and its antioxidant roles. Here, we expanded the previous studies and investigated the effect of selenium supplementation as inorganic (sodium selenate) forms on the levels of albumin expression and oxidative stress in PBMC of STZ-induced diabetic mice. Selenium intake recovered the decreased albumin levels to those of normal mice and reduced the production of reactive oxygen species (ROS). These results support that selenium intake may alleviate the etiology and pathology of PBMC in type 1 diabetic mice by restoring the decrease in albumin contents and the production of ROS. PMID:26726102

  15. Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

    SciTech Connect

    Popovich, B.; Barrieux, A.; Dillmann, W.H.

    1987-05-01

    Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4 wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.

  16. Partnership to decrease antipsychotic medication use in nursing homes: impact at the state level.

    PubMed

    Mort, Jane R; Sailor, Ryan; Hintz, Lori

    2014-02-01

    In 2012, the Centers for Medicare & Medicaid Services (CMS) established a partnership among stakeholders to decrease the percentage of residents in nursing homes receiving an antipsychotic agent by 15 percent. This goal emanated from concerns including the large percentage of residents taking antipsychotic agents, the questionable use of antipsychotics (e.g., off-label use), the high cost of inappropriate antipsychotic use, and toxicity in patients with dementia (e.g., black box warning regarding mortality). The successful achievement of this goal is evaluated via quality measures, which are greatly influenced by changes in exclusion of residents from the population examined. The partnership is focused on optimizing use of antipsychotic agents by training clinicians on nonpharmacologic approaches, educating on the dangers of antipsychotic medication use and sharing data on antipsychotic medications. In South Dakota, these efforts have yielded a 12 percent relative reduction (21.3 percent to 18.7 percent) in the percent of residents prescribed antipsychotic agents from the second quarter of 2012 to the second quarter of 2013. Future efforts in South Dakota include a Nursing Home Quality Care Collaborative that involves the majority of facilities across the state learning from peers and national experts. The South Dakota Dementia Coalition includes 17 stakeholders who guide education activities and communicate these opportunities to their constituents. PMID:24624602

  17. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    SciTech Connect

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-23

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development.

  18. TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways

    PubMed Central

    Jung, Jong Gab; Yi, Sang-A; Choi, Sung-E; Kang, Yup; Kim, Tae Ho; Jeon, Ja Young; Bae, Myung Ae; Ahn, Jin Hee; Jeong, Hana; Hwang, Eun Sook; Lee, Kwan-Woo

    2015-01-01

    The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2′-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-phosphoeIF2α-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance. PMID:26537193

  19. Decreased Serum Level of miR-146a as Sign of Chronic Inflammation in Type 2 Diabetic Patients

    PubMed Central

    Baldeón R., Lucy; Weigelt, Karin; de Wit, Harm; Ozcan, Behiye; van Oudenaren, Adri; Sempértegui, Fernando; Sijbrands, Eric; Grosse, Laura; Freire, Wilma; Drexhage, Hemmo A.; Leenen, Pieter J. M.

    2014-01-01

    Background There is increasing evidence that chronic inflammation is an important determinant in insulin resistance and in the pathogenesis of type 2 diabetes (T2D). MicroRNAs constitute a newly discovered system of cell regulation and in particular two microRNAs (miR-146a and miR-155) have been described as regulators and biomarkers of inflammation. Aim To determine a putative association between the levels of miR-146a and miR-155 in serum of T2D patients, clinical parameters and serological indicators of inflammation. Methods We performed quantitative Real Time PCR (qPCR) of microRNAs from serum (56 Ecuadorian T2D ambulatory patients and 40 non-diabetic controls). In addition, we evaluated T2D-related serum cytokines.chemokines and growth factors using a commercially available multi-analyte cytometric bead array system. We correlated outcomes to clinical parameters, including BMI, HbA1c and lipid state. Results The Ecuadorian non-diabetic controls appeared as overweight (BMI>25: patients 85%, controls 82.5%) and as dyslipidemic (hypercholesterolemia: patients 60.7%, controls 67.5%) as the patients. The serum levels of miR-146a were significantly reduced in T2D patients as compared to these non-diabetic, but obese/dyslipidemic control group (mean patients 0.61, mean controls set at 1; p = 0.042), those of miR-155 were normal. The serum levels of both microRNAs correlated to each other (r = 0.478; p<0.001) and to leptin levels. The microRNAs did not correlate to BMI, glycemia and dyslipidemia. From the tested cytokines, chemokines and growth factors, we found IL-8 and HGF significantly raised in T2D patients versus non-diabetic controls (p = 0.011 and 0.023 respectively). Conclusions This study shows decreased serum anti-inflammatory miR-146a, increased pro-inflammatory IL-8 and increased HGF (a vascular/insular repair factor) as discriminating markers of failure of glucose control occurring on the background of obesity and dyslipidemia. PMID:25500583

  20. Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

    PubMed Central

    Weisbrod, Robert M; Griswold, Mark C; Yaghoubi, Mohammad; Komalavilas, Padmini; Lincoln, Thomas M; Cohen, Richard A

    1998-01-01

    The role of cyclic GMP in the ability of nitric oxide (NO) to decrease intracellular free calcium concentration [Ca2+]i and divalent cation influx was studied in rabbit aortic smooth muscle cells in primary culture. In cells stimulated with angiotensin II (AII, 10−7 M), NO (10−10–10−6 M) increased cyclic GMP levels measured by radioimmunoassay and decreased [Ca2+]i and cation influx as indicated by fura-2 fluorimetry.Zaprinast (10−4 M), increased NO-stimulated levels of cyclic GMP by 3–20 fold. Although the phosphodiesterase inhibitor lowered the level of [Ca2+]i reached after administration of NO, the initial decreases in [Ca2+]i initiated by NO were not significantly different in magnitude or duration from those that occurred in the absence of zaprinast.The guanylyl cyclase inhibitor, H-(1,2,4) oxadiazolo(4,3-a) quinoxallin-1-one (ODQ, 10−5 M), blocked cyclic GMP accumulation and activation of protein kinase G, as measured by back phosphorylation of the inositol trisphosphate receptor. ODQ and Rp-8-Br-cyclic GMPS, a protein kinase G inhibitor, decreased the effects of NO, 10−10–10−8 M, but the decrease in [Ca2+]i or cation influx caused by higher concentrations of NO (10−7–10−6 M) were unaffected. Relaxation of intact rabbit aorta rings to NO (10−7–10−5 M) also persisted in the presence of ODQ without a significant increase in cyclic GMP. Rp-8-Br-cyclic GMPS blocked the decreases in cation influx caused by a cell permeable cyclic GMP analog, but ODQ and/or the protein kinase G inhibitor had no significant effect on the decrease caused by NO.Although inhibitors of cyclic GMP, protein kinase G and phosphodiesterase can be shown to affect the decrease in [Ca2+]i and cation influx via protein kinase G, these studies indicate that when these mechanisms are blocked, cyclic GMP-independent mechanisms also contribute significantly to the decrease in [Ca2+]i and smooth muscle relaxation to NO. PMID:9886761

  1. [Hospital-acquired anemia and decrease of hemoglobin levels in hospitalized patients].

    PubMed

    Gianserra, Carina V; Agüero, Andrés P; Chapelet, Adrián G; Paradiso, Bruno; Spanevello, Valeria A; Del Pino, María A

    2011-01-01

    It is common to observe the development of anemia in hospitalized patients, especially in critical cases. Few studies have evaluated its prevalence and associated factors in patients in the general ward. The purpose of this study is to determine the prevalence, characteristics and associated clinical factors of hospital-acquired anemia and the drop of hemoglobin concentration in hospitalized patients. This is a cross-sectional, prospective and descriptive study. A total of 192 consecutive in-patients in the general ward were studied. Associated risk factors to the drop in hemoglobin by ≥ 2g/dl were analyzed; 139 patients (72.4%) presented anemia; 89 of them (46.4%) had it at admission and 50 (26%) developed hospital-acquired anemia, 47 out of 192 showed a drop in hemoglobin ≥ 2 g/dl(24.48%). They also presented lower values of hematocrite and hemoglobin at discharge (p = 0.01), parenteral hydration at a higher volume (p = 0.01), and lengthier hospitalizations (p = 0.0001). In the univariate analysis, the following variables were statistically significant risk factors: leukocytosis ≥ 11000 mm3 (OR; IC95%: 2,02; 1.03-4; p = 0.01), hospitalization days ≥ 7 (OR; IC95%:3.39; 1.62-7.09; p = 0.0006), parenteral hydration ≥ 1500 ml/day (OR; IC95%: 2.47; 1.06-6.4; p = 0.01), central venous access (OR; IC95%:10.29; 1.75-108.07; p = 0.003) and hospital-acquired anemia (OR; IC95%: 7.06; 3.41-15.83; p = 0.00000004). In the multivariate analysis, the following variables were independent predictive factors of the hemoglobin decrease = 2 g/dl: leukocytosis ≥ 11000 mm3 (OR; IC95%: 2.45; 1.14-5,27; p = 0.02), hospitalization days ≥ 7 (OR; IC95%:5.15; 2.19-12.07; p = 0.0002), parenteral hydration ≥ 1500 ml/day (OR; IC95%: 2.95; 1.13-7.72; p = 0.02), central venous access (OR; IC95%:8.82; 1.37-56.82; p = 0.02). Hospital-acquired anemia has a high prevalence. Lengthier stays, presence of leukocytosis, parenteral hydration and central venous access placement are

  2. A decrease in protein level and a missense polymorphism of KIF17 are associated with schizophrenia.

    PubMed

    Ratta-Apha, Woraphat; Mouri, Kentaro; Boku, Shuken; Ishiguro, Hiroki; Okazaki, Satoshi; Otsuka, Ikuo; Sora, Ichiro; Arinami, Tadao; Shirakawa, Osamu; Hishimoto, Akitoyo

    2015-12-15

    It has been shown that the dysfunction of N-methyl-d-asparate (NMDA) receptors-mediated neurotransmission plays a role in the pathophysiology of schizophrenia. Especially, GluN2B, a subunit of NMDA receptors, associated trafficking complex is altered in the prefrontal cortex of schizophrenia. The kinesin superfamily motor protein 17 (KIF17) is known as a transporter of NR2B.Previous studies showed that a structural variant of KIF17 gene is associated with a schizophrenic phenotype. Therefore, here we investigated KIF17 levels in postmortem prefrontal cortex in schizophrenia and the association of a missense polymorphism (Ile341Val) in KIF17 with schizophrenia. The protein expression of KIF17 in schizophrenic postmortem brains was significantly lower than that in controls. Next, the association of missense polymorphisms (rs631375, rs13375609, rs522496 and rs2296225) of KIF17 gene in 567 schizophrenia and 710 healthy subjects was examined. Both genotypic distribution and allelic frequency of rs2296225 polymorphism were significantly different between the chronic schizophrenia subjects and controls. However, our findings described above were not replicated with the independent subjects (555 schizophrenia and 814 healthy controls). Furthermore, the two alleles of rs2296225 polymorphism did not affect the mRNA expression of KIF17. These results suggest that the dysfunction of KIF17 might be involved in the pathophysiology of schizophrenia.

  3. High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation.

    PubMed

    Rakhmanov, Mirzokhid; Sic, Heiko; Kienzler, Anne-Kathrin; Fischer, Beate; Rizzi, Marta; Seidl, Maximilian; Melkaoui, Kerstina; Unger, Susanne; Moehle, Luisa; Schmit, Nadine E; Deshmukh, Sachin D; Ayata, Cemil Korcan; Schuh, Wolfgang; Zhang, Zhibing; Cosset, François-Loic; Verhoeyen, Els; Peter, Hans-Hartmut; Voll, Reinhard E; Salzer, Ulrich; Eibel, Hermann; Warnatz, Klaus

    2014-01-01

    Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response. PMID:24945754

  4. Decreased Levels of VAMP2 and Monomeric Alpha-Synuclein Correlate with Duration of Dementia.

    PubMed

    Vallortigara, Julie; Whitfield, David; Quelch, William; Alghamdi, Amani; Howlett, David; Hortobágyi, Tibor; Johnson, Mary; Attems, Johannes; O'Brien, John T; Thomas, Alan; Ballard, Clive G; Aarsland, Dag; Francis, Paul T

    2015-01-01

    Alpha-synuclein (α-syn) aggregations are the key pathological hallmark of dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), but are also frequently present in Alzheimer's disease (AD). Much remains unknown about the role of α-syn in the synapse and the wider role of synaptic dysfunction in these dementias. Changes in concentrations of key 'SNAP (Soluble N-ethylmaleimide Sensitive Factor Attachment Protein) Receptor' (SNARE) proteins as a consequence of alterations in the aggregation state of α-syn may contribute to synaptic dysfunction in patients with DLB, PDD, and AD and result in impaired cognition. We have studied a large cohort (n = 130) of autopsy confirmed DLB, PDD, AD, and control brains. Using semi-quantitative western blotting, we have demonstrated significant changes across the diagnostic groups of DLB, PDD, and AD in the SNARE and vesicle proteins syntaxin, Munc18, VAMP2, and monomeric α-syn in the prefrontal cortex, with a significant reduction of Munc18 in AD patients (p <  0.001). This correlated to the final MMSE score before death (p = 0.016). We also identified a significant negative correlation between the duration of dementia and the levels of the binding partners VAMP2 (p = 0.0004) and monomeric α-syn (p = 0.0002). Our findings may indicate that an upregulation of SNARE complex related proteins occurs in the early stages of disease as an attempt at compensating for failing synapses, prior to widespread deposition of pathological α-syn.

  5. Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

    SciTech Connect

    Aslan, Mutay; Basaranlar, Goksun; Unal, Mustafa; Ciftcioglu, Akif; Derin, Narin; Mutus, Bulent

    2014-11-01

    Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress. - Highlights: • Inhibition of N-SMase decreases NOS2 levels in ocular hypertension. • Inhibition of N-SMase decreases protein nitration in ocular hypertension. • Inhibition of N-SMase decreases caspase activation in ocular hypertension. • Inhibition of N-SMase decreases apoptosis in ocular hypertension.

  6. The Effectiveness of an Additional Stretching Exercise Program in Improving Flexibility Level among Preschool Boys

    ERIC Educational Resources Information Center

    Lee, Wee Akina Sia Seng; Rengasamy, Shabeshan A/L; Raju, Subramaniam A/L

    2014-01-01

    This study was conducted to examine the effectiveness of a two minutes' additional stretching exercise program in a 30 minutes games teaching lesson in improving the flexibility level of 6 year old preschool boys (M = 5.92, SD = 0.27) in a preschool in Malaysia. Fifty (50) preschool boys were selected for the study based on the intact sampling…

  7. Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration?

    PubMed

    Cheah, Irwin K; Feng, Lei; Tang, Richard M Y; Lim, Keith H C; Halliwell, Barry

    2016-09-01

    Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases. PMID:27444382

  8. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms

    PubMed Central

    Ji, Hong-Long; Song, Weifeng; Gao, Zhiqian; Su, Xue-Feng; Nie, Hong-Guang; Jiang, Yi; Peng, Ji-Bin; He, Yu-Xian; Liao, Ying; Zhou, Yong-Jian; Tousson, Albert; Matalon, Sadis

    2009-01-01

    Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na+) channels (ENaC), the rate-limiting protein in transepithelial Na+ vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human α-, β-, and γ-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na+ currents and γ-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either α- or γ-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCα/β1 and PKCζ. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCα/β1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells. PMID:19112100

  9. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

  10. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  11. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats.

    PubMed

    Moriya, Chihiro; Satoh, Hiroaki

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  12. Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism.

    PubMed

    McClain, Donald A; Abuelgasim, Khadega A; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A; Sergueeva, Adelina; Okhotin, Daniel J; Cherqaoui, Rabia; Okhotin, David; Cox, James E; Swierczek, Sabina; Song, Jihyun; Simon, M Celeste; Huang, Jingyu; Simcox, Judith A; Yoon, Donghoon; Prchal, Josef T; Gordeuk, Victor R

    2013-01-01

    In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia-inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzyme genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHL ( R200W ) homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wild-type VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHL ( R200W ) homozygotes. We expanded these observations in VHL ( R200W ) homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc, but not Pdk2, was decreased, and skeletal muscle expression of Glut1, Pdk1, and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. PMID:23015148

  13. High dose of N-acetylcysteine increase H₂O₂ and MDA levels and decrease GSH level of HUVECs exposed with malaria serum.

    PubMed

    Fitri, L E; Sardjono, T W; Simamora, D; Sumarno, R P; Setyawati, S K

    2011-04-01

    Dysfunction of endothelial cells in severe malaria may result from excessive activation of tumor necrosis factor (TNF)-α which leads to an increase in production of reactive oxygen species (ROS) and decrease of antioxidant level of endothelial cells. To investigate the effect of N-acetylcysteine (NAC) on hydrogen peroxide (H2O2), malondialdehyde (MDA) and glutathione (GSH) levels produced by endothelial cells exposed with serum of malaria falciparum patient, an in vitro model of human umbilical vein endothelial cells (HUVECs) culture was used. Sample groups were normal HUVECs (group A), HUVECs that was exposed with malaria serum without any treatment (group B), HUVECs that were exposed with malaria serum and treated with NAC 2 μM (group C), HUVECs that were exposed with malaria serum and treated with NAC 4 μM (group D), and HUVECs that were exposed with malaria serum and treated with NAC 8 μM (group E). The level of MDA was measured by thio-barbituric acid reaction assay and H2O2 level was measured by NWLSS Hydrogen Peroxyde/Peroxydase Assay kit. The level of GSH was determined by using NWLSS Glutathione Assay kit. The level of H2O2 and MDA decreased after administration of low dose of NAC. Unfortunately, increased H2O2 and MDA levels were found on HUVECs treated with high dose of NAC (8 μM). There was a positive correlation between NAC dose and H2O2 level (r= 0,603) and between NAC dose and MDA level (r= 0,721). A significant decreased level of GSH was found on HUVECs treated with high dose of NAC (p = 0,023). It can be concluded that the use of high dose of NAC as supportive therapy in severe malaria infection must be taken carefully.

  14. A possible mechanism for 2,3',4,4',5'-pentachlorobiphenyl-mediated decrease in serum thyroxine level in mice.

    PubMed

    Kato, Yoshihisa; Onishi, Mao; Haraguchi, Koichi; Ikushiro, Shinichi; Ohta, Chiho; Koga, Nobuyuki; Endo, Tetsuya; Yamada, Shizuo; Degawa, Masakuni

    2013-01-01

    The effect of 2,3',4,4',5'-pentachlorobiphenyl (CB118) on serum total thyroxine (T₄) level was comparatively examined between C57BL/6 and DBA/2 mice, which are sensitive and insensitive, respectively, to aryl hydrocarbon receptor-mediated biological changes. After 5 d of CB118 administration (50 mg/kg, intraperitoneally (i.p.)), the serum total T₄ levels in both strains of mice were markedly decreased. However, significant decreases in serum thyroid-stimulating hormone levels were observed in DBA/2 mice, but not in C57BL/6 mice. In contrast, significant increases in the level and activity of hepatic T₄-uridine 5'-diphosphate (UDP)-glucuronosyltransferase by CB118 treatment were observed only in C57BL/6 mice. Likewise, significant increases in the amounts of biliary [(125)I]T₄ and [(125)I]T₄-glucuronide after injection of [(125)I]T4 were observed only in the CB118-pretreated C57BL/6 mice. The CB118-mediated changes in the levels of [(125)I]T₄ bound to transthyretin (TTR), albumin, and thyroxine binding globulin (TBG) were also observed in C57BL/6 mice, but not in DBA/2 mice. Despite such strain differences, significant increases in the liver-selective accumulation of [(125)I]T₄ by CB118-pretreatment was observed in both C57BL/6 and DBA/2 mice. The present findings indicate that CB118-mediated decreases in levels of serum T₄ in C57BL/6 and DBA/2 mice occur mainly through enhanced accumulation of hepatic T₄.

  15. [Lateral medullary infarction presenting with truncal lateropulsion and decreased pain and temperature sensation below T10 sensory level].

    PubMed

    Nishihira, Takahito; Suzuki, Keisuke; Takekawa, Hidehiro; Nakamura, Toshiki; Iwasaki, Akio; Hirata, Koichi

    2014-01-01

    A 45-year-old man noted a tendency to fall to the left side on standing following headache and vomiting. Neurological findings were unremarkable except for truncal lateropulsion to the left side. Brain magnetic resonance imaging (MRI) showed a small infarct in the left inferolateral part of medulla. Clinical and imaging findings suggested vertebral artery dissection as the cause of stroke. On hospital day 6, the patient developed decreased pain and temperature sensation in the right side below T10 sensory level and decreased sweating on the left side of the face with miosis of the left pupil. Brain MRI revealed an expanded lesion of the left inferolateral part of medulla. In our patient, the involvement of the spinocerebellar tract and the lateral spinothalamic tract likely contributed to the development of truncal lateropulsion and sensory disturbance below thoracic levels, respectively. Our case is clinically important in understanding a correlation between clinical symptoms and lateral medullary lesions.

  16. Addition by Subtraction: The Relation Between Dropout Rates and School-Level Academic Achievement

    PubMed Central

    GLENNIE, ELIZABETH; BONNEAU, KARA; VANDELLEN, MICHELLE; DODGE, KENNETH A.

    2013-01-01

    Background/Context Efforts to improve student achievement should increase graduation rates. However, work investigating the effects of student-level accountability has consistently demonstrated that increases in the standards for high school graduation are correlated with increases in dropout rates. The most favored explanation for this finding is that high-stakes testing policies that mandate grade repetition and high school exit exams may be the tipping point for students who are already struggling academically. These extra demands may, in fact, push students out of school. Purpose/Objective/Focus This article examines two hypotheses regarding the relation between school-level accountability and dropout rates. The first posits that improvements in school performance lead to improved success for everyone. If school-level accountability systems improve a school for all students, then the proportion of students performing at grade level increases, and the dropout rate decreases. The second hypothesis posits that schools facing pressure to improve their overall accountability score may pursue this increase at the cost of other student outcomes, including dropout rate. Research Design Our approach focuses on the dynamic relation between school-level academic achievement and dropout rates over time—that is, between one year’s achievement and the subsequent year’s dropout rate, and vice versa. This article employs longitudinal data of records on all students in North Carolina public schools over an 8-year period. Analyses employ fixed-effects models clustering schools and districts within years and controls each year for school size, percentage of students who were free/reduced-price lunch eligible, percentage of students who are ethnic minorities, and locale. Findings/Results This study finds partial evidence that improvements in school-level academic performance will lead to improvements (i.e., decreases) in school-level dropout rates. Schools with improved

  17. Orthostatic hypotension is associated with decreased cerebrospinal fluid levels of chromogranin A in early stage of Parkinson disease.

    PubMed

    Kaiserova, Michaela; Prikrylova Vranova, Hana; Galuszka, Jan; Stejskal, David; Mensikova, Katerina; Zapletalova, Jana; Mares, Jan; Kanovsky, Petr

    2015-10-01

    An association between the CSF chromogranin A (CgA) and orthostatic blood pressure changes was investigated in 20 patients in the early stage of Parkinson disease (PD). There was a positive correlation between the CSF CgA and diastolic blood pressure change, when CSF CgA levels were lower in patients with orthostatic hypotension (OH). Decreased CSF CgA may be useful in predicting OH in the early stage of PD.

  18. HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

    PubMed Central

    López-Dupla, Miguel; Maymó-Masip, Elsa; Martínez, Esteban; Domingo, Pere; Leal, Manuel; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; Arnedo, Mireia; Ferrando-Martínez, Sara; Beltrán-Debón, Raúl; Alba, Verónica; Gatell, Josep Mª; Vendrell, Joan; Vidal, Francesc; Chacón, Matilde R.

    2015-01-01

    Background and Objectives Obesity and HIV-1/HAART–associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student’s t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001–0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels. PMID:26658801

  19. Energy level formula for the Morse oscillator with an additional kinetic coupling potential

    NASA Astrophysics Data System (ADS)

    Fan, Hong-yi; Chen, Bo-zhan; Fan, Yue

    1996-02-01

    Based on the <η| representation which is the common eigenstate of the relative position x1 - x2 and the total momentum P1 + P2 of two particles we derive the energy level formula for a Morse oscillator with an additional kinetic coupling potential. The <η| representation seems to provide a direct and convenient approach for solving certain dynamical problems for two-body systems.

  20. The critical level of water deficit causing a decrease in human exercise performance: a practical field study.

    PubMed

    Yoshida, Tetsuya; Takanishi, Toshimasa; Nakai, Seiichi; Yorimoto, Akira; Morimoto, Taketoshi

    2002-10-01

    To analyse the critical level of water deficit which causes a decrease in aerobic and anaerobic exercise performance, a step test score (STS) and 10 s maximal anaerobic power (MAP) output during cycling exercise were measured in two experiments (Ex-1, n=7, and Ex-2, n=9), before and after baseball practice, using subjects who played regularly. The measurements in both Ex-1 and Ex-2 were repeated under four conditions of fluid ingestion (FI) (FI of 80%, 60%, 40%, and 20% of the total sweat loss) on hot summer days. The subjects were allowed free access to a sports beverage, maintained at 10-15 degrees C, within any given FI condition during the exercise. The [mean (SEM)] duration of the exercise and the environmental conditions (wet bulb globe temperature) were similar between Ex-1 [3.52 (0.14) h and 29.2 (0.6) degrees C, respectively] and Ex-2 [3.82 (0.12) h and 29.2 (0.4) degrees C, respectively]. In both Ex-1 and Ex-2, the loss of body mass (Delta m(b)) increased significantly as FI decreased. In Ex-1, the STS significantly decreased ( P<0.05) at values of delta m(b) in excess of 2.4 (0.2)% (40%FI). In Ex-2, the MAP remained unchanged at values of delta m(b) up to 2.5 (0.3)% (40%FI), while the MAP significantly decreased ( P<0.05) at values of delta m(b) of 3.9 (0.2)% (20%FI). These results suggest that there is a critical level of water deficit at which a decrease in aerobic and anaerobic performance occurs, and that aerobic performance may be more adversely influenced by dehydration than anaerobic power output during exercise-induced dehydration.

  1. Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

    PubMed Central

    Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

    2016-01-01

    To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

  2. Decrease in class pi glutathione transferase mRNA levels by ultraviolet irradiation of cultured rat keratinocytes.

    PubMed

    Nakano, H; Kimura, J; Kumano, T; Hanada, K; Satoh, K; Hashimoto, I; Tsuchida, S

    1997-11-01

    The effect of ultraviolet (UV) B irradiation on pi class glutathione transferase (GST-P) gene expression was examined in cultured rat keratinocytes. Immunoblotting demonstrated GST-P to be the major GST form in the cells, and it was significantly decreased following irradiation. Northern blot analysis revealed that the mRNA decreased to 10-25% of the initial value 24 h after irradiation at a dose of 40 mJ/cm2. No remarkable changes were observed at earlier time points. Hydrogen peroxide treatment enhanced GST-P mRNA expression, with a 70% increase at 250 microM concentration. Alterations in possible trans-acting factors were examined to clarify the mechanism of repression by UV irradiation. c-Jun mRNA was induced 3.5-fold at 4 h after irradiation, but by 24 h fell to a lower level than that observed initially. c-Fos mRNA was increased 10-fold at 1 h but was completely suppressed at 12 and 24 h. Thus, the changes of c-Jun and c-Fos mRNA differed from that of GST-P mRNA. The level of mRNA for silencer factor-B was decreased to less than 10% at 12 h. UV irradiation of cells transfected with the chloramphenicol acetyltransferase (CAT) reporter gene containing enhancer (GPE I) or silencer regions of the GST-P gene did not suppress CAT activity. Although basal expression of the GST-P gene was mainly dependent on GPE I, altered expression of c-jun, c-fos and other genes coding for factors possibly trans-acting on GPE I did not appear to be responsible for the decreased GST-P mRNA levels.

  3. 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level

    SciTech Connect

    Zhao, Ziyi; Chen, Changjin; Liu, Yu; Wu, Chuanfang

    2014-03-07

    Highlights: • E2 affects not only estrogen-receptor α positive breast cells but also negative ones. • 100 nM E2 treatment affects breast cells proliferation, migration. • 100 nM E2 treatment functions in an estrogen-receptor α-independent way. • E2 treatment decreases MALAT-1 RNA level by post-transcriptional regulation. - Abstract: Breast cancer cells, which express estrogen receptor α (ERα), respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. But breast cancer cells without ERα show no effect on low concentration of estrogen treatment. Proliferation, migration and invasion of MCF10a, MCF7 and MB231 cells treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) was performed. We identified the effects of E2 on these breast cell lines, and looked for the difference in the presence and absence of ERα. Specifically, we looked for the changes of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is found extensively and highly expressed in several kinds of tumor cells, including breast carcinoma. It was observed that proliferation, migration and invasion of breast cells were greatly affected by high concentration E2 treatment and were not affected by low concentration E2 treatment in an ERα independent way. We found that the high concentration E2 treatment largely decreased MALAT-1 RNA level. Interestingly, MALAT-1 decreasing by knocking down showed similar effects on proliferation, migration and invasion. E2 treatment affects breast tumor or non-tumor cells proliferation, migration and invasion in an ERα -independent, but a dose-dependent way by decreasing the MALAT-1 RNA level.

  4. Overexpression of troponin T in Drosophila muscles causes a decrease in the levels of thin-filament proteins

    PubMed Central

    2004-01-01

    Formation of the contractile apparatus in muscle cells requires co-ordinated activation of several genes and the proper assembly of their products. To investigate the role of TnT (troponin T) in the mechanisms that control and co-ordinate thin-filament formation, we generated transgenic Drosophila lines that overexpress TnT in their indirect flight muscles. All flies that overexpress TnT were unable to fly, and the loss of thin filaments themselves was coupled with ultrastructural perturbations of the sarcomere. In contrast, thick filaments remained largely unaffected. Biochemical analysis of these lines revealed that the increase in TnT levels could be detected only during the early stages of adult muscle formation and was followed by a profound decrease in the amount of this protein as well as that of other thin-filament proteins such as tropomyosin, troponin I and actin. The decrease in thin-filament proteins is not only due to degradation but also due to a decrease in their synthesis, since accumulation of their mRNA transcripts was also severely diminished. This decrease in expression levels of the distinct thin-filament components led us to postulate that any change in the amount of TnT transcripts might trigger the down-regulation of other co-regulated thin-filament components. Taken together, these results suggest the existence of a mechanism that tightly co-ordinates the expression of thin-filament genes and controls the correct stoichiometry of these proteins. We propose that the high levels of unassembled protein might act as a sensor in this process. PMID:15469415

  5. 3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines.

    PubMed

    Kuder, Craig H; Weivoda, Megan M; Zhang, Ying; Zhu, Junjia; Neighbors, Jeffrey D; Wiemer, David F; Hohl, Raymond J

    2015-12-01

    The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.

  6. Estradiol decreases taurine level by reducing cysteine sulfinic acid decarboxylase via the estrogen receptor-α in female mice liver.

    PubMed

    Ma, Qiwang; Zhao, Jianjun; Cao, Wei; Liu, Jiali; Cui, Sheng

    2015-02-15

    Cysteine sulfinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO) are two rate-limiting enzymes in taurine de novo synthesis, and their expressions are associated with estrogen concentration. The present study was designed to determine the relationship between 17β-estradiol (E₂) and taurine in female mice liver. We initially observed the mice had lower levels of CSAD, CDO, and taurine during estrus than diestrus. We then, respectively, treated the ovariectomized mice, the cultured hepatocytes, and Hep G2 cells with different doses of E₂, and the CSAD and CDO expressions and taurine levels were analyzed. The results showed that E₂ decreased taurine level in the serum and the cultured cells by inhibiting CSAD and CDO expressions. Furthermore, we identified the molecular receptor types through which E₂ plays its role in regulating taurine synthesis, and our results showed that estrogen receptor-α (ERα) expression was much higher than estrogen receptor-β (ERβ) in the liver and hepatocytes, and the inhibiting effects of E₂ on CSAD, CDO, and taurine level were partially abrogated in the ICI-182,780-pretreated liver and hepatocytes, and in ERα knockout mice. These results indicate that estradiol decreases taurine content by reducing taurine biosynthetic enzyme expression in mice liver.

  7. Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

    PubMed

    Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri

    2015-01-01

    People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

  8. Decreased prolactin levels reduce parental commitment, egg temperatures, and breeding success of incubating male Adélie penguins.

    PubMed

    Thierry, Anne-Mathilde; Brajon, Sophie; Massemin, Sylvie; Handrich, Yves; Chastel, Olivier; Raclot, Thierry

    2013-09-01

    Hormones regulate many aspects of an individual's phenotype, including various physiological and behavioral traits. Two hormones have been described as important players in the regulation of parental investment in birds: the glucocorticoid hormone corticosterone and prolactin, a pituitary hormone, widely involved in mediating parental behavior. In comparison with corticosterone, the role of prolactin on parental investment remains poorly documented, and most studies so far have been correlative. In this study, the effects of an experimental decrease of prolactin levels on the incubation behavior of a long-lived seabird species were assessed. Male Adélie penguins were treated with self-degradable bromocriptine pellets, inhibiting prolactin secretion. Filming and subsequent video analysis allowed the determination of a behavioral time budget for birds and their position on the nest, while dummy eggs recorded incubation parameters. Incubation duration and breeding success at hatching were also monitored. As expected, bromocriptine-treatment significantly decreased plasma prolactin levels, but did not affect corticosterone levels. The behavioral time budget of penguins was not affected by the treatment. However, treated birds spent significantly more time in an upright position on the nest. These birds also incubated their eggs at lower temperatures and turned their eggs more frequently than controls, resulting in a lengthened incubation period. Despite this, the treatment was insufficient to trigger nest desertion and eggs of treated birds still hatched, indicating that several endocrine signals are required for the induction of nest abandonment. We suggest that the decreased prolactin levels in treated birds offset their timeline of breeding, so that birds displayed behavior typical of early incubation.

  9. Arabidopsis serotonin N-acetyltransferase knockout mutant plants exhibit decreased melatonin and salicylic acid levels resulting in susceptibility to an avirulent pathogen.

    PubMed

    Lee, Hyoung Yool; Byeon, Yeong; Tan, Dun-Xian; Reiter, Russel J; Back, Kyoungwhan

    2015-04-01

    Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in the melatonin biosynthesis pathway in plants. We examined the effects of SNAT gene inactivation in two Arabidopsis T-DNA insertion mutant lines. After inoculation with the avirulent pathogen Pseudomonas syringe pv. tomato DC3000 harboring the elicitor avrRpt2 (Pst-avrRpt2), melatonin levels in the snat knockout mutant lines were 50% less than in wild-type Arabidopsis Col-0 plants. The snat knockout mutant lines exhibited susceptibility to pathogen infection that coincided with decreased induction of defense genes including PR1, ICS1, and PDF1.2. Because melatonin acts upstream of salicylic acid (SA) synthesis, the reduced melatonin levels in the snat mutant lines led to decreased SA levels compared to wild-type, suggesting that the increased pathogen susceptibility of the snat mutant lines could be attributed to decreased SA levels and subsequent attenuation of defense gene induction. Exogenous melatonin treatment failed to induce defense gene expression in nahG Arabidopsis plants, but restored the induction of defense gene expression in the snat mutant lines. In addition, melatonin caused translocation of NPR1 (nonexpressor of PR1) protein from the cytoplasm into the nucleus indicating that melatonin-elicited pathogen resistance in response to avirulent pathogen attack is SA-dependent in Arabidopsis.

  10. Expression of Human Paraoxonase 1 Decreases Superoxide Levels and Alters Bacterial Colonization in the Gut of Drosophila melanogaster

    PubMed Central

    Pezzulo, Alejandro A.; Hornick, Emma E.; Rector, Michael V.; Estin, Miriam; Reisetter, Anna C.; Taft, Peter J.; Butcher, Stephen C.; Carter, A. Brent; Manak, J. Robert; Stoltz, David A.; Zabner, Joseph

    2012-01-01

    Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum sensing in bacteria and with reactive oxygen species (ROS) in humans and mice. PON1 gene mutations have been linked to multiple traits, including aging, and diseases of the cardiovascular, nervous and gastrointestinal system. The overlapping enzymatic activities in the PON family members and high linkage disequilibrium rates within their polymorphisms confound animal and human studies of PON1 function. In contrast, arthropods such as Drosophila melanogaster have no PON homologs, resulting in an ideal model to study interactions between PON genotype and host phenotypes. We hypothesized that expression of PON1 in D. melanogaster would alter ROS. We found that PON1 alters expression of multiple oxidative stress genes and decreases superoxide anion levels in normal and germ-free D. melanogaster. We also found differences in the composition of the gut microbiota, with a remarkable increase in levels of Lactobacillus plantarum and associated changes in expression of antimicrobial and cuticle-related genes. PON1 expression directly decreased superoxide anion levels and altered bacterial colonization of the gut and its gene expression profile, highlighting the complex nature of the interaction between host genotype and gut microbiota. We speculate that the interaction between some genotypes and human diseases may be mediated by the presence of certain gut bacteria that can induce specific immune responses in the gut and other host tissues. PMID:22952763

  11. Effect of Refiner Addition Level on Zirconium-Containing Aluminium Alloys

    NASA Astrophysics Data System (ADS)

    Jaradeh, M. M. R.; Carlberg, T.

    2012-01-01

    It is well known that in aluminium alloys containing Zr, grain refiner additions do not function as desired, producing an effect often referred to as nuclei poisoning. This paper investigates the structure of direct chill-cast ingots of commercial AA3003 aluminium alloys, with and without Zr, at various addition levels of Al5Ti1B master alloy. In Bridgman experiments simulating ingot solidification, Zr-containing alloys were studied after the addition of various amounts of Ti. It could be demonstrated, in both ingot casting and simulation experiments, that Zr poisoning can be compensated for by adding more Ti and/or Al5Ti1B. The results confirm better refinement behaviour with the addition of Ti + B than of only Ti. The various combinations of Zr and Ti also influenced the formation of AlFeMn phases, and the precipitation of large Al6(Mn,Fe) particles was revealed. AlZrTiSi intermetallic compounds were also detected.

  12. Decreased glial cell line-derived neurotrophic factor levels in patients with depression: a meta-analytic study.

    PubMed

    Lin, Pao-Yen; Tseng, Ping-Tao

    2015-04-01

    Glial cell-line derived neurotrophic factor (GDNF) has been shown to promote development, differentiation, and protection of CNS neurons and was thought to play an important role in various neuropsychiatric disorders. Several studies have examined the GDNF levels in patients with depression but shown inconsistent results. In this study, we compared blood GDNF levels between depressive patients and control subjects through meta-analytic method. The effect sizes (ESs) from all eligible studies were synthesized by using a random effect model. In this meta-analysis, we included 526 patients and 502 control subjects from 12 original articles. Compared to control subjects, blood GDNF levels are significantly decreased in patients with depression (ES = -0.62, p = 0.0011). However, significant heterogeneity was found among included studies. Through subgroup analysis, we found that GDNF was still decreased in studies with major depressive disorder (ES = -0.73, p = 0.0001); in studies with non-old-age depression (ES = -1.25, p = 0.0001), but not with old-age depression; and in studies using serum samples (ES = -0.86, p < 0.0001), but not in studies using plasma sample. Meta-regression did not show moderating effects of mean age of subjects, gender distribution, and age of onset of depression. Our findings support blood GDNF levels as a biomarker of depression as a whole, but the results were modulated by psychiatric diagnosis, age of included subjects, and sampling sources. With these results, future studies are required to examine whether effective antidepressant treatment is associated with an increase in serum GDNF levels.

  13. Don’t Always Prefer My Chosen Objects: Low Level of Trait Autonomy and Autonomy Deprivation Decreases Mere Choice Effect

    PubMed Central

    Shang, Zhe; Tao, Tuoxin; Wang, Lei

    2016-01-01

    Choice effect is a robust phenomenon in which even “mere choice” that does not include actual choosing actions could result in more preference for the self-chosen objects over other-chosen objects. In the current research, we proposed that autonomy would impact the mere choice effect. We conducted two studies to examine the hypothesis. The results showed that the mere choice effect measured by Implicit Association Test (IAT) significantly decreased for participants with lower levels of trait autonomy (Study 1) and when participants were primed to experience autonomy deprivation (Study 2). The theoretical and practical implications are discussed. PMID:27148132

  14. Decrease of physical activity level in adolescents with limb fractures: an accelerometry-based activity monitor study

    PubMed Central

    2011-01-01

    Background Immobilization and associated periods of inactivity can cause osteopenia, the physiological response of the bone to disuse. Mechanical loading plays an essential role in maintaining bone integrity. Skeletal fractures represent one cause of reduction of the physical activity (PA) level in adolescents. The purpose of this study was to quantify the reduction of PA in adolescents with limb fractures during the cast immobilization period compared with healthy controls. Methods Two hundred twenty adolescents were divided into three groups: those with upper limb fractures (50 cases); lower limb fractures (50 cases); and healthy cases (120 cases). Patients and their healthy peers were matched for gender, age, and seasonal assessment of PA. PA level was assessed during cast immobilization by accelerometer. Time spent in PA in each of the different intensity levels - sedentary, light, moderate, and vigorous - was determined for each participant and expressed in minutes and as a percentage of total valid time. Results Reduction in PA during cast immobilization was statistically significant in patients with limb fractures compared to healthy controls. The total PA count (total number of counts/min) was significantly lower in those with upper and lower limb fractures (-30.1% and -62.4%, respectively) compared with healthy controls (p < 0.0001 and p = 0.0003, respectively). Time spent in moderate-to-vigorous PA by patients with upper and lower limb injuries decreased by 36.9% (p = 0.0003) and 76.6% (p < 0.0001), respectively, and vigorous PA was reduced by 41.4% (p = 0.0008) and 84.4% (p < 0.0001), respectively. Conclusions PA measured by accelerometer is a useful and valid tool to assess the decrease of PA level in adolescents with limb fractures. As cast immobilization and reduced PA are known to induce bone mineral loss, this study provides important information to quantify the decrease of skeletal loading in this patient population. The observed reduction of high

  15. Increased levels of p21((CIP1/WAF1)) correlate with decreased chondrogenic differentiation potential in synovial membrane progenitor cells.

    PubMed

    Masson, Anand Oliveira; Hess, Ricarda; O'Brien, Kate; Bertram, Karri L; Tailor, Pankaj; Irvine, Edward; Ren, Guomin; Krawetz, Roman J

    2015-07-01

    Cartilage injuries are a major concern in the field of orthopedics. They occur following trauma, as well as from a variety of pathological conditions including Osteoarthritis (OA). Although cartilage does not exhibit robust endogenous repair, it has been demonstrated that modulating the activity of p21 can increase the regenerative abilities of cartilage in vitro and in vivo. Since the synovial membrane is abundant with mesenchymal progenitor cells (MPCs) capable of differentiating into cartilage both in vitro and in vivo, we examined if p21 expression levels varied between MPCs derived from normal vs. OA knee joints. Analysis of p21 at the mRNA and protein levels within normal and OA MPCs demonstrated differential levels of expression between these two groups, with OA MPCs having higher p21 expression levels. The higher levels of p21 in OA MPCs are also correlated with a decreased chondrogenic differentiation capacity and synovial inflammation, however, there was no evidence of senescence in the OA cells. The results of this study suggest that cell cycle regulation in MPCs may be altered in OA and that modulation of this pathway may have therapeutic potential once the mechanism by which this regulates stem/progenitor cells is better understood.

  16. Decreased drug accumulation and increased tolerance to DNA damage in tumor cells with a low level of cisplatin resistance.

    PubMed

    Lanzi, C; Perego, P; Supino, R; Romanelli, S; Pensa, T; Carenini, N; Viano, I; Colangelo, D; Leone, R; Apostoli, P; Cassinelli, G; Gambetta, R A; Zunino, F

    1998-04-15

    In an attempt to examine the cellular changes associated with cisplatin resistance, we selected a cisplatin-resistant (A43 1/Pt) human cervix squamous cell carcinoma cell line following continuous in vitro drug exposure. The resistant subline was characterized by a 2.5-fold degree of resistance. In particular, we investigated the expression of cellular defence systems and other cellular factors probably involved in dealing with cisplatin-induced DNA damage. Resistant cells exhibited decreased platinum accumulation and reduced levels of DNA-bound platinum and interstrand cross-link frequency after short-term drug exposure. Analysis of the effect of cisplatin on cell cycle progression revealed a cisplatin-induced G2M arrest in sensitive and resistant cells. Interestingly, a slowdown in S-phase transit was found in A431/Pt cells. A comparison of the ability of sensitive and resistant cells to repair drug-induced DNA damage suggested that resistant cells were able to tolerate higher levels of cisplatin-induced DNA damage than their parental counterparts. Analysis of the expression of proteins involved in DNA mismatch repair showed a decreased level of MSH2 in resistant cells. Since MSH2 seems to be involved in recognition of drug-induced DNA damage, this change may account for the increased tolerance to DNA damage observed in the resistant subline. In conclusion, the involvement of accumulation defects and the increased tolerance to cisplatin-induced DNA damage in these cisplatin-resistant cells support the notion that multiple changes contribute to confer a low level of cisplatin resistance. PMID:9719480

  17. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

    PubMed Central

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  18. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    PubMed

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

  19. Histamine H3 receptor agonists decrease hypothalamic histamine levels and increase stereotypical biting in mice challenged with methamphetamine

    PubMed Central

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F. Scott; Uhl, George R.; Tatsuta, Tomohiro; Morita, Yoshio; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

    2014-01-01

    The effects of the histamine H3 receptor agonists (R)-α-methylhistamine, imetit and immepip on methamphetamine (METH)-induced stereotypical behavior were examined in mice. The administration of METH (10 mg/kg, i.p.) to male ddY mice induced behaviors including persistent locomotion and stereotypical behaviors, which were classified into four categories: stereotypical head-bobbing (1.9%), circling (1.7%), sniffing (14.3%), and biting (82.1%). Pretreatment with (R)-α-methylhistamine (3 and 10 mg/kg, i.p.) significantly decreased stereotypical sniffing, but increased stereotypical biting induced by METH, in a dose-dependent manner. This effect of (R)-α-methylhistamine on behavior was mimicked by imetit or immepip (brain-penetrating selective histamine H3 receptor agonists; 10 mg/kg, i.p. for each drug). Hypothalamic histamine levels 1 h after METH challenge were significantly increased in mice pretreated with saline. These increases in histamine levels were significantly decreased by pretreatment with histamine H3 receptor agonists, effects which would appear to underlie the shift from METH-induced stereotypical sniffing to biting. PMID:21573995

  20. Comparison of additive image fusion vs. feature-level image fusion techniques for enhanced night driving

    NASA Astrophysics Data System (ADS)

    Bender, Edward J.; Reese, Colin E.; Van Der Wal, Gooitzen S.

    2003-02-01

    The Night Vision & Electronic Sensors Directorate (NVESD) has conducted a series of image fusion evaluations under the Head-Tracked Vision System (HTVS) program. The HTVS is a driving system for both wheeled and tracked military vehicles, wherein dual-waveband sensors are directed in a more natural head-slewed imaging mode. The HTVS consists of thermal and image-intensified TV sensors, a high-speed gimbal, a head-mounted display, and a head tracker. A series of NVESD field tests over the past two years has investigated the degree to which additive (A+B) image fusion of these sensors enhances overall driving performance. Additive fusion employs a single (but user adjustable) fractional weighting for all the features of each sensor's image. More recently, NVESD and Sarnoff Corporation have begun a cooperative effort to evaluate and refine Sarnoff's "feature-level" multi-resolution (pyramid) algorithms for image fusion. This approach employs digital processing techniques to select at each image point only the sensor with the strongest features, and to utilize only those features to reconstruct the fused video image. This selection process is performed simultaneously at multiple scales of the image, which are combined to form the reconstructed fused image. All image fusion techniques attempt to combine the "best of both sensors" in a single image. Typically, thermal sensors are better for detecting military threats and targets, while image-intensified sensors provide more natural scene cues and detect cultural lighting. This investigation will address the differences between additive fusion and feature-level image fusion techniques for enhancing the driver's overall situational awareness.

  1. Acute exercise decreases PTP-1B protein level and improves insulin signaling in the liver of old rats

    PubMed Central

    2013-01-01

    It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. These results provide new insights into the mechanisms by which exercise restores insulin signalling in liver during aging. PMID:23442260

  2. Pseudomembranous Type of Oral Candidiasis is Associated with Decreased Salivary Flow Rate and Secretory Immunoglobulin A Levels.

    PubMed

    Mahajan, Bela; Bagul, Neeta; Desai, Rajiv; Reddy, Mamatha; Mahajan, Amit; Shete, Ashwini; Risbud, Arun; Mane, Arati

    2015-08-01

    Saliva plays an important role in maintaining microbial homeostasis in the oral cavity, while salivary gland hypofunction predisposes the oral mucosa to pathologic alteration and increases the risk for oral candidiasis. This study sought to determine the salivary flow rate (SFR) and secretory immunoglobulin A (SIgA) levels in HIV-positive and HIV-negative individuals and evaluate their relationship with the determinants of oral candidiasis. Sixty HIV-positive (30 with and 30 without oral candidiasis) and 30 healthy HIV-negative individuals were enrolled. Cotton pellet was weighed pre- and post-saliva collection for the assessment of SFR, while SIgA levels were estimated by commercial ELISA (Diametra, Italy) kit. The mean ± SD, SFR and SIgA levels in HIV-positive individuals with candidiasis, without candidiasis and HIV-negative controls were 0.396 ± 0.290, 0.546 ± 0.355 and 0.534 ± 0.214 ml/min and 115.891 ± 37.621, 136.024 ± 51.075 and 149.418 ± 31.765 µg/ml, respectively. A positive correlation between low CD4 counts (indicator of immunodeficiency) and SIgA was observed in HIV-positive individuals with candidiasis (r = 0.373, p = 0.045). We also report here for the first time the significant decrease in SFR and SIgA levels in individuals presenting with pseudomembranous type of oral candidiasis and Candida albicans infection.

  3. Novel sandwich ELISAs for rat DMP1: age-related decrease of circulatory DMP1 levels in male rats.

    PubMed

    Sato, Sunao; Hashimoto, Jun; Usami, Yu; Ohyama, Kaname; Isogai, Yukihiro; Hagiwara, Yoshiaki; Maruyama, Nobuhiro; Komori, Toshihisa; Kuroda, Tatsuhiko; Toyosawa, Satoru

    2013-12-01

    Dentin matrix protein 1 (DMP1), a noncollagenous bone matrix protein produced by osteocytes, regulates matrix mineralization and phosphate homeostasis. The lack of a precise assay for circulating DMP1 levels impairs further investigation of the protein's biological significance. Because full-length precursor DMP1 is cleaved into NH2- and COOH-terminal fragments during the secretory process, we developed two new sandwich ELISAs for the NH2- and COOH-terminal fragments of rat DMP1. One of these ELISAs, ELISA 1-2, is based on two affinity-purified polyclonal antibodies against the DMP1-1 and DMP1-2 peptides of the NH2-terminal fragment, whereas the other, ELISA 4-3, is based on two affinity-purified polyclonal antibodies against the DMP1-3 and DMP1-4 peptides of the COOH-terminal fragment. The polyclonal antibodies were characterized in immunohistochemical and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) studies. Immunohistochemical analyses of rat bone using these polyclonal antibodies revealed DMP1 immunoreactivity in osteocytes and pericanalicular matrix, consistent with the previously reported osteocyte-specific expression of DMP1. LC-MS/MS analyses of rat plasma-derived immunoreactive products affinity-extracted with these antibodies revealed the presence of DMP1 in circulating blood. The ELISAs established with these antibodies met accepted standards for reproducibility, repeatability, precision, and accuracy. Circulating DMP1 and levels of other biochemical markers (osteocalcin, Trap5b, Dkk-1, and SOST) were measured in 2-, 4-, 8-, 12-, 18-, 24-, 72-, and 96-week-old Wistar male rats. Circulating DMP1 levels determined by ELISAs 1-2 and 4-3 significantly decreased with age. During rapid skeletal growth (2-12weeks), DMP1 levels measured by ELISA 4-3 were over three times higher than those measured by ELISA 1-2; however, DMP1 levels in old animals (72 and 96weeks) were almost the same when measured by either ELISA. DMP1 levels

  4. Bioavailable dietary phosphate, a mediator of cardiovascular disease, may be decreased with plant-based diets, phosphate binders, niacin, and avoidance of phosphate additives.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2014-01-01

    Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23, and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in individuals with normal renal function, increased phosphate intake can provoke a rise in fibroblast growth factor 23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less bioavailable forms); avoidance of processed foods containing inorganic phosphate food additives; and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.

  5. Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1).

    PubMed

    Beraldo, Flavio H; Thomas, Anu; Kolisnyk, Benjamin; Hirata, Pedro H; De Jaeger, Xavier; Martyn, Amanda C; Fan, Jue; Goncalves, Daniela F; Cowan, Matthew F; Masood, Talal; Martins, Vilma R; Gros, Robert; Prado, Vania F; Prado, Marco A M

    2015-11-01

    Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes.

  6. Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1)

    PubMed Central

    Beraldo, Flavio H.; Thomas, Anu; Kolisnyk, Benjamin; Hirata, Pedro H.; De Jaeger, Xavier; Martyn, Amanda C.; Fan, Jue; Goncalves, Daniela F.; Cowan, Matthew F.; Masood, Talal; Martins, Vilma R.; Gros, Robert; Prado, Vania F.; Prado, Marco A. M.

    2015-01-01

    ABSTRACT Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes. PMID:26398952

  7. C3a Increases VEGF and Decreases PEDF mRNA Levels in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Long, Qin; Cao, Xiaoguang; Bian, Ailing

    2016-01-01

    Complement activation, specifically complement 3 (C3) activation and C3a generation, contributes to an imbalance between angiogenic stimulation by vascular endothelial growth factor (VEGF) and angiogenic inhibition by pigment epithelial derived factor (PEDF), leading to pathological angiogenesis. This study aimed to investigate the effects of C3a and small interfering RNA (siRNA) targeting C3 on the levels of VEGF and PEDF mRNAs in human retinal pigment epithelial (RPE) cells. ARPE-19 cells were cultured in the presence of exogenous C3a at 0.1 μM and 0.3 μM C3a for 24, 48, and 72 hours. 0.1 pmol/μL duplexes of siRNA targeting C3 were applied for C3a inhibition by transfecting ARPE-19 cells for 48 hours. RT-PCR was performed to examine the level of VEGF and PEDF mRNA. A random siRNA duplex was set for control siRNA. Results demonstrated that exogenous C3a significantly upregulated VEGF and downregulated PEDF mRNA levels in cultured ARPE-19 cells, and siRNA targeting C3 transfection reversed the above changes, significantly reducing VEGF and enhancing PEDF mRNAs level in ARPE-19 cells compared to the control. The present data provided evidence that reducing C3 activation can decreases VEGF and increase PEDF mRNA level in RPE and may serve as a potential therapy in pathological angiogenesis. PMID:27747237

  8. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

    PubMed

    Alkabbani, Abdulrahman G; Mon, Sann Y; Hatipoglu, Betul; Kennedy, Laurence; Faiman, Charles; Weil, Robert J; Hamrahian, Amir H

    2014-04-01

    The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

  9. Decreased phosphorylation levels of cardiac myosin-binding protein-C in human and experimental heart failure.

    PubMed

    El-Armouche, Ali; Pohlmann, Lutz; Schlossarek, Saskia; Starbatty, Jutta; Yeh, Yung-Hsin; Nattel, Stanley; Dobrev, Dobromir; Eschenhagen, Thomas; Carrier, Lucie

    2007-08-01

    Cardiac myosin-binding protein-C (cMyBP-C) is an important regulator of cardiac contractility, and its phosphorylation by PKA is a mechanism that contributes to increased cardiac output in response to beta-adrenergic stimulation. It is presently unknown whether heart failure alters cMyBP-C phosphorylation. The present study determined the level of phosphorylated cMyBP-C in failing human hearts and in a canine model of pacing-induced heart failure. A polyclonal antibody directed against the major phosphorylation site of cMyBP-C (Ser-282) was generated and its specificity was confirmed by PKA phosphorylation with isoprenaline in cardiomyocytes and Langendorff-perfused mouse hearts. Left ventricular myocardial tissue from (i) patients with terminal heart failure (hHF; n=12) and nonfailing donor hearts (hNF; n=6) and (ii) dogs with rapid-pacing-induced end-stage heart failure (dHF; n=10) and sham-operated controls (dNF; n=10) were used for quantification of total cMyBP-C and phospho-cMyBP-C by Western blotting. Total cMyBP-C protein levels were similar in hHF and hNF as well as in dHF and dNF. In contrast, the ratio of phospho-cMyBP-C to total cMyBP-C levels were >50% reduced in hHF and >40% reduced in dHF. In summary, cMyBP-C phosphorylation levels are markedly decreased in human and experimental heart failure. Thus, the compromised contractile function of the failing heart might be in part attributable to reduced cMyBP-C phosphorylation levels.

  10. Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1).

    PubMed

    Beraldo, Flavio H; Thomas, Anu; Kolisnyk, Benjamin; Hirata, Pedro H; De Jaeger, Xavier; Martyn, Amanda C; Fan, Jue; Goncalves, Daniela F; Cowan, Matthew F; Masood, Talal; Martins, Vilma R; Gros, Robert; Prado, Vania F; Prado, Marco A M

    2015-11-01

    Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes. PMID:26398952

  11. Moderate-intensity interval training increases serum brain-derived neurotrophic factor level and decreases inflammation in Parkinson's disease patients.

    PubMed

    Zoladz, J A; Majerczak, J; Zeligowska, E; Mencel, J; Jaskolski, A; Jaskolska, A; Marusiak, J

    2014-06-01

    It has been demonstrated that physical training increases serum brain-derived neurotrophic factor (BDNF) in healthy people. The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson's disease patients (PD patients) in relation to their health status. Twelve PD patients (mean ± S.E.M: age 70 ± 3 years; body mass 70 ± 2 kg; height 163 ± 3 cm) performed a moderate-intensity interval training (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1) (i.e. by 34%, P=0.03). This was accompanied by an attenuation of total Unified Parkinson's Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and serum tumor necrosis factor-α (TNF-α) (P=0.03) levels. We have concluded that the improvement of health status of the Parkinson's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients. PMID:24930517

  12. E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3

    PubMed Central

    Chesarino, Nicholas M.; McMichael, Temet M.; Yount, Jacob S.

    2015-01-01

    Interferon (IFN)-induced transmembrane protein 3 (IFITM3) is a cell-intrinsic factor that limits influenza virus infections. We previously showed that IFITM3 degradation is increased by its ubiquitination, though the ubiquitin ligase responsible for this modification remained elusive. Here, we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. This IFITM3 ubiquitination is dependent upon the presence of a PPxY motif within IFITM3 and the WW domain-containing region of NEDD4. In NEDD4 knockout mouse embryonic fibroblasts, we observed defective IFITM3 ubiquitination and accumulation of high levels of basal IFITM3 as compared to wild type cells. Heightened IFITM3 levels significantly protected NEDD4 knockout cells from infection by influenza A and B viruses. Similarly, knockdown of NEDD4 in human lung cells resulted in an increase in steady state IFITM3 and a decrease in influenza virus infection, demonstrating a conservation of this NEDD4-dependent IFITM3 regulatory mechanism in mouse and human cells. Consistent with the known association of NEDD4 with lysosomes, we demonstrate for the first time that steady state turnover of IFITM3 occurs through the lysosomal degradation pathway. Overall, this work identifies the enzyme NEDD4 as a new therapeutic target for the prevention of influenza virus infections, and introduces a new paradigm for up-regulating cellular levels of IFITM3 independently of IFN or infection. PMID:26263374

  13. Interacting Electrons in Parabolic Quantum Dots:. Energy Levels, Addition Energies, and Charge Distributions

    NASA Astrophysics Data System (ADS)

    Schreiber, Michael; Siewert, Jens; Vojta, Thomas

    We investigate the properties of interacting electrons in a parabolic confinement. To this end we numerically diagonalize the Hamiltonian using the Hartree-Fock based diagonalization method which is related to the configuration interaction approach. We study different types of interactions, Coulomb as well as short range. In addition to the ground state energy we calculate the spatial charge distribution and compare the results to those of the classical calculation. We find that a sufficiently strong screened Coulomb interaction produces energy level bunching for classical as well as for quantum-mechanical dots. Bunching in the quantum-mechanical system occurs due to an interplay of kinetic and interaction energy, moreover, it is observed well before reaching the limit of a Wigner crystal. It also turns out that the shell structure of classical and quantum mechanical spatial charge distributions is quite similar.

  14. Interacting Electrons in Parabolic Quantum Dots:. Energy Levels, Addition Energies, and Charge Distributions

    NASA Astrophysics Data System (ADS)

    Schreiber, Michael; Siewert, Jens; Vojta, Thomas

    2001-08-01

    We investigate the properties of interacting electrons in a parabolic confinement. To this end we numerically diagonalize the Hamiltonian using the Hartree-Fock based diagonalization method which is related to the configuration interaction approach. We study different types of interactions, Coulomb as well as short range. In addition to the ground state energy we calculate the spatial charge distribution and compare the results to those of the classical calculation. We find that a sufficiently strong screened Coulomb interaction produces energy level bunching for classical as well as for quantum-mechanical dots. Bunching in the quantum-mechanical system occurs due to an interplay of kinetic and interaction energy, moreover, it is observed well before reaching the limit of a Wigner crystal. It also turns out that the shell structure of classical and quantum mechanical spatial charge distributions is quite similar.

  15. Ground-Level Ozone Following Astrophysical Ionizing Radiation Events: An Additional Biological Hazard?

    PubMed

    Thomas, Brian C; Goracke, Byron D

    2016-01-01

    Astrophysical ionizing radiation events such as supernovae, gamma-ray bursts, and solar proton events have been recognized as a potential threat to life on Earth, primarily through depletion of stratospheric ozone and subsequent increase in solar UV radiation at Earth's surface and in the upper levels of the ocean. Other work has also considered the potential impact of nitric acid rainout, concluding that no significant threat is likely. Not yet studied to date is the potential impact of ozone produced in the lower atmosphere following an ionizing radiation event. Ozone is a known irritant to organisms on land and in water and therefore may be a significant additional hazard. Using previously completed atmospheric chemistry modeling, we examined the amount of ozone produced in the lower atmosphere for the case of a gamma-ray burst and found that the values are too small to pose a significant additional threat to the biosphere. These results may be extended to other ionizing radiation events, including supernovae and extreme solar proton events.

  16. Ground-Level Ozone Following Astrophysical Ionizing Radiation Events: An Additional Biological Hazard?

    PubMed

    Thomas, Brian C; Goracke, Byron D

    2016-01-01

    Astrophysical ionizing radiation events such as supernovae, gamma-ray bursts, and solar proton events have been recognized as a potential threat to life on Earth, primarily through depletion of stratospheric ozone and subsequent increase in solar UV radiation at Earth's surface and in the upper levels of the ocean. Other work has also considered the potential impact of nitric acid rainout, concluding that no significant threat is likely. Not yet studied to date is the potential impact of ozone produced in the lower atmosphere following an ionizing radiation event. Ozone is a known irritant to organisms on land and in water and therefore may be a significant additional hazard. Using previously completed atmospheric chemistry modeling, we examined the amount of ozone produced in the lower atmosphere for the case of a gamma-ray burst and found that the values are too small to pose a significant additional threat to the biosphere. These results may be extended to other ionizing radiation events, including supernovae and extreme solar proton events. PMID:26745353

  17. Decreasing Global Transcript Levels over Time Suggest that Phytoplasma Cells Enter Stationary Phase during Plant and Insect Colonization

    PubMed Central

    Pacifico, D.; Galetto, L.; Rashidi, M.; Abbà, S.; Palmano, S.; Firrao, G.; Bosco, D.

    2015-01-01

    To highlight different transcriptional behaviors of the phytoplasma in the plant and animal host, expression of 14 genes of “Candidatus Phytoplasma asteris,” chrysanthemum yellows strain, was investigated at different times following the infection of a plant host (Arabidopsis thaliana) and two insect vector species (Macrosteles quadripunctulatus and Euscelidius variegatus). Target genes were selected among those encoding antigenic membrane proteins, membrane transporters, secreted proteins, and general enzymes. Transcripts were detected for all analyzed genes in the three hosts; in particular, those encoding the antigenic membrane protein Amp, elements of the mechanosensitive channel, and two of the four secreted proteins (SAP54 and TENGU) were highly accumulated, suggesting that they play important roles in phytoplasma physiology during the infection cycle. Most transcripts were present at higher abundance in the plant host than in the insect hosts. Generally, transcript levels of the selected genes decreased significantly during infection of A. thaliana and M. quadripunctulatus but were more constant in E. variegatus. Such decreases may be explained by the fact that only a fraction of the phytoplasma population was transcribing, while the remaining part was aging to a stationary phase. This strategy might improve long-term survival, thereby increasing the likelihood that the pathogen may be acquired by a vector and/or inoculated to a healthy plant. PMID:25636844

  18. Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

    PubMed Central

    Dabora, Sandra L.; Franz, David Neal; Ashwal, Stephen; Sagalowsky, Arthur; DiMario, Francis J.; Miles, Daniel; Cutler, Drew; Krueger, Darcy; Uppot, Raul N.; Rabenou, Rahmin; Camposano, Susana; Paolini, Jan; Fennessy, Fiona; Lee, Nancy; Woodrum, Chelsey; Manola, Judith; Garber, Judy; Thiele, Elizabeth A.

    2011-01-01

    Background Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2. Methods We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas. Results 36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1–2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline). Conclusions Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration

  19. Geniposide decreases the level of Aβ1-42 in the hippocampus of streptozotocin-induced diabetic rats.

    PubMed

    Liu, Jianhui; Zhang, Yonglan; Deng, Xiaohong; Yin, Fei

    2013-09-01

    Although cognitive dysfunction in diabetic patients has been explored extensively, diabetic complications of the central nervous system have not been studied. We have reported previously that geniposide has neurotrophic and neuroprotective activities with the activation of glucagons-like peptide 1 receptor, and regulates glucose-stimulated insulin secretion in vitro. But the role of geniposide on diabetic complications, especially on the neurodegenerative diseases, remains to be investigated. In this study, we investigated the effect of geniposide on the level of Aβ1-42 in the hippocampi of streptozotocin-induced diabetic rats and explored its possible mechanism. The results demonstrated that, accompanied with the improvement of insulin and blood glucose, treatment with geniposide decreased the Aβ1-42 level and improved the expression of insulin-degrading enzyme, which is the key degrading enzyme of Aβ peptide. The results of present study will help to understand the biochemical mechanisms of neuronal dysfunction and death in diabetes and to develop an efficient therapeutic strategy on Alzheimer's disease.

  20. Icariin decreases both APP and Aβ levels and increases neurogenesis in the brain of Tg2576 mice.

    PubMed

    Li, F; Dong, H X; Gong, Q H; Wu, Q; Jin, F; Shi, J S

    2015-09-24

    Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aβ1-40 (69%) and Aβ1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD.

  1. Decreased pool of mesenchymal stem cells is associated with altered chemokines serum levels in atrophic nonunion fractures.

    PubMed

    Mathieu, Myrielle; Rigutto, Sabrina; Ingels, Aude; Spruyt, Delphine; Stricwant, Nadia; Kharroubi, Ilham; Albarani, Valentina; Jayankura, Marc; Rasschaert, Joanne; Bastianelli, Enrico; Gangji, Valérie

    2013-04-01

    Nonunion fractures can cause severe dysfunction and are often difficult to treat mainly due to a poor understanding of their physiopathology. Although many aspects of impaired fracture healing have been extensively studied, little is known about the cellular and molecular mechanisms leading to atrophic nonunion. Therefore, the aim of the present study was to assess the pools and biological functions of bone marrow-derived mesenchymal stem cells (hMSCs) and circulating endothelial progenitor cells (EPCs) in atrophic nonunion patients compared to healthy subjects, and the systemic levels of growth factors involved in the recruitment, proliferation and differentiation of these cells. In nonunions, the pool of hMSCs was decreased and their proliferation delayed. However, once committed, hMSCs from nonunions were able to proliferate, differentiate into osteoblastic cells and mineralize in vitro as efficiently as hMSCs from healthy subjects. In parallel, we found altered serum levels of chemokines and growth factors involved in the chemotaxis and proliferation of hMSCs such as leptin, interleukin-6 (IL-6) and its soluble receptor, platelet-derived growth factor-BB (PDGF-BB), stem cell factor (SCF) and insulin-like growth factor-1 (IGF-1). Moreover, we showed that the number of EPCs and their regulating growth factors were not affected in nonunion patients. If nonunion is generally attributed to a vascular defect, our results also support a role for a systemic mesenchymal and osteogenic cell pool defect that might be related to alterations in systemic levels of factors implicated in their chemotaxis and proliferation. PMID:23318974

  2. Elevated corticosterone levels and severe weather conditions decrease parental investment of incubating Adélie penguins.

    PubMed

    Thierry, Anne-Mathilde; Massemin, Sylvie; Handrich, Yves; Raclot, Thierry

    2013-03-01

    Corticosterone, the main stress hormone in birds, mediates resource allocation, allowing animals to adjust their physiology and behaviour to changes in the environment. Incubation is a time and energy-consuming phase of the avian reproductive cycle. It may be terminated prematurely, when the parents' energy stores are depleted or when environmental conditions are severe. In this study, the effects of experimentally elevated baseline corticosterone levels on the parental investment of incubating male Adélie penguins were investigated. Incubation duration and reproductive success of 60 penguins were recorded. The clutches of some birds were replaced by dummy eggs, which recorded egg temperatures and rotation rates, enabling a detailed investigation of incubation behaviour. Corticosterone levels of treated birds were 2.4-fold higher than those of controls 18 days post treatment. Exogenous corticosterone triggered nest desertion in 61% of the treated birds; consequently reducing reproductive success, indicating that corticosterone can reduce or disrupt parental investment. Regarding egg temperatures, hypothermic events became more frequent and more pronounced in treated birds, before these birds eventually abandoned their nest. The treatment also significantly decreased incubation temperatures by 1.3°C and lengthened the incubation period by 2.1 days. However, the number of chicks at hatching was similar among successful nests, regardless of treatment. Weather conditions appeared to be particularly important in determining the extent to which corticosterone levels affected the behaviour of penguins, as treated penguins were more sensitive to severe weather conditions. This underlines the importance of considering the interactions of organisms with their environment in studies of animal behaviour and ecophysiology.

  3. Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels

    SciTech Connect

    Wang, Dang; Fang, Liurong; Luo, Rui; Ye, Rui; Fang, Ying; Xie, Lilan; Chen, Huanchun; Xiao, Shaobo

    2010-08-13

    Research highlights: {yields} FMDV L{sup pro} inhibits poly(I:C)-induced IFN-{alpha}1/{beta} mRNA expression. {yields} L{sup pro} inhibits MDA5-mediated activation of the IFN-{alpha}1/{beta} promoter. {yields} L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes. {yields} L{sup pro} inhibits IFN-{alpha}1/{beta} promoter activation by decreasing IRF-3/7 in protein levels. {yields} The ability to process eIF-4G of L{sup pro} is not necessary to inhibit IFN-{alpha}1/{beta} activation. -- Abstract: The leader proteinase (L{sup pro}) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-{beta} (IFN-{beta}) antagonist that disrupts the integrity of transcription factor nuclear factor {kappa}B (NF-{kappa}B). In this study, we showed that the reduction of double stranded RNA (dsRNA)-induced IFN-{alpha}1/{beta} expression caused by L{sup pro} was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-{alpha}/{beta}. Furthermore, overexpression of L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L{sup pro} mutants indicated that the ability to process eIF-4G of L{sup pro} is not required for suppressing dsRNA-induced activation of the IFN-{alpha}1/{beta} promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-{kappa}B, L{sup pro} also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.

  4. Decreased PCDD/F formation when co-firing a waste fuel and biomass in a CFB boiler by addition of sulphates or municipal sewage sludge

    SciTech Connect

    Åmand, Lars-Erik; Kassman, Håkan

    2013-08-15

    Highlights: • Two strategies to reduce PCDD/F formation when co-firing solid recovered fuel (SRF) and biomass. • They were co-combustion with municipal sewage sludge (MSS) and addition of ammonium sulphate. • PCDD/Fs were significantly reduced for a biomass rich in chlorine when adding ammonium sulphate. • MSS had a suppressing effect on PCDD/F formation during co-combustion with SRF. • A link is presented between gaseous alkali chlorides, chlorine in deposits and PCDD/F formation. - Abstract: Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are formed during waste incineration and in waste-to-energy boilers. Incomplete combustion, too short residence times at low combustion temperatures (<700 °C), incineration of electronic waste and plastic waste containing chlorine are all factors influencing the formation of PCDD/Fs in boilers. The impact of chlorine and catalysing metals (such as copper and iron) in the fuel on PCDD/F formation was studied in a 12 MW{sub th} circulating fluidised bed (CFB) boiler. The PCDD/F concentrations in the raw gas after the convection pass of the boiler and in the fly ashes were compared. The fuel types were a so-called clean biomass with low content of chlorine, biomass with enhanced content of chlorine from supply of PVC, and solid recovered fuel (SRF) which is a waste fuel containing higher concentrations of both chlorine, and catalysing metals. The PCDD/F formation increased for the biomass with enhanced chlorine content and it was significantly reduced in the raw gas as well as in the fly ashes by injection of ammonium sulphate. A link, the alkali chloride track, is demonstrated between the level of alkali chlorides in the gas phase, the chlorine content in the deposits in the convection pass and finally the PCDD/F formation. The formation of PCDD/Fs was also significantly reduced during co-combustion of SRF with municipal sewage sludge (MSS) compared to when SRF was fired without MSS

  5. Decreased fractional urinary calcium excretion and serum 1,25-dihydroxyvitamin D and IGF-I levels in preeclampsia.

    PubMed

    Halhali, Ali; Díaz, Lorenza; Avila, Euclides; Ariza, Ana Carolina; Garabédian, Michèle; Larrea, Fernando

    2007-03-01

    During preeclampsia several alterations of calcium metabolism have been described, the most common of them is hypocalciuria, which pathophysiology is still unclear. In order to assess the contribution of calciotropic hormones to urinary calcium excretion, a cross-sectional study was done including 26 preeclamptic Mexican women (PE group) and 26 normotensive control pregnant women (NT group). Total and fractional urinary calcium excretion were significantly lower (P<0.0001) in the PE group than in the NT group (82+/-7 versus 171+/-7 mg/24h and 0.62+/-0.38 versus 1.38+/-0.71%, respectively), without significant differences in creatinine clearance, urinary sodium excretion and phosphate tubular reabsorption. In addition, serum 1,25-(OH)(2)D and IGF-I levels were significantly (P<0.05) lower in the PE than in NT group (43+/-9 versus 50+/-9 pg/mL and 195+/-67 versus 293+/-105 ng/mL, respectively), without significant differences in serum PTH levels. In the NT group, association analysis showed that total and fractional urinary calcium excretions positively correlated with serum levels of 1,25-(OH)(2)D (P<0.01) and IGF-I (P<0.001). In the PE group, total urinary calcium excretion positively correlated only with serum 1,25-(OH)(2)D (P<0.05). In conclusion, the results obtained in this study confirm that PE is associated with hypocalciuria and suggest that 1,25-(OH)(2)D and/or IGF-I may be involved in the regulation of urinary calcium excretion.

  6. Activation of epidermal growth factor receptor by metal-ligand complexes decreases levels of extracellular amyloid beta peptide.

    PubMed

    Price, Katherine A; Filiz, Gulay; Caragounis, Aphrodite; Du, Tai; Laughton, Katrina M; Masters, Colin L; Sharples, Robyn A; Hill, Andrew F; Li, Qiao-Xin; Donnelly, Paul S; Barnham, Kevin J; Crouch, Peter J; White, Anthony R

    2008-01-01

    The epidermal growth factor receptor is a receptor tyrosine kinase expressed in a range of tissues and cell-types. Activation of the epidermal growth factor receptor by a number of ligands induces downstream signalling that modulates critical cell functions including growth, survival and differentiation. Abnormal epidermal growth factor receptor expression and activation is also involved in a number of cancers. In addition to its cognate ligands, the epidermal growth factor receptor can be activated by metals such as zinc (Zn) and copper (Cu). Due to the important role of these metals in a number of diseases including neurodegenerative disorders, therapeutic approaches are being developed based on the use of lipid permeable metal-complexing molecules. While these agents are showing promising results in animal models and clinical trials, little is known about the effects of metal-ligand complexes on cell signalling pathways. In this study, we investigated the effects of clioquinol (CQ)-metal complexes on activation of epidermal growth factor receptor. We show here that CQ-Cu complexes induced potent epidermal growth factor receptor phosphorylation resulting in downstream activation of extracellular signal-regulated kinase. Similar levels of epidermal growth factor receptor activation were observed with alternative lipid permeable metal-ligands including neocuproine and pyrrolidine dithiocarbamate. We found that CQ-Cu complexes induced a significant reduction in the level of extracellular Abeta1-40 in cell culture. Inhibition of epidermal growth factor receptor activation by PD153035 blocked extracellular signal-regulated kinase phosphorylation and restored Abeta1-40 levels. Activation of the epidermal growth factor receptor by CQ-Cu was mediated through up-regulation of src kinase activity by a cognate ligand-independent process involving membrane integrins. These findings provide the first evidence that metal-ligand complexes can activate the epidermal growth

  7. Hydroxytyrosol in functional hydroxytyrosol-enriched biscuits is highly bioavailable and decreases oxidised low density lipoprotein levels in humans.

    PubMed

    Mateos, Raquel; Martínez-López, Sara; Baeza Arévalo, Gema; Amigo-Benavent, Miryam; Sarriá, Beatriz; Bravo-Clemente, Laura

    2016-08-15

    Hydroxytyrosol (HT) and its derivatives in olive oil protect low-density lipoproteins (LDL) against oxidation. Biscuits could be a convenient alternative to broaden consumers' choice of HT-rich foods, although the biscuit matrix could affect HT bioavailability. We performed a crossover, randomized, double-blind study to evaluate HT bioavailability in HT-enriched biscuits (HT-B) versus non-enriched biscuits (C-B), and the effects on oxidative postprandial status. On two separate days, 13 subjects consumed 30 g of C-B or HT-B (5.25mg HT) after overnight-fasting. Blood and urine were collected at different intervals and analysed by LC-MS-QToF. After HT-B consumption, plasma metabolites peaked between 0.5 and 1h and were extensively excreted in urine. HT-sulphate and 3,4-dihydroxyphenylacetic acid (DOPAC)-sulphate were the main metabolites, followed by DOPAC and homovanillic acid (HVA). HT-glucuronide, DOPAC-glucuronide, HVA-glucuronide and HVA-sulphate were also detected. Postprandial oxidised-LDL concentrations decreased with HT-B. HT is a promising functional ingredient and, in biscuits, it is highly bioavailable and lowers postprandial oxidised-LDL levels. PMID:27006237

  8. Decreased PCDD/F formation when co-firing a waste fuel and biomass in a CFB boiler by addition of sulphates or municipal sewage sludge.

    PubMed

    Åmand, Lars-Erik; Kassman, Håkan

    2013-08-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are formed during waste incineration and in waste-to-energy boilers. Incomplete combustion, too short residence times at low combustion temperatures (<700 °C), incineration of electronic waste and plastic waste containing chlorine are all factors influencing the formation of PCDD/Fs in boilers. The impact of chlorine and catalysing metals (such as copper and iron) in the fuel on PCDD/F formation was studied in a 12 MW(th) circulating fluidised bed (CFB) boiler. The PCDD/F concentrations in the raw gas after the convection pass of the boiler and in the fly ashes were compared. The fuel types were a so-called clean biomass with low content of chlorine, biomass with enhanced content of chlorine from supply of PVC, and solid recovered fuel (SRF) which is a waste fuel containing higher concentrations of both chlorine, and catalysing metals. The PCDD/F formation increased for the biomass with enhanced chlorine content and it was significantly reduced in the raw gas as well as in the fly ashes by injection of ammonium sulphate. A link, the alkali chloride track, is demonstrated between the level of alkali chlorides in the gas phase, the chlorine content in the deposits in the convection pass and finally the PCDD/F formation. The formation of PCDD/Fs was also significantly reduced during co-combustion of SRF with municipal sewage sludge (MSS) compared to when SRF was fired without MSS as additional fuel.

  9. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  10. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo.

    PubMed

    Chen, Pei-Jen; Padgett, William T; Moore, Tanya; Winnik, Witold; Lambert, Guy R; Thai, Sheau-Fung; Hester, Susan D; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  11. Simulation of uphill/downhill running on a level treadmill using additional horizontal force.

    PubMed

    Gimenez, Philippe; Arnal, Pierrick J; Samozino, Pierre; Millet, Guillaume Y; Morin, Jean-Benoit

    2014-07-18

    Tilting treadmills allow a convenient study of biomechanics during uphill/downhill running, but they are not commonly available and there is even fewer tilting force-measuring treadmill. The aim of the present study was to compare uphill/downhill running on a treadmill (inclination of ± 8%) with running on a level treadmill using additional backward or forward pulling forces to simulate the effect of gravity. This comparison specifically focused on the energy cost of running, stride frequency (SF), electromyographic activity (EMG), leg and foot angles at foot strike, and ground impact shock. The main results are that SF, impact shock, and leg and foot angle parameters determined were very similar and significantly correlated between the two methods, the intercept and slope of the linear regression not differing significantly from zero and unity, respectively. The correlation of oxygen uptake (V̇O2) data between both methods was not significant during uphill running (r=0.42; P>0.05). V̇O2 data were correlated during downhill running (r=0.74; P<0.01) but there was a significant difference between the methods (bias=-2.51 ± 1.94 ml min(-1) kg(-1)). Linear regressions for EMG of vastus lateralis, biceps femoris, gastrocnemius lateralis, soleus and tibialis anterior were not different from the identity line but the systematic bias was elevated for this parameter. In conclusion, this method seems appropriate for the study of SF, leg and foot angle, impact shock parameters but is less applicable for physiological variables (EMG and energy cost) during uphill/downhill running when using a tilting force-measuring treadmill is not possible.

  12. Response of Functional Structure of Soil Microbial Community to Multi-level Nitrogen Additions on the Central Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Zhang, G.; Yuan, Y.

    2015-12-01

    The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen in the atmosphere over the past century. Tibet is the one of the most threatened regions by nitrogen deposition, thus understanding how its microbial communities function maybe of high importance to predicting microbial responses to nitrogen deposition. Here we describe a short-time nitrogen addition conducted in an alpine steppe ecosystem to investigate the response of functional structure of soil microbial community to multi-level nitrogen addition. Using a GeoChip 4.0, we showed that functional diversities and richness of functional genes were unchanged at low level of nitrogen fertilizer inputs (<20 kg N ha-1 yr-1), but significantly decreased at higher nitrogen fertilizer inputs (>=40 kg N ha-1 yr-1). Detrended correspondence analysis indicated that the functional structure of microbial communities was markedly different across the nitrogen gradients. Most C degradation genes whose abundances significantly increased under elevated N fertilizer were those involved in the degradation of relatively labile C (starch, hemicellulose, cellulose), whereas the abundance of certain genes involved in the degradation of recalcitrant C (i.e. lignin) was largely decreased (such as manganese peroxidase, mnp). The results suggest that the elevated N fertilization rates might significantly accelerate the labile C degradation, but might not spur recalcitrant C degradation. The combined effect of gdh and ureC genes involved in N cycling appeared to shift the balance between ammonia and organic N toward organic N ammonification and hence increased the N mineralization potential. Moreover, Urease directly involved in urea mineralization significantly increased. Lastly, Canonical correspondence analysis showed that soil (TOC+NH4++NO3-+NO2-+pH) and plant (Aboveground plant productivity + Shannon Diversity) variables could explain 38.9% of the variation of soil microbial community

  13. THE INTAKE OF FIBER MESOCARP PASSIONFRUIT (PASSIFLORA EDULIS) LOWERS LEVELS OF TRIGLYCERIDE AND CHOLESTEROL DECREASING PRINCIPALLY INSULIN AND LEPTIN

    PubMed Central

    Corrêa, E.M.; Medina, L.; Barros-Monteiro, J.; Valle, N.O.; Sales, R.; Magalães, A.; Souza, F.C.A.; Carvalho, T.B.; Lemos, J.R.; Lira, E.F.; Lima, E.S.; Galeno, D.M.L.; Morales, L.; Ortiz, C.; Carvalho, R.P.

    2014-01-01

    Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease, renal failure, retinopathy, and neuropathy. Over the last years, there has been an increasing demand in folk medicine for natural sources that could help in the treatment of chronic diseases, including diabetes. The rind of passion fruit (Passiflora edulis f. Flavicarpa) is traditionally used as a functional food due to its high concentration of soluble and insoluble fiber. Objective The aim of this study was to determine the effect of high-fiber diet albedo of passion fruit on the metabolic and biochemical profile in diabetic rats induced by alloxan (2%). Design The passion fruit mesocarp fiber was dried in an oven with circulating air at 60°C and pulverized. We used 32 adult male rats, divided into 4 groups: Wistar group 1 control (GC), Wistar group 2, 15% fiber (GF15), Wistar group 3, 30% fiber (GF30), Wistar group 4, fiber disolved in water (GFH2O). The ratio of passion fruit was prepared according to the AIN 93M guidelines, varying only the source of dietary fiber. The corresponding diet for each group was offered to the animals for 60 days. Results There was a statically significant decrease in plasma glucose for GFH2O, GF15%, and GF30% groups with 27.0%, 37.4%, and 40.2%, respectively. Conclusion The use of mesocarp fiber of passion fruit at concentrations of 15% and 30% are an important dietary supplement for the treatment of DM due to its potential hypoglycemic effect, and its ability to reduce triglycerides and VLDL-cholesterol levels with a principal reduction of insulin and leptin. PMID:25346913

  14. The novel Raf inhibitor Raf265 decreases Bcl-2 levels and confers TRAIL-sensitivity to neuroendocrine tumour cells.

    PubMed

    Zitzmann, Kathrin; de Toni, Enrico; von Rüden, Janina; Brand, Stephan; Göke, Burkhard; Laubender, Rüdiger P; Auernhammer, Christoph J

    2011-04-01

    The tumour-selective death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for the treatment of human cancer. However, many tumours have evolved mechanisms to resist TRAIL-induced apoptosis. A number of studies have demonstrated that aberrant PI(3)K-Akt-mTOR survival signalling may confer TRAIL resistance by altering the balance between pro- and anti-apoptotic proteins. Here, we show that neuroendocrine tumour (NET) cell lines of heterogeneous origin exhibit a range of TRAIL sensitivities and that TRAIL sensitivity correlates with the expression of FLIP(S), caspase-8, and Bcl-2. Neither single mTOR inhibition by everolimus nor dual mTOR/PI(3)K inhibition by NVP-BEZ235 was able to enhance TRAIL susceptibility in any of the tested cell lines. In contrast, dual PI(3)K-Akt-mTOR and Raf-MEK-Erk pathway inhibition by the IGF-1R inhibitor NVP-AEW541 effectively restored TRAIL sensitivity in NCI-H727 bronchus carcinoid cells. Furthermore, blocking Raf-MEK-Erk signalling by the novel Raf inhibitor Raf265 significantly enhanced TRAIL sensitivity in NCI-H727 and CM insulinoma cells. While having no effect on FLIP(S) or caspase-8 expression, Raf265 strongly decreased Bcl-2 levels in those cell lines susceptible to its TRAIL-sensitizing action. Taken together, our findings suggest that combinations of Raf-MEK-Erk pathway inhibitors and TRAIL might offer a novel therapeutic strategy in NET disease.

  15. Persistent organic pollutant levels in eggs of leatherback turtles (Dermochelys coriacea) point to a decrease in hatching success.

    PubMed

    De Andrés, Eva; Gómara, Belén; González-Paredes, Daniel; Ruiz-Martín, José; Marco, Adolfo

    2016-03-01

    Sea turtles are susceptible to environmental pollution, since many harmful effects have been reported for different chemicals over the last two decades. In this context, persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are of particular concern due to their endocrine-disrupting nature. The aims of this study were to provide additional baseline data on PCB and PBDE concentrations in eggs of Dermochelys coriacea; and to investigate whether any of the congeners could compromise reproductive success in this species. A total of 18 nests from different females were studied during the nesting season of 2008 at Reserva Pacuare Beach, in the Caribbean side of Costa Rica. Reproductive parameters (viability, fertility and hatching rates) were calculated for all nests and hatchling morphometrics were successfully measured in 8 of them. Two to three fresh eggs per nest were taken for contaminant study. Different congeners of POPs were purified and identified using gas chromatography (GC) coupled to an ion trap detector (GC-ITD MS/MS), as described below. Mean ± SD concentrations were calculated for POP congeners within each nest and clustering was also evaluated. Correlations were performed searching for potential relationships with reproductive parameters. POP levels were similar to those reported in French-Guiana populations and slightly lower than those associated to Florida populations. Sum of PBDEs showed a negative correlation to the hatching success, suggesting potential harmful effects of these contaminants on the reproduction of leatherbacks. PMID:26735737

  16. Persistent organic pollutant levels in eggs of leatherback turtles (Dermochelys coriacea) point to a decrease in hatching success.

    PubMed

    De Andrés, Eva; Gómara, Belén; González-Paredes, Daniel; Ruiz-Martín, José; Marco, Adolfo

    2016-03-01

    Sea turtles are susceptible to environmental pollution, since many harmful effects have been reported for different chemicals over the last two decades. In this context, persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are of particular concern due to their endocrine-disrupting nature. The aims of this study were to provide additional baseline data on PCB and PBDE concentrations in eggs of Dermochelys coriacea; and to investigate whether any of the congeners could compromise reproductive success in this species. A total of 18 nests from different females were studied during the nesting season of 2008 at Reserva Pacuare Beach, in the Caribbean side of Costa Rica. Reproductive parameters (viability, fertility and hatching rates) were calculated for all nests and hatchling morphometrics were successfully measured in 8 of them. Two to three fresh eggs per nest were taken for contaminant study. Different congeners of POPs were purified and identified using gas chromatography (GC) coupled to an ion trap detector (GC-ITD MS/MS), as described below. Mean ± SD concentrations were calculated for POP congeners within each nest and clustering was also evaluated. Correlations were performed searching for potential relationships with reproductive parameters. POP levels were similar to those reported in French-Guiana populations and slightly lower than those associated to Florida populations. Sum of PBDEs showed a negative correlation to the hatching success, suggesting potential harmful effects of these contaminants on the reproduction of leatherbacks.

  17. Interleukin-1 receptor antagonist decreases cerebrospinal fluid nitric oxide levels and increases vasopressin secretion in the late phase of sepsis in rats.

    PubMed

    Wahab, Fazal; Tazinafo, Lucas F; Cárnio, Evelin C; Aguila, Fábio A; Batalhão, Marcelo E; Rocha, Maria José A

    2015-05-01

    The aim of this study was to analyze the effect of IL-1ra (an Interleukin-1 receptor antagonist) on sepsis-induced alterations in vasopressin (AVP) and nitric oxide (NO) levels. In addition, IL-1ra effect on the hypothalamic nitric oxide synthase (NOS) activities and survival rate was also analyzed. After Wistar rats were intracerebroventricular injected with IL-1ra (9 pmol) or vehicle (PBS 0.01 M), sepsis was induced by cecal-ligation and puncture (CLP). Blood, CSF, and hypothalamic samples were collected from different groups of rats (n = 8/group) after 4, 6, and 24 h. AVP and NO levels were greatly increased in CLP. Both total NOS and inducible NOS (iNOS) activities were also greatly increased in CLP rats. These changes in AVP, NO, and NOS were not observed in sham-operated control rats. IL-1ra administration did not alter plasma AVP levels after 4 and 6 h as compared to vehicle in CLP animals but after 24 h were significantly (P < 0.01) higher in IL-1ra-treated animals. IL-1ra administration significantly (P < 0.01) decreased NO concentration in CSF but not in plasma. Both total NOS and iNOS activities were also significantly decreased by IL-1ra at 24 h in CLP animals. Moreover, the 24 h survival rate of IL-1ra-treated rats increased by 38 % in comparison to vehicle administered animals. The central administration of IL-1ra increased AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL-1ra is through reduction of NO concentration in CSF and hence lower hypothalamic iNOS activities in the septic rats.

  18. The effect of different levels of sunflower head pith addition on the properties of model system emulsions prepared from fresh and frozen beef.

    PubMed

    Sariçoban, Cemalettin; Yilmaz, Mustafa Tahsin; Karakaya, Mustafa; Tiske, Sümeyra Sultan

    2010-01-01

    The effect of sunflower head pith on the functional properties of emulsions was studied by using a model system. Oil/water (O/W) model emulsion systems were prepared from fresh and frozen beef by the addition of the pith at five concentrations. Emulsion capacity (EC), stability (ES), viscosity (EV), colour and flow properties of the prepared model system emulsions were analyzed. The pith addition increased the EC and ES and the highest EC and ES values were reached when 5% of pith added; however, further increase in the pith concentration caused an inverse trend in these values. Fresh beef emulsions had higher EC and ES values than did frozen beef emulsions. One percent pith concentration was the critic level for the EV values of fresh beef emulsions. EV values of the emulsions reached a maximum level at 5% pith level, followed by a decrease at 7% pit level.

  19. Effect of Greens and Soil Type, Sulfur Addition and Lithium Level on Leaf Constituents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A greenhouse experiment was conducted near Weslaco, Texas (Lat. 26o 8' N, Long. 97o 57' W) between Dec. 2006 and Feb 2007 to evaluate the effect of soil type, added sulfur and lithium level on the growth and leaf nutrients, particularly biofortified levels of Li and S, in spinach and mustard gree...

  20. Spinach and mustard greens response to soil type, sulfur addition and lithium level

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A greenhouse experiment was conducted near Weslaco, Texas (Lat. 26o 8' N, Long. 97o 57' W) between Dec. 2006 and Feb 2007 to evaluate the effect of soil type, added sulfur and lithium level on the growth and leaf nutrients, particularly biofortified levels of Li and S, in spinach and mustard gree...

  1. Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C

    PubMed Central

    2014-01-01

    Background The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC). Methods Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-β1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes. Results Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak’s fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-β1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients. Conclusions Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFβ1 and IL-6 levels

  2. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality. PMID:26515667

  3. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality.

  4. Solving Additive Problems at Pre-Elementary School Level with the Support of Graphical Representation

    ERIC Educational Resources Information Center

    Selva, Ana Coelho Vieira; Falcao, Jorge Tarcisio da Rocha; Nunes, Terezinha

    2005-01-01

    This research offers empirical evidence of the importance of supplying diverse symbolic representations in order to support concept development in mathematics. Graphical representation can be a helpful symbolic tool for concept development in the conceptual field of additive structures. Nevertheless, this symbolic tool has specific difficulties…

  5. Decrease of droplet size of the reverse microemulsion 1-butyl-3-methylimidazolium tetrafluoroborate/Triton X-100/cyclohexane by addition of water.

    PubMed

    Gao, Yanan; Hilfert, Liane; Voigt, Andreas; Sundmacher, Kai

    2008-03-27

    In the present contribution, results concerning the role of small amounts of water in the 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4)-in-cyclohexane ionic liquid (IL) reverse microemulsions are reported. Dynamic light scattering (DLS) revealed that the size of microemulsion droplets decreased remarkably with increasing water content although water is often used as a polar component to swell reverse microemulsions. It was thus deduced that the number of microemulsion droplets was increased which was confirmed by conductivity measurements. The states of dissolved water were investigated by Fourier transform IR (FTIR) spectroscopic analysis showing that water molecules mainly act as bound water. 1H NMR along with two-dimensional rotating frame nuclear Overhauser effect (NOE) experiments (ROESY) further revealed that water molecules were mainly located in the periphery of the polar core of the microemulsion droplets and behave like a chock being inserted in the palisade layer of the droplet. This increased the curvature of the surfactant film at the IL/cyclohexane interface and thus led to the decrease of the microemulsion droplet size. The order of surfactant molecules arranged in the interface film was increased and thus induced a loss of entropy. Isothermal titration calorimetry (ITC) indicated that an enthalpy increase compensates for the loss of entropy during the process of microstructural transition. PMID:18318531

  6. Fine-mapping at three loci known to affect fetal hemoglobin levels explains additional genetic variation.

    PubMed

    Galarneau, Geneviève; Palmer, Cameron D; Sankaran, Vijay G; Orkin, Stuart H; Hirschhorn, Joel N; Lettre, Guillaume

    2010-12-01

    We used resequencing and genotyping in African Americans with sickle cell anemia (SCA) to characterize associations with fetal hemoglobin (HbF) levels at the BCL11A, HBS1L-MYB and β-globin loci. Fine-mapping of HbF association signals at these loci confirmed seven SNPs with independent effects and increased the explained heritable variation in HbF levels from 38.6% to 49.5%. We also identified rare missense variants that causally implicate MYB in HbF production.

  7. A Pilot Study to Examine the Effect of Additional Structured Outdoor Playtime on Preschoolers' Physical Activity Levels

    ERIC Educational Resources Information Center

    Alhassan, Sofiya; Nwaokelemeh, Ogechi; Lyden, Kate; Goldsby, TaShauna; Mendoza, Albert

    2013-01-01

    The impact of additional structured outdoor playtime on preschoolers'; physical activity (PA) level is unclear. The purpose of this pilot study was to explore the effects of increasing structured outdoor playtime on preschoolers'; PA levels. Eight full-day classrooms (n = 134 children) from two preschool programmes were randomised into a treatment…

  8. Presentation of a functional pituitary adenoma as a significant decrease in prostate-specific antigen level in a patient followed for prostate cancer.

    PubMed

    Grotas, Aaron B; Nagler, Harris M

    2006-12-01

    The stimulatory role of testosterone in the production and release of prostate-specific antigen (PSA) has been well characterized. Testosterone production by the testes is dependent on a functional hypothalamic-pituitary-gonadal axis. High prolactin levels have been shown to disrupt this axis, resulting in decreases in gonadotropins and testosterone levels. We report a patient with prostate cancer and elevated PSA levels followed with "watchful waiting" for several years who experienced a precipitous decrease in PSA level over a 3 month period. The patient was found to have an asymptomatic prolactin-secreting pituitary macroadenoma.

  9. Addition by Subtraction: The Relation between Dropout Rates and School-Level Academic Achievement

    ERIC Educational Resources Information Center

    Glennie, Elizabeth; Bonneau, Kara; vanDellen, Michelle; Dodge, Kenneth A.

    2012-01-01

    Background/Context: Efforts to improve student achievement should increase graduation rates. However, work investigating the effects of student-level accountability has consistently demonstrated that increases in the standards for high school graduation are correlated with increases in dropout rates. The most favored explanation for this finding…

  10. Nonlinear responses of coastal salt marshes to nutrient additions and sea level rise

    EPA Science Inventory

    Increasing nutrients and accelerated sea level rise (SLR) can cause marsh loss in some coastal systems. Responses to nutrients and SLR are complex and vary with soil matrix, marsh elevation, sediment inputs, and hydroperiod. We describe field and greenhouse studies examining sing...

  11. Tretinoin-loaded lipid-core nanocapsules decrease reactive oxygen species levels and improve bovine embryonic development during in vitro oocyte maturation.

    PubMed

    Lucas, Caroline Gomes; Remião, Mariana Härter; Komninou, Eliza Rossi; Domingues, William Borges; Haas, Cristina; Leon, Priscila Marques Moura de; Campos, Vinicius Farias; Ourique, Aline; Guterres, Silvia S; Pohlmann, Adriana R; Basso, Andrea Cristina; Seixas, Fabiana Kömmling; Beck, Ruy Carlos Ruver; Collares, Tiago

    2015-12-01

    In vitro oocyte maturation (IVM) protocols can be improved by adding chemical supplements to the culture media. Tretinoin is considered an important retinoid in embryonic development and its association with lipid-core nanocapsules (TTN-LNC) represents an innovative way of improving its solubility, and chemical stability, and reducing its toxicity. The effects of supplementing IVM medium with TTN-LNC was evaluated by analyzing production of reactive oxygen species (ROS), S36-phosphorilated-p66Shc levels and caspase activity in early embryonic development, and expression of apoptosis and pluripotency genes in blastocysts. The lowest concentration tested (0.25μM) of TTN-LNC generated higher blastocyst rate, lower ROS production and S36-p66Shc amount. Additionally, expression of BAX and SHC1 were lower in both non-encapsulated tretinoin (TTN) and TTN-LNC-treated groups. Nanoencapsulation allowed the use of smaller concentrations of tretinoin to supplement IVM medium thus reducing toxic effects related with its use, decreasing ROS levels and apoptose frequency, and improving the blastocyst rates.

  12. Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats.

    PubMed

    Saadati, Hakimeh; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Darvishzadeh-Mahani, Fatemeh; Mazhari, Shahrzad

    2014-11-01

    Previous studies indicated that brain-derived neurotrophic factor (BDNF) is the main candidate to mediate the beneficial effects of exercise on cognitive function in sleep deprived male rats. In addition, our previous findings demonstrate that female rats are more vulnerable to the deleterious effects of sleep deprivation on cognitive performance and synaptic plasticity. Therefore, the current study was designed to investigate the effects of treadmill exercise and/or sleep deprivation (SD) on the levels of BDNF mRNA and protein in the hippocampus of female rats. Intact and ovariectomized (OVX) female Wistar rats were used in the present experiment. The exercise protocol was four weeks treadmill running and sleep deprivation was accomplished using the multiple platform method. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis were used to evaluate the level of BDNF mRNA and protein in the rat hippocampus respectively. Our results showed that protein and mRNA expression of BDNF was significantly (p<0.05) decreased after 72 h SD in OVX rats in compared with other groups. Furthermore, sleep deprived OVX rats under exercise conditions had a significant (p<0.05) up-regulation of the BDNF protein and mRNA in the hippocampus. These findings suggest that regular exercise can exert a protective effect against hippocampus-related functions and impairments induced by sleep deprivation probably by inducing BDNF expression.

  13. Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells

    SciTech Connect

    Chen Haobin; Davidson, Todd; Singleton, Steven; Garrick, Michael D.; Costa, Max . E-mail: costam@env.med.nyu.edu

    2005-08-15

    Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1{alpha}). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic

  14. Priming effect in agricultural and forest soils depending on glucose level and N addition

    NASA Astrophysics Data System (ADS)

    Splettstoesser, Thomas; Kumar, Amit; Sun, Yue

    2015-04-01

    Growing plants continuously release easily available organic compounds into the rhizosphere. By their interactions with soil microbial biomass (MB) these compounds result in changes of organic matter turnover rates. The understanding of this priming effect (PE) is important for the estimation of climate change impacts on different land use systems. In order to investigate the PE, we conducted a soil incubation experiment under laboratory conditions with two loamy soils: one under cropland and the second under a deciduous forest near Göttingen. 13C and 14C Glucose were added in four levels reaching from 10% to 300% of MB-C. Furthermore two nitrogen levels were established in order to investigate the effects of fertilization on PE. During the whole experiment CO2 release was monitored by trapping in a NaOH solution. Nitrogen mineralization rate, activity of enzymes, and composition of MB were analyzed at the start, after one day, after one week and at the end of the experiment. The results on priming effects induced in agricultural and forest soils depending on N and glucose levels will be presented.

  15. Decreased vitellogenin inducibility and 17β-estradiol levels correlated with reduced egg production in killifish (Fundulus heteroclitus) from Newark Bay, NJ

    PubMed Central

    Bugel, Sean M.; White, Lori A.; Cooper, Keith R.

    2016-01-01

    Aquatic species inhabiting polluted estuaries are exposed to complex mixtures of xenobiotics which can alter normal reproduction. We previously reported that female Atlantic killifish (Fundulus heteroclitus) from the highly contaminated Newark Bay, NJ (USA) exhibited an inhibition of oocyte development due to reduced vitellogenin (egg-yolk precursor) levels. Our hypothesis was that the inhibition of oocyte development in Newark Bay killifish is due to (1) deficient levels of circulating 17β-estradiol, and (2) a decreased sensitivity of the vitellogenin pathway to physiological doses of 17β-estradiol. In the first study, adult naïve killifish from Tuckerton, NJ (reference) were caged at Tuckerton and Newark Bay. After 1 month, males caged at Newark Bay exhibited inductions of hepatic vitellogenin and estrogen receptor α, which were transient and returned to basal levels after 2 months (p ≤ 0.05). In the second study, fecundity and 17β-estradiol levels were measured in reproductively active adult females from Tuckerton and Newark Bay. Tuckerton females produced 140 eggs per female and Newark Bay females produced 11 eggs per female. Embryos from Newark Bay had 34% greater mortality and 28% less hatch, relative to Tuckerton. In addition, embryo mass and yolk-volume of Newark Bay embryos compared to Tuckerton embryos was 16% and 25% lower, respectively. Circulating 17β-estradiol levels in Newark Bay females (0.26 ng/mL) were measured to be 8-fold lower than Tuckerton females (2.25 ng/mL). In the third study, adult killifish from both sites were dosed with 17β-estradiol to assess the sensitivity of the vitellogenin pathway. At doses of 0.01, 0.1, 1 and 10 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay males were significantly inhibited by 97, 99, 98 and 44%, respectively, compared to Tuckerton males. At doses of 0.01, 0.1, 1, 10 and 100 ng/g body weight, induction levels of circulating vitellogenin in Newark Bay females were

  16. p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: roscovitine augments p21 levels

    PubMed Central

    Park, Jin-Young; Schutzer, William E; Lindsley, Jessie N; Bagby, Susan P; Oyama, Terry T; Anderson, Sharon; Weiss, Robert H

    2007-01-01

    Background Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease with few treatment options other than renal replacement therapy. p21, a cyclin kinase inhibitor which has pleiotropic effects on the cell cycle, in many cases acts to suppress cell cycle progression and to prevent apoptosis. Because defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in PKD, and in light of earlier reports that polycystin-1 upregulates p21 and that the cyclin-dependent kinase inhibitor roscovitine arrests progression in a mouse model, we asked whether (1) p21 deficiency might underlie ADPKD and (2) the mechanism of the salutary roscovitine effect on PKD involves p21. Methods p21 levels in human and animal tissue samples as well as cell lines were examined by immunoblotting and/or immunohistochemisty. Apoptosis was assessed by PARP cleavage. p21 expression was attenuated in a renal tubular epithelial cell line by antisense methods, and proliferation in response to p21 attenuation and to roscovitine was assessed by the MTT assay. Results We show that p21 is decreased in human as well as a non-transgenic rat model of ADPKD. In addition, hepatocyte growth factor, which induces transition from a cystic to a tubular phenotype, increases p21 levels. Furthermore, attenuation of p21 results in augmentation of cell cycle transit in vitro. Thus, levels of p21 are inversely correlated with renal tubular epithelial cell proliferation. Roscovitine, which has been shown to arrest progression in a murine model of PKD, increases p21 levels and decreases renal tubular epithelial cell proliferation, with no affect on apoptosis. Conclusion The novelty of our study is the demonstration in vivo in humans and rat models of a decrement of p21 in cystic kidneys as compared to non-cystic kidneys. Validation of a potential pathogenetic model of increased cyst formation due to enhanced epithelial proliferation and apoptosis mediated by p21 suggests a

  17. Structure of a microbial community in soil after prolonged addition of low levels of simulated acid rain

    PubMed

    Pennanen; Fritze; Vanhala; Kiikkila; Neuvonen; Baath

    1998-06-01

    Humus samples were collected 12 growing seasons after the start of a simulated acid rain experiment situated in the subarctic environment. The acid rain was simulated with H2SO4, a combination of H2SO4 and HNO3, and HNO3 at two levels of moderate acidic loads close to the natural anthropogenic pollution levels of southern Scandinavia. The higher levels of acid applications resulted in acidification, as defined by humus chemistry. The concentrations of base cations decreased, while the concentrations of exchangeable H+, Al, and Fe increased. Humus pH decreased from 3.83 to 3.65. Basal respiration decreased with decreasing humus pH, and total microbial biomass, measured by substrate-induced respiration and total amount of phospholipid fatty acids (PLFA), decreased slightly. An altered PLFA pattern indicated a change in the microbial community structure at the higher levels of acid applications. In general, branched fatty acids, typical of gram-positive bacteria, increased in the acid plots. PLFA analysis performed on the bacterial community growing on agar plates also showed that the relative amount of PLFA specific for gram-positive bacteria increased due to the acidification. The changed bacterial community was adapted to the more acidic environment in the acid-treated plots, even though bacterial growth rates, estimated by thymidine and leucine incorporation, decreased with pH. Fungal activity (measured as acetate incorporation into ergosterol) was not affected. This result indicates that bacteria were more affected than fungi by the acidification. The capacity of the bacterial community to utilize 95 different carbon sources was variable and only showed weak correlations to pH. Differences in the toxicities of H2SO4 and HNO3 for the microbial community were not found.

  18. Decreased serum IL-27 and IL-35 levels are associated with disease severity in neuromyelitis optica spectrum disorders.

    PubMed

    Zhang, Da-Qi; Jia, Kun; Wang, Rong; Li, Ting; Zhao, Ning; Yang, Li-Na; Yang, Li

    2016-04-15

    The interleukin 12 (IL-12) family plays important roles in autoimmune diseases. To explore the roles of the IL-12 family members IL-27 and IL-35 in the pathogenesis of neuromyelitis optica spectrum disorders (NMOSD), we determined their serum and cerebral spinal fluid levels and assessed potential correlations with clinical characteristics. Serum IL-27 levels were negatively correlated with disease severity and spinal cord lesion length, while serum IL-35 levels were negatively correlated with disease severity and annual relapse rate. Thus, IL-27 and IL-35 may be important biomarkers of NMOSD severity and these molecules might represent potential therapeutic cytokines for treating NMOSD.

  19. Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells.

    PubMed

    Chen, Haobin; Davidson, Todd; Singleton, Steven; Garrick, Michael D; Costa, Max

    2005-08-15

    Nickel (Ni) compounds are well-established carcinogens and are known to initiate a hypoxic response in cells via the stabilization and transactivation of hypoxia-inducible factor-1 alpha (HIF-1alpha). This change may be the consequence of nickel's interference with the function of several Fe(II)-dependent enzymes. In this study, the effects of soluble nickel exposure on cellular iron homeostasis were investigated. Nickel treatment decreased both mitochondrial and cytosolic aconitase (c-aconitase) activity in A549 cells. Cytosolic aconitase was converted to iron-regulatory protein 1, a form critical for the regulation of cellular iron homeostasis. The increased activity of iron-regulatory protein 1 after nickel exposure stabilized and increased transferrin receptor (Tfr) mRNA and antagonized the iron-induced ferritin light chain protein synthesis. The decrease of aconitase activity after nickel treatment reflected neither direct interference with aconitase function nor obstruction of [4Fe-4S] cluster reconstitution by nickel. Exposure of A549 cells to soluble nickel decreased total cellular iron by about 40%, a decrease that likely caused the observed decrease in aconitase activity and the increase of iron-regulatory protein 1 activity. Iron treatment reversed the effect of nickel on cytosolic aconitase and iron-regulatory protein 1. To assess the mechanism for the observed effects, human embryonic kidney (HEK) cells over expressing divalent metal transporter-1 (DMT1) were compared to A549 cells expressing only endogenous transporters for inhibition of iron uptake by nickel. The inhibition data suggest that nickel can enter via DMT1 and compete with iron for entry into the cell. This disturbance of cellular iron homeostasis by nickel may have a great impact on the ability of the cell to regulate a variety of cell functions, as well as create a state of hypoxia in cells under normal oxygen tension. These effects may be very important in how nickel exerts phenotypic

  20. Additions to the spectrum and energy levels and critical compilation of doubly ionized boron, B III

    NASA Astrophysics Data System (ADS)

    Kramida, A. E.; Ryabtsev, A. N.; Ekberg, J. O.; Kink, I.; Mannervik, S.; Martinson, I.

    2008-08-01

    We have undertaken the study of the Li-like spectrum of doubly ionized boron, B III. The spectroscopic data have been obtained with beam-foil spectroscopy and high-resolution spark spectroscopy. The experimental work was combined with theoretical calculations using ab initio and semi-empirical techniques. About 50 new transitions have been observed, and most of the previously known lines have been measured with improved accuracy. We have also critically evaluated all previous and recent data for this spectrum. Complete data on wavelengths and energy levels based on this analysis are tabulated.

  1. Effects of feeding different levels of dietary fiber through the addition of corn stover on nutrient utilization of dairy heifers precision-fed high and low concentrate diets.

    PubMed

    Lascano, G J; Heinrichs, A J

    2011-06-01

    The objective of this experiment was to assess the effects of manipulating dietary fiber by replacing corn silage (CS) with lower quality forage as corn stover (CST) when used in high concentrate (HC) and low concentrate (LC) diets for precision-fed dairy heifers. Eight Holstein heifers (335.6 ± 7.41 kg of body weight) were randomly assigned to 2 levels of concentrate: HC (20% forage) and LC (80% forage), and to a forage type sequence [0% of forage as corn stover (CST), 100% corn silage (CS); 20% CST, 80% CS; 40% CST, 60% CS; and 60% CST, 40% CS] within concentrate level administered according to a split-plot, 4 × 4 Latin square design (21-d periods). Heifers fed HC had higher apparent total-tract dry matter digestibility (DMD). Increasing the fiber level by increasing the amount of CST in the diet resulted in a linear decrease of DMD and organic matter digestibility. Heifers fed LC diets had higher neutral detergent fiber (NDF) digestibility and tended to have lower acid detergent fiber (ADF) digestibility than those fed HC diets. Substituting CS with 20% CST resulted in the highest NDF and ADF digestibilities. Digestibility of N was not different, but N retention increased for HC and decreased quadratically for LC diets. Heifers fed HC diets decreased fecal output, and CST linearly increased these parameters. Urine volume tended to be higher for HC-fed heifers, and increasing dietary fiber through CST inclusion tended to decrease urine output. This shift in water excretion resulted in similar total manure output. Total purine derivative excretion did not differ between treatments, but interacted with CST addition, resulting in a linear increase in microbial protein flow to the duodenum in HC-fed heifers and in a linear decrease in LC diets as CST increased. In conclusion, increasing dietary fiber through CST decreased DMD and organic matter digestibility linearly, whereas NDF and ADF digestibility were maximized when 20% CST was added to HC and LC diets

  2. Evaluation of alternative chemical additives for high-level waste vitrification feed preparation processing

    SciTech Connect

    Seymour, R.G.

    1995-06-07

    During the development of the feed processing flowsheet for the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS), research had shown that use of formic acid (HCOOH) could accomplish several processing objectives with one chemical addition. These objectives included the decomposition of tetraphenylborate, chemical reduction of mercury, production of acceptable rheological properties in the feed slurry, and controlling the oxidation state of the glass melt pool. However, the DEPF research had not shown that some vitrification slurry feeds had a tendency to evolve hydrogen (H{sub 2}) and ammonia (NH{sub 3}) as the result of catalytic decomposition of CHOOH with noble metals (rhodium, ruthenium, palladium) in the feed. Testing conducted at Pacific Northwest Laboratory and later at the Savannah River Technical Center showed that the H{sub 2} and NH{sub 3} could evolve at appreciable rates and quantities. The explosive nature of H{sub 2} and NH{sub 3} (as ammonium nitrate) warranted significant mitigation control and redesign of both facilities. At the time the explosive gas evolution was discovered, the DWPF was already under construction and an immediate hardware fix in tandem with flowsheet changes was necessary. However, the Hanford Waste Vitrification Plant (HWVP) was in the design phase and could afford to take time to investigate flowsheet manipulations that could solve the problem, rather than a hardware fix. Thus, the HWVP began to investigate alternatives to using HCOOH in the vitrification process. This document describes the selection, evaluation criteria, and strategy used to evaluate the performance of the alternative chemical additives to CHOOH. The status of the evaluation is also discussed.

  3. LPS ligand and culture additives improve production of monomeric MD-1 and 2 in Pichia pastoris by decreasing aggregation and intermolecular disulfide bonding.

    PubMed

    Mengwasser, Kristen E; Bryant, Clare E; Gay, Nick J; Gangloff, Monique

    2011-04-01

    Myeloid differentiation proteins MD-1 and MD-2 have both been shown to form a heterogeneous collection of oligomers when expressed in absence of their respective receptor, RP105 and TLR4. The biological relevance of these oligomers is not clear. Only monomeric proteins have been found to be active and able to trigger an immune response to endotoxin by modulating the TLR4 pathway. In this study, we produced variants of MD-1 and MD-2 in Pichia pastoris. To minimize the time and expense of initial expression tests, small-scale cultures have been set up to allow the rapid identification of the highest expressing clone and the optimal expression conditions. The expression vectors used, the site of linearization and the locus of integration affected the yield of transformation. Next we screened culture additives and found that they significantly increased the fraction of monomeric proteins secreted in the culture medium (up to 15% of the total MD protein produced). We confirmed their presence by size-exclusion chromatography. Optimal anti-aggregation agents were protein-dependent except for LPS that presented stabilizing effects for all MD proteins. Contrary to previous reports, this study suggests that MD-1 can bind to LPS. PMID:21130168

  4. Elevated corticosterone levels decrease reproductive output of chick-rearing Adélie penguins but do not affect chick mass at fledging

    PubMed Central

    Thierry, Anne-Mathilde; Ropert-Coudert, Yan; Raclot, Thierry

    2013-01-01

    Study of physiological mechanisms can help us to understand how animals respond to changing environmental conditions. In particular, stress hormones (i.e. glucocorticoids, such as corticosterone) are described as mediating resource allocation, allowing animals to adjust their physiology and behaviour to predictable and unpredictable changes in the environment. In this study, we investigated the effects of an experimental increase in baseline corticosterone levels on the breeding effort and the reproductive output of chick-rearing male Adélie penguins (Pygoscelis adeliae). The number of chicks per nest, their body mass, and their size were monitored throughout the study. Direct observations allowed measurement of the time spent foraging at sea and caring for the young on the nest. At the end of the treatment, blood samples were collected for isotope analysis. Although all birds raised at least one chick, reproductive output was decreased by 42% in corticosterone-treated birds compared with control birds. The increase in corticosterone levels during the guard stage did not affect the mass of surviving chicks or the brood mass at fledging. Corticosterone-treated males spent on average 21% more time at the nest than control birds. However, the duration of foraging trips was similar between both groups. In addition, the similarity of isotopic signatures suggests that both groups foraged at similar locations and ingested the same prey species. The detailed on-land behaviour of birds should be examined in further studies to clarify the possible links between corticosterone levels, brooding time, and reproductive output. Understanding the relationships between glucocorticoids, fitness, and ultimately population dynamics is fundamental to enabling conservation physiology as a discipline to be successful in helping to manage species of conservation concern. PMID:27293591

  5. Potato chip intake increases ascorbic acid levels and decreases reactive oxygen species in SMP30/GNL knockout mouse tissues.

    PubMed

    Kondo, Yoshitaka; Sakuma, Rui; Ichisawa, Megumi; Ishihara, Katsuyuki; Kubo, Misako; Handa, Setsuko; Mugita, Hiroyuki; Maruyama, Naoki; Koga, Hidenori; Ishigami, Akihito

    2014-09-24

    Potato chips (PC) contain abundant amounts of the free radical scavenger ascorbic acid (AA) due to the rapid dehydration of potato tubers (Solanum tuberosum) that occurs during frying. To evaluate the antioxidant activity of PC, this study examined reactive oxygen species (ROS) levels in tissues from SMP30/GNL knockout (KO) mice that cannot synthesize AA and determined AA and ROS levels after the animals were fed 20 and 10% PC diets for 7 weeks. Compared with AA-sufficient mice, AA-depleted SMP30/GNL KO mice showed high ROS levels in tissues. SMP30/GNL KO mice fed a PC diet showed high AA and low ROS levels in the brain, heart, lung, testis, soleus muscle, plantaris muscle, stomach, small intestine, large intestine, eyeball, and epididymal fat compared with AA-depleted mice. The data suggest that PC intake increases AA levels and enhances ROS scavenging activity in tissues of SMP30/GNL KO mice, which are a promising model for evaluating the antioxidant activity of foods. PMID:25180784

  6. C1q binding to dengue virus decreases levels of infection and inflammatory molecules transcription in THP-1 cells.

    PubMed

    Douradinha, Bruno; McBurney, Sean P; Soares de Melo, Klecia M; Smith, Amanda P; Krishna, Neel K; Barratt-Boyes, Simon M; Evans, Jared D; Nascimento, Eduardo J M; Marques, Ernesto T A

    2014-01-22

    Dengue virus infection elicits a spectrum of clinical presentations ranging from asymptomatic to severe disease. The mechanisms leading to severe dengue are not known, however it has been reported that the complement system is hyper-activated in severe dengue. Screening of complement proteins demonstrated that C1q, a pattern recognition molecule, can bind directly to dengue virus envelope protein and to whole dengue virus serotype 2. Incubation of dengue virus serotype 2 with C1q prior to infection of THP-1 cells led to decreased virus infectivity and modulation of mRNA expression of immunoregulatory molecules suggesting reduced inflammatory responses.

  7. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-β levels in female rats

    PubMed Central

    Berry, Anne S.; Tomidokoro, Yasushi; Ghiso, Jorge; Thornton, Jan

    2008-01-01

    Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult E-treated female rats. In the Object Location Memory Task, ovariectomized (ovxed) rats treated with E and either a single high dose (400IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 hours) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400IU/kg) can impair memory: although E + veh treated animals made significantly fewer hole errors across time, E + hCG treated did not. In humans, high LH levels have been correlated with Alzheimer’s Disease (AD). Because brain amyloid-beta (Aβ) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Aβ levels. Levels of Aβ from whole brains or hippocampi were assessed by Western Blot. hCG treatment to E-implanted females significantly increased soluble Aβ40 and Aβ42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Aβ species may account for the memory impairment in hCG-treated rats. PMID:18413150

  8. The ATP levels in kidneys and blood are mainly decreased by acute ingestion of tullidora (Karwinskia humboldtiana).

    PubMed

    Jaramillo-Juárez, F; Rodríguez-Vázquez, M L; Muñoz-Martínez, J; Quezada-Tristán, T; Posadas del Río, F A; Llamas-Viramontes, J; Ortíz, G Gabriel; Feria-Velasco, Alfredo; Reyes, J L

    2005-07-01

    Our previous acute toxicity studies with Karwinskia humboldtiana (Kh) in rats showed renal hemodynamic changes with a marked increase in the fractional excretion of sodium and morphological damage. To analyse the effects of Kh or 'tullidora' on energetic metabolism, a single dose of an oral preparation from the seed fruits was given to Wistar rats (1.25 g/kg). In tullidora-treated rats there was 8% mortality. ATP concentrations in renal tissue decreased significantly (control: 53.85+/-3.34, tullidora 38.28+/-5.31 micromol/g fresh tissue, P<0.05). Total blood (54.8+/-0.96, tullidora: 40.2+/-1.55 micromol/dL, P<0.01) and haemoglobin-ATP concentrations (3.69+/-0.12, tullidora: 2.56+/-0.11 micromol/g, P<0.01) were also significantly diminished. Moreover, the total protein in renal cortex from tullidora-treated rats decreased as compared to control group (control: 71.43+/-2.88, tullidora: 55.20+/-4.06 mg/g fresh tissue, P<0.05). In contrast, Na+-K+-ATPase activity in tullidora-treated animals was not different from control rats. These findings might partially explain the acute effects and mortality observed in the Kh treated rats.

  9. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

    PubMed Central

    Qi, Xin; Du, Xin; Yang, Yongxin; Du, Guijin; Gao, Peihong; Zhang, Yang; Qin, Wen; Li, Xiaodong; Zhang, Quan

    2015-01-01

    Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents. PMID:26578922

  10. Effects of decreased ground-water withdrawal on ground-water levels and chloride concentrations in Camden County, Georgia, and ground-water levels in Nassau County, Florida, from September 2001 to May 2003

    USGS Publications Warehouse

    Peck, Michael F.; McFadden, Keith W.; Leeth, David C.

    2005-01-01

    During October 2002, the Durango Paper Company formerly Gillman Paper Company) in St. Marys, Georgia, shut down paper-mill operations; the shutdown resulted in decreased ground-water withdrawal in Camden County by 35.6 million gallons per day. The decrease in withdrawal resulted in water-level rise in wells completed in the Floridan aquifer system and the overlying surficial and Brunswick aquifer systems; many wells in the St. Marys area flowed for the first time since the mill began operations during 1941. Pumping at the mill resulted in the development of a cone of depression that coalesced with a larger adjacent cone of depression at Fernandina Beach, Florida. Since closure of the mill, the cone at St. Marys is no longer present, although the cone still exists at Fernandina Beach, Florida. Historical water-level data from the production wells at the mill indicate that the pumping water level ranged from 68 to 235 feet (ft) below North American Vertical Datum of 1988 (NAVD 88) and averaged about 114 ft when the mill was operating. Since the shutdown, it is estimated that water levels at the mill have risen about 140 ft and are now at about 30 ft above NAVD 88. The water-level rise in wells in outlying areas in Camden County was less pronounced and ranged from about 5 to 10 ft above NAVD 88. Because of the regional upward water-level trend in the Upper Floridan aquifer that started during 19992000 in most of the coastal area, combined with a steeper upward trend beginning during October 2002, it was not possible to determine if the 510 ft rise in water levels in wells away from St. Marys was due to the mill closure. In addition to water-level rise of 2226 ft in the Floridan aquifer system, water-level rises in the overlying surficial and Brunswick aquifer systems at St. Marys after the shutdown indicate upward leakage of water. Water levels had stabilized in the confined surficial and Upper and Lower Floridan aquifers by AprilMay 2003; however, the water level in

  11. Enhanced critical currents in (Gd,Y)Ba2Cu3Ox superconducting tapes with high levels of Zr addition

    SciTech Connect

    Selvamanickam, V; Chen, Y; Shi, T; Liu, Y; Khatri, ND; Liu, J; Yao, Y; Xiong, X; Lei, C; Soloveichik, S; Galstyan, E; Majkic, G

    2013-01-21

    The critical current and structural properties of (Gd,Y)BaCuO tapes made by metal organic chemical vapor deposition (MOCVD) with Zr addition levels up to 30 at.% have been investigated. The reduction in critical current beyond the previously optimized Zr addition level of 7.5 at.% was found to be due to structural deterioration of the (Gd,Y)Ba2Cu3Ox film. By a modified MOCVD process,enhanced critical current densities have been achieved with high levels of Zr addition,including 3.83 MA cm(-2) in 15 at.% Zr- added 1.1 mu m thick film at 77 K in zero magnetic field. Critical currents as high as 1072 A/ 12 mm have been reached in (Gd,Y) BaCuO tapes with 15 at.% Zr addition at 30 K in a field of 3 T applied perpendicular to the tape,corresponding to a pinning force value of 268 GN m(-3). The enhanced critical currents achievable with a high density of nanoscale defects by employing high levels of second- phase additions enable the performance targets needed for the use of HTS tapes in coil applications involving high magnetic fields at temperatures below 50 K to be met.

  12. Enhanced critical currents in (Gd,Y)Ba2Cu3Ox superconducting tapes with high levels of Zr addition

    NASA Astrophysics Data System (ADS)

    Selvamanickam, V.; Chen, Y.; Shi, T.; Liu, Y.; Khatri, N. D.; Liu, J.; Yao, Y.; Xiong, X.; Lei, C.; Soloveichik, S.; Galstyan, E.; Majkic, G.

    2013-03-01

    The critical current and structural properties of (Gd,Y)BaCuO tapes made by metal organic chemical vapor deposition (MOCVD) with Zr addition levels up to 30 at.% have been investigated. The reduction in critical current beyond the previously optimized Zr addition level of 7.5 at.% was found to be due to structural deterioration of the (Gd,Y)Ba2Cu3Ox film. By a modified MOCVD process, enhanced critical current densities have been achieved with high levels of Zr addition, including 3.83 MA cm-2 in 15 at.% Zr-added 1.1 μm thick film at 77 K in zero magnetic field. Critical currents as high as 1072 A/12 mm have been reached in (Gd,Y)BaCuO tapes with 15 at.% Zr addition at 30 K in a field of 3 T applied perpendicular to the tape, corresponding to a pinning force value of 268 GN m-3. The enhanced critical currents achievable with a high density of nanoscale defects by employing high levels of second-phase additions enable the performance targets needed for the use of HTS tapes in coil applications involving high magnetic fields at temperatures below 50 K to be met.

  13. Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of anaerobic training.

    PubMed

    Hack, V; Weiss, C; Friedmann, B; Suttner, S; Schykowski, M; Erbe, N; Benner, A; Bärtsch, P; Dröge, W

    1997-05-01

    The purpose of the present study was to investigate the role of plasma amino acids and glutathione (GSH) on the absolute number of leukocyte and lymphocyte subpopulations in response to different training programs. Healthy untrained subjects were randomly assigned to an 8-wk aerobic (AET) or anaerobic (ANT) exercise training program. Absolute number of cell counts did not significantly change in AET, whereas a decrease of CD4+ T cell counts (P < 0.05), a fall in cells expressing CD45RA+ antigen (P < 0.05), and a marked increase in CD8+ T cell numbers (P < 0.01) were noted in ANT at the end of the training period compared with baseline values. Furthermore, ANT demonstrated a marked rise (P < 0.001) in plasma glutamate from 27.6 +/- 2.8 to 49.8 +/- 5.2 microM and a considerable reduction (P < 0.001) of the plasma glutamine pool from 713 +/- 22 to 601 +/- 30 microM after 8 wk of training. The decrease in glutamine showed a strong positive correlation to the individual loss of CD4+ T cells (r = 0.67, P < 0.001). AET demonstrated a rise (P < 0.05) in GSH from 20.7 +/- 2.5 to 28.1 +/- 1.5 nmol/mg protein at terminal examination. In conclusion, our data indicate impairment of the number and activity of CD4+ T cells in response to 8 wk of ANT, which might be linked to metabolic factors such as glutamine.

  14. Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy.

    PubMed

    Mashima, Y; Murakami, A; Weleber, R G; Kennaway, N G; Clarke, L; Shiono, T; Inana, G

    1992-07-01

    A generalized deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy (GA), an autosomal recessive degenerative disease of the retina and choroid of the eye. Mutations in the OAT gene show a high degree of molecular heterogeneity in GA, reflecting the genetic heterogeneity in this disease. Using the combined techniques of PCR, denaturing gradient gel electrophoresis, and direct sequencing, we have identified three nonsense-codon mutations and one nonsense codon-generating mutation of the OAT gene in GA pedigrees. Three of them are single-base substitutions, and one is a 2-bp deletion resulting in a reading frameshift. A nonsense codon created at position 79 (TGA) by a frameshift and nonsense mutations at codons 209 (TAT----TAA) and 299 (TAC----TAG) result in abnormally low levels of OAT mRNA in the patient's skin fibroblasts. A nonsense mutation at codon 426 (CGA----TGA) in the last exon, however, has little effect on the mRNA level. Thus, the mRNA level can be reduced by nonsense-codon mutations, but the position of the mutation may be important, with earlier premature-translation termination having a greater effect than a later mutation.

  15. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    PubMed

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-01

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU.

  16. Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria.

    PubMed

    Laschi, Marcella; Bernardini, Giulia; Dreassi, Elena; Millucci, Lia; Geminiani, Michela; Braconi, Daniela; Marzocchi, Barbara; Botta, Maurizio; Manetti, Fabrizio; Santucci, Annalisa

    2016-04-01

    Alkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with type I tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. PMID:26947423

  17. MR spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter.

    PubMed

    Sijens, P E; Fock, J M; Meiners, L C; Potze, J H; Irwan, R; Oudkerk, M

    2007-06-01

    Brain magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in one patient with merosin-deficient congenital muscular dystrophy (MDCMD) revealed significant metabolite (choline, creatine, N-acetyl aspartate) level reductions, fractional anisotropy (FA) reduction and increased apparent diffusion coefficient (ADC) in the white matter (p<0.01, all). In the gray matter, the MRS properties did not differ significantly from those in controls. The ADC and FA, however, differed significantly as in the white matter, although the differences were less pronounced. This is the first quantitative MR study of the brain in a patient with MDCMD, which revealed that the concentrations of all MRS measured metabolites were decreased only in the white matter. This observation, combined with the DTI observed ADC increases and FA decrease, indicated a presence of vasogenic edema in the white matter.

  18. Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene–Disrupted Mice

    PubMed Central

    2013-01-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity—decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions—calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

  19. Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism.

    PubMed

    Yamada, Shunsuke; Tokumoto, Masanori; Taniguchi, Masatomo; Toyonaga, Jiro; Suehiro, Takaichi; Eriguchi, Rieko; Fujimi, Satoru; Ooboshi, Hiroaki; Kitazono, Takanari; Tsuruya, Kazuhiko

    2015-08-01

    The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history.

  20. How to Further Decrease the Efficiency of Care at a Level I Trauma Center: Implement the Amended Resident Work Hours.

    PubMed

    Schroeppel, Thomas J; Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Croce, Martin A; Fabian, Timothy C

    2015-07-01

    Work-hour restrictions were amended in 2011 to limit interns to 16 continuous duty hours, essentially requiring a night float system of 12-hour shifts. We hypothesize that there has been no improvement in outcomes after implementation of the amended work-hour restrictions. Outcomes from trauma admissions were queried from the trauma registry from 2009 to 2011 (PRE) and 2011 to 2013 (POST). The primary outcome was mortality with secondary outcomes intensive care unit length of stay (LOS)and LOS. Patients were stratified based on age, mechanism, gender, blood pressure, heart rate, and injury severity (Injury Severity Score, Glasgow Coma Scale, Base Deficit). Outcomes were then compared from admissions PRE to POST. A total of 9178 patients were included in the study population. The mean age was 42 with most being male (72%) and blunt mechanism (81%). Patient populations were well matched except patients in the POST period were slightly older (43 vs 42 years; P = 0.01). Intensive care unit LOS and LOS were higher in the POST period. After adjusted analysis, admission in the POST period was not a predictor of mortality (odds ratio 0.857; confidence interval 0.655-1.12). The POST period was an independent predictor for LOS (β = 0.74; P = 0.002). This study adds to the mounting evidence that the implementation of the amended limits on work hours leads to furthermore decreased efficiency of care.

  1. Increased DUX4 expression during muscle differentiation correlates with decreased SMCHD1 protein levels at D4Z4.

    PubMed

    Balog, Judit; Thijssen, Peter E; Shadle, Sean; Straasheijm, Kirsten R; van der Vliet, Patrick J; Krom, Yvonne D; van den Boogaard, Marlinde L; de Jong, Annika; F Lemmers, Richard J L; Tawil, Rabi; Tapscott, Stephen J; van der Maarel, Silvère M

    2015-01-01

    Facioscapulohumeral muscular dystrophy is caused by incomplete epigenetic repression of the transcription factor DUX4 in skeletal muscle. A copy of DUX4 is located within each unit of the D4Z4 macrosatellite repeat array and its derepression in somatic cells is caused by either repeat array contraction (FSHD1) or by mutations in the chromatin repressor SMCHD1 (FSHD2). While DUX4 expression has thus far only been detected in FSHD muscle and muscle cell cultures, and increases with in vitro myogenic differentiation, the D4Z4 chromatin structure has only been studied in proliferating myoblasts or non-myogenic cells. We here show that SMCHD1 protein levels at D4Z4 decline during muscle cell differentiation and correlate with DUX4 derepression. In FSHD2, but not FSHD1, the loss of SMCHD1 repressor activity is partially compensated by increased Polycomb Repressive Complex 2 (PRC2)-mediated H3K27 trimethylation at D4Z4, a situation that can be mimicked by SMCHD1 knockdown in control myotubes. In contrast, moderate overexpression of SMCHD1 results in DUX4 silencing in FSHD1 and FSHD2 myotubes demonstrating that DUX4 derepression in FSHD is reversible. Together, we show that in FSHD1 and FSHD2 the decline in SMCHD1 protein levels during muscle cell differentiation renders skeletal muscle sensitive to DUX4. PMID:26575099

  2. Increased DUX4 expression during muscle differentiation correlates with decreased SMCHD1 protein levels at D4Z4

    PubMed Central

    Balog, Judit; Thijssen, Peter E.; Shadle, Sean; Straasheijm, Kirsten R.; van der Vliet, Patrick J.; Krom, Yvonne D.; van den Boogaard, Marlinde L.; de Jong, Annika; F Lemmers, Richard J. L.; Tawil, Rabi; Tapscott, Stephen J.; van der Maarel, Silvère M.

    2015-01-01

    Facioscapulohumeral muscular dystrophy is caused by incomplete epigenetic repression of the transcription factor DUX4 in skeletal muscle. A copy of DUX4 is located within each unit of the D4Z4 macrosatellite repeat array and its derepression in somatic cells is caused by either repeat array contraction (FSHD1) or by mutations in the chromatin repressor SMCHD1 (FSHD2). While DUX4 expression has thus far only been detected in FSHD muscle and muscle cell cultures, and increases with in vitro myogenic differentiation, the D4Z4 chromatin structure has only been studied in proliferating myoblasts or non-myogenic cells. We here show that SMCHD1 protein levels at D4Z4 decline during muscle cell differentiation and correlate with DUX4 derepression. In FSHD2, but not FSHD1, the loss of SMCHD1 repressor activity is partially compensated by increased Polycomb Repressive Complex 2 (PRC2)–mediated H3K27 trimethylation at D4Z4, a situation that can be mimicked by SMCHD1 knockdown in control myotubes. In contrast, moderate overexpression of SMCHD1 results in DUX4 silencing in FSHD1 and FSHD2 myotubes demonstrating that DUX4 derepression in FSHD is reversible. Together, we show that in FSHD1 and FSHD2 the decline in SMCHD1 protein levels during muscle cell differentiation renders skeletal muscle sensitive to DUX4. PMID:26575099

  3. Detection of optimal PEEP for equal distribution of tidal volume by volumetric capnography and electrical impedance tomography during decreasing levels of PEEP in post cardiac-surgery patients

    PubMed Central

    Blankman, P.; Shono, A.; Hermans, B. J. M.; Wesselius, T.; Hasan, D.; Gommers, D.

    2016-01-01

    Background Homogeneous ventilation is important for prevention of ventilator-induced lung injury. Electrical impedance tomography (EIT) has been used to identify optimal PEEP by detection of homogenous ventilation in non-dependent and dependent lung regions. We aimed to compare the ability of volumetric capnography and EIT in detecting homogenous ventilation between these lung regions. Methods Fifteen mechanically-ventilated patients after cardiac surgery were studied. Ventilator settings were adjusted to volume-controlled mode with a fixed tidal volume (Vt) of 6–8 ml kg−1 predicted body weight. Different PEEP levels were applied (14 to 0 cm H2O, in steps of 2 cm H2O) and blood gases, Vcap and EIT were measured. Results Tidal impedance variation of the non-dependent region was highest at 6 cm H2O PEEP, and decreased significantly at 14 cm H2O PEEP indicating decrease in the fraction of Vt in this region. At 12 cm H2O PEEP, homogenous ventilation was seen between both lung regions. Bohr and Enghoff dead space calculations decreased from a PEEP of 10 cm H2O. Alveolar dead space divided by alveolar Vt decreased at PEEP levels ≤6 cm H2O. The normalized slope of phase III significantly changed at PEEP levels ≤4 cm H2O. Airway dead space was higher at higher PEEP levels and decreased at the lower PEEP levels. Conclusions In postoperative cardiac patients, calculated dead space agreed well with EIT to detect the optimal PEEP for an equal distribution of inspired volume, amongst non-dependent and dependent lung regions. Airway dead space reduces at decreasing PEEP levels. PMID:27199318

  4. Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.

    PubMed

    Orihuela, Daniel; Meichtry, Verónica; Pregi, Nicolás; Pizarro, Manuel

    2005-09-01

    To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions. PMID:16084594

  5. Short-term oral exposure to aluminium decreases glutathione intestinal levels and changes enzyme activities involved in its metabolism.

    PubMed

    Orihuela, Daniel; Meichtry, Verónica; Pregi, Nicolás; Pizarro, Manuel

    2005-09-01

    To study the effects of aluminium (Al) on glutathione (GSH) metabolism in the small intestine, adult male Wistar rats were orally treated with AlCl3.6H2O at doses of 30, 60, 120 and 200 mg/kg body weight (b.w.) per day, during seven days. Controls received deionized water. At doses above 120 mg/kg b.w., Al produced both a significant reduction of GSH content and an increase of oxidized/reduced glutathione ratio (P < 0.05). The index of oxidative stress of the intestine mucosa in terms of lipid peroxidation evaluated by thiobarbituric acid reactive substances was significantly increased (52%) at higher Al dose used. The duodenal expression of the multidrug resistance-associated protein 2 in brush border membranes, determined by Western blot technique, was increased 2.7-fold in rats treated with 200mg AlCl3/kg b.w (P < 0.01). Intestine activities of both GSH-synthase (from 60 mg/kg b.w.) and GSSG-reductase (from 120 mg/kg b.w.) were significantly reduced (26% and 31%, respectively) while glutathione-S-transferase showed to be slightly modified in the Al-treated groups. Conversely, gamma-glutamyltranspeptidase activity was significantly increased (P < 0.05) due to the Al treatment. Al reduced in vitro mucosa-to-lumen GSH efflux (P < 0.05). A positive linear correlation between the intestine GSH depletion and reduction of in situ 45Ca intestinal absorption, both produced by Al, was found (r = 0.923, P = 0.038). Taking as a whole, these results show that Al would alter GSH metabolism in small intestine by decreasing its turnover, leading to an unbalance of redox state in the epithelial cells, thus contributing to deteriorate GSH-dependent absorptive functions.

  6. Chronic Alcohol Exposure Decreases 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured Primary Cortical Neurons.

    PubMed

    Romero, Ana M; Palanca, Ana; Ruiz-Soto, Maria; Llorca, Javier; Marín, María P; Renau-Piqueras, Jaime; Berciano, Maria T; Lafarga, Miguel

    2016-01-01

    Chronic alcohol consumption may cause neurodevelopmental and neurodegenerative disorders. Alcohol neurotoxicity is associated with the production of acetaldehyde and reactive oxygen species that induce oxidative DNA damage. However, the molecular mechanisms by which ethanol disturbs the DNA damage response (DDR), resulting in a defective DNA repair, remain unknown. Here, we have used cultured primary cortical neurons exposed to 50 or 100 mM ethanol for 7 days to analyze the ethanol-induced DDR. Ethanol exposure produced a dose-dependent generation of double strand breaks and the formation of DNA damage foci immunoreactive for the histone γH2AX, a DNA damage marker, and for the ubiquitylated H2A, which is involved in chromatin remodeling at DNA damage sites. Importantly, these DNA damage foci failed to recruit the protein 53BP1, a crucial DNA repair factor. This effect was associated with a drop in 53BP1 mRNA and protein levels and with an inhibition of global transcription. Moreover, ethanol-exposed neurons treated with ionizing radiation (2 Gy) also failed to recruit 53BP1 at DNA damage foci and exhibited a greater vulnerability to DNA lesions than irradiated control neurons. Our results support that defective DNA repair, mediated by the deficient expression and recruitment of 53BP1 to DNA damage sites, represents a novel mechanism involved in ethanol neurotoxicity. The design of therapeutic strategies that increase or stabilize 53BP1 levels might potentially promote DNA repair and partially compensate alcohol neurotoxicity.

  7. Greater decreases in cholesterol levels among individuals with high cardiovascular risk than among the general population: the northern Sweden MONICA study 1994 to 2014

    PubMed Central

    Eriksson, Marie; Forslund, Ann-Sofi; Jansson, Jan-Håkan; Söderberg, Stefan; Wennberg, Maria; Eliasson, Mats

    2016-01-01

    Aim Decreasing cholesterol levels in Western populations is the main reason for decreasing mortality due to coronary heart disease. Our aim was to analyze trends in cholesterol levels in the population during a period of 20 years in relation to previous cardiovascular disease (CVD), other cardiovascular risk factors, and socioeconomic status. Methods and results A total of 4546 women and 4349 men aged 25–74 years participated in five population-based surveys in the Northern Sweden MONICA Study between 1994 and 2014 (participation rate 76.8–62.5%). Total cholesterol levels decreased from 6.2 mmol/L (95% confidence interval, CI, 6.1–6.2) in 1994 to 5.5 mmol/L (CI 5.4–5.5) in 2014. The decrease was more pronounced in elderly vs. younger participants (1.0 vs. 0.5 mmol/L). In 2014, participants with previous CVD, diabetes, or hypertension had lower cholesterol levels than the general population, whereas their levels were higher or similar to the general population in 1994. The use of lipid-lowering drugs increased markedly and was used by 14.3% in 2014. Previously described differences in cholesterol levels between participants with obesity and normal weight, and between those with and without university education, diminished, or vanished over time. Conclusion Cholesterol levels decreased by 0.7 mmol/L over 20 years with no sign of abating. The improvement occurred in all age and gender groups but more prominently among those at high risk of ischaemic heart disease. PMID:26941200

  8. The efficacy of music therapy protocols for decreasing pain, anxiety, and muscle tension levels during burn dressing changes: a prospective randomized crossover trial.

    PubMed

    Tan, Xueli; Yowler, Charles J; Super, Dennis M; Fratianne, Richard B

    2010-01-01

    The purpose of this study was to explore the efficacy of two music therapy protocols on pain, anxiety, and muscle tension levels during dressing changes in burn patients. Twenty-nine inpatients participated in this prospective, crossover randomized controlled trial. On two consecutive days, patients were randomized to receive music therapy services either on the first or second day of the study. On control days, they received no music. On music days, patients practiced music-based imagery (MBI), a form of music-assisted relaxation with patient-specific mental imagery before and after dressing changes. Also, on music days during dressing changes, the patients engaged in music alternate engagement (MAE), which consisted of active participation in music making. The dependent variables were the patients' subjective ratings of their pain and anxiety levels and the research nurse's objective ratings of their muscle tension levels. Two sets of data were collected before, three sets during, and another two sets after dressing changes. The results showed significant decrease in pain levels before (P < .025), during (P < .05), and after (P < .025) dressing changes on days the patients received music therapy in contrast to control days. Music therapy was also associated with a decrease in anxiety and muscle tension levels during the dressing changes (P < .05) followed by a reduction in muscle tension levels after dressing changes (P < .025). Music therapy significantly decreases the acute procedural pain, anxiety, and muscle tension levels associated with daily burn care.

  9. Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism

    PubMed Central

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  10. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism.

    PubMed

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  11. Decreased glutathione transferase levels in rd1/rd1 mouse retina: replenishment protects photoreceptors in retinal explants.

    PubMed

    Ahuja, P; Caffé, A R; Ahuja, S; Ekström, P; van Veen, T

    2005-01-01

    Currently much attention is focused on glutathione S transferase (GST)-induced suppression of apoptosis. The objective of our studies was therefore to see if GST isoenzymes rescue photoreceptors in retinal explants from rd1/rd1 mice, in which photoreceptors degenerate rapidly. Eyes from C3H rd1/rd1 and +/+ mice were collected at various time points between postnatal day (PN) 2 and PN28. Localization and content of alpha-GST and mu-GST was investigated by immunofluorescence and semi-quantitative Western blot analysis, respectively. In addition, PN2 and PN7 retinal explants were cultured till PN28, during which they were treated with 10 ng/ml alpha-GST or mu-GST. The spatiotemporal expression of both GST isoforms was closely similar: early presence in ganglion cell layer after which staining became restricted to Muller cells (particularly in the endfeet) and horizontal cell fibers in both rd1/rd1 and +/+. Doublets of alpha-GST and mu-GST were detected by Western blot analysis. Densitometry of these bands indicated steady reduction of alpha-GST content in rd1/rd1 retina starting from the second postnatal week. When alpha-GST and mu-GST were added exogenously to rd1/rd1 explants, photoreceptor rescue was produced that was more prominent in PN2 than in PN7 explants and more effective by alpha-GST than mu-GST. We propose that alpha-GST neuroprotection is mediated by reduction of tissue oxidative stress. PMID:15749346

  12. Aldosterone Inactivates the Endothelin-B Receptor via a Cysteinyl Thiol Redox Switch to Decrease Pulmonary Endothelial Nitric Oxide Levels and Modulate Pulmonary Arterial Hypertension

    PubMed Central

    Maron, Bradley A.; Zhang, Ying-Yi; White, Kevin; Chan, Stephen Y.; Handy, Diane E.; Mahoney, Christopher E.; Loscalzo, Joseph; Leopold, Jane A.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is characterized, in part, by decreased endothelial nitric oxide (NO•) production and elevated levels of endothelin-1. Endothelin-1 is known to stimulate endothelial nitric oxide synthase (eNOS) via the endothelin-B receptor (ETB), suggesting that this signaling pathway is perturbed in PAH. Endothelin-1 also stimulates adrenal aldosterone synthesis; in systemic blood vessels, hyperaldosteronism induces vascular dysfunction by increasing endothelial reactive oxygen species (ROS) generation and decreasing NO• levels. We hypothesized that aldosterone modulates PAH by disrupting ETB-eNOS signaling through a mechanism involving increased pulmonary endothelial oxidant stress. Methods and Results In rats with PAH, elevated endothelin-1 levels were associated with elevated aldosterone levels in plasma and lung tissue and decreased lung NO• metabolites in the absence of left heart failure. In human pulmonary artery endothelial cells (HPAECs), endothelin-1 increased aldosterone levels via PGC-1α/steroidogenesis factor-1-dependent upregulation of aldosterone synthase. Aldosterone also increased ROS production, which oxidatively modified cysteinyl thiols in the eNOS-activating region of ETB to decrease endothelin-1-stimulated eNOS activity. Substitution of ETB-Cys405 with alanine improved ETB-dependent NO• synthesis under conditions of oxidant stress, confirming that Cys405 is a redox sensitive thiol that is necessary for ETB-eNOS signaling. In HPAECs, mineralocorticoid receptor antagonism with spironolactone decreased aldosterone-mediated ROS generation and restored ETB-dependent NO• production. Spironolactone or eplerenone prevented or reversed pulmonary vascular remodeling and improved cardiopulmonary hemodynamics in two animal models of PAH in vivo. Conclusions Our findings demonstrate that aldosterone modulates an ETB cysteinyl thiol redox switch to decrease pulmonary endothelium-derived NO• and promote PAH

  13. Source processes of near-field deformation accompanying recent lava lake level decrease at Nyiragongo, DR. Congo

    NASA Astrophysics Data System (ADS)

    Geirsson, Halldor; Smets, Benoît; d'Oreye, Nicolas; Cayol, Valerie; Samsonov, Sergey; De Rauw, Dominique; Kervyn, Francois

    2016-04-01

    Nyiragongo volcano in the Democratic Republic of Congo, Central Africa, is one of the rare volcanoes that host a long-living lava lake. The evolution of this lava lake is very dynamic, with height changes spanning hundreds of meters over the past decades and including drastic height changes in relation to flank eruptions of the volcano in 1977 and 2002 (Smets et al., this meeting). Since September 30, 2011, the level of the lava lake has been progressively falling, reaching ~70 m below the lowest platform (termed "platform P3" hereafter) in July 2014. Platform P3 is constructed from successive overflows of the lava lake from 2002 to 2011, amounting to ~400 m thickness since the emptying of the lava lake following the 2002 flank eruption. Coinciding with the recent fall of the lava lake, differences of photogrammetry-derived DEM models, and InSAR time series, show a very near-field (out to ~200-300 m distance from the ~200 m-wide lava lake, i.e. on platform P3) deformation signal with up to meter-scale deformation near the crater. Ring-fractures have also formed in platform P3. Here we compare and contrast plausible models of processes contributing to this near-field deformation, including thermal contraction, elastic response, block rotation, structural weaknesses, and subsurface shape of the lava lake.

  14. Decreased peroxisome proliferator-activated receptor γ level and signalling in sebaceous glands of patients with acne vulgaris.

    PubMed

    Dozsa, A; Mihaly, J; Dezso, B; Csizmadia, E; Keresztessy, T; Marko, L; Rühl, R; Remenyik, E; Nagy, L

    2016-07-01

    Little is known about the altered lipid metabolism-related transcriptional events occuring in sebaceous glands of patients with acne vulgaris. Peroxisome proliferator-activated receptor (PPAR)γ, a lipid-activated transcription factor, is implicated in differentiation and lipid metabolism of sebocytes. We have observed that PPARγ and its target genes, ADRP (adipose differentiation related protein) and PGAR (PPARγ angioprotein related protein) are expressed at lower levels in sebocytes from patients with acne than in those from healthy controls (HCs) Furthermore, endogenous PPARγ activator lipids such as arachidonic acid-derived keto-metabolites (e.g. 5KETE, 12KETE) are increased in acne-involved and nonacne-involved skin of patients with acne, compared with skin from healthy individuals. Our findings highlight the possible anti-inflammatory role of endogenous ligand-activated PPARγ signaling in human sebocyte biology, and suggest that modulating PPARγ- expression and thereby signaling might be a promising strategy for the clinical management of acne vulgaris.

  15. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population.

    PubMed

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-05-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation-selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. "Animal model" analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population.

  16. Very low levels of direct additive genetic variance in fitness and fitness components in a red squirrel population

    PubMed Central

    McFarlane, S Eryn; Gorrell, Jamieson C; Coltman, David W; Humphries, Murray M; Boutin, Stan; McAdam, Andrew G

    2014-01-01

    A trait must genetically correlate with fitness in order to evolve in response to natural selection, but theory suggests that strong directional selection should erode additive genetic variance in fitness and limit future evolutionary potential. Balancing selection has been proposed as a mechanism that could maintain genetic variance if fitness components trade off with one another and has been invoked to account for empirical observations of higher levels of additive genetic variance in fitness components than would be expected from mutation–selection balance. Here, we used a long-term study of an individually marked population of North American red squirrels (Tamiasciurus hudsonicus) to look for evidence of (1) additive genetic variance in lifetime reproductive success and (2) fitness trade-offs between fitness components, such as male and female fitness or fitness in high- and low-resource environments. “Animal model” analyses of a multigenerational pedigree revealed modest maternal effects on fitness, but very low levels of additive genetic variance in lifetime reproductive success overall as well as fitness measures within each sex and environment. It therefore appears that there are very low levels of direct genetic variance in fitness and fitness components in red squirrels to facilitate contemporary adaptation in this population. PMID:24963372

  17. Calorie restriction at increasing levels leads to augmented concentrations of corticosterone and decreasing concentrations of testosterone in rats.

    PubMed

    Levay, Elizabeth A; Tammer, Amanda H; Penman, Jim; Kent, Stephen; Paolini, Antonio G

    2010-05-01

    The influence of calorie restriction (CR) on increasing life span, enhancing immunocompetence, and reducing the incidence of age-related diseases is well established. Evidence points to the involvement of neuroendocrine alterations in these beneficial effects. Accordingly, we hypothesized that CR will result in significant alterations to the hormones investigated. Little attention has been directed toward ascertaining the doses of CR required to obtain such alterations and, indeed, whether a dose-response exists. Adult rats were subjected to 1 of 5 dietary regimens: control, CR12.5%, CR25%, CR37.5%, or CR50%. Rats were decapitated 3 weeks following the onset of restriction; and trunk blood was collected and assayed for concentrations of serum adrenocorticotropic hormone, corticosterone, and testosterone, as well as plasma concentrations of noradrenalin and adrenalin. No effect was found as a result of dietary manipulation for serum concentrations of adrenocorticotropic hormone. However, all doses of CR resulted in increased serum corticosterone in a dose-response trend. A dose-response was also observed for serum testosterone, with higher doses of CR associated with lower testosterone. Concentrations of noradrenalin were not found to be altered by any CR dose, although a trend toward a down-regulation at CR50% was observed. Plasma adrenalin displayed a biphasic distribution with reductions observed at CR25% and CR50%, although the down-regulations only attained statistical significance relative to the CR37.5% and not the control group. As well as reporting the effect of CR on multiple hormones within individual animals, these results go some way in determining the optimal levels of CR needed to induce neuroendocrinologic alterations.

  18. TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F F{sub 1}-ATP synthase and ubiquinone

    SciTech Connect

    Shertzer, Howard G. . E-mail: shertzhg@ucmail.uc.edu; Genter, Mary Beth; Shen, Dongxiao; Nebert, Daniel W.; Chen, Ying; Dalton, Timothy P.

    2006-12-15

    Mitochondria generate ATP and participate in signal transduction and cellular pathology and/or cell death. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) decreases hepatic ATP levels and generates mitochondrial oxidative DNA damage, which is exacerbated by increasing mitochondrial glutathione redox state and by inner membrane hyperpolarization. This study identifies mitochondrial targets of TCDD that initiate and sustain reactive oxygen production and decreased ATP levels. One week after treating mice with TCDD, liver ubiquinone (Q) levels were significantly decreased, while rates of succinoxidase and Q-cytochrome c oxidoreductase activities were increased. However, the expected increase in Q reduction state following TCDD treatment did not occur; instead, Q was more oxidized. These results could be explained by an ATP synthase defect, a premise supported by the unusual finding that TCDD lowers ATP/O ratios without concomitant changes in respiratory control ratios. Such results suggest either a futile cycle in ATP synthesis, or hydrolysis of newly synthesized ATP prior to release. The TCDD-mediated decrease in Q, concomitant with an increase in respiration, increases complex 3 redox cycling. This acts in concert with glutathione to increase membrane potential and reactive oxygen production. The proposed defect in ATP synthase explains both the greater respiratory rates and the lower tissue ATP levels.

  19. AGEs decrease insulin synthesis in pancreatic β-cell by repressing Pdx-1 protein expression at the post-translational level.

    PubMed

    Shu, Tingting; Zhu, Yunxia; Wang, Hongdong; Lin, Yan; Ma, Zhuo; Han, Xiao

    2011-04-18

    Advanced glycation end products (AGEs) have been implicated in diverse pathological settings of many diabetic complications, and the possible mechanisms have been widely reported. However, the relationship between AGEs and pancreatic β-cell dysfunction is still poorly understood. Recent studies have shown that AGEs can impair β-cell function by inducing apoptosis or decreasing insulin secretion. Our previous research revealed that AGEs could significantly down-regulate insulin transcription and reduce β-cell glucose-stimulated insulin secretion (GSIS). Here, we investigated the possible mechanisms underlying AGE-related suppression of insulin synthesis. In the rat pancreatic β-cell line INS-1, we found that AGEs induced dephosphorylation of Foxo1 and increased its accumulation in the nucleus. The translocation of Foxo1 subsequently inhibited pancreatic-duodenal homeobox factor-1 (Pdx-1) levels in both nuclear and cytoplasmic compartments. We observed that with AGEs treatment, Pdx-1 protein levels decreased after 4 h, but there was no change in the Pdx-1 mRNA level or promoter activity at the same time point; this demonstrated that the decrease in Pdx-1 expression was not regulated at the transcriptional level. In our study, the decrease in Pdx-1 protein level was related to its reduced stability, overexpression of DN-Foxo1 could partially reverse the inhibition of Pdx-1 expression. Pretreatment with AGEs receptor (RAGE) antibody also prevented the AGE-induced diminution of Pdx-1 protein and insulin mRNA expression. In summary, AGEs induced nuclear accumulation of Foxo1; this in turn reduced Pdx-1 expression by decreasing its protein stability, ultimately affecting insulin synthesis.

  20. Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study

    PubMed Central

    Qiao, Shanlei; Hu, Nan; Hu, Yanhui; Wu, Wei; Qiu, Lianglin; Zhang, Ruyang; Wang, Yubang; Wang, Shoulin; Zhou, Zuomin; Xia, Yankai; Wang, Xinru

    2012-01-01

    Background Male reproductive toxicity induced by exposure to bisphenol A (BPA) has been widely reported. The testes have proven to be a major target organ of BPA toxicity, so studying testicular metabolite variation holds promise for the discovery of mechanisms linked to the toxic effects of BPA on reproduction. Methodology/Principal Findings Male Sprague-Dawley rats were orally administered doses of BPA at the levels of 0, 50 mg/kg/d for 8 weeks. We used an unbiased liquid chromatography-quadrupole time-of-flight (LC-QTOF)-based metabolomics approach to discover, identify, and analyze the variation of testicular metabolites. Two n-6 fatty acids, linoleic acid (LA) and arachidonic acid (AA) were identified as potential testicular biomarkers. Decreased levels of LA and increased levels of AA as well as AA/LA ratio were observed in the testes of the exposed group. According to these suggestions, testicular antioxidant enzyme levels were detected. Testicular superoxide dismutase (SOD) declined significantly in the exposed group compared with that in the non-exposed group, and the glutathione peroxidase (GSH-Px) as well as catalase (CAT) also showed a decreasing trend in BPA treated group. Conclusions/Significance BPA caused testicular n-6 fatty acid composition variation and decreased antioxidant enzyme levels. This study emphasizes that metabolomics brings the promise of biomarkers identification for the discovery of mechanisms underlying reproductive toxicity. PMID:23024759

  1. The onset of the progression of acute phase response mechanisms induced by extreme impacts can be followed by the decrease in blood levels of positive acute phase proteins.

    NASA Astrophysics Data System (ADS)

    Larina, Olga; Bekker, Anna

    Studies performed at space flights and earth-based simulation models detected the plasma indices of acute phase reaction (APR), i.e. the increase of APR cytokine mediators and alterations in the production of blood acute phase proteins (APP) at the initial stages of adaptation to altered gravity conditions. Acute phase response is the principal constituent of the functional activity of innate immunity system. Changes in plasma APPs contents are considered to serve the restoration of homeostasis state. According to trends of their concentration shifts at the evolving of acute phase reaction APPs are denoted as positive, neutral, or negative. Plasma concentrations of positive acute phase proteins α1-acid glycoprotein (α1-AGP), α1-antitrypsin (α1-AT), and neutral α2-macroglobulin (α2-M) were measured in human study at 12-hour antiorthostatic position (AOP) with 15° head down tilt and hypoxia experiments at 14% oxygen in pressure chamber. Both of these impacts were shown to produce alterations in the APP levels indicative for acute phase response. Nevertheless, in AOP experiment noticeable decrease in α1-AGP concentration occurred by hour 12, and even more pronounced decline of α1-AGP and α1-AT were found on hypoxia hours 12 and 36. Acute phase proteins α1-AGP and α2-M possess the features of proteinase inhibitors. This function is implemented by the formation of complexes with the molecules of proteolytic enzymes which subsequently are removed from the blood flow. Transient decrease in plasma concentrations of protease inhibitors on early phases of APR development was reported to result from the growth of plasma protease activity due to cathepsin release from activated leukocytes, which had not yet been compensated by enhanced APP synthesis. Being a carrier protein for positively charged and neutral substances, α1-AGP shows pronounced elevation in its blood content during APR development. As assumed, it is required for the transportation of the increased

  2. Effect of Various Food Additives on the Levels of 4(5)-Methylimidazole in a Soy Sauce Model System.

    PubMed

    Lee, Sumin; Lee, Jung-Bin; Hwang, Junho; Lee, Kwang-Geun

    2016-01-01

    In this study, the effect of food additives such as iron sulfate, magnesium sulfate, zinc sulfate, citric acid, gallic acid, and ascorbic acid on the reduction of 4(5)-methylimidazole (4(5)-MI) was investigated using a soy sauce model system. The concentration of 4(5)-MI in the soy sauce model system with 5% (v/v) caramel colorant III was 1404.13 μg/L. The reduction rate of 4(5)-MI level with the addition of 0.1M additives followed in order: iron sulfate (81%) > zinc sulfate (61%) > citric acid (40%) > gallic acid (38%) > ascorbic acid (24%) > magnesium sulfate (13%). Correlations between 4(5)-MI levels and the physicochemical properties of soy sauce, including the amount of caramel colorant, pH value, and color differences, were determined. The highest correlations were found between 4(5)-MI levels and the amount of caramel colorant and pH values (r(2) = 0.9712, r(2) = 0.9378). The concentration of caramel colorants in 8 commercial soy sauces were estimated, and ranged from 0.01 to 1.34% (v/v). PMID:26661512

  3. Effect of Various Food Additives on the Levels of 4(5)-Methylimidazole in a Soy Sauce Model System.

    PubMed

    Lee, Sumin; Lee, Jung-Bin; Hwang, Junho; Lee, Kwang-Geun

    2016-01-01

    In this study, the effect of food additives such as iron sulfate, magnesium sulfate, zinc sulfate, citric acid, gallic acid, and ascorbic acid on the reduction of 4(5)-methylimidazole (4(5)-MI) was investigated using a soy sauce model system. The concentration of 4(5)-MI in the soy sauce model system with 5% (v/v) caramel colorant III was 1404.13 μg/L. The reduction rate of 4(5)-MI level with the addition of 0.1M additives followed in order: iron sulfate (81%) > zinc sulfate (61%) > citric acid (40%) > gallic acid (38%) > ascorbic acid (24%) > magnesium sulfate (13%). Correlations between 4(5)-MI levels and the physicochemical properties of soy sauce, including the amount of caramel colorant, pH value, and color differences, were determined. The highest correlations were found between 4(5)-MI levels and the amount of caramel colorant and pH values (r(2) = 0.9712, r(2) = 0.9378). The concentration of caramel colorants in 8 commercial soy sauces were estimated, and ranged from 0.01 to 1.34% (v/v).

  4. Short-term UV-B and UV-C radiations preferentially decrease spermidine contents and arginine decarboxylase transcript levels of Synechocystis sp. PCC 6803.

    PubMed

    Jantaro, Saowarath; Pothipongsa, Apiradee; Khanthasuwan, Suparaporn; Incharoensakdi, Aran

    2011-02-01

    To investigate the short term effect of ultraviolet (UV) radiations on changes in pigments and polyamine contents, Synechocystis sp. PCC 6803 cells after exposure to UV-radiation were extracted by dimethylformamide and perchloric acid for pigments and polyamines determination, respectively. Cell growth was slightly decreased after 1 h exposure to UV-A and UV-B radiations. UV-C had little effect on cell growth despite the decrease of photosynthetic rate by about 18%. UV-A and UV-B decreased the contents of chlorophyll a and carotenoids whereas UV-C decreased chlorophyll a but had no effect on carotenoids. Spermidine contents were unaffected by UV-A, in contrast to the reduction of 25 and 50% by UV-B and UV-C, respectively. All three types of UV-radiation particularly reduced perchloric acid-insoluble spermidine. Importantly, putrescine and spermine which accounted for less than 1% of intracellular polyamines were increased by about three- to eight-fold by UV-B and UV-C, respectively. The changes in polyamines contents by UV-B and UV-C were consistent with the changes in transcript levels of arginine decarboxylase mRNA, but not with the protein levels. The decrease in the transcripts of adc2 but not adc1 was observed with UV-B and UV-C treatments.

  5. Developmental coexposure to polychlorinated biphenyls and polybrominated diphenyl ethers has additive effects on circulating thyroxine levels in rats.

    PubMed

    Miller, Veronica M; Sanchez-Morrissey, Susana; Brosch, Karl O; Seegal, Richard F

    2012-05-01

    Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are widespread environmental contaminants found in seafood and dairy products. PCBs and PBDEs are structurally similar chemicals and affect thyroid hormone function and behavior in children and laboratory rodents. Although coexposure frequently exists, the in vivo developmental effects of combined exposure to PCBs and PBDEs on thyroxine (T4) levels are unknown. We examined the effects of PCB and PBDE coexposure from gestational day 6 through postnatal day (p) 21, alone and in combination, on T4 levels in rat offspring. In males, exposure to PCBs and PBDEs at 1.7, 5, 10, 20, 40, and 60 μmol/kg/day induced equivalent and dose-dependent reductions in T4 from p 7 to p 21. Exposure to equimolar mixtures of PCBs and PBDEs at 3.4, 10, 20, 40, and 80 μmol/kg/day additively reduced T4 from p 7 to p 21 in males. In a second series of experiments, we determined sex effects on the mixture exposures and found that coexposure to PCBs and PBDEs had similar additive effects on T4 levels in male and female offspring. This study demonstrates that equimolar exposure to PCBs and PBDEs induces similar reductions in T4 levels and that coexposure to a mixture of PCBs and PBDEs has additive effects on T4 levels. These thyroid hormone effects of coexposure to PCBs and PBDEs are important when considering the cumulative effects of coexposure to multiple environmental thyroid hormone-disrupting agents in risk assessment for developmental disorders. PMID:22345314

  6. The value of decreased plasma gelsolin levels in patients with systemic lupus erythematosus and rheumatoid arthritis in diagnosis and disease activity evaluation.

    PubMed

    Hu, Yl; Li, H; Li, W H; Meng, H X; Fan, Y Z; Li, W J; Ji, Y T; Zhao, H; Zhang, L; Jin, X M; Zhang, F M

    2013-12-01

    Plasma gelsolin, the extracellular gelsolin isoform, circulates in the blood of healthy individuals at a concentration of 200 ± 50 mg/l and plays important roles in the extracellular actin-scavenging system during tissue damage. Decreased plasma gelsolin levels have been observed in many inflammatory diseases. In the present study, the variation and potential clinical application of plasma gelsolin levels in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were analysed. Plasma samples and clinical data were collected from informed and consenting participants: 47 SLE patients, 60 RA patients and 50 age- and gender-matched healthy individuals. Semiquantitative western blotting was used for measuring plasma gelsolin levels. The plasma gelsolin levels in patients with SLE and RA were significantly decreased compared with healthy controls (145.3 ± 40.4 versus 182.7 ± 38.3 mg/l and 100.8 ± 36 versus 182.7 ± 38.3 mg/l, p < 0.001), and plasma gelsolin levels were especially lower in RA than in SLE patients (100.8 ± 36 versus 145.3 ± 40.4 mg/L, p < 0.001). An analysis of the clinical data showed a significant negative correlation between plasma gelsolin levels and SLE Disease Activity Index (SLEDAI) scores (r = 0.659, p < 0.001) but no correlation between plasma gelsolin levels and RA disease activity score 28 (DAS28) (r = 0.076, p = 0.569). Different clinical characteristics were also observed in SLE and RA patients with normal and decreased plasma gelsolin levels.This study found significantly lower plasma gelsolin levels in patients with SLE and RA compared with healthy controls and documented a significant negative correlation between plasma gelsolin levels and SLEDAI, which suggested the potential clinical application of plasma gelsolin in SLE diagnosis and disease activity evaluation. The different clinical characteristics in SLE and RA patients with normal and decreased plasma gelsolin levels indicate differences in the basis of

  7. Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

    PubMed

    Usta, Julnar; Hachem, Yassmine; El-Rifai, Omar; Bou-Moughlabey, Yolla; Echtay, Karim; Griffiths, David; Nakkash-Chmaisse, Hania; Makki, Rajaa Fakhoury

    2013-02-01

    We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,β-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death. PMID:22940465

  8. Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

    PubMed

    Usta, Julnar; Hachem, Yassmine; El-Rifai, Omar; Bou-Moughlabey, Yolla; Echtay, Karim; Griffiths, David; Nakkash-Chmaisse, Hania; Makki, Rajaa Fakhoury

    2013-02-01

    We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,β-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death.

  9. Decreased serum levels of T-cell immunoglobulin mucin-1 and T-cell immunoglobulin mucin-3 in systemic lupus erythematosus patients.

    PubMed

    Yuan, H; Yao, Y S; Chen, G M; Sheng, J; Xu, L; Pan, H F

    2016-01-01

    This study aims to investigate the serum T-cell immunoglobulin mucin (TIM)-1 and TIM-3 levels in systemic lupus erythematosus (SLE) patients and analyze their correlations with clinical features. Sixtyone SLE patients and 69 healthy controls were enrolled, serum TIM-1 and TIM-3 levels were detected by ELISA. Results demonstrated that both serum TIM-1 and TIM-3 levels were significantly decreased in SLE patients compared with controls (both P less than 0.05). Lower serum TIM-3 levels in SLE patients with nephritis were observed when compared to those without nephritis, with a marginal statistical significance (P=0.059). However, both serum TIM-1 and TIM-3 levels had no significant correlation with SLE disease activity (both >0.05). In summary, decreased serum TIM-1 and TIM-3 levels and association of TIM-3 with nephritis suggest their possible role in the development and pathogenesis of SLE. However, further studies are needed to confirm these preliminary results. PMID:27049082

  10. Cerebral level of vGlut1 is increased and level of glycine is decreased in TgSwDI mice.

    PubMed

    Timmer, Nienke M; Metaxas, Athanasios; van der Stelt, Inge; Kluijtmans, Leo A J; van Berckel, Bart N; Verbeek, Marcel M

    2014-01-01

    Amyloid-β (Aβ) deposition, one of the main hallmarks of Alzheimer's disease (AD), has been linked to glutamatergic dysfunction, i.e., increased stimulation of synaptic glutamate receptors that may ultimately result in neuronal loss. It was our aim to study the effect of Aβ on multiple components of the glutamatergic system, and therefore we assessed the expression of several glutamate-related proteins and amino acids in the TgSwDI mouse model for Aβ pathology. We determined that in TgSwDI mice, levels of several amino acids are altered, in particular that of glycine. Protein changes were only found in 9-month-old TgSwDI mice with extensive Aβ deposits, with the most prominent change an increased expression of vesicular glutamate transporter 1 (vGlut1). Autoradiography experiments demonstrated that, while the number of activated N-methyl-D-aspartic acid (NMDA) receptors was unchanged in TgSwDI mice, binding of the NMDA receptor radioligand [3H]MDL-105,519 to the glycine-binding site of these receptors was increased. Although there are some discrepancies between our results and those found in AD patients, our results suggest that several components of the glutamatergic system might serve as meaningful markers to monitor the progression of AD. PMID:24145381

  11. Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

    SciTech Connect

    Gao Jin; Tao Yalan; Li Guo; Yi Wei; Xia Yunfei

    2012-03-15

    Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specific survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.

  12. Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading

    PubMed Central

    2010-01-01

    Background There are safety concerns regarding widespread consumption of phytosterol and phytostanol supplemented food products. The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY) inbred rats that have a mutation in the Abcg5 gene and thus over absorb phytosterols and phytostanols. Methods Thirty 35-day old male WKY inbred rats (10/group) were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet) for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR. Results Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats (P < 0.05). The phytostanol diet dramatically increased (> 9-fold) the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P < 0.05). The phytosterol diet decreased cholesterol levels by 40%, 31%, and 19% in liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet decreased cholesterol levels by 15%, 16%, 20% and 14% in plasma, liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet also decreased phytosterol levels by 29% to 54% in plasma and tissues (P < 0.05). Both the phytosterol and phytostanol diets produced significant decreases in the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney. Rats that consumed the phytosterol or phytostanol diets displayed significant increases in systolic and diastolic blood pressure compared to rats that consumed the control diet (P < 0.05). The phytosterol diet increased renal

  13. Chronic estradiol treatment decreases brain derived neurotrophic factor (BDNF) expression and monoamine levels in the amygdala--implications for behavioral disorders.

    PubMed

    Balasubramanian, Priya; Subramanian, Madhan; Nunez, Joseph L; Mohankumar, Sheba M J; Mohankumar, P S

    2014-03-15

    Changes in serum estradiol levels are associated with mood disorders in women. However, the underlying mechanisms are not clear. Because alterations in Brain-Derived Neurotrophic Factor (BDNF) and monoamine levels in the hippocampus and amygdala have been associated with anxiety disorders, we hypothesized that chronic treatment with a low dose of estradiol would cause anxiety-like disorder by altering BDNF and monoamine levels in these regions. To test this hypothesis, female rats were sham-implanted (Controls) or implanted with pellets that release estradiol-17β (E2) for 90-days at the rate of 20 ng/day. Animals underwent behavioral tests such as the open field test and elevated plus maze test at the end of treatment. Brains from these animals were frozen, sectioned and the hippocampus, central amygdala and caudate putamen were microdissected and analyzed for monoamine levels using HPLC. BDNF protein levels in these areas were measured using ELISA and BDNF mRNA levels were analyzed using RT-PCR. In the open field test, animals chronically treated with E2 displayed anxiety-like behavior that was marked by a decrease in the number of inner zone crossings and increase in the rate of defecation compared to controls. However, no behavioral changes were observed in the elevated plus maze test. Chronic E2 treatment also decreased BDNF protein and mRNA levels in the central amygdala that was accompanied by a reduction in dopamine levels. No changes were observed in the hippocampus and caudate putamen. These results suggest that BDNF and dopamine in the central amygdala might possibly mediate chronic E2-induced behavioral alterations.

  14. Piperine, a component of black pepper, decreases eugenol-induced cAMP and calcium levels in non-chemosensory 3T3-L1 cells.

    PubMed

    Yoon, Yeo Cho; Kim, Sung-Hee; Kim, Min Jung; Yang, Hye Jeong; Rhyu, Mee-Ra; Park, Jae-Ho

    2015-01-01

    This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant-induced signal transduction in non-chemosensory cells. An ethanol extract of black pepper decreased eugenol-induced cAMP and calcium levels in preadipocyte 3T3-L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element-binding protein) was down-regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC-MS/MS. Pretreatment with piperine decreased eugenol-induced cAMP and calcium levels in 3T3-L1 cells. Piperine also decreased the phosphorylation of CREB, which is up-regulated by eugenol. These results suggest that piperine inhibits the eugenol-induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non-chemosensory cells. PMID:25685661

  15. Piperine, a component of black pepper, decreases eugenol-induced cAMP and calcium levels in non-chemosensory 3T3-L1 cells.

    PubMed

    Yoon, Yeo Cho; Kim, Sung-Hee; Kim, Min Jung; Yang, Hye Jeong; Rhyu, Mee-Ra; Park, Jae-Ho

    2015-01-01

    This study investigated the effects of an ethanol extract of black pepper and its constituent, piperine, on odorant-induced signal transduction in non-chemosensory cells. An ethanol extract of black pepper decreased eugenol-induced cAMP and calcium levels in preadipocyte 3T3-L1 cells with no toxicity. Phosphorylation of CREB (cAMP response element-binding protein) was down-regulated by the black pepper extract. The concentration (133.8 mg/g) and retention time (5.5 min) of piperine in the ethanol extract were quantified using UPLC-MS/MS. Pretreatment with piperine decreased eugenol-induced cAMP and calcium levels in 3T3-L1 cells. Piperine also decreased the phosphorylation of CREB, which is up-regulated by eugenol. These results suggest that piperine inhibits the eugenol-induced signal transduction pathway through modulation of cAMP and calcium levels and phosphorylation of CREB in non-chemosensory cells.

  16. Interleukin-10 neutralizing antibody for detection of intestinal luminal levels and as a dietary additive in Eimeria challenged broiler chicks.

    PubMed

    Arendt, Maria K; Sand, Jordan M; Marcone, Taylor M; Cook, Mark E

    2016-02-01

    Interleukin-10 (IL-10) mRNA levels are increased within intestinal mucosa after Eimeria infection. IL-10 apical receptor presence on enterocytes suggests IL-10 is secreted into the intestinal lumen. Increased IL-10 has been shown to be central to the pathogenesis of numerous intracellular pathogens; we hypothesize luminal secretion of IL-10 enables Eimeria spp. infection in chickens. This study examines intestine luminal IL-10 levels and performance in broilers challenged with Eimeria when fed an anti-IL-10 antibody. Chicks were fed a diet (1 to 21 d) with control or anti-IL-10 antibody (0.34 g egg yolk antibody powder/Kg diet) with a saline or 10× dose of Advent coccidiosis vaccine on d 3. One chick per pen was euthanized on days 2, 4, 7, 10, 13, 16, and 19 post-challenge, bled, and intestines were collected for luminal fluid IL-10 concentrations. Body weight and feed intake were measured on d 21, and oocyst shedding was assessed on d 7 post-challenge. A significant Eimeria × antibody interaction on d 21 body weight (P < 0.05) showed chicks fed control antibody, but not anti-IL-10, had significant reductions in body weight when challenged with Eimeria spp. Oocyst shedding was increased with Eimeria challenge, but dietary antibody had no effect. Plasma carotenoid levels were reduced in Eimeria challenged chicks 4, 7, 10, and 16 days post-challenge compared to unchallenged chicks. Lack of an Eimeria × antibody interaction showed anti-IL-10 was not protective against Eimeria-induced decreases in plasma carotenoids. Eimeria challenge increased intestine luminal IL-10 on days 4 and 7 post-challenge in the cecum and jejunum, respectively, compared to unchallenged. Dietary anti-IL-10 decreased luminal IL-10 in the ileum on day 2 post-challenge when compared to control antibody fed chicks. No interaction between Eimeria challenge and antibody was observed on intestine luminal contents of IL-10, suggesting anti-IL-10 was ineffective at preventing increased Eimeria

  17. Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats

    PubMed Central

    Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M.

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels. PMID:27752492

  18. Swim-exercised mice show a decreased level of protein O-GlcNAcylation and expression of O-GlcNAc transferase in heart.

    PubMed

    Belke, Darrell D

    2011-07-01

    Swim-training exercise in mice leads to cardiac remodeling associated with an improvement in contractile function. Protein O-linked N-acetylglucosamine (O-GlcNAcylation) is a posttranslational modification of serine and threonine residues capable of altering protein-protein interactions affecting gene transcription, cell signaling pathways, and general cell physiology. Increased levels of protein O-GlcNAcylation in the heart have been associated with pathological conditions such as diabetes, ischemia, and hypertrophic heart failure. In contrast, the impact of physiological exercise on protein O-GlcNAcylation in the heart is currently unknown. Swim-training exercise in mice was associated with the development of a physiological hypertrophy characterized by an improvement in contractile function relative to sedentary mice. General protein O-GlcNAcylation was significantly decreased in swim-exercised mice. This effect was mirrored in the level of O-GlcNAcylation of individual proteins such as SP1. The decrease in protein O-GlcNAcylation was associated with a decrease in the expression of O-GlcNAc transferase (OGT) and glutamine-fructose amidotransferase (GFAT) 2 mRNA. O-GlcNAcase (OGA) activity was actually lower in swim-trained than sedentary hearts, suggesting that it did not contribute to the decreased protein O-GlcNAcylation. Thus it appears that exercise-induced physiological hypertrophy is associated with a decrease in protein O-GlcNAcylation, which could potentially contribute to changes in gene expression and other physiological changes associated with exercise. PMID:21493720

  19. Adenovirus E1A-induced apoptosis elicits a steep decrease in the topoisomerase II alpha level during the latent phase.

    PubMed

    Nakajima, T; Ohi, N; Arai, T; Nozaki, N; Kikuchi, A; Oda, K

    1995-02-16

    The human KB derivative cell line MA1, established by introduction of the adenovirus E1A 12S cDNA linked to the hormone-inducible promoter, elicits apoptosis upon treatment with dexamethasone. The cell lines partially refractory to apoptosis were established by introducing the expression plasmid for the adenovirus E1B 19k protein to MA1 cells. After induction of E1A in MA1 cells by dexamethasone, the level of p53 increased to about 10-fold within 24 h, and morphological changes characteristics of apoptosis began to be observed within 48 h. Most of cells were killed at 72 h releasing apoptotic bodies. The level of topoisomerase II alpha began to decrease steeply within 36 h, preceding the onset of DNA degradation while its mRNA level unchanged throughout the apoptotic process. E1B 19k protected the decrease in topoisomerase II alpha as well as DNA fragmentation depending on its expression levels. Topoisomerase II alpha is induced specifically at G2/M, and computer search revealed the presence of cyclin B type destruction box in topoisomerase II alpha. These results strongly suggest that E1A or E1A stabilized p53 induces apoptosis by targeting topoisomerase II alpha to the ubiquitination pathway and E1B 19k alleviates its action. PMID:7862442

  20. Untangling the Effect of Fatty Acid Addition at Species Level Revealed Different Transcriptional Responses of the Biogas Microbial Community Members.

    PubMed

    Treu, Laura; Campanaro, Stefano; Kougias, Panagiotis G; Zhu, Xinyu; Angelidaki, Irini

    2016-06-01

    In the present study, RNA-sequencing was used to elucidate the change of anaerobic digestion metatranscriptome after long chain fatty acids (oleate) exposure. To explore the general transcriptional behavior of the microbiome, the analysis was first performed on shotgun reads without considering a reference metagenome. As a second step, RNA reads were aligned on the genes encoded by the microbial community, revealing the expression of more than 51 000 different transcripts. The present study is the first research which was able to dissect the transcriptional behavior at a single species level by considering the 106 microbial genomes previously identified. The exploration of the metabolic pathways confirmed the importance of Syntrophomonas species in fatty acids degradation, and also highlighted the presence of protective mechanisms toward the long chain fatty acid effects in bacteria belonging to Clostridiales, Rykenellaceae, and in species of the genera Halothermothrix and Anaerobaculum. Additionally, an interesting transcriptional activation of the chemotaxis genes was evidenced in seven species belonging to Clostridia, Halothermothrix, and Tepidanaerobacter. Surprisingly, methanogens revealed a very versatile behavior different from each other, even among similar species of the Methanoculleus genus, while a strong increase of the expression level in Methanosarcina sp. was evidenced after oleate addition.

  1. Reduction of saltiness and acrylamide levels in palm sugar-like flavouring through buffer modification and the addition of calcium chloride.

    PubMed

    Tan, Phui Yee; Tan, Chin Ping; Abas, Faridah; Ho, Chun Wai; Mustapha, Wan Aida Wan

    2013-06-10

    Palm sugar-like flavouring (PSLF) is a type of flavour product that is formed by heating amino acids and sugar under specific heating conditions. Unfortunately, PSLF has a salty taste and contains high amounts of acrylamide. Hence, the objective of this research was to reduce saltiness and acrylamide without negatively affecting the aroma properties of PSLF. A decrease in the sodium phosphate (NaHPO₄) buffer concentration from 0.20 to 0.02 M was found to reduce sodium to approximately 15% of the level found in original PSLF. A further decrease (~25%) in the sodium content was achieved by removing monobasic sodium phosphate (NaH₂PO₄) from the buffer system. Meanwhile, the addition of CaCl₂ at 20-40 mg/L reduced the acrylamide content in PSLF by as much as 58%. A CaCl₂ concentration of 20 mg/mL was most favourable as it most efficiently suppressed acrylamide formation while providing an acceptably high flavour yield in PSLF. In view of the high acrylamide content in PSLF, additional work is necessary to further reduce the amount of acrylamide by controlling the asparagine concentration in the precursor mixture.

  2. Decreasing prolactin levels leads to a lower diving effort but does not affect breeding success in Adélie penguins.

    PubMed

    Cottin, Manuelle; Chastel, Olivier; Kato, Akiko; Debin, Marion; Takahashi, Akinori; Ropert-Coudert, Yan; Raclot, Thierry

    2014-02-01

    Current research on seabirds suggests a key role of hormones in the trade-off between self-maintenance and parental investment through their influence on foraging decisions during the breeding period. Although prolactin is known to have major effects on parental care, its role in foraging behavior has rarely been investigated in seabirds to date. The aim of this study was to assess the influence of an experimental decrease in prolactin levels on foraging decisions and its consequences on breeding success in free-living seabirds. To achieve this, we implanted bromocriptine (an inhibitor of prolactin secretion) in male Adélie penguins (Pygoscelis adeliae), monitored their foraging behavior using time-depth recorders over several trips, and recorded their reproductive output. On average 8±0.5days after implantation, we showed that bromocriptine administration led to an efficient decrease in prolactin levels. However, no differences were seen in foraging trip durations between bromocriptine-implanted birds and controls. Moreover, the time spent diving and the number of dives performed per trip were similar in both groups. By contrast, all diving parameters (including diving efficiency) were negatively affected by the treatment during the first at-sea trip following the treatment. Finally, the treatment did not affect adult body condition or chick growth and survival. Our study highlights the short-term negative effect of low prolactin levels on diving effort, but indicates that a short-term and/or low-magnitude decrease in prolactin levels alone is not sufficient to modify consistently the body maintenance or the parental investment of Adélie penguins.

  3. A possible mechanism for 2,2',4,4',5,5'-hexachlorobiphenyl-mediated decrease in serum thyroxine level in mice

    SciTech Connect

    Kato, Yoshihisa; Onishi, Mao; Haraguchi, Koichi; Ikushiro, Shinichi; Ohta, Chiho; Koga, Nobuyuki; Endo, Tetsuya; Yamada, Shizuo; Degawa, Masakuni

    2011-07-01

    Serum total thyroxine (T{sub 4}) level was markedly decreased, without significant increases in the levels of hepatic T{sub 4}-UDP-glucuronosyltransferase (T{sub 4}-UGT) and serum thyroid-stimulating hormone, 3 days after treatment with 2,2',4,4',5,5'-hexachlorobiphenyl (CB153) (100 mg/kg, ip) in both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive C57BL/6 and TCDD-resistant DBA/2 mice. Likewise, in either strain of mice, no CB153-mediated changes in the binding levels of [{sup 125}I]T{sub 4} to serum proteins, such as transthyretin, albumin, and thyroxine binding globulin, were observed, while in CB153-pretreated C57BL/6 mice, but not in CB153-pretreated DBA/2 mice, the levels of biliary [{sup 125}I]T{sub 4} and [{sup 125}I]T{sub 4}-glucuronide at 90-120 min after injection of [{sup 125}I]T{sub 4} slightly increased, as compared with those in the corresponding control mice. Concerning tissue distribution of [{sup 125}I]T{sub 4}, liver-selective increases in the [{sup 125}I]T{sub 4} accumulation by CB153-pretreatment were observed in both C57BL/6 and DBA/2 mice, and the hepatic levels of [{sup 125}I]T{sub 4} in the C57BL/6 and DBA/2 mice became more than 44% and 34% of the [{sup 125}I]T{sub 4} dosed, respectively. The present findings indicated that the CB153-mediated decreases in the level of serum total T{sub 4} in C57BL/6 and DBA/2 mice occur mainly through an increase in the accumulation of T{sub 4} in the liver.

  4. Additive Effect of Qidan Dihuang Grain, a Traditional Chinese Medicine, and Angiotensin Receptor Blockers on Albuminuria Levels in Patients with Diabetic Nephropathy: A Randomized, Parallel-Controlled Trial

    PubMed Central

    Xiang, Lei; Jiang, Pingping; Zhou, Lin; Sun, Xiaomin; Bi, Jianlu; Cui, Lijuan; Nie, Xiaoli; Luo, Ren; Liu, Yanyan

    2016-01-01

    Albuminuria is characteristic of early-stage diabetic nephropathy (DN). The conventional treatments with angiotensin receptor blockers (ARB) are unable to prevent the development of albuminuria in normotensive individuals with type 2 diabetes mellitus (T2DM). Purpose. The present study aimed to evaluate the effect of ARB combined with a Chinese formula Qidan Dihuang grain (QDDHG) in improving albuminuria and Traditional Chinese Medicine Symptom (TCMS) scores in normotensive individuals with T2DM. Methods. Eligible patients were randomized to the treatment group and the control group. Results. Compared with baseline (week 0), both treatment and control groups markedly improved the 24-hour albuminuria, total proteinuria (TPU), and urinary albumin to creatinine ratio (A/C) at 4, 8, and 12 weeks. Between treatment and the control group, the levels of albuminuria in the treatment group were significantly lower than in the control group at 8 and 12 weeks (p < 0.05). In addition, treatment group markedly decreased the scores of TCMS after treatment. Conclusion. This trial suggests that QDDHG combined with ARB administration decreases the levels of albuminuria and the scores for TCMS in normotensive individuals with T2DM. PMID:27375762

  5. A Meiosis-Specific Form of the APC/C Promotes the Oocyte-to-Embryo Transition by Decreasing Levels of the Polo Kinase Inhibitor Matrimony

    PubMed Central

    Whitfield, Zachary J.; Chisholm, Jennifer; Hawley, R. Scott; Orr-Weaver, Terry L.

    2013-01-01

    Oocytes are stockpiled with proteins and mRNA that are required to drive the initial mitotic divisions of embryogenesis. But are there proteins specific to meiosis whose levels must be decreased to begin embryogenesis properly? The Drosophila protein Cortex (Cort) is a female, meiosis-specific activator of the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. We performed immunoprecipitation of Cortex followed by mass spectrometry, and identified the Polo kinase inhibitor Matrimony (Mtrm) as a potential interactor with Cort. In vitro binding assays showed Mtrm and Cort can bind directly. We found Mtrm protein levels to be reduced dramatically during the oocyte-to-embryo transition, and this downregulation did not take place in cort mutant eggs, consistent with Mtrm being a substrate of APCCort. We showed that Mtrm is subject to APCCort-mediated proteasomal degradation and have identified a putative APC/C recognition motif in Mtrm that when mutated partially stabilized the protein in the embryo. Furthermore, overexpression of Mtrm in the early embryo caused aberrant nuclear divisions and developmental defects, and these were enhanced by decreasing levels of active Polo. These data indicate APCCort ubiquitylates Mtrm at the oocyte-to-embryo transition, thus preventing excessive inhibition of Polo kinase activity due to Mtrm's presence. PMID:24019759

  6. Ragweed-allergic subjects have decreased serum levels of chemokines CCL2, CCL3, CCL4 and CCL5 out of the pollen season

    PubMed Central

    Kostova, Zhivka; Batsalova, Tsvetelina; Moten, Dzhemal; Teneva, Ivanka

    2016-01-01

    CC-chemokines are important mediators of the allergic responses and regulate the cell trafficking. The aim of this study was to examine the serum levels of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES, and to determine whether there are differences between ragweed-allergic subjects and healthy individuals out of the pollen season. Peripheral blood samples were collected from 24 subjects allergic to ragweed pollen and 12 healthy controls. Serum concentrations of chemokines/cytokines were measured by an enzyme-linked immunosorbent assay. We observed significantly decreased concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES in the sera of ragweed-allergic patients compared to the healthy individuals (32.2 vs. 106.4 pg/ml, 89.5 vs. 135.7 pg/ml, 63.4 vs. 119.2 pg/ml and 11.2 vs. 18.1 ng/ml, respectively, p < 0.01). In contrast to the CC-chemokines, the serum levels of IL-8/CXCL8 showed a significant increase (p < 0.05) in the allergic group compared to the non-allergic subjects. Interleukin 4 levels were similar in both groups. In the sera of allergic patients, we have also detected significantly elevated levels of ragweed-specific IgE and IgG. However, decreased serum concentrations of the four CC-chemokines and elevated levels of IL-8/CXCL8 can be used as biomarkers for more accurate evaluation of the allergic status of patients with pollen allergy out of the season, to study the mechanisms for activation/inhibition of the subclinical allergic responses and for development of therapeutic strategies. PMID:26862308

  7. Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study

    PubMed Central

    Elkan, Ann-Charlotte; Sjöberg, Beatrice; Kolsrud, Björn; Ringertz, Bo; Hafström, Ingiäld; Frostegård, Johan

    2008-01-01

    Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (anti-PCs). Methods Sixty-six patients with active RA were randomly assigned to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 year. Thirty patients in the vegan group completed more than 3 months on the diet regimen. Blood lipids were analyzed by routine methods, and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay. Data and serum samples were obtained at baseline and after 3 and 12 months. Results Mean ages were 50.0 years for the vegan group and 50.8 years for controls. Gluten-free vegan diet induced lower body mass index (BMI) and low-density lipoprotein (LDL) and higher anti-PC IgM than control diet (p < 0.005). In the vegan group, BMI, LDL, and cholesterol decreased after both 3 and 12 months (p < 0.01) and oxLDL after 3 months (p = 0.021) and trendwise after 12 months (p = 0.090). Triglycerides and high-density lipoprotein did not change. IgA anti-PC levels increased after 3 months (p = 0.027) and IgM anti-PC levels increased trendwise after 12 months (p = 0.057). There was no difference in IgG anti-PC levels. In the control diet group, IgM anti-PC levels decreased both after 3 and 12 months (p < 0.01). When separating vegan patients into clinical responders and non-responders at 12 months, the effects on oxLDL and anti-PC IgA were seen only in responders (p < 0.05). Conclusion A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory, including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels. PMID:18348715

  8. Former Abusers of Anabolic Androgenic Steroids Exhibit Decreased Testosterone Levels and Hypogonadal Symptoms Years after Cessation: A Case-Control Study

    PubMed Central

    Selmer, Christian; Østergren, Peter Busch; Pedersen, Karen Boje; Schou, Morten; Gustafsson, Finn; Faber, Jens; Juul, Anders; Kistorp, Caroline

    2016-01-01

    Aims Abuse of anabolic androgenic steroids (AAS) is highly prevalent among male recreational athletes. The objective of this study was to investigate the impact of AAS abuse on reproductive hormone levels and symptoms suggestive of hypogonadism in current and former AAS abusers. Methods This study had a cross-sectional case-control design and involved 37 current AAS abusers, 33 former AAS abusers (mean (95%CI) elapsed duration since AAS cessation: 2.5 (1.7; 3.7) years) and 30 healthy control participants. All participants were aged 18–50 years and were involved in recreational strength training. Reproductive hormones (FSH, LH, testosterone, inhibin B and anti-Müllerian hormone (AMH)) were measured using morning blood samples. Symptoms of hypogonadism (depressive symptoms, fatigue, decreased libido and erectile dysfunction) were recorded systematically. Results Former AAS abusers exhibited significantly lower median (25th –75th percentiles) total and free testosterone levels than control participants (total testosterone: 14.4 (11.9–17.7) nmol/l vs. 18.8 (16.6–22.0) nmol/l) (P < 0.01). Overall, 27.2% (13.3; 45.5) of former AAS abusers exhibited plasma total testosterone levels below the lower reference limit (12.1 nmol/l) whereas no control participants exhibited testosterone below this limit (P < 0.01). Gonadotropins were significantly suppressed, and inhibin B and AMH were significantly decreased in current AAS abusers compared with former AAS abusers and control participants (P < 0.01). The group of former AAS abusers had higher proportions of participants with depressive symptoms ((24.2%) (11.1; 42.2)), erectile dysfunction ((27.3%) (13.3; 45.6)) and decreased libido ((40.1%) (23.2; 57.0)) than the other two groups (trend analyses: P < 0.05). Conclusions Former AAS abusers exhibited significantly lower plasma testosterone levels and higher frequencies of symptoms suggestive of hypogonadism than healthy control participants years after AAS cessation

  9. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    PubMed

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD.

  10. Intracerebroventricular administration of α-ketoisocaproic acid decreases brain-derived neurotrophic factor and nerve growth factor levels in brain of young rats.

    PubMed

    Wisniewski, Miriam S W; Carvalho-Silva, Milena; Gomes, Lara M; Zapelini, Hugo G; Schuck, Patrícia F; Ferreira, Gustavo C; Scaini, Giselli; Streck, Emilio L

    2016-04-01

    Maple syrup urine disease (MSUD) is an inherited aminoacidopathy resulting from dysfunction of the branched-chain keto acid dehydrogenase complex, leading to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine as well as their corresponding transaminated branched-chain α-ketoacids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. However, the effect of accumulating α-ketoacids in MSUD on neurotrophic factors has not been investigated. Thus, the objective of the present study was to evaluate the effects of acute intracerebroventricular administration of α-ketoisocaproic acid (KIC) on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in the brains of young male rats. Ours results showed that intracerebroventricular administration of KIC decreased BDNF levels in hippocampus, striatum and cerebral cortex, without induce a detectable change in pro-BDNF levels. Moreover, NGF levels in the hippocampus were reduced after intracerebroventricular administration of KIC. In conclusion, these data suggest that the effects of KIC on demyelination and memory processes may be mediated by reduced trophic support of BDNF and NGF. Moreover, lower levels of BDNF and NGF are consistent with the hypothesis that a deficit in this neurotrophic factor may contribute to the structural and functional alterations of brain underlying the psychopathology of MSUD, supporting the hypothesis of a neurodegenerative process in MSUD. PMID:26586008

  11. Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life.

    PubMed

    Aksu, Ilkay; Baykara, Basak; Ozbal, Seda; Cetin, Ferihan; Sisman, Ali Riza; Dayi, Ayfer; Gencoglu, Celal; Tas, Aysegul; Büyük, Erkan; Gonenc-Arda, Sevil; Uysal, Nazan

    2012-05-16

    In a previous study we demonstrated that, regular aerobic exercise during pregnancy decreased maternal deprivation induced anxiety. The purpose of this study is to investigate whether the positive effects of maternal exercise on the male and female offspring's early and late period of life. Half of the test subjects in each group were evaluated when they were 26 days old, and the other half were evaluated when they were 4 months old. The anxiety levels of maternally exercised groups were less than the control groups in both sexes and in both prepubertal and adult periods. The locomotor activity more increased in females. The prefrontal VEGF and BDNF levels were greater for both age groups and sexes in the maternally exercised group compared to control group. Moreover, there was a strong positive correlations between prefrontal cortex BDNF levels and results of open field tests; and VEGF levels and results of elevated plus maze tests. There was no difference in serum corticosterone levels between groups. These results indicate that maternal exercise during pregnancy may protect the pups from anxiety in early and late periods of life, and affects the prefrontal cortex positively.

  12. Green tea increases anti-inflammatory tristetraprolin and decreases pro-inflammatory tumor necrosis factor mRNA levels in rats

    PubMed Central

    Cao, Heping; Kelly, Meghan A; Kari, Frank; Dawson, Harry D; Urban, Joseph F; Coves, Sara; Roussel, Anne M; Anderson, Richard A

    2007-01-01

    Background Tristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA, and represent a potential therapeutic target for inflammation-related diseases. Tea has anti-inflammatory properties but the molecular mechanisms have not been completely elucidated. We hypothesized that TTP and/or its homologues might contribute to the beneficial effects of tea as an anti-inflammatory product. Methods Quantitative real-time PCR was used to investigate the effects of green tea (0, 1, and 2 g solid extract/kg diet) on the expression of Ttp family genes (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3), pro-inflammatory genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2), and Elavl1/Hua/Hur and Vegf genes in liver and muscle of rats fed a high-fructose diet known to induce insulin resistance, oxidative stress, inflammation, and TNF-alpha levels. Results Ttp and Zfp36l1 mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle. Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid extract/kg diet) increased Ttp mRNA levels by 50–140% but Tnf mRNA levels decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in the muscle. Tea (2 g solid extract/kg diet) increased Elavl1/Hua/Hur mRNA levels by 40% in the liver but did not affect any of the other mRNA levels in liver or muscle. Conclusion These results show that tea can modulate Ttp mRNA levels in animals and suggest that a post-transcriptional mechanism through TTP could partially account for tea's anti-inflammatory properties. The results also suggest that drinking adequate amounts of green tea may play a role in the prevention of inflammation-related diseases. PMID:17207279

  13. O- and H-induced surface core level shifts on Ru(0001): prevalence of the additivity rule

    NASA Astrophysics Data System (ADS)

    Lizzit, S.; Zhang, Y.; Kostov, K. L.; Petaccia, L.; Baraldi, A.; Menzel, D.; Reuter, K.

    2009-04-01

    In previous work on adsorbate-induced surface core level shifts (SCLSs), the effects caused by O atom adsorption on Rh(111) and Ru(0001) were found to be additive: the measured shifts for first-layer Ru atoms depended linearly on the number of directly coordinated O atoms. Density-functional theory calculations quantitatively reproduced this effect, allowed separation of initial- and final-state contributions, and provided an explanation in terms of a roughly constant charge transfer per O atom. We have now conducted similar measurements and calculations for three well-defined adsorbate and coadsorbate layers containing O and H atoms: (1 × 1)-H, (2 × 2)-(O+H) and (2 × 2)-(O+3H) on Ru(0001). As H is stabilized in fcc sites in the prior two structures and in hcp sites in the latter, this enables us to not only study coverage and coadsorption effects on the adsorbate-induced SCLSs, but also the sensitivity to similar adsorption sites. Remarkably good agreement is obtained between experiment and calculations for the energies and geometries of the layers, as well as for all aspects of the SCLS values. The additivity of the next-neighbor adsorbate-induced SCLSs is found to prevail even for the coadsorbate structures. While this confirms the suggested use of SCLSs as fingerprints of the adsorbate configuration, their sensitivity is further demonstrated by the slightly different shifts unambiguously determined for H adsorption in either fcc or hcp hollow sites.

  14. Fertilizer addition lessens the flux of microbial carbon to higher trophic levels in soil food webs of grassland.

    PubMed

    Lemanski, Kathleen; Scheu, Stefan

    2014-10-01

    Roots and root-derived C compounds are increasingly recognised as important resources for soil animal food webs. We used (13)C-labelled glucose as a model C compound representing root exudates to follow the incorporation of root-derived C into the soil animal food web of a temperate grassland over a period of 52 weeks. We investigated variations in glucose C incorporation with fertilizer addition and sward composition, i.e. variations in plant functional groups. The approach allowed the differentiation of trophic chains based on primary decomposers feeding on litter and phytophagous species feeding on roots (i.e. not incorporating glucose C) from those based on secondary decomposers feeding on microorganisms (thereby assimilating glucose C). Each of the studied soil animal species incorporated glucose C, indicating that the majority of grassland soil animal species rely on microorganisms as food resources with microorganisms being fuelled by root exudates. However, incorporation of glucose C into soil animal species varied markedly with species identity, suggesting that detritivorous microarthropods complement each other in channelling microbial C through soil food webs. Fertilizer addition markedly reduced the concentration of glucose C in most soil animal species as well as the absolute transfer of glucose C into oribatid mites as major secondary decomposers. The results suggest that fertilizer addition shifts the basis of the decomposer food web towards the use of unlabelled resources, presumably roots, i.e. towards a herbivore system, thereby lessening the link between microorganisms and microbial grazers and hampering the propagation of microbial C to higher trophic levels.

  15. Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4+ T Helper Cells

    PubMed Central

    Hynes, Thomas R.; Yost, Evan A.; Hartle, Cassandra M.; Ott, Braden J.

    2015-01-01

    Background: Inhibition of G-protein βγ (Gβγ) signaling was found previously to enhance T cell receptor (TCR)-stimulated increases in interleukin 2 (IL-2) mRNA in CD4+ T helper cells, suggesting that Gβγ might be a useful drug target for treating autoimmune diseases, as low dose IL-2 therapy can suppress autoimmune responses. Because IL-2 may counteract autoimmunity in part by shifting CD4+ T helper cells away from the Type 1 T helper cell (TH1) and TH17 subtypes towards the TH2 subtype, the purpose of this study was to determine if blocking Gβγ signaling affected the balance of TH1, TH17, and TH2 cytokine mRNAs produced by CD4+ T helper cells. Methods: Gallein, a small molecule inhibitor of Gβγ, and siRNA-mediated silencing of the G-protein β1 subunit (Gβ1) were used to test the effect of blocking Gβγ on mRNA levels of cytokines in primary human TCR-stimulated CD4+ T helper cells. Results: Gallein and Gβ1 siRNA decreased interferon-γ (IFN-γ) and IL-17A mRNA levels in TCR-stimulated CD4+ T cells grown under TH1-promoting conditions. Inhibiting Gβγ also decreased mRNA levels of STAT4, which plays a positive role in TH1 differentiation and IL-17A production. Moreover, mRNA levels of the STAT4-regulated TH1-associated proteins, IL-18 receptor β chain (IL-18Rβ), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), lymphocyte activation gene 3 (LAG-3), natural killer cell group 7 sequence (NKG7), and oncostatin M (OSM) were also decreased upon Gβγ inhibition. Gallein also increased IL-4, IL-5, IL-9, and IL-13 mRNA levels in TCR-stimulated memory CD4+ T cells grown in TH2-promoting conditions. Conclusions: Inhibiting Gβγ to produce these shifts in cytokine mRNA production might be beneficial for patients with autoimmune diseases such as rheumatoid arthritis (RA), Crohn’s disease (CD), psoriasis, multiple sclerosis (MS), and Hashimoto’s thyroiditis (HT), in which both IFN-γ and IL-17A are elevated. PMID:27095999

  16. Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

    PubMed Central

    Mao, Zhigang; Wu, Jeffrey H.; Dong, Tingting; Wu, Mei X.

    2016-01-01

    Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study. PMID:26830658

  17. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification

    NASA Astrophysics Data System (ADS)

    Kadir, K.; Gao, H.; Payne, A.; Soraghan, J.; Berry, C.

    2012-10-01

    In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm2 between individual investigator one (IV1) and LSM, and -122 mm2 between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients.

  18. Effectiveness of a nursing intervention in decreasing the anxiety levels of family members of patients undergoing cardiac surgery: a randomized clinical trial

    PubMed Central

    Hamester, Letícia; de Souza, Emiliane Nogueira; Cielo, Cibele; Moraes, Maria Antonieta; Pellanda, Lúcia Campos

    2016-01-01

    ABSTRACT Objective: to verify the effectiveness of nursing orientation provided to families of patients in the immediate post-operative following cardiac surgery before the first visit to the post-anesthesia care unit, in decreasing anxiety levels, compared to the unit's routine orientation. Method: open randomized clinical trial addressing family members in the waiting room before the first visit in the immediate post-operative period. The family members assigned to the intervention group received audiovisual orientation concerning the patients' conditions at the time and the control group received the unit's routine orientation. Outcome anxiety was assessed using the STAI-State. Results: 210 individuals were included, 105 in each group, aged 46.4 years old on average (±14.5); 69% were female and 41% were the patients' children. The mean score obtained on the anxiety assessment in the intervention group was 41.3±8.6, while the control group scored 50.6±9.4 (p<0.001). Conclusion: a nursing intervention focused on providing guidance to families before their first visit to patients in the immediate post-operative period of cardiac surgery helps to decrease the levels of anxiety of companions, making them feel better prepared for the moment. ReBEC (Brazilian Clinical Trials Registry) and The Universal Trial Number (UTN), No. U1111-1145-6172. PMID:27533263

  19. Mitigating the effects of Xuebijing injection on hematopoietic cell injury induced by total body irradiation with γ rays by decreasing reactive oxygen species levels.

    PubMed

    Li, Deguan; Lu, Lu; Zhang, Junling; Wang, Xiaochun; Xing, Yonghua; Wu, Hongying; Yang, Xiangdong; Shi, Zhexin; Zhao, Mingfeng; Fan, Saijun; Meng, Aimin

    2014-06-12

    Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ) is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR). Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI). Our results showed that XBJ (0.4 mL/kg) significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs) and hematopoietic cells, given that bone marrow (BM) cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM) than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS) by increasing glutathione (GSH) and superoxide dismutase (SOD) levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

  20. Use of Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry to Demonstrate Decreased Serum Statin Levels after Extracorporeal LDL-Cholesterol Elimination

    PubMed Central

    Bláha, M.; Vlčková, H.; Nováková, L.; Solichová, D.; Solich, P.; Lánská, M.; Malý, J.; Bláha, V.

    2011-01-01

    Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3–12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme. PMID:21076535

  1. Induction of differentiation in v-Ha-ras-transformed MDCK cells by prostaglandin E2 and 8-bromo-cyclic AMP is associated with a decrease in steady-state level of inositol 1,4,5-trisphosphate.

    PubMed Central

    Wu, Y Y; Lin, M C

    1990-01-01

    We used Ha-ras-transformed Madin-Darby canine kidney (MDCK) cells as a model to study possible signal transduction mechanisms underlying the induction of glucagon responsiveness by the differentiation inducers prostaglandin E2 (PGE2) and 8-bromo-cyclic (8-Br-cAMP) AMP and the inhibition of induction by phorbol ester or a serum factor. The steady-state level of inositol 1,4,5-trisphosphate (IP3) was higher in Ha-ras-transformed MDCK cells than in parental MDCK cells. In contrast, the steady-state level of intracellular cAMP of transformed cells was similar to that of normal cells. PGE2 and 8-Br-cAMP increased cAMP content but decreased IP3 levels in a concentration-dependent fashion after 5 days of treatment. We examined the time course for effects of PGE2 and 8-Br-cAMP and found that there was a lag period of 8 to 16 h between elevation of cAMP after the addition of 8-Br-cAMP or PGE2 and the decrease of IP3 levels. Another lag period of 2 days existed before the induction of differentiation. Both the reduction of IP3 levels and the induction of glucagon responsiveness were blocked by phorbol-12-myristate-13-acetate or serum, suggesting that a decrease in the IP3 level might be causally involved in induction of differentiation in transformed MDCK cells. However, induction of differentiation was not due to changes in the expression or guanine nucleotide-binding properties of p21 protein. It is likely that cAMP has a direct regulatory effect on the phospholipid signaling pathway. We conclude that perturbation of the inositol phosphate signaling pathway may be responsible for the induction of differentiation by PGE2 and 8-Br-cAMP in transformed MDCK cells. Images PMID:2152966

  2. Decreased body fat, elevated plasma transforming growth factor-β levels, and impaired BMP4-like signaling in biglycan-deficient mice

    PubMed Central

    Tang, Tao; Thompson, Joel C.; Wilson, Patricia G.; Nelson, Christina; Williams, Kevin Jon; Tannock, Lisa R.

    2015-01-01

    Biglycan (BGN), a small leucine-rich proteoglycan, binds the pro-fibrotic cytokine TGFβ and inhibits its bioactivity in vitro. Nevertheless, it is controversial whether BGN plays an inhibitory role in vivo. Therefore, the purpose of this study was to evaluate the effect of BGN deficiency on TGFβ activity in vivo by studying one-year-old Bgn null and wildtype mice on an Ldlr-null background. Phenotypic and metabolic characterization showed that the Bgn null mice had lower body weight, shorter body length and shorter femur length (all p<0.05). Surprisingly, the Bgn null mice also exhibited a striking reduction in percent body fat compared to wildtype mice (p=0.006), but no changes were observed in plasma triglycerides, total cholesterol, or glycohemoglobin. Both total and bioactive TGFβ1 concentrations in plasma were markedly elevated in Bgn null mice compared to wildtype mice (4-fold and 11-fold increase, respectively, both p<0.001), but no changes were found in hepatic levels of mRNA for Tgfβ1 or its receptors. Bgn null mice exhibited elevated expression of hepatic fibronectin protein (p=0.034) without changes in hepatic or renal histology, and Bgn null mice had decreased urinary albumin/creatinine ratio (p=0.01). Two key downstream targets of bone morphorgenic protein (BMP) 4 signaling, SMAD1/3/5 phosphorylation and Id2 gene expression, were found dramatically reduced in Bgn null livers (p=0.034). Thus, BGN deficiency decreases body fat in this hyperlipidemic mouse model without changing liver or kidney histology. Overall, we propose that this unexpected phenotype arises from effects of BGN deficiency in vivo to elevate TGFβ levels while decreasing BMP4-like signaling. PMID:22834985

  3. Decreased body fat, elevated plasma transforming growth factor-β levels, and impaired BMP4-like signaling in biglycan-deficient mice.

    PubMed

    Tang, Tao; Thompson, Joel C; Wilson, Patricia G; Nelson, Christina; Williams, Kevin Jon; Tannock, Lisa R

    2013-01-01

    Biglycan (BGN), a small leucine-rich proteoglycan, binds the pro-fibrotic cytokine transforming growth factor β (TGFβ) and inhibits its bioactivity in vitro. Nevertheless, it is controversial whether BGN plays an inhibitory role in vivo. Therefore, the purpose of this study was to evaluate the effect of BGN deficiency on TGFβ activity in vivo by studying 1-year-old Bgn null and wild-type (WT) mice on an Ldlr-null background. Phenotypic and metabolic characterization showed that the Bgn null mice had lower body weight, shorter body length, and shorter femur length (all p < 0.05). Surprisingly, the Bgn null mice also exhibited a striking reduction in percent body fat compared to WT mice (p == 0.006), but no changes were observed in plasma triglycerides, total cholesterol, or glycohemoglobin. Both total and bioactive TGFβ1 concentrations in plasma were markedly elevated in Bgn null mice compared to WT mice (4-fold and 11-fold increase, respectively, both p < 0.001), but no changes were found in hepatic levels of mRNA for Tgfβ1 or its receptors. Bgn null mice exhibited elevated expression of hepatic fibronectin protein (p = 0.034) without changes in hepatic or renal histology, and Bgn null mice had decreased urinary albumin/creatinine ratio (p = 0.01). Two key downstream targets of bone morphogenetic protein 4-like signaling, SMAD1/3/5 phosphorylation and Id2 gene expression, were found dramatically reduced in Bgn null livers (p = 0.034). Thus, BGN deficiency decreases body fat in this hyperlipidemic mouse model without changing liver or kidney histology. Overall, we propose that this unexpected phenotype arises from the effects of BGN deficiency in vivo to elevate TGFβ levels while decreasing bone morphogenetic protein 4-like signaling.

  4. Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

    PubMed

    Almasi, Bettina; Béziers, Paul; Roulin, Alexandre; Jenni, Lukas

    2015-09-01

    Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits.

  5. Agricultural land use and human presence around breeding sites increase stress-hormone levels and decrease body mass in barn owl nestlings.

    PubMed

    Almasi, Bettina; Béziers, Paul; Roulin, Alexandre; Jenni, Lukas

    2015-09-01

    Human activities can have a suite of positive and negative effects on animals and thus can affect various life history parameters. Human presence and agricultural practice can be perceived as stressors to which animals react with the secretion of glucocorticoids. The acute short-term secretion of glucocorticoids is considered beneficial and helps an animal to redirect energy and behaviour to cope with a critical situation. However, a long-term increase of glucocorticoids can impair e.g. growth and immune functions. We investigated how nestling barn owls (Tyto alba) are affected by the surrounding landscape and by human activities around their nest sites. We studied these effects on two response levels: (a) the physiological level of the hypothalamus-pituitary-adrenal axis, represented by baseline concentrations of corticosterone and the concentration attained by a standardized stressor; (b) fitness parameters: growth of the nestlings and breeding performance. Nestlings growing up in intensively cultivated areas showed increased baseline corticosterone levels late in the season and had an increased corticosterone release after a stressful event, while their body mass was decreased. Nestlings experiencing frequent anthropogenic disturbance had elevated baseline corticosterone levels, an increased corticosterone stress response and a lower body mass. Finally, breeding performance was better in structurally more diverse landscapes. In conclusion, anthropogenic disturbance affects offspring quality rather than quantity, whereas agricultural practices affect both life history traits. PMID:25903390

  6. Increased accumulation of carbohydrates and decreased photosynthetic gene transcript levels in wheat grown at an elevated CO{sub 2} concentration in the field

    SciTech Connect

    Nie, G.; Hendrix, D.L.; Webber, A.N.

    1995-07-01

    Repression of photosynthetic genes by increased soluble carbohydrate concentrations may explain acclimation of photosynthesis to elevated CO{sub 2} concentration. This hypothesis was examined in a field crop of spring wheat (Triticum aestivum L.) grown at both ambient (approximately 360 {mu}mol{sup -1}) and elevated (550 {mu}mol mol{sup -1}) atmospheric CO{sub 2} concentrations using free-air CO{sub 2} enrichment at Maricopa, Arizona. The correspondence of steady-state levels of mRNA transcripts (coding for the 83-kD photosystem 1 apoprotein, sedoheptulose-1,7-bisphosphatase, phosphoribulokinase, phosphoglcerodkinase, and the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase) with leaf carbohydrate concentrations (glucose-6-phosphate, glucose, fructose, sucrose, fructans, and starch) was examined at different stages of crop and leaf development and through the diurnal cycle. Overall only a weak correspondence between increased soluble carbohydrate concentrations and decreased levels for nuclear gene transcripts was found. The difference in soluble carbohydrate concentration between leaves grown at elevated and current ambient CO{sub 2} concentrations diminished with crop development, whereas the difference in transcript levels increased. In the flag leaf, soluble carbohydrate concentrations declined markedly with the onset of grain filling; yet transcript levels also declined. The results suggest that, many other factors modified its significance in this field wheat crop. 52 refs., 8 figs.

  7. A Pilot Study: Effects of Decreasing Serum Insulin with Diazoxide on Vitamin D Levels in Obese Women with Polycystic Ovary Syndrome

    PubMed Central

    Nestler, John E.; Reilly, Elizabeth R.; Cheang, Kai I.; Bachmann, Lorin M.; Downs, Robert W.

    2012-01-01

    Introduction. We conducted a pilot project to test the hypothesis that decreasing insulin concentrations with diazoxide would affect parameters of vitamin D in obese women with and without polycystic ovary syndrome (PCOS). Materials and Methods. Eight obese women with PCOS and nine matched controls participated in the study. Diazoxide was administered orally 100 mg three times daily for 10 days, and parameters of vitamin D were measured at baseline and end-of-study. Results. At baseline, women with polycystic ovary syndrome had significantly lower serum 25-hydroxyvitamin D (25[OH]D) levels than controls. After treatment with diazoxide, there were no significant changes in vitamin D parameters when PCOS and control women were evaluated separately. Diazoxide exhibited differential effects on 25(OH)D concentrations in PCOS as compared with normal women (P for interaction =0.045), and serum 25(OH)D levels converged after diazoxide treatment. Conclusions. Obese women with PCOS had significantly lower serum 25(OH)D levels at baseline than age- and body mass index–matched controls. Short-term administration with diazoxide seemed to have differential effects on 25(OH)D levels in PCOS as compared with control women. Further studies are necessary to confirm this finding. PMID:23303986

  8. Decreased astrocytic thrombospondin-1 secretion after chronic ammonia treatment reduces the level of synaptic proteins: in vitro and in vivo studies.

    PubMed

    Jayakumar, Arumugam R; Tong, Xiao Y; Curtis, Kevin M; Ruiz-Cordero, Roberto; Shamaladevi, Nagarajarao; Abuzamel, Missa; Johnstone, Joshua; Gaidosh, Gabriel; Rama Rao, Kakulavarapu V; Norenberg, Michael D

    2014-11-01

    Chronic hepatic encephalopathy (CHE) is a major complication in patients with severe liver disease. Elevated blood and brain ammonia levels have been implicated in its pathogenesis, and astrocytes are the principal neural cells involved in this disorder. Since defective synthesis and release of astrocytic factors have been shown to impair synaptic integrity in other neurological conditions, we examined whether thrombospondin-1 (TSP-1), an astrocytic factor involved in the maintenance of synaptic integrity, is also altered in CHE. Cultured astrocytes were exposed to ammonia (NH₄Cl, 0.5-2.5 mM) for 1-10 days, and TSP-1 content was measured in cell extracts and culture media. Astrocytes exposed to ammonia exhibited a reduction in intra- and extracellular TSP-1 levels. Exposure of cultured neurons to conditioned media from ammonia-treated astrocytes showed a decrease in synaptophysin, PSD95, and synaptotagmin levels. Conditioned media from TSP-1 over-expressing astrocytes that were treated with ammonia, when added to cultured neurons, reversed the decline in synaptic proteins. Recombinant TSP-1 similarly reversed the decrease in synaptic proteins. Metformin, an agent known to increase TSP-1 synthesis in other cell types, also reversed the ammonia-induced TSP-1 reduction. Likewise, we found a significant decline in TSP-1 level in cortical astrocytes, as well as a reduction in synaptophysin content in vivo in a rat model of CHE. These findings suggest that TSP-1 may represent an important therapeutic target for CHE. Defective release of astrocytic factors may impair synaptic integrity in chronic hepatic encephalopathy. We found a reduction in the release of the astrocytic matricellular proteins thrombospondin-1 (TSP-1) in ammonia-treated astrocytes; such reduction was associated with a decrease in synaptic proteins caused by conditioned media from ammonia-treated astrocytes. Exposure of neurons to CM from ammonia-treated astrocytes, in which TSP-1 is over

  9. EFFECTS OF QUARTZ PARTICLE SIZE AND SUCROSE ADDITION ON MELTING BEHAVIOR OF A MELTER FEED FOR HIGH-LEVEL GLASS

    SciTech Connect

    MARCIAL J; KRUGER AA; HRMA PR; SCHWEIGER MJ; SWEARINGEN KJ; TEGROTENHUIS WE; HENAGER SH

    2010-07-28

    The behavior of melter feed (a mixture of nuclear waste and glass-forming additives) during waste-glass processing has a significant impact on the rate of the vitrification process. We studied the effects of silica particle size and sucrose addition on the volumetric expansion (foaming) of a high-alumina feed and the rate of dissolution of silica particles in feed samples heated at 5 C/min up to 1200 C. The initial size of quartz particles in feed ranged from 5 to 195 {micro}m. The fraction of the sucrose added ranged from 0 to 0.20 g per g glass. Extensive foaming occurred only in feeds with 5-{micro}m quartz particles; particles {ge}150 {micro}m formed clusters. Particles of 5 {micro}m completely dissolved by 900 C whereas particles {ge}150 {micro}m did not fully dissolve even when the temperature reached 1200 C. Sucrose addition had virtually zero impact on both foaming and the dissolution of silica particles. Over 100 sites in the United States are currently tasked with the storage of nuclear waste. The largest is the Hanford Site located in southeastern Washington State with 177 subterranean tanks containing over fifty-million gallons of nuclear waste from plutonium production from 1944 through 1987. This waste will be vitrified at the Hanford Tank Waste Treatment and Immobilization Plant. In the vitrification process, feed is charged into a melter and converted into glass to be ultimately stored in a permanent repository. The duration of waste-site cleanups by the vitrification process depends on the rate of melting, i.e., on the rate of the feed-to-glass conversion. Foaming associated with the melting process and the rate of dissolution of quartz particles (silica being the major glass-forming additive) are assumed to be important factors that influence the rate of melting. Previous studies on foaming of high-alumina feed demonstrated that varying the makeup of a melter feed has a significant impact on foaming. The volume of feeds that contained 5-{micro

  10. Impact of decreasing ratios of insecticide-treated seed on flea beetle (Coleoptera: Chrysomelidae, Phyllotreta spp.) feeding levels and canola seed yields.

    PubMed

    Soroka, Juliana J; Grenkow, Larry F; Irvine, R Byron

    2008-12-01

    Field studies were conducted at two locations on the Canadian prairies to investigate use of reduced ratios of insecticide-treated seed in controlling flea beetle (Coleoptera: Chrysomelidae, Phyllotreta spp.) damage to canola (Brassica napus L. and Brassica rapa L.). Five treatments were evaluated: bare seed control, fungicide-only (0X), and three ratios of insecticide plus fungicide in proportions of all (1X), two thirds (0.67X), or one third (0.33X) of the seeds coated with insecticide. Decreasing treated seed ratios by one third had no consistent deleterious effects on flea beetle damage, seedling growth, plant density, seed yield, or net cash return. Flea beetle injury to seedlings in the 1X treatment was similar to that of seedlings in the 0.67X treatment, with only two exceptions, and it was almost always lower than that of seedlings without insecticide. The 0.33X treatment generally had flea beetle feeding levels between those of the two high and the two noninsecticide treatments. Plant stand and seedling growth rates with 1X and 0.67X treatments were similar and higher than with bare seed or fungicide-alone treatments. Seed yields were inversely proportional to flea beetle feeding levels. Under very heavy flea beetle feeding, seed yields and net cash returns were highest in 1X plots, but when flea beetle feeding pressure was less extreme and canola growing conditions were favorable, 0.67X seed yields and profits from them were comparable to those in 1X treatments. On an economic basis, currently there is no advantage to decreasing the level of insecticide treated canola seed, but other considerations may affect this assessment.

  11. High-level carbapenem resistance in a Citrobacter freundii clinical isolate is due to a combination of KPC-2 production and decreased porin expression.

    PubMed

    Zhang, Rong; Yang, Lijiang; Cai, Jia Chang; Zhou, Hong Wei; Chen, Gong-Xiang

    2008-03-01

    An imipenem-resistant isolate of Citrobacter freundii ZJ163 (MIC 256 microg ml(-1)) isolated from a Chinese hospital was investigated. The C. freundii ZJ163 isolate exhibited high-level resistance to carbapenems, penicillins, cephalosporins, cefoxitin, aztreonam, quinolones and aminoglycosides. Isoelectric focusing (IEF) demonstrated three beta-lactamases with pIs of 5.4 (TEM-1), 6.7 (KPC-2) and 7.9 (CTX-M-14). Two different transconjugants (types A and B) were obtained by conjugation studies. The type A transconjugant exhibited reduced susceptibility or resistance to penicillins, cephalosporins and aztreonam, but was susceptible to carbapenems, quinolones and aminoglycosides. The antimicrobial susceptibility patterns of the type B transconjugant were similar to that of type A, except for its significantly reduced carbapenem susceptibility (imipenem MIC 2 microg ml(-1)). IEF, specific PCRs and DNA sequence analysis indicated that the type A transconjugant produced CTX-M-14 beta-lactamase with a pI of 7.9, that the type B transconjugant produced KPC-2 beta-lactamase with a pI of 6.7 and that the beta-lactamase with a pI of 5.4 was TEM-1. PCR analysis and sequencing confirmed the presence of the ampC gene in the chromosomal DNA from C. freundii ZJ163, although no activity of AmpC beta-lactamase was detected by IEF. Urea/SDS-PAGE analysis of outer-membrane proteins revealed that the levels of the 41 and 38 kDa porins were decreased in C. freundii ZJ163. It was concluded that production of KPC-2 combined with decreased expression of porins contributes to high-level resistance to carbapenems in C. freundii ZJ163.

  12. Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression

    PubMed Central

    Chowdhury, Subrata; Grimm, Larson; Gong, Ying Jia Kate; Wang, Beixi; Li, Bing; Srikant, Coimbatore B.; Gao, Zu-hua; Liu, Jun-Li

    2015-01-01

    We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents) to active cortisol (corticosterone) in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX) and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion. PMID:26305481

  13. Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

    PubMed

    Chowdhury, Subrata; Grimm, Larson; Gong, Ying Jia Kate; Wang, Beixi; Li, Bing; Srikant, Coimbatore B; Gao, Zu-hua; Liu, Jun-Li

    2015-01-01

    We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents) to active cortisol (corticosterone) in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX) and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.

  14. Supplementation by thylakoids to a high carbohydrate meal decreases feelings of hunger, elevates CCK levels and prevents postprandial hypoglycaemia in overweight women.

    PubMed

    Stenblom, Eva-Lena; Montelius, Caroline; Östbring, Karolina; Håkansson, Maria; Nilsson, Sofia; Rehfeld, Jens F; Erlanson-Albertsson, Charlotte

    2013-09-01

    Thylakoids are chlorophyll-containing membranes in chloroplasts that have been isolated from green leaves. It has been previously shown that thylakoids supplemented with a high-fat meal can affect cholecystokinin (CCK), ghrelin, insulin and blood lipids in humans, and can act to suppress food intake and prevent body weight gain in rodents. This study investigates the addition of thylakoids to a high carbohydrate meal and its effects upon hunger motivation and fullness, and the levels of glucose, insulin, CCK, ghrelin and tumour necrosis factor (TNF)-alpha in overweight women. Twenty moderately overweight female subjects received test meals on three different occasions; two thylakoid enriched and one control, separated by 1 week. The test meals consisted of a high carbohydrate Swedish breakfast, with or without addition of thylakoids. Blood samples and VAS-questionnaires were evaluated over a 4-h period. Addition of thylakoids suppressed hunger motivation and increased secretion of CCK from 180 min, and prevented postprandial hypoglycaemia from 90 min following food intake. These effects indicate that thylakoids may intensify signals of satiety. This study therefore suggests that the dietary addition of thylakoids could aid efforts to reduce food intake and prevent compensational eating later in the day, which may help to reduce body weight over time.

  15. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification.

    PubMed

    Kadir, K; Gao, H; Payne, A; Soraghan, J; Berry, C

    2012-10-01

    In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm(2) between individual investigator one (IV1) and LSM, and -122 mm(2) between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients.

  16. Luteinizing hormone releasing hormone (LHRH) neurons maintained in nasal explants decrease LHRH messenger ribonucleic acid levels after activation of GABA(A) receptors.

    PubMed

    Fueshko, S M; Key, S; Wray, S

    1998-06-01

    Inhibition of the LHRH system appears to play an important role in preventing precocious activation of the hypothalamic-pituitary-gonadal axis. Evidence points to gamma-aminobutyric acid (GABA) as the major negative regulator of postnatal LHRH neuronal activity. Changes in LHRH messenger RNA (mRNA) levels after alterations of GABAergic activity have been reported in vivo. However, the extent to which GABA acts directly on LHRH neurons to effect LHRH mRNA levels has been difficult to ascertain. The present work evaluates the effect of GABAergic activity, via GABA(A) receptors, on LHRH neuropeptide gene expression in LHRH neurons maintained in olfactory explants generated from E11.5 mouse embryos. These explants maintain large numbers of primary LHRH neurons that migrate from bilateral olfactory pits in a directed manner. Using in situ hybridization histochemistry and single cell analysis, we report dramatic alterations in LHRH mRNA levels. Inhibition of spontaneous synaptic activity by GABA(A) antagonists, bicuculline (10(-5) M) or picrotoxin (10(-4) M), or of electrical activity by tetrodotoxin (TTX, 10(-6) M) significantly increased LHRH mRNA levels. In contrast, LHRH mRNA levels decreased in explants cultured with the GABA(A) receptor agonist, muscimol (10(-4) M), or KCl (50 mM). The observed responses suggest that LHRH neurons possess functional pathways linking GABA(A) receptors to repression of neuropeptide gene expression and indicate that gene expression in embryonic LHRH neurons, outside the CNS, is highly responsive to alterations in neuronal activity.

  17. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation

    PubMed Central

    Choi, Insup; Woo, Joo Hong; Jou, Ilo

    2016-01-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development. PMID:26924929

  18. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation.

    PubMed

    Choi, Insup; Woo, Joo Hong; Jou, Ilo; Joe, Eun-Hye

    2016-02-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development.

  19. Inhibition of GSK-3 reduces prostaglandin E2 production by decreasing the expression levels of COX-2 and mPGES-1 in monocyte/macrophage lineage cells.

    PubMed

    Noma, Toshihiro; Takahashi-Yanaga, Fumi; Arioka, Masaki; Mori, Yoshihide; Sasaguri, Toshiyuki

    2016-09-15

    Inflammatory stimuli induce prostaglandin E2 (PGE2) synthesis by upregulating cycloxgenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Glycogen synthase kinase-3 (GSK-3) reportedly plays an important role in inflammatory reactions, whereas the role of this enzyme in inflammatory PGE2 production remains unclear. In the present study, therefore, we examined whether inhibition of GSK-3 can reduce inflammatory PGE2 production in vitro and in vivo. When macrophage-like cells differentiated from THP-1 were stimulated with lipopolysaccharide (LPS), PGE2 production and the expression levels of COX-2 and mPGES-1 were markedly elevated. GSK-3 inhibitors LiCl and SB216763 strongly suppressed their protein levels through inhibition of mRNA expressions. Subsequently, we examined the effect of GSK-3 inhibitors on nuclear factor κB (NF-κB) and early growth response-1 (Egr-1). The GSK-3 inhibitors had no significant effect on the NF-κB pathway, whereas they significantly decreased the expression level of Egr-1. Pharmacological and genetic inhibitions of GSK-3 also strongly suppressed PGE2 production in cultured peritoneal macrophages and in inflammatory air pouches made under the skin of living mice. These results suggested that GSK-3 plays a key role in PGE2 production by increasing COX-2 and mPGES-1 probably through Egr-1-mediated transcription and GSK-3 inhibitors may be potential as novel anti-inflammatory drugs. PMID:27453433

  20. The varying effects of warm-water bathing therapies: partial bathing decreases exercise tolerance to levels similar to full-body bathing.

    PubMed

    Ohshige, Tadasu; Ohwatashi, Akihiko; Kiyama, Ryoji

    2015-11-01

    [Purpose] The purpose of this study was to determine differences in postural sway and tolerance to exercise before and after full-body, forearm, and lower leg bathing in warm-water. [Subjects and Methods] Thirteen healthy, young adult males were subjected to full-body, forearm, and lower leg bathing at 41 °C for 10 minutes. [Results] The 2-point discrimination sense value and total trajectory length significantly decreased after bathing. [Conclusion] In summary, we found that warm-water bathing sharpens plantar sensation, and thus may help to prevent falls in the elderly. Even partial forearm and lower leg bathing increased exercise tolerance to levels similar to full-body bathing. PMID:26696701

  1. Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels

    PubMed Central

    Jeon, Seong Gak; Kim, Kyoung Ah; Chung, Hyunju; Choi, Junghyun; Song, Eun Ji; Han, Seung-Yun; Oh, Myung Sook; Park, Jong Hwan; Kim, Jin-il; Moon, Minho

    2016-01-01

    Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic. PMID:27432189

  2. Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels.

    PubMed

    Jeon, Seong Gak; Kim, Kyoung Ah; Chung, Hyunju; Choi, Junghyun; Song, Eun Ji; Han, Seung-Yun; Oh, Myung Sook; Park, Jong Hwan; Kim, Jin-Il; Moon, Minho

    2016-08-31

    Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic. PMID:27432189

  3. Utilization management affects health care practices at Walter Reed Army Medical Center: analytical methods applied to decrease length of stay and assign appropriate level of care.

    PubMed

    Phillips, J S; Hamm, C K; Pierce, J R; Kussman, M J

    1999-12-01

    The Department of Defense has embraced utilization management (UM) as an important tool to control and possibly decrease medical costs. Budgetary withholds have been taken by the Office of the Assistant Secretary of Defense (Health Affairs) to encourage the military services to implement UM programs. In response, Walter Reed Army Medical Center implemented a UM program along with other initiatives to effect changes in the delivery of inpatient care. This paper describes this UM program and other organizational initiatives, such as the introduction of new levels of care in an attempt to effect reductions in length of stay and unnecessary admissions. We demonstrate the use of a diversity of databases and analytical methods to quantify improved utilization and management of resources. The initiatives described significantly reduced hospital length of stay and inappropriate inpatient days. Without solid command and clinical leadership support and empowerment of the professional staffs, these significant changes and improvements could not have occurred.

  4. Reduced levels of NADH-dependent glutamate dehydrogenase decrease the glutamate content of ripe tomato fruit but have no effect on green fruit or leaves.

    PubMed

    Ferraro, Gisela; D'Angelo, Matilde; Sulpice, Ronan; Stitt, Mark; Valle, Estela M

    2015-06-01

    Glutamate (Glu) is a taste enhancer that contributes to the characteristic flavour of foods. In fruit of tomato (Solanum lycopersicum L.), the Glu content increases dramatically during the ripening process, becoming the most abundant free amino acid when the fruit become red. There is also a concomitant increase in NADH-dependent glutamate dehydrogenase (GDH) activity during the ripening transition. This enzyme is located in the mitochondria and catalyses the reversible amination of 2-oxoglutarate to Glu. To investigate the potential effect of GDH on Glu metabolism, the abundance of GDH was altered by artificial microRNA technology. Efficient silencing of all the endogenous SlGDH genes was achieved, leading to a dramatic decrease in total GDH activity. This decrease in GDH activity did not lead to any clear morphological or metabolic phenotype in leaves or green fruit. However, red fruit on the transgenic plants showed markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit. These results suggest that GDH is involved in the synthesis of Glu in tomato fruit during the ripening processes. This contrasts with the biological role ascribed to GDH in many other tissues and species. Overall, these findings suggest that GDH has a major effect on the control of metabolic composition during tomato fruit ripening, but not at other stages of development. PMID:25878356

  5. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles.

    PubMed

    Weilner, Sylvia; Keider, Verena; Winter, Melanie; Harreither, Eva; Salzer, Benjamin; Weiss, Florian; Schraml, Elisabeth; Messner, Paul; Pietschmann, Peter; Hildner, Florian; Gabriel, Christian; Redl, Heinz; Grillari-Voglauer, Regina; Grillari, Johannes

    2016-01-01

    Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk. Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC. PMID:26752347

  6. Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles

    PubMed Central

    Weilner, Sylvia; Keider, Verena; Winter, Melanie; Harreither, Eva; Salzer, Benjamin; Weiss, Florian; Schraml, Elisabeth; Messner, Paul; Pietschmann, Peter; Hildner, Florian; Gabriel, Christian; Redl, Heinz; Grillari-Voglauer, Regina; Grillari, Johannes

    2016-01-01

    Aging results in a decline of physiological functions and in reduced repair capacities, in part due to impaired regenerative power of stem cells, influenced by the systemic environment. In particular osteogenic differentiation capacity (ODC) of mesenchymal stem cells (MSCs) has been shown to decrease with age, thereby contributing to reduced bone formation and an increased fracture risk. Searching for systemic factors that might contribute to this age related decline of regenerative capacity led us to investigate plasma-derived extracellular vesicles (EVs). EVs of the elderly were found to inhibit osteogenesis compared to those of young individuals. By analyzing the differences in the vesicular content Galectin-3 was shown to be reduced in elderly-derived vesicles. While overexpression of Galectin-3 resulted in an enhanced ODC of MSCs, siRNA against Galectin-3 reduced osteogenesis. Modulation of intravesicular Galectin-3 levels correlated with an altered osteo-inductive potential indicating that vesicular Galectin-3 contributes to the biological response of MSCs to EVs. By site-directed mutagenesis we identified a phosphorylation-site on Galectin-3 mediating this effect. Finally, we showed that cell penetrating peptides comprising this phosphorylation-site are sufficient to increase ODC in MSCs. Therefore, we suggest that decrease of Galectin-3 in the plasma of elderly contributes to the age-related loss of ODC. PMID:26752347

  7. Reduced levels of NADH-dependent glutamate dehydrogenase decrease the glutamate content of ripe tomato fruit but have no effect on green fruit or leaves.

    PubMed

    Ferraro, Gisela; D'Angelo, Matilde; Sulpice, Ronan; Stitt, Mark; Valle, Estela M

    2015-06-01

    Glutamate (Glu) is a taste enhancer that contributes to the characteristic flavour of foods. In fruit of tomato (Solanum lycopersicum L.), the Glu content increases dramatically during the ripening process, becoming the most abundant free amino acid when the fruit become red. There is also a concomitant increase in NADH-dependent glutamate dehydrogenase (GDH) activity during the ripening transition. This enzyme is located in the mitochondria and catalyses the reversible amination of 2-oxoglutarate to Glu. To investigate the potential effect of GDH on Glu metabolism, the abundance of GDH was altered by artificial microRNA technology. Efficient silencing of all the endogenous SlGDH genes was achieved, leading to a dramatic decrease in total GDH activity. This decrease in GDH activity did not lead to any clear morphological or metabolic phenotype in leaves or green fruit. However, red fruit on the transgenic plants showed markedly reduced levels of Glu and a large increase in aspartate, glucose and fructose content in comparison to wild-type fruit. These results suggest that GDH is involved in the synthesis of Glu in tomato fruit during the ripening processes. This contrasts with the biological role ascribed to GDH in many other tissues and species. Overall, these findings suggest that GDH has a major effect on the control of metabolic composition during tomato fruit ripening, but not at other stages of development.

  8. Otosclerosis Associated with a De Novo Mutation −832G > A in the TGFB1 Gene Promoter Causing a Decreased Expression Level

    PubMed Central

    Priyadarshi, Saurabh; Hansdah, Kirtal; Ray, Chinmay Sundar; Biswal, Narayan Chandra; Ramchander, Puppala Venkat

    2016-01-01

    Otosclerosis (OTSC) is defined by abnormal bone remodeling in the otic capsule of middle ear which leads to conductive hearing loss. In our previous study, we have identified a de novo heterozygous mutation −832G > A in the promoter of TGFB1 in an otosclerosis patient. In the present study, we progressively screened this mutation in a cohort of 254 cases and 262 controls. The family members of the patient positive for −832G > A variation were also screened and found inheritance of this variation only to her daughter. Interestingly, this variation is associated with a decreased level of the TGFB1 transcript in the patient compared to her parents and controls. In silico analysis of this mutation predicted the altered binding of two transcription factors v-Myb and MZF1 in the mutated promoter sequence. Further, functional analysis of this mutation using in vitro luciferase and electrophoretic mobility shift assays revealed that this variation is associated with decreased gene expression. In conclusion, this study established the fact that TGFB1 mutation −832G > A altered the TGFB1 promoter activity, which could affect the susceptibility to otosclerosis development. Further, systemic analysis of TGFB1 gene sequence and expression analysis of this gene might reveal its precise role in the pathogenesis of otosclerosis. PMID:27404893

  9. Mechanism of decrease in levels of hepatic P450 isozymes induced by intracerebral endotoxin: independence from sympathetic nervous and adrenocortical systems.

    PubMed

    Shimamoto, Y; Kitamura, H; Iwai, M; Saito, M; Kazusaka, A; Fujita, S

    1999-02-01

    -depentylase (PROD), imipramine N-demethylase (IMND) and erythromycin N-demethylase (ERND) after 24 h in both sympathetectomized rats and non-denervated rats. Adrenalectomy (ADX) reduced the level of corticosterone in serum by 81% compared to sham-operated rats, indicating that adrenalectomy was successful. ADX did not inhibit the decrease in the total P450 content and the metabolism of drugs induced by i.c.v.-LPS, but more profoundly emphasized the inhibitory effect of i.c.v.-LPS than the sham-operation. These results suggest that the sympathetic nervous systems both directly and indirectly innervating the liver do not participate in the primary mechanism of the decrease in the activities of CYP isozymes in rat liver microsomes induced by i.c.v.-LPS. Also, the adrenal glands, especially the adrenocortical system, play a suppressive role in the decrease in CYP isozymes caused by i.c.v.-LPS.

  10. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial

    PubMed Central

    Cornillie, Freddy; Hanauer, Stephen B; Diamond, Robert H; Wang, Jianping; Tang, Kezhen L; Xu, Zhenhua; Rutgeerts, Paul; Vermeire, Séverine

    2014-01-01

    Background Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment. Objective To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline). Design ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs. Results After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab. Conclusions Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher

  11. Long-term exposure to endogenous levels of tributyltin decreases GluR2 expression and increases neuronal vulnerability to glutamate

    SciTech Connect

    Nakatsu, Yusuke; Kotake, Yaichiro Takishita, Tomoko; Ohta, Shigeru

    2009-10-15

    Tributyltin (TBT), an endocrine-disrupting chemical, has been used commercially as a heat stabilizer, agricultural pesticide and component of antifouling paints. In this study, we investigated the effect of long-term exposure to endogenous levels of TBT on neuronal glutamate receptors. Cultured rat cortical neurons were exposed to 1-50 nM TBT for 9 days (from day 2 to day 10 in vitro). The number of neurons was reduced by long-term exposure to 50 nM TBT, but not to 1-20 nM TBT. Long-term exposure to 20 nM TBT decreased the mRNA expression of glutamate receptors NR1, NR2A, GluR1 and GluR2, and increased that of NR2B, GluR3 and GluR4. GluR2 protein was also reduced by long-term exposure to TBT. Because AMPA receptor lacking GluR2 exhibits Ca{sup 2+} permeability, we investigated whether Ca{sup 2+} influx or glutamate toxicity was affected. Indeed, glutamate-induced Ca{sup 2+} influx was increased in TBT-treated neurons. Consistent with this, neurons became more susceptible to glutamate toxicity as a result of long-term exposure to TBT and this susceptibility was abolished by an antagonist of GluR2-lacking AMPA receptor. Thus, it is suggested that long-term exposure to endogenous levels of TBT induces a decrease of GluR2 protein, causing neurons become more susceptible to glutamate toxicity.

  12. Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor β1 level

    PubMed Central

    Asghari, Mohammad Hossein; Hobbenaghi, Rahim; Nazarizadeh, Ali; Mikaili, Peyman

    2015-01-01

    Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-β1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into six groups, including: (I) positive (BLM) control group, (II) negative (normal saline) control group, (III) sham group (R. sativus extract 150 mg/kg), and (IV-VI) treatment groups. In order to induce pulmonary fibrosis, four groups were treated with a single dose of BLM sulfate (7.5 U/kg) through intratracheal instillation. Treatment groups (IV-VI) received RSN extract (75, 150, and 300 mg/kg) orally a week before and two weeks after the administration of BLM. At the end of the treatment course, blood and lung tissue samples were taken and the measurement of TGF-β1 and histopathological examination of the lung tissues performed. The results showed that RSN, at 300 mg/kg dose, could significantly decrease the serum level of TGF-β1 and severity of the histological lesions as compared to the positive control group. The results of the current study indicate that the components present in the extract can remarkably prevent the aggravation of pulmonary fibrosis via decreasing TGF-β1 level. PMID:26752991

  13. Hypericum Perforatum Decreased Hippocampus TNF-α and Corticosterone Levels with No Effect on Kynurenine/Tryptophan Ratio in Bilateral Ovariectomized Rats

    PubMed Central

    Hasanin, Amany H

    2014-01-01

    The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-α levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17α -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-α along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by 17α-ethinylestradiol 30 µg/kg/day for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-α and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and 17α-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-α and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-α might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-α and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway. PMID:24976763

  14. DECREASED EXPRESSION LEVEL OF APOPTOSIS-RELATED GENES AND/OR PROTEINS IN SKELETAL MUSCLES, BUT NOT IN HEARTS, OF GROWTH HORMONE RECEPTOR KNOCKOUT MICE

    PubMed Central

    Gesing, Adam; Masternak, Michal M.; Wang, Feiya; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Bartke, Andrzej

    2013-01-01

    The long-lived growth hormone (GH) receptor knockout (GHRKO; KO) mice are GH resistant due to targeted disruption of the GH receptor (Ghr) gene. Apoptosis is a physiological process in which cells play an active role in their own death and is a normal component of the development and health of multicellular organisms. Aging is associated with the progressive loss of strength of skeletal and heart muscles. Calorie restriction (CR) is a well known experimental model to delay aging and increase lifespan. The aim of the study was to examine the expression of the following apoptosis-related genes: caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, p53 and cytochrome c1 (cyc1) in the skeletal muscles and hearts of female normal and GHRKO mice, fed ad libitum or subjected to 40% CR for 6 months, starting at 2 months of age. Moreover, skeletal muscle caspase-3, caspase-9, caspase-8, bax, bcl-2, Smac/DIABLO, Apaf-1, bad, phospho-bad (pbad), phospho-p53 (pp53) and cytochrome c (cyc) protein expression levels were assessed. Results Expression of caspase-3, caspase-9, bax and Smac/DIABLO genes and proteins was decreased in GHRKO’s skeletal muscles. The Apaf-1 protein expression also was diminished in this tissue. In contrast, bcl-2 and pbad protein levels were increased in skeletal muscles in knockouts. No changes were demonstrated for the examined genes expression in GHRKO’s hearts except for the increased level of cyc1 mRNA. CR did not alter the expression of the examined genes and proteins in skeletal muscles of knockouts vs. normal (N) mice. In heart homogenates, CR increased caspase-3 mRNA level as compared to ad libitum (AL) mice. Conclusion decreased expression of certain pro-apoptotic genes and/or proteins may constitute the potential mechanism of prolonged longevity in GHRKO mice, protecting these animals from aging; this potential beneficial mechanism is not affected by calorie restriction. PMID:21321312

  15. Increased chemerin and decreased omentin-1 levels in morbidly obese patients are correlated with insulin resistance, oxidative stress and chronic inflammation

    PubMed Central

    CĂTOI, ADRIANA FLORINELA; SUCIU, ŞOIMIŢA; PÂRVU, ALINA ELENA; COPĂESCU, CĂTĂLIN; GALEA, ROMEO FLORIN; BUZOIANU, ANCA DANA; VEREŞIU, IOAN ANDREI; CĂTOI, CORNEL; POP, IOANA DELIA

    2014-01-01

    Background and aim Morbid obesity represents a proinflammatory and pro-oxidative state associated with dysregulation of adipokines. We aimed to evaluate the circulating levels of chemerin and omentin-1 in morbidly obese (MO) patients and to investigate the relationship between these two adipokines and between each of them and anthropometric, metabolic, oxidative stress and chronic inflammatory parameters. Material and methods 32 MO patients and 20 controls were investigated in this study. Anthropometric, metabolism parameters, inflammatory markers, oxidative stress indicators as well as chemerin and omentin-1 were measured. Results Serum levels of chemerin were increased while omentin-1 levels were decreased in MO patients when compared with controls. Chemerin correlated positively with insulin, HOMA-IR, LDL cholesterol and negatively with total antioxidant response. Omentin-1 correlated negatively with tumor necrosis factor alpha and total cholesterol. In a multiple linear stepwise regression analysis we learnt that only HOMA-IR (β=0.70, p<0.001), total cholesterol (β=0.42, p<0.001) and triglycerides (β=0.31, p<0.05) remained significantly associated with chemerin changes. Using the same analysis we noticed that total cholesterol (β=−0.71, p<0.001), fasting glucose (β= −0.40, p<0.05) and body mass index (BMI) (β= −0.38, p<0.05) were considered to be significant predictors for omentin-1 changes. Conclusions Chemerin and omentin-1 synthesis was dysregulated in MO patients. Chemerin might play a role in insulin resistance and oxidative stress. Chemerin changes seemed to be predicted mainly by insulin resistance. Omentin-1 levels were inversely associated with chronic inflammation and dyslipidemia while the main modulating factors seemed to be dyslipidemia, hyperglycemia and BMI. PMID:26527991

  16. Increasing serum Pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers

    PubMed Central

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A.; Crabb, David W.; Lai, Xianyin; Witzmann, Frank A.

    2014-01-01

    Background Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. Methods One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Results Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p < 0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Conclusions Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use. PMID:25449367

  17. High serum homocysteine levels correlate with a decrease in the blood flow velocity of the ophthalmic artery in highway toll collectors.

    PubMed

    Memişoğullari, Ramazan; Yüksel, Harun; Coskun, Abdurrahman; Yüksel, Hatice Kurt; Yazgan, Omer; Bilgin, Cahit

    2007-07-01

    Highway workers, such as policemen, automotive service companies, and toll collectors, are placed at risk of the accelerated atherosclerotic process, since recent studies have suggested that exposure to exhaust particles and ambient air pollution increases carotid intima-media thickness and reduces ocular blood flow velocity. Therefore, we assessed the relationship between serum homocysteine, a potential parameter for atherosclerosis, and the ocular blood flow velocity and the resistivity index in highway toll collectors. The peak systolic and end diastolic flow velocities and the resistivity index were measured in 22 toll collectors and 24 control subjects by color Doppler ultrasonography. The resistivity index, which is an indirect measure of the atherosclerotic process, was calculated: resistivity index = (peak systolic velocity - end diastolic velocity)/peak systolic velocity. Serum homocysteine levels were determined by fluorometric high-performance liquid chromatography. In the highway toll collectors, the serum homocysteine level (14.4 +/- 4.8 micromol/l; p < 0.005) and the resistivity index of the ophthalmic artery (0.741 +/- 0.015; p < 0.05) were higher and the ophthalmic blood flow velocity (33.0 +/- 3.0 cm/s; p < 0.001) was lower than those in the controls (10.6 +/- 3.1 micromol/l; 0.728 +/- 0.023; 36.8 +/- 2.2 cm/s; respectively). There were significant correlations between the serum homocysteine level and ophthalmic artery resistivity index in both highway toll collectors (p < 0.001) and controls (p < 0.005). Exposure to exhaust particles might increase the serum homocysteine level, which in turn could lead to the decreased ocular blood flow and the increased resistivity index. PMID:17592212

  18. Increasing serum pre-adipocyte factor-1 (Pref-1) correlates with decreased body fat, increased free fatty acids, and level of recent alcohol consumption in excessive alcohol drinkers.

    PubMed

    Liangpunsakul, Suthat; Bennett, Rachel; Westerhold, Chi; Ross, Ruth A; Crabb, David W; Lai, Xianyin; Witzmann, Frank A

    2014-12-01

    Patients with alcoholic liver disease have been reported to have a significantly lower percentage of body fat (%BF) than controls. The mechanism for the reduction in %BF in heavy alcohol users has not been elucidated. In adipose tissue, Pref-1 is specifically expressed in pre-adipocytes but not in adipocytes. Pref-1 inhibits adipogenesis and elevated levels are associated with reduced adipose tissue mass. We investigated the association between serum Pref-1 and %BF, alcohol consumption, and serum free fatty acids (FFA) in a well-characterized cohort of heavy alcohol users compared to controls. One hundred forty-eight subjects were prospectively recruited. The Time Line Follow-Back (TLFB) questionnaire was used to quantify the amount of alcohol consumed over the 30-day period before their enrollment. Anthropometric measurements were performed to calculate %BF. Serum Pref-1 and FFA were measured. Fifty-one subjects (mean age 32 ± 9 years, 88% men) were non-excessive drinkers whereas 97 were excessive drinkers (mean age 41 ± 18 years, 69% men). Compared to non-excessive drinkers, individuals with excessive drinking had significantly higher levels of Pref-1 (p<0.01), FFA (p < 0.001), and lower %BF (p = 0.03). Serum levels of Pref-1 were associated with the amount of alcohol consumed during the previous 30 days. Serum Pref-1 was negatively correlated with %BF, but positively associated with serum FFA. Our data suggest that elevated Pref-1 levels in excessive drinkers might inhibit the expansion of adipose tissue, decreasing %BF in alcoholics. Further work is needed to validate these findings and to better understand the role of Pref-1 and its clinical significance in subjects with heavy alcohol use.

  19. Decrease of serum triglyceride in normal rat fed with 2000 ppm aluminum diet for 67 days. II. Feeding young and adult rats a sucrose diet with addition of aluminum hydroxide and aluminum potassium sulfate.

    PubMed

    Sugawara, C; Sugawara, N; Kiyosawa, H; Miyake, H

    1988-05-01

    To confirm the hypotriglyceridemic effect of aluminum (Al), male weanling and adult Wistar rats were fed sucrose diets with the addition of aluminum hydroxide (Al(OH)3) or aluminum potassium sulfate (AlK(SO4)2) for 67 days. As in the foregoing report (C. Sugawara, N. Sugawara, H. Kiyosawa, and H. Miyake, Fundam. Appl. Toxicol. 10, 607-615), no Al-induced anemia or hypophosphatemia was observed and serum Al did not exceed 20 ng/ml. Serum triglyceride (TG) was decreased by aluminum. Serum TG was significantly correlated with the serum nonesterified fatty acid (NEFA) concentration in both the Young groups (R = 0.757, n = 22, p less than 0.01) and the Adult groups (R = 0.727, n = 19, p less than 0.01). Neither serum cholesterol nor phospholipids was affected by Al ingestion. Aluminum caused a decrease in hepatic glycogen in all groups, but the decrease was significant only in Adult groups. Glycerol tri[9,10(n)-3H]oleate was administered by gastric tube into rats fed for 81 days with experimental diets. In all the Al-treated groups serum 3H was significantly greater than in control groups at 3 hr after intubation. At 24 hr after intubation, serum 3H did not differ between Control and Al-treated groups. Total 3H at 24 hr found in serum, liver, and epididymal adipose tissue was not changed significantly by Al feeding. These effects were observed without measurable increase of Al in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Coffee intake can promote activity of antioxidant enzymes with increasing MDA level and decreasing HDL-cholesterol in physically trained rats.

    PubMed

    Choi, Eun-Young; Jang, Jin-Young; Cho, Youn-Ok

    2010-08-01

    This study investigated the effect of coffee intake and exercise on the antioxidative activity and plasma cholesterol profile of physically trained rats while they were exercising. Forty eight rats were under either the control diet with water (C) or control diet with coffee (CF) and at the same time they were given physical training for 4 weeks. In terms of physical training, the rats were exercised on a treadmill for 30 minutes everyday. At the end of 4 weeks, animals in each dietary group were subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). Animals in the DE group were exercised on a treadmill for one hour, immediately before being sacrificed. Animals in the AE group were allowed to take a rest for one hour after exercise. TG levels were significantly high in coffee intake group than in control group. Also TG level of AE group was significantly higher than that of BE group. Exercise and coffee-exercise interaction effects were significant in total cholesterol (P = 0.0004, 0.0170). The AE of coffee intake group showed highest total cholesterol levels. HDL-cholesterol was significantly lower in coffee intake group than in control group. Coffee, exercise, and coffee-exercise interaction effects were significant in SOD (P = 0.0001, 0.0001, and 0.0001). The AE and BE of coffee intake group showed higher SOD levels than the other four groups. Catalase activities were significantly higher in coffee intake group than control group. No significant main effect was found in GSH/GSSG. Coffee, exercise, and coffee-exercise interaction effects were significant in MDA levels (P = 0.0464, 0.0016, and 0.0353). The DE and AE of coffee intake group and the DE of control group showed higher MDA levels than the BE of control group. Therefore, coffee intake can promote activities of antioxidant enzyme but it also increases MDA and decreases HDL-cholesterol in physically trained rats.

  1. Coffee intake can promote activity of antioxidant enzymes with increasing MDA level and decreasing HDL-cholesterol in physically trained rats

    PubMed Central

    Choi, Eun-Young; Jang, Jin-Young

    2010-01-01

    This study investigated the effect of coffee intake and exercise on the antioxidative activity and plasma cholesterol profile of physically trained rats while they were exercising. Forty eight rats were under either the control diet with water (C) or control diet with coffee (CF) and at the same time they were given physical training for 4 weeks. In terms of physical training, the rats were exercised on a treadmill for 30 minutes everyday. At the end of 4 weeks, animals in each dietary group were subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). Animals in the DE group were exercised on a treadmill for one hour, immediately before being sacrificed. Animals in the AE group were allowed to take a rest for one hour after exercise. TG levels were significantly high in coffee intake group than in control group. Also TG level of AE group was significantly higher than that of BE group. Exercise and coffee-exercise interaction effects were significant in total cholesterol (P = 0.0004, 0.0170). The AE of coffee intake group showed highest total cholesterol levels. HDL-cholesterol was significantly lower in coffee intake group than in control group. Coffee, exercise, and coffee-exercise interaction effects were significant in SOD (P = 0.0001, 0.0001, and 0.0001). The AE and BE of coffee intake group showed higher SOD levels than the other four groups. Catalase activities were significantly higher in coffee intake group than control group. No significant main effect was found in GSH/GSSG. Coffee, exercise, and coffee-exercise interaction effects were significant in MDA levels (P = 0.0464, 0.0016, and 0.0353). The DE and AE of coffee intake group and the DE of control group showed higher MDA levels than the BE of control group. Therefore, coffee intake can promote activities of antioxidant enzyme but it also increases MDA and decreases HDL-cholesterol in physically trained rats. PMID:20827343

  2. Decreased Hematocrit-To-Viscosity Ratio and Increased Lactate Dehydrogenase Level in Patients with Sickle Cell Anemia and Recurrent Leg Ulcers

    PubMed Central

    Connes, Philippe; Lamarre, Yann; Hardy-Dessources, Marie-Dominique; Lemonne, Nathalie; Waltz, Xavier; Mougenel, Danièle; Mukisi-Mukaza, Martin; Lalanne-Mistrih, Marie-Laure; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Romana, Marc

    2013-01-01

    Leg ulcer is a disabling complication in patients with sickle cell anemia (SCA) but the exact pathophysiological mechanisms are unknown. The aim of this study was to identify the hematological and hemorheological alterations associated with recurrent leg ulcers. Sixty-two SCA patients who never experienced leg ulcers (ULC-) and 13 SCA patients with a positive history of recurrent leg ulcers (ULC+) - but with no leg ulcers at the time of the study – were recruited. All patients were in steady state condition. Blood was sampled to perform hematological, biochemical (hemolytic markers) and hemorheological analyses (blood viscosity, red blood cell deformability and aggregation properties). The hematocrit-to-viscosity ratio (HVR), which reflects the red blood cell oxygen transport efficiency, was calculated for each subject. Patients from the ULC+ group were older than patients from the ULC- group. Anemia (red blood cell count, hematocrit and hemoglobin levels) was more pronounced in the ULC+ group. Lactate dehydrogenase level was higher in the ULC+ group than in the ULC- group. Neither blood viscosity, nor RBC aggregation properties differed between the two groups. HVR was lower and RBC deformability tended to be reduced in the ULC+ group. Our study confirmed increased hemolytic rate and anemia in SCA patients with leg ulcers recurrence. Furthermore, our data suggest that although systemic blood viscosity is not a major factor involved in the pathophysiology of this complication, decreased red blood cell oxygen transport efficiency (i.e., low hematocrit/viscosity ratio) may play a role. PMID:24223994

  3. Decreased cerebrospinal fluid levels of neurosin (KLK6), an aging-related protease, as a possible new risk factor for Alzheimer's disease.

    PubMed

    Mitsui, Shinichi; Okui, Akira; Uemura, Hidetoshi; Mizuno, Toshiki; Yamada, Tatsuo; Yamamura, Yoshio; Yamaguchi, Nozomi

    2002-11-01

    Neurosin is a kallikrein-like serine protease expressed preferentially in the human brain. It is localized in senile plaques and neurofibrillary tangles in the brains of individuals with Alzheimer's disease (AD) and in Lewy bodies in patients with Parkinson's disease. Neurosin is present in the cerebrospinal fluid (CSF) as a proenzyme and does not show any enzymatic activity. We have developed a sandwich ELISA system using monoclonal and polyclonal antibodies against human neurosin and have measured neurosin levels in the CSF from AD and non-CNS disease patients. Both male and female patients with peripheral neuropathy showed statistically positive correlations between CSF neurosin concentrations and age (males, n = 52, r = 0.482, p < 0.005; females, n = 43, r = 0.365, p < 0.005). In contrast, such positive correlation was not observed in the CSF from patients with AD. Further, some such patients showed extremely low levels of CSF neurosin. Our results suggest that neurosin is an aging-related protease and that a decreased CSF concentration of neurosin may be a risk factor for developing AD.

  4. DECREASED LEVELS OF FOLATE RECEPTOR-β AND REDUCED NUMBERS OF FETAL MACROPHAGES (HOFBAUER CELLS) IN PLACENTAS FROM PREGNANCIES WITH SEVERE PREECLAMPSIA (PE)*

    PubMed Central

    Tang, Zhonghua; Buhimschi, Irina A.; Buhimschi, Catalin S.; Tadesse, Serkalem; Norwitz, Errol; Niven-Fairchild, Tracy; Huang, Se-Te J; Guller, Seth

    2013-01-01

    Problem Preeclampsia (PE), a pregnancy complication of unknown etiology, is a major cause of maternal and fetal mortality and morbidity. Previous studies have described placental genes which are up-regulated in expression in PE, but few studies have addressed placental gene suppression in this syndrome. Method of Study Gene profiling and quantitative reverse transcription PCR (qRTPCR) analyses were used to identify genes down-regulated in placentas from women with severe preterm PE compared to gestational age-matched normotensive controls with spontaneous preterm birth (sPTB). Western blotting and immunohistochemistry were used to evaluate levels and patterns of cell type-specific protein expression in PE and sPTB group placentas. Results Levels of macrophage marker [folate receptor (FR)-β, CD163, and CD68] mRNA and FR-β protein were significantly down-regulated in PE group placentas compared to the sPTB group. Numbers of Hofbauer cells (HBCs, fetal macrophages) and FR-β protein in these cells were reduced in PE group placentas. Conclusion Severe PE is associated with decreased placental expression of FR-β and a reduction in the number of HBCs. Reduced placental macrophage function is likely to play a key role in the pathophysiology of PE. PMID:23480364

  5. Genetic Inactivation of ATRX Leads to a Decrease in the Amount of Telomeric Cohesin and Level of Telomere Transcription in Human Glioma Cells

    PubMed Central

    Eid, Rita; Demattei, Marie-Véronique; Episkopou, Harikleia; Augé-Gouillou, Corinne; Decottignies, Anabelle; Grandin, Nathalie

    2015-01-01

    Mutations in ATRX (alpha thalassemia/mental retardation syndrome X-linked), a chromatin-remodeling protein, are associated with the telomerase-independent ALT (alternative lengthening of telomeres) pathway of telomere maintenance in several types of cancer, including human gliomas. In telomerase-positive glioma cells, we found by immunofluorescence that ATRX localized not far from the chromosome ends but not exactly at the telomere termini. Chromatin immunoprecipitation (ChIP) experiments confirmed a subtelomeric localization for ATRX, yet short hairpin RNA (shRNA)-mediated genetic inactivation of ATRX failed to trigger the ALT pathway. Cohesin has been recently shown to be part of telomeric chromatin. Here, using ChIP, we showed that genetic inactivation of ATRX provoked diminution in the amount of cohesin in subtelomeric regions of telomerase-positive glioma cells. Inactivation of ATRX also led to diminution in the amount of TERRAs, noncoding RNAs resulting from transcription of telomeric DNA, as well as to a decrease in RNA polymerase II (RNAP II) levels at the telomeres. Our data suggest that ATRX might establish functional interactions with cohesin on telomeric chromatin in order to control TERRA levels and that one or the other or both of these events might be relevant to the triggering of the ALT pathway in cancer cells that exhibit genetic inactivation of ATRX. PMID:26055325

  6. Formation Of Transparent Exopolymeric Particles (TEP) In Mesocosms Under Increasing Turbulence Levels With And Without Additional Nutrients.

    NASA Astrophysics Data System (ADS)

    Beauvais, S.; Pedrotti, Ml.

    Transparent Exopolymeric Particles (TEP) are formed abiotically by spontaneous co- agulation of the colloidal fraction of dissolved organic polysaccharides released via phytoplankton and bacteria exudation. Their importance in the vertical fluxes of or- ganic matter in coastal and pelagic ecosystems is now well recognised. However, their production as a function of the environment features has yet to be investigated. Evolu- tion of TEP formation was followed during a two week mesocosm experiment under 4 several turbulence levels and with or without added nutrients. This study was per- formed in the framework of EC-ELOISE-NATP project. The results showed a rapid formation of TEP 24h after the phytoplankton bloom occurred. This suggests that TEP consist of fresh organic material, derived from biological process, such as phyto- plankton blooms. Their abundance increased with time in mesocosms with additional nutrients indicating that phytoplankton cells were actively exuding the precursors. The C/N ratio of particualte organic matter (POM) in mesocosms enriched with nutrients was highly correlated with TEP abundance, it confirms that TEP can have a strong impact on the biogeochemical fluxes in oceans, in particular on the carbon cycle. TEP were more abundant in the mesocosms with the highest turbulence intensity. It sug- gests that the effect of turbulence could promote encounter rates between particles increasing coagulation processes. Even if biological processes are of primary impor- tance in TEP production, this study also highlights the role of physical processes in their formation dynamics. The role of TEP in the microbial food web will be also discussed.

  7. Induction of Rad51 protein levels by p38 MAPK decreases cytotoxicity and mutagenicity in benzo[a]pyrene-exposed human lung cancer cells

    SciTech Connect

    Chuang, S.-M.; Wang, L.-H.; Hong, J.-H.; Lin, Y.-W.

    2008-08-01

    Rad51 is an essential component of the homologous recombination repair pathway. Abnormal expression of Rad51 has been reported in various carcinomas. Benzo[a]pyrene (B[a]P), a polycyclic hydrocarbon carcinogen found in the environment, induces cancer in multiple organs. B[a]P has been shown to activate the p38 MAPK signaling pathway in mammalian cells. The prime purpose of this study was to determine how B[a]P activates the p38 MAPK signaling pathway, and how this then regulates Rad51 expression in human cancer cells. Exposure of human lung cancer cells with B[a]P increased Rad51 protein levels in a time- and dose-dependent fashion. B[a]P also induced Rad51 mRNA and protein synthesis. Blockage of p38 MAPK activation by SB202190 or small interfering RNA (si-p38) decreased B[a]P-elicited Rad51 protein levels by increasing Rad51 protein instability, but did not affect Rad51 mRNA transcription. Furthermore, enhancement of p38 MAPK signaling by constitutively active MKK6 (MKK6E) increased Rad51 protein levels and protein stability. Moreover, B[a]P-induced cytotoxicity and mutagenicity were significantly increased in cells depleted of endogenous Rad51. Taken together, these results indicate that Rad51 protein provides a critical role in inhibiting the cytotoxicity and mutagenicity of B[a]P in B[a]P-treated human lung cancer cells. Furthermore, the work points to an unexpected role of p38 MAPK signaling in the control of Rad51 protein stability in response to B[a]P exposure.

  8. Decreased hippocampal homoarginine and increased nitric oxide and nitric oxide synthase levels in rats parallel training in a radial arm maze.

    PubMed

    Sase, Ajinkya; Nawaratna, Gayan; Hu, Shengdi; Wu, Guoyao; Lubec, Gert

    2016-09-01

    L-homoarginine (hArg) is derived from enzymatic guanidination of lysine. It was demonstrated that hArg is a substrate for nitric oxide (NO) synthesis, blocks lysine transport and inhibits the uptake of arginine into synaptosomes and modulates GABA responses ex vivo. As there is limited information on its physiological roles in the brain, the aim of the study was to show whether hippocampal or frontal lobe (FL) hArg is paralleling training in the radial arm maze (RAM) or NO formation. Hippocampi and FL of male Sprague-Dawley rats were taken from trained or yoked in a RAM. Then hArg and metabolites, NO and NO synthase (NOS) were determined by standard methods. The animals learned the task in the RAM showing significant reduction of working memory errors. hArg showed decreased levels in both brain regions of trained animals as compared to yoked animals. Nitrate plus nitrite (NOx) concentrations and NOS activity were significantly increased in hippocampi, F(1,36) = 170.5; P ≤ 0.0001 and FL, F(1,36) = 74.67; P ≤ 0.0001 of trained animals as compared to yoked animals. Levels of hArg were negatively correlated with NOx in hippocampus (r = -0.6355; P = 0.0483) but not in FL and with lysine in the FL (r = -0.6650; P = 0.0358). NOx levels were positively correlated with NOS in both the hippocampus (r = 0.7474; P = 0.0129) and FL (r = 0.9563; P ≤  0.0001). These novel findings indicate that hArg is linked to NO formation in hippocampus but not in FL and is paralleling spatial memory in the RAM. PMID:27178025

  9. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase

    PubMed Central

    Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

    2015-01-01

    In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by 1H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent. PMID:26236582

  10. Decreased hippocampal homoarginine and increased nitric oxide and nitric oxide synthase levels in rats parallel training in a radial arm maze.

    PubMed

    Sase, Ajinkya; Nawaratna, Gayan; Hu, Shengdi; Wu, Guoyao; Lubec, Gert

    2016-09-01

    L-homoarginine (hArg) is derived from enzymatic guanidination of lysine. It was demonstrated that hArg is a substrate for nitric oxide (NO) synthesis, blocks lysine transport and inhibits the uptake of arginine into synaptosomes and modulates GABA responses ex vivo. As there is limited information on its physiological roles in the brain, the aim of the study was to show whether hippocampal or frontal lobe (FL) hArg is paralleling training in the radial arm maze (RAM) or NO formation. Hippocampi and FL of male Sprague-Dawley rats were taken from trained or yoked in a RAM. Then hArg and metabolites, NO and NO synthase (NOS) were determined by standard methods. The animals learned the task in the RAM showing significant reduction of working memory errors. hArg showed decreased levels in both brain regions of trained animals as compared to yoked animals. Nitrate plus nitrite (NOx) concentrations and NOS activity were significantly increased in hippocampi, F(1,36) = 170.5; P ≤ 0.0001 and FL, F(1,36) = 74.67; P ≤ 0.0001 of trained animals as compared to yoked animals. Levels of hArg were negatively correlated with NOx in hippocampus (r = -0.6355; P = 0.0483) but not in FL and with lysine in the FL (r = -0.6650; P = 0.0358). NOx levels were positively correlated with NOS in both the hippocampus (r = 0.7474; P = 0.0129) and FL (r = 0.9563; P ≤  0.0001). These novel findings indicate that hArg is linked to NO formation in hippocampus but not in FL and is paralleling spatial memory in the RAM.

  11. An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

    PubMed

    Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

    2015-12-01

    In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent. PMID:26236582

  12. Increased messenger RNA levels of the antagonist thyroid hormone receptor erbA-alpha 2 and decreased levels of erbA-alpha 1 and erbA-beta 1 receptor messenger RNAs in neoplastic rodent cells.

    PubMed

    Too, C K; Guernsey, D L

    1992-04-15

    Nothern blot analysis of total RNA from the mouse C3H/10T1/2 cell line indicated that the erbA alpha gene transcribed three mRNA species of similar sizes (2.6, 5.5, 6.6 kilobases) as found in rodents. The 2.6-kilobase mRNA (erbA-alpha 2) was approximately 7- to 8-fold more abundant than either the 5.5- (erbA-alpha 1) or 6.6-kilobase species. The expression of the erbA-alpha 2 transcript increased 3- to 30-fold when "normal" mouse or rat cells were growth arrested by concluence. Triiodothyronine, at a concentration of 1 nM, had no effect on the levels of the erbA-alpha mRNA species in confluent cells nor on the levels of erbA-alpha 2 in proliferative normal or transformed C3H/10T1/2 cells. In log-phase growing cells there was a 2.5- to 5-fold increase in the relative expression of erbA-alpha 2 mRNA in transformed mouse C3H/10T1/2 cells, transformed cloned rat embryo fibroblasts (CREF), transformed rat embryo fibroblasts (REF), and a transformed temperature-sensitive rat mutant cell line (ts7E) when compared with their non-transformed counterparts. In contrast to the elevation of erbA-alpha 2 in transformed cells, erbA-alpha 1 and erbA-beta 1 mRNAs decreased in transformed mouse and rat cell lines. In conclusion, it is suggested that the increased levels of the erbA-alpha 2 transcript and the decreased levels of erbA-alpha 1 and erbA-beta 1 in neoplastic cells may account for the loss of thyroid hormone regulation of inducible pathways and decreased nuclear triiodothyronine binding as previously reported.

  13. Effects of plant species, stage of maturity, and level of formic acid addition on lipolysis, lipid content, and fatty acid composition during ensiling.

    PubMed

    Koivunen, E; Jaakkola, S; Heikkilä, T; Lampi, A-M; Halmemies-Beauchet-Filleau, A; Lee, M R F; Winters, A L; Shingfield, K J; Vanhatalo, A

    2015-09-01

    Forage type and management influences the nutritional quality and fatty acid composition of ruminant milk. Replacing grass silage with red clover (RC; L.) silage increases milk fat 18:3-3 concentration. Red clover has a higher polyphenol oxidase (PPO) activity compared with grasses, which has been suggested to decrease lipolysis and . The present study characterized the abundance and fatty acid composition of esterified lipid and NEFA before and after ensiling of grass and RC to investigate the influence of forage species, growth stage, and extent of fermentation on lipolysis. A randomized block design with a 2 × 3 × 4 factorial arrangement of treatments was used. Treatments comprised RC or a mixture of timothy ( L.) and meadow fescue ( Huds.) harvested at 3 growth stages and treated with 4 levels of formic acid (0, 2, 4, and 6 L/t). Lipid in silages treated with 0 or 6 L/t formic acid were extracted and separated into 4 fractions by TLC. Total PPO activity in fresh herbage and the content of soluble bound phenols in all silages were determined. Concentrations of 18:3-3 and total fatty acids (TFA) were higher ( < 0.001) for RC than for grass. For both forage species, 18:3-3 and TFA content decreased linearly ( < 0.001) with advancing growth stage, with the highest abundance at the vegetative stage. Most of lipid in fresh RC and grass herbage (97%) was esterified, whereas NEFA accounted for 71% of TFA in both silages. Ensiling resulted in marginal increases in TFA content and the amounts of individual fatty acids compared with fresh herbages. Herbage total PPO activity was higher ( < 0.001) for RC than grass (11 vs. 0.11 μkatal/g leaf fresh weight). Net lipolysis during ensiling was extensive for both forage species (660 to 759 g/kg fatty acid for grass and 563 to 737 g/kg fatty acid for RC). Formic acid application (0 vs. 6 L/t) resulted in a marked decrease ( = 0.026) in net lipolysis during the ensiling of RC, whereas the opposite was true ( = 0.026) for grass

  14. Stair climbing/descending exercise for a short time decreases blood glucose levels after a meal in participants with type 2 diabetes

    PubMed Central

    Honda, Hiroto; Igaki, Makoto; Hatanaka, Yuki; Komatsu, Motoaki; Tanaka, Shin-ichiro; Miki, Tetsuo; Suzuki, Taiga; Takaishi, Tetsuo; Hayashi, Tatsuya

    2016-01-01

    Objective We examined whether stair climbing–descending exercise (ST-EX), a convenient method to increase physical activity in daily life, for a short period would acutely improve the postprandial blood glucose (BG) response in participants with type 2 diabetes (T2D). Methods 16 participants with T2D (age 65.4±1.1 years) participated in 2 separate sessions. After an overnight fast, each participant consumed a test meal and then kept resting for 180 min, except when performing each 3 min bout of ST-EX at 60 and 120 min after the meal (ST-EX session), or kept resting for 180 min (REST session). ST-EX comprised 6 continuous repetitions of climbing to the second floor (21 steps) at a rate of 80–110 steps/min followed by walking down slowly to the first floor at a free step rate. Results The BG at 60 min after the meal during the ST-EX session (immediately before the first ST-EX) did not differ from that during the REST session, but analysis of variance revealed a significant interaction between time and treatment (p<0.01). The BG at 150 min after the meal (30 min after the second ST-EX) was significantly lower than that during the REST session (p<0.01). The area under the curve was also 18% lower during the ST-EX session than during the REST session (p<0.05). The heart rate and blood lactate levels indicated that the actual intensity of ST-EX was ‘hard’. In contrast, the rating of perceived exertion (RPE) indicated that the overall intensity of ST-EX was ‘moderate’ because of decreased RPE scores during descent. Conclusions The present findings suggest that performing 3 min ST-EX 60 and 120 min after a meal may be a useful strategy to accelerate the decrease in postprandial BG levels in participants with T2D. PMID:27547414

  15. Stair climbing/descending exercise for a short time decreases blood glucose levels after a meal in people with type 2 diabetes

    PubMed Central

    Honda, Hiroto; Igaki, Makoto; Hatanaka, Yuki; Komatsu, Motoaki; Tanaka, Shin-ichiro; Miki, Tetsuo; Suzuki, Taiga; Takaishi, Tetsuo; Hayashi, Tatsuya

    2016-01-01

    Objective We examined whether stair climbing–descending exercise (ST-EX), a convenient method to increase physical activity in daily life, for a short period would acutely improve the postprandial blood glucose (BG) response in people with type 2 diabetes (T2D). Methods 16 people with T2D (age 65.4±1.1 years) participated in 2 separate sessions. After an overnight fast, each participant consumed a test meal and then kept resting for 180 min, except when performing each 3 min bout of ST-EX at 60 and 120 min after the meal (ST-EX session), or kept resting for 180 min (REST session). ST-EX comprised 6 continuous repetitions of climbing to the second floor (21 steps) at a rate of 80–110 steps/min followed by walking down slowly to the first floor at a free step rate. Results The BG at 60 min after the meal during the ST-EX session (immediately before the first ST-EX) did not differ from that during the REST session, but analysis of variance revealed a significant interaction between time and treatment (p<0.01). The BG at 150 min after the meal (30 min after the second ST-EX) was significantly lower than that during the REST session (p<0.01). The area under the curve was also 18% lower during the ST-EX session than during the REST session (p<0.05). The heart rate and blood lactate levels indicated that the actual intensity of ST-EX was ‘hard’. In contrast, the rating of perceived exertion (RPE) indicated that the overall intensity of ST-EX was ‘moderate’ because of decreased RPE scores during descent. Conclusions The present findings suggest that performing 3 min ST-EX 60 and 120 min after a meal may be a useful strategy to accelerate the decrease in postprandial BG levels in people with T2D. PMID:27547414

  16. Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma.

    PubMed

    Takano, Toru; Miyauchi, Akira; Yoshida, Hiroshi; Kuma, Kanji; Amino, Nobuyuki

    2005-02-28

    The expression level of trefoil factor 3 (TFF3) mRNA is a marker for distinguishing thyroid follicular adenomas from carcinomas. However, when measuring the expression level of TFF3 mRNA in fine needle aspiration biopsies, an appropriate internal control mRNA, of which expression is restricted in thyroid epithelial--derived cells, is necessary, since they are often contaminated with a considerable number of blood cells, which do not express TFF3 mRNA. In this study, we evaluated the efficiency of molecular-based diagnosis of thyroid follicular carcinoma by measuring the relative expression of TFF3 mRNA by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using galectin-3 mRNA as an internal control. The TFF3/galectin-3 mRNA ratio (T/G ratio) was measured in 54 follicular adenomas and 29 follicular carcinomas. It was markedly decreased in 7 follicular carcinomas of widely invasive type and with evident distant metastases. When the cutoff point was set at 16.0 by a receiver operator characteristic curve, the TG ratio showed good agreement with the pathological diagnosis [kappa=0.55; 95% confidence interval (CI), 0.34-0.77]. This agreement was better when the pathologically questionable cases were excluded (kappa=0.72; 95% CI, 0.49-0.95). Quantification of the T/G ratio may be a useful tool for the distinction between follicular adenomas and carcinomas, which is the most difficult in thyroid pathology.

  17. The Small Molecule Triclabendazole Decreases the Intracellular Level of Cyclic AMP and Increases Resistance to Stress in Saccharomyces cerevisiae

    PubMed Central

    Lee, Yong Joo; Shi, Runhua; Witt, Stephan N.

    2013-01-01

    The Ras-adenylyl cyclase-protein kinase A nutrient-sensing pathway controls metabolism, proliferation and resistance to stress in Saccharomyces cerevisiae. The genetic disruption of this pathway increases resistance to a variety of stresses. We show here that the pharmacological inhibition of this pathway by the drug triclabendazole increases resistance to oxidants, heat stress and extends the chronological life. Evidence is presented that triclabendazole decreases the intracellular level of cyclic AMP by inhibiting adenylyl cyclase and triggers the parallel rapid translocation of the stress-resistance transcription factor Msn2 from the cytosol into the nucleus, as deduced from experiments employing a strain in which MSN2 is replaced with MSN2-GFP (GFP, green fluorescent protein). Msn2 and Msn4 are responsible for activating the transcription of numerous genes that encode proteins that protect cells from stress. The results are consistent with triclabendazole either inhibiting the association of Ras with adenylyl cyclase or directly inhibiting adenylyl cyclase, which in turn triggers Msn2/4 to enter the nucleus and activate stress-responsible element gene expression. PMID:23667708

  18. MALDI Mass Spectrometry Imaging Reveals Decreased CK5 Levels in Vulvar Squamous Cell Carcinomas Compared to the Precursor Lesion Differentiated Vulvar Intraepithelial Neoplasia

    PubMed Central

    Zhang, Chao; Arentz, Georgia; Winderbaum, Lyron; Lokman, Noor A.; Klingler-Hoffmann, Manuela; Mittal, Parul; Carter, Christopher; Oehler, Martin K.; Hoffmann, Peter

    2016-01-01

    Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC. PMID:27399691

  19. A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels.

    PubMed

    Clair, Emilie; Mesnage, Robin; Travert, Carine; Séralini, Gilles-Éric

    2012-03-01

    The major herbicide used worldwide, Roundup, is a glyphosate-based pesticide with adjuvants. Glyphosate, its active ingredient in plants and its main metabolite (AMPA) are among the first contaminants of surface waters. Roundup is being used increasingly in particular on genetically modified plants grown for food and feed that contain its residues. Here we tested glyphosate and its formulation on mature rat fresh testicular cells from 1 to 10000ppm, thus from the range in some human urine and in environment to agricultural levels. We show that from 1 to 48h of Roundup exposure Leydig cells are damaged. Within 24-48h this formulation is also toxic on the other cells, mainly by necrosis, by contrast to glyphosate alone which is essentially toxic on Sertoli cells. Later, it also induces apoptosis at higher doses in germ cells and in Sertoli/germ cells co-cultures. At lower non toxic concentrations of Roundup and glyphosate (1ppm), the main endocrine disruption is a testosterone decrease by 35%. The pesticide has thus an endocrine impact at very low environmental doses, but only a high contamination appears to provoke an acute rat testicular toxicity. This does not anticipate the chronic toxicity which is insufficiently tested, and only with glyphosate in regulatory tests.

  20. Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy.

    PubMed

    Chan, Maggie; Brooks, Heather J L; Moratti, Stephen C; Hanton, Lyall R; Cabral, Jaydee D

    2015-06-16

    A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel's antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions.

  1. Reducing the Oxidation Level of Dextran Aldehyde in a Chitosan/Dextran-Based Surgical Hydrogel Increases Biocompatibility and Decreases Antimicrobial Efficacy

    PubMed Central

    Chan, Maggie; Brooks, Heather J. L.; Moratti, Stephen C.; Hanton, Lyall R.; Cabral, Jaydee D.

    2015-01-01

    A highly oxidized form of a chitosan/dextran-based hydrogel (CD-100) containing 80% oxidized dextran aldehyde (DA-100) was developed as a post-operative aid, and found to significantly prevent adhesion formation in endoscopic sinus surgery (ESS). However, the CD-100 hydrogel showed moderate in vitro cytotoxicity to mammalian cell lines, with the DA-100 found to be the cytotoxic component. In order to extend the use of the hydrogel to abdominal surgeries, reformulation using a lower oxidized DA (DA-25) was pursued. The aim of the present study was to compare the antimicrobial efficacy, in vitro biocompatibility and wound healing capacity of the highly oxidized CD-100 hydrogel with the CD-25 hydrogel. Antimicrobial studies were performed against a range of clinically relevant abdominal microorganisms using the micro-broth dilution method. Biocompatibility testing using human dermal fibroblasts was assessed via a tetrazolium reduction assay (MTT) and a wound healing model. In contrast to the original DA-100 formulation, DA-25 was found to be non-cytotoxic, and showed no overall impairment of cell migration, with wound closure occurring at 72 h. However, the lower oxidation level negatively affected the antimicrobial efficacy of the hydrogel (CD-25). Although the CD-25 hydrogel’s antimicrobial efficacy and anti-fibroblast activity is decreased when compared to the original CD-100 hydrogel formulation, previous in vivo studies show that the CD-25 hydrogel remains an effective, biocompatible barrier agent in the prevention of postoperative adhesions. PMID:26086827

  2. Bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate decreases after the addition of folate-binding protein to yogurt as studied in a dynamic in vitro gastrointestinal model.

    PubMed

    Arkbåge, Karin; Verwei, Miriam; Havenaar, Robert; Witthöft, Cornelia

    2003-11-01

    Milk products are only moderate sources of folate. Nevertheless, they are of interest due to their content of folate-binding proteins (FBP), which in some studies have been reported to increase folate bioavailability. The effect of FBP on folate bioavailability has been widely discussed. The aim of this study was to investigate the bioaccessibility of folic acid and (6S)-5-methyltetrahydrofolate (5-CH3-H4folate) from fortified yogurt using a dynamic in vitro gastrointestinal model (TIM). In addition, the effect of FBP on folate bioaccessibility and the stability of FBP added to yogurt during gastrointestinal passage were investigated. Folate bioaccessibility was 82% from yogurt fortified with folic acid and 5-CH3-H4folate. The addition of FBP to yogurt decreased (P < 0.05) folate bioaccessibility. The lowering effect of FBP was more pronounced in yogurt fortified with folic acid (34% folate bioaccessibility) than from yogurt fortified with 5-CH3-H4folate (57% folate bioaccessibility). After gastrointestinal passage, 17% of the FBP in yogurt fortified with 5-CH3-H4folate and 34% of the FBP in yogurt fortified with folic acid were recovered. No difference in folate bioaccessibility was found between folate-fortified yogurt and folate-fortified pasteurized milk (P = 0.10), whereas the lowering effect of FBP was (P < 0.05) greater in yogurt compared with pasteurized milk. In conclusion, based on the high bioaccessibility of folic acid and 5-CH3-H4folate, yogurt without active FBP can be considered to be an appropriate food matrix for folate fortification.

  3. Standard addition flow method for potentiometric measurements at low concentration levels: application to the determination of fluoride in food samples.

    PubMed

    Galvis-Sánchez, Andrea C; Santos, João Rodrigo; Rangel, António O S S

    2015-02-01

    A standard addition method was implemented by using a flow manifold able to perform automatically multiple standard additions and in-line sample treatment. This analytical strategy was based on the in-line mixing of sample and standard addition solutions, using a merging zone approach. The flow system aimed to exploit the standard addition method to quantify the target analyte particularly in cases where the analyte concentration in the matrix is below the lower limit of linear response of the detector. The feasibility of the proposed flow configuration was assessed through the potentiometric determination of fluoride in sea salts of different origins and different types of coffee infusions. The limit of quantification of the proposed manifold was 5×10(-6) mol L(-1), 10-fold lower than the lower limit of linear response of the potentiometric detector used. A determination rate of 8 samples h(-1) was achieved considering an experimental procedure based on three standard additions per sample. The main advantage of the proposed strategy is the simple approach to perform multiple standard additions, which can be implemented with other ion selective electrodes, especially in cases when the primary ion is below the lower limit of linear response of the detector.

  4. [Effects of water levels and the additions of different nitrogen forms on soil net nitrogen transformation rate and N2O emission in subtropical forest soils].

    PubMed

    Ma, Fen; Ma, Hong-liang; Qiu, Hong; Yang, Hong-yu

    2015-02-01

    An incubation experiment was conducted to investigate the effects of the additions of different nitrogen forms on nitrogen transformation in red soils of subtropical forest under soil moisture conditions with 40%, 70% and 110% of water holding capacity (WHC). The results showed that soil net mineralization and ammonification rates were maximum at 70% WHC and minimum at 40% WHC. Compared with the control, the addition of NO(3-)-N decreased the soil net mineralization and ammonification rates by 56.1% and 43.0% under 70% WHC condition, and decreased by 68.2% and 19.0% under 110% WHC, respectively. However, the proportion of ammonification to mineralization increased at 70% and 110% WHC, which suggested that nitrate addition inhibited the nitrification. With addition of NO(3-)-N at 110% WHC, the net nitrification rate was lowest while N20 emission was highest with the concomitant decrease of nitrate content, indicating that N2O emission was largely derived from denitrification. However, at 40% WHC and 70% WHC, the maximum N20 flux was found at the early stage of incubation. Even with addition of NH(4+)-N and NO(3-)-N, N2O flux did not change much at the latter stage of incubation, indicating that autotrophic nitrification was dominant for N20 production at the early stage of incubation. Under 40% WHC condition, soluble organic carbon increased more and it increased largely with NH(4+)-N addition, which meant NH(4+)-N addition could enhance the mineralization of soil organic matter. Under 40% and 110% WHC conditions, the addition of NH(4+)-N increased significantly the soil soluble organic nitrogen (SON) by 73.6% and 176.6% compared with the control, respectively. A significant increase of 78.7% for SON was only found at 40% WHC under addition of NO(3-)-N compared with the control. These results showed that high soil moisture condition and addition of NH(4+)-N were of benefit to SON formation.

  5. Decreased levels of the high molecular weight subunit of neurofilaments and accelerated neurofilament transport during the recovery phase of 2,5-hexanedione exposure.

    PubMed

    Pyle, S J; Amarnath, V; Graham, D G; Anthony, D C

    1993-01-01

    The neurotoxicant 2,5-hexanedione (HD) causes the accumulation of neurofilaments in the distal axon and an acceleration of neurofilament transport proximal to the site of their accumulation. It has been proposed that the acceleration of transport is due to the direct reaction of HD with neurofilament proteins and, conversely, that this acceleration is a secondary response to the axon to injury. The objective of this study was to determine whether the response of axons to HD intoxication includes acceleration of neurofilament transport. Pulse labelling was used to analyze neurofilament transport in age-matched rats exposed to HD or PBS. The animals receiving HD were exposed either throughout the period of radiolabel transport, or prior to the pulse labeling of neurofilament proteins. If acceleration of the rate of neurofilament transport was due to the direct reaction of HD with proteins, then neurofilaments synthesized after the exposure period should travel at control rates, since these proteins would not have been exposed to the toxicant. After 28 days of transport, optic nerve proteins were examined using SDS-PAGE, fluorography, and computerized densitometry. In both HD-treated groups, neurofilament transport was accelerated relative to age-matched control animals. In addition, the amount of NFH was decreased relative to other neurofilament subunits. The combination of accelerated transport and a diminished proportion of NFH is similar to the observations of neurofilament axonal transport during growth and development. These observations suggest that this persistent, secondary effect is a reparative response to injury that recapitulates axonal growth and development.

  6. Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.

    PubMed

    Giménez-Bastida, Juan Antonio; González-Sarrías, Antonio; Vallejo, Fernando; Espín, Juan Carlos; Tomás-Barberán, Francisco A

    2016-01-01

    Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 μM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.

  7. Metabolite profiling of sex developmental steroid conjugates reveals an association between decreased levels of steroid sulfates and adiposity in obese girls.

    PubMed

    Lee, Su Hyeon; Kim, Shin Hye; Lee, Won-Yong; Chung, Bong Chul; Park, Mi Jung; Choi, Man Ho

    2016-09-01

    Free and conjugated steroids coexist in a dynamic equilibrium due to complex biosynthetic and metabolic processes. This may have clinical significance related to various physiological conditions, including sex development involving the reproductive system. Therefore, we performed quantitative profiling of 16 serum steroids conjugated with glucuronic and sulfuric acids using liquid chromatography-mass spectrometry (LC-MS). All steroid conjugates were purified by solid-phase extraction and then separated through a 3-μm particle size C18 column (150mm×2.1mm) at a flow rate of 0.3 mL/min in the negative ionization mode. The LC-MS-based analysis was found to be linear (r(2)>0.99), and all steroid conjugates had a limit-of-quantification (LOQ) of 10ng/mL, except for cholesterol sulfate and 17β-estradiol-3,17-disulfate (20ng/mL). The extraction recoveries of all steroid conjugates ranged from 97.9% to 110.7%, while the overall precision (% CV) and accuracy (% bias) ranged from 4.8% to 10.9% and from 94.4% to 112.9% at four different concentrations, respectively. Profiling of steroid conjugates corrected by adiposity revealed decreased levels of steroid sulfates (P<0.01) in overweight and obese girls compared to normal girls. The suggested technique can be used for evaluating metabolic changes in steroid conjugates and for understanding the pathophysiology and relative contributions of adiposity in childhood obesity. PMID:27154415

  8. Effects of a phytogenic feed additive on susceptibility of channel catfish to Edwardsiella ictaluri and levels of mannose binding lectin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to investigate the effect of a phytogenic feed additive (Digestarom® P.E.P. MGE) on growth performance and disease susceptibility to Edwardsiella ictaluri. Two hundred and fifty juvenile channel catfish (7.2 ± 0.1 g) were allotted into the following treatments: Control (float...

  9. The Effects of Computer-Assisted Instruction on Student Achievement in Addition and Subtraction at First Grade Level.

    ERIC Educational Resources Information Center

    Spivey, Patsy M.

    This study was conducted to determine whether the traditional classroom approach to instruction involving the addition and subtraction of number facts (digits 0-6) is more or less effective than the traditional classroom approach plus a commercially-prepared computer game. A pretest-posttest control group design was used with two groups of first…

  10. Additions to the Spectrum and Energy Levels and a Critical Compilation of Singly-Ionized Boron, B II

    NASA Astrophysics Data System (ADS)

    Ryabtsev, A. N.; Kink, I.; Awaya, Y.; Ekberg, J. O.; Mannervik, S.; Ölme, A.; Martinson, I.

    2005-01-01

    We have undertaken a number of experimental studies of the structure of singly ionized boron, B II. Much of this work was initially motivated by a search for the "missing" 2s3s 1S term. There was a surprising disagreement between theory and experiment for this level. In this context lots of data for B II were collected over the years, from beam-foil experiments, high-resolution spark spectroscopy and theoretical calculations. The new material, which includes more than 80 newly classified (or revised) spectral lines, has now been thoroughly analyzed. This was followed by a critical compilation of all known levels and lines of B II, along with the theoretical interpretation of the levels, classifications of the lines and calculated transition probabilities for most lines.

  11. Comprehensive data base of high-level nuclear waste glasses: September 1987 status report: Volume 2, Additional appendices

    SciTech Connect

    Kindle, C.H.; Kreiter, M.R.

    1987-12-01

    The Materials Characterization Center (MCC) is assembling a comprehensive data base (CDB) of experimental data collected for high-level nuclear waste package components. The status of the CDB is summarized in Volume I of this report. Volume II contains appendices that present data from the data base and an evaluation of glass durability models applied to the data base.

  12. Additions to the spectra and energy levels of the zinc-like ions Y X-Cd XIX

    NASA Astrophysics Data System (ADS)

    Litzén, Ulf; Hansson, Anna

    1989-10-01

    Transitions from 4p4d 1F and 3F have been identified in the spectra Y X-Cd XIX emitted from laserproduced plasmas. Energy levels have been derived, and the term structure has been studied with special emphasis on the 4s4f-4p4d configuration interaction.

  13. Infant Formula: The Addition of Minimum and Maximum Levels of Selenium to Infant Formula and Related Labeling Requirements. Final rule.

    PubMed

    2015-06-23

    The Food and Drug Administration (FDA or we) is amending the regulations on nutrient specifications and labeling for infant formula to add the mineral selenium to the list of required nutrients and to establish minimum and maximum levels of selenium in infant formula.

  14. Electroacupuncture decreases excessive alcohol consumption involving reduction of FosB/ΔFosB levels in reward-related brain regions.

    PubMed

    Li, Jing; Sun, Yanan; Ye, Jiang-Hong

    2012-01-01

    New therapies are needed for alcohol abuse, a major public health problem in the U.S. and worldwide. There are only three FDA-approved drugs for treatment of alcohol abuse (naltrexone, acamprosate and disulfuram). On average these drugs yield only moderate success in reducing long-term alcohol consumption. Electroacupuncture has been shown to alleviate various drugs of abuse, including alcohol. Although previous studies have shown that electroacupuncture reduced alcohol consumption, the underlying mechanisms have not been fully elucidated. ΔFosB and FosB are members of the Fos family of transcription factors implicated in neural plasticity in drug addiction; a connection between electroacupuncture's treatment of alcohol abuse and the Fos family has not been established. In this study, we trained rats to drink large quantities of ethanol in a modified intermittent access two-bottle choice drinking procedure. When rats achieved a stable baseline of ethanol consumption, electroacupuncture (100 Hz or 2 Hz, 30 min each day) was administered at Zusanli (ST36) for 6 consecutive days. The level of FosB/ΔFosB in reward-related brain regions was assessed by immunohistochemistry. We found that the intake of and preference for ethanol in rats under 100 Hz, but not 2 Hz electroacupuncture regiment were sharply reduced. The reduction was maintained for at least 72 hours after the termination of electroacupuncture treatment. Conversely, 100 Hz electroacupuncture did not alter the intake of and preference for the natural rewarding agent sucrose. Additionally, FosB/ΔFosB levels in the prefrontal cortex, striatal region and the posterior region of ventral tegmental area were increased following excessive ethanol consumption, but were reduced after six-day 100 Hz electroacupuncture. Thus, this study demonstrates that six-day 100 Hz electroacupuncture treatment effectively reduces ethanol consumption and preference in rats that chronically drink excessive amount of ethanol. This

  15. Optimal choice: assessing the probability of additional damage to buildings caused by water level changes of larger areas

    NASA Astrophysics Data System (ADS)

    Bijnagte, J. L.; Luger, D.

    2012-12-01

    In the Northern parts of the Netherlands exploration of natural gas reservoirs causes subsidence over large areas. As a consequence, the water levels in canals and polders have to be adjusted over time in order to keep the groundwater levels at a constant depth relative to the surface level. In the middle of the subsidence area it is relatively easy to follow the settlements by a uniform lowering of the water level. This would however result in a relative lowering of the groundwater table at the edges of the subsidence area. Given the presence of soft compressible soils, this would result in induced settlements. For buildings in these areas this will increase the chance of damage. A major design challenge lies therefore in the optimisation of the use of compartments. The more compartments the higher the cost therefore the aim is to make compartments in the water management system that are as large as possible without causing inadmissible damage to buildings. In order to asses expected damage from different use of compartments three tools are needed. The first is a generally accepted method of damage determination, the second a method to determine the contribution to damage of a new influence, e.g. a groundwater table change. Third, and perhaps most importantly, a method is needed to evaluate effects not for single buildings but for larger areas. The first need is covered by established damage criteria like those of Burland & Wroth or Boscardin & Cording. Up until now the second and the third have been problematic. This paper presents a method which enables to assign a contribution to the probability of damage of various recognised mechanisms such as soil and foundation inhomogeneity, uneven loading, ground water level changes. Shallow subsidence due to peat oxidation and deep subsidence due to reservoir depletion can be combined. In order to address the third issue: evaluation of effects for larger areas, the method uses a probabilistic approach. Apart from a

  16. [Effects of water levels and the additions of different nitrogen forms on soil net nitrogen transformation rate and N2O emission in subtropical forest soils].

    PubMed

    Ma, Fen; Ma, Hong-liang; Qiu, Hong; Yang, Hong-yu

    2015-02-01

    An incubation experiment was conducted to investigate the effects of the additions of different nitrogen forms on nitrogen transformation in red soils of subtropical forest under soil moisture conditions with 40%, 70% and 110% of water holding capacity (WHC). The results showed that soil net mineralization and ammonification rates were maximum at 70% WHC and minimum at 40% WHC. Compared with the control, the addition of NO(3-)-N decreased the soil net mineralization and ammonification rates by 56.1% and 43.0% under 70% WHC condition, and decreased by 68.2% and 19.0% under 110% WHC, respectively. However, the proportion of ammonification to mineralization increased at 70% and 110% WHC, which suggested that nitrate addition inhibited the nitrification. With addition of NO(3-)-N at 110% WHC, the net nitrification rate was lowest while N20 emission was highest with the concomitant decrease of nitrate content, indicating that N2O emission was largely derived from denitrification. However, at 40% WHC and 70% WHC, the maximum N20 flux was found at the early stage of incubation. Even with addition of NH(4+)-N and NO(3-)-N, N2O flux did not change much at the latter stage of incubation, indicating that autotrophic nitrification was dominant for N20 production at the early stage of incubation. Under 40% WHC condition, soluble organic carbon increased more and it increased largely with NH(4+)-N addition, which meant NH(4+)-N addition could enhance the mineralization of soil organic matter. Under 40% and 110% WHC conditions, the addition of NH(4+)-N increased significantly the soil soluble organic nitrogen (SON) by 73.6% and 176.6% compared with the control, respectively. A significant increase of 78.7% for SON was only found at 40% WHC under addition of NO(3-)-N compared with the control. These results showed that high soil moisture condition and addition of NH(4+)-N were of benefit to SON formation. PMID:26094450

  17. Rat dams exposed repeatedly to a daily brief separation from the pups exhibit increased maternal behavior, decreased anxiety and altered levels of receptors for estrogens (ERα, ERβ), oxytocin and serotonin (5-HT1A) in their brain.

    PubMed

    Stamatakis, Antonios; Kalpachidou, Theodora; Raftogianni, Androniki; Zografou, Efstratia; Tzanou, Athanasia; Pondiki, Stavroula; Stylianopoulou, Fotini

    2015-02-01

    In the present study we investigated the neurobiological mechanisms underlying expression of maternal behavior. Increased maternal behavior was experimentally induced by a brief 15-min separation between the mother and the pups during postnatal days 1 to 22. On postnatal days (PND) 12 and 22, we determined in experimental and control dams levels of anxiety in the elevated plus maze (EPM) as well as the levels of receptors for estrogens (ERα, ERβ), oxytocin (OTR) and serotonin (5-HT1AR) in areas of the limbic system (prefrontal cortex-PFC, hippocampus, lateral septum-SL, medial preoptic area-MPOA, shell of nucleus accumbens-nAc-Sh, central-CeA and basolateral-BLA amygdala), involved in the regulation of maternal behavior. Experimental dams, which showed increased maternal behavior towards their offspring, displayed reduced anxiety in the EPM on both PND12 and PND22. These behavioral differences could be attributed to neurochemical alterations in their brain: On both PND12 and PND22, experimental mothers had higher levels of ERα and OTRs in the PFC, hippocampus, CeA, SL, MPOA and nAc-Sh. The experimental manipulation-induced increase in ERβ levels was less widespread, being localized in PFC, the hippocampal CA2 area, MPOA and nAc-Sh. In addition, 5-HT1ARs were reduced in the PFC, hippocampus, CeA, MPOA and nAc-Sh of the experimental mothers. Our results show that the experience of the daily repeated brief separation from the pups results in increased brain ERs and OTRs, as well as decreased 5-HT1ARs in the dam's brain; these neurochemical changes could underlie the observed increase in maternal behavior and the reduction of anxiety.

  18. Effect of Feed Melting, Temperature History and Minor Component Addition on Spinel Crystallization in High-Level Waste Glass

    SciTech Connect

    Izak, Pavel; Hrma, Pavel R.; Arey, Bruce W.; Plaisted, Trevor J.

    2001-08-01

    This study was undertaken to help design mathematical models for high-level waste (HLW) glass melter that simulate spinel behavior in molten glass. Spinel, (Fe,Ni,Mn) (Fe,Cr)2O4, is the primary solid phase that precipitates from HLW glasses containing Fe and Ni in sufficient concentrations. Spinel crystallization affects the anticipated cost and risk of HLW vitrification. To study melting reactions, we used simulated HLW feed, prepared with co-precipitated Fe, Ni, Cr, and Mn hydroxides. Feed samples were heated up at a temperature-increase rate (4C/min) close to that which the feed experiences in the HLW glass melter. The decomposition, melting, and dissolution of feed components (such as nitrates, carbonates, and silica) and the formation of intermediate crystalline phases (spinel, sodalite [Na8(AlSiO4)6(NO2)2], and Zr-containing minerals) were characterized using evolved gas analysis, volume-expansion measurement, optical microscope, scanning electron microscope, thermogravimetric analysis, differential scanning calorimetry, and X-ray diffraction. Nitrates and quartz, the major feed components, converted to a glass-forming melt by 880C. A chromium-free spinel formed in the nitrate melt starting from 520C and Sodalite, a transient product of corundum dissolution, appeared above 600C and eventually dissolved in glass. To investigate the effects of temperature history and minor components (Ru,Ag, and Cu) on the dissolution and growth of spinel crystals, samples were heated up to temperatures above liquidus temperature (TL), then subjected to different temperature histories, and analyzed. The results show that spinel mass fraction, crystals composition, and crystal size depend on the chemical and physical makeup of the feed and temperature history.

  19. Influence of type and level of water-soluble additives on drug release and surface and mechanical properties of Surelease films.

    PubMed

    Rohera, Bhagwan D; Parikh, Nilesh H

    2002-11-01

    Ethylcellulose in combination with water-soluble additives has been used in the development of microporous membrane-coated dosage forms. In the present study, application of three types of water-soluble additives, namely polyethylene glycols (PEG 400, 3350, and 8000), maltodextrins (Maltrin M150, M100, and M040 in the order of lower to higher average polymer size and molecular weight; dextrose equivalence 16.9, 11.1, and 4.8, respectively), and xylitol, as porosity modifiers in the films of a commercially available aqueous ethylcellulose dispersion (Surelease/E-7-7060 plasticized with glyceryl tricaprylate/caprate) was investigated. The effect of type and level of these additives on drug release characteristics and surface and mechanical properties of the polymeric films was studied. Each additive was incorporated at 20 and 30% levels in the polymeric dispersion based on its solids content. Ibuprofen tablets were coated using the polymeric dispersion with and without additive at 3% w/w coat level in a fluid-bed equipment. The coated tablets were evaluated for their drug release rate, coat reflectivity (gloss), Brinell hardness, and elastic modulus. Differential scanning calorimetric analysis of the films was performed to determine the physico-chemical changes in the applied film-coats. The rate of drug release, hence film porosity, was observed to be dependent on the type and level of the additive added. The molecular weight of the additive and its concentration in the polymeric dispersion had significant influence on the rate of drug release, hardness, and elasticity of the film-coats.

  20. Decreasing aqueous mercury concentrations to achieve safe levels in fish: examining the water-fish relationship in two point-source contaminated streams

    SciTech Connect

    Mathews, Teresa J; Southworth, George R; Peterson, Mark J; Roy, W Kelly; Ketelle, Richard H; Valentine, Charles S; Gregory, Scott M

    2013-01-01

    East Fork Poplar Creek (EFPC) and White Oak Creek (WOC) are two mercury-contaminated streams located on the Department of Energy s Oak Ridge Reservation in east Tennessee. East Fork Poplar Creek is the larger and more contaminated of the two, with average aqueous mercury (Hg) concentrations exceeding those in reference streams by several hundred-fold. Remedial actions over the past 20 years have decreased aqueous Hg concentrations in EFPC by 85 %. Fish fillet concentrations, however, have not responded to this decrease in aqueous Hg and remain above the U.S. Environmental Protection Agency s ambient water quality criterion (AWQC) of 0.3 mg/kg. The lack of correlation between aqueous and fish tissue Hg concentrations in this creek has led to questions regarding the usefulness of target aqueous Hg concentrations and strategies for future remediation efforts. White Oak Creek has a similar contamination history but aqueous Hg concentrations in WOC are an order of magnitude lower than in EFPC. Despite the lower aqueous Hg concentrations, fish fillet concentrations in WOC have also been above the AWQC, making the most recent aqueous Hg target of 200 ng/L in EFPC seem unlikely to result in an effective decrease in fillet Hg concentrations. Recent monitoring efforts in WOC, however, suggest an aqueous total Hg threshold above which Hg bioaccumulation in fish may not respond. This new information could be useful in guiding remedial actions in EFPC and in other point-source contaminated streams.

  1. Inflammation decreases the level of alpha7 nicotinic acetylcholine receptors in the brain mitochondria and makes them more susceptible to apoptosis induction.

    PubMed

    Lykhmus, Olena; Gergalova, Galyna; Zouridakis, Marios; Tzartos, Socrates; Komisarenko, Sergiy; Skok, Maryna

    2015-11-01

    α7 nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating inflammatory reactions, as well as the cell viability. They are expressed in both the plasma membrane and mitochondria of eukaryotic cells. Previously we found that neuroinflammation resulted in the decrease of α7 nAChR density in the brain of mice and was accompanied by accumulation of amyloid-beta (Aβ) peptides and memory impairment. In the present paper, it is shown that inflammation induced by either regular bacterial lipopolysaccharide (LPS) injections or immunizations with α7 nAChR extracellular domain (1-208) affected also the brain cell mitochondria. Using various modifications of sandwich ELISA, we observed the decrease of α7 nAChRs and accumulation of Aβ(1-40) and Aβ(1-42) in mitochondria of immunized or LPS-treated mice compared to control ones. Mitochondria of treated mice responded with cytochrome c release to lower Ca(2+) concentrations than mitochondria of control mice and were less sensitive to its attenuation with α7 nAChR agonist PNU282987. It is concluded that inflammation decreases α7 nAChR expression in both mitochondria and cell plasma membrane and makes mitochondria more susceptible to apoptosis induction.

  2. High basal levels of functional toll-like receptor 3 (TLR3) and noncanonical Wnt5a are expressed in papillary thyroid cancer and are coordinately decreased by phenylmethimazole together with cell proliferation and migration.

    PubMed

    McCall, Kelly D; Harii, Norikazu; Lewis, Christopher J; Malgor, Ramiro; Kim, Won Bae; Saji, Motoyasu; Kohn, Aimee D; Moon, Randall T; Kohn, Leonard D

    2007-09-01

    High basal levels of TLR3 and Wnt5a RNA are present in papillary thyroid carcinoma (PTC) cell lines consistent with their overexpression and colocalization in PTC cells in vivo. This is not the case in thyrocytes from normal tissue and in follicular carcinoma (FC) or anaplastic carcinoma (AC) cells or tissues. The basally expressed TLR3 are functional in PTC cells as evidenced by the ability of double-strand RNA (polyinosine-polycytidylic acid) to significantly increase the activity of transfected NF-kappaB and IFN-beta luciferase reporter genes and the levels of two end products of TLR3 signaling, IFN-beta and CXCL10. Phenylmethimazole (C10), a drug that decreases TLR3 expression and signaling in FRTL-5 thyrocytes, decreases TLR3 levels and signaling in PTC cells in a concentration-dependent manner. C10 also decreased Wnt5a RNA levels coordinate with decreases in TLR3. E-cadherin RNA levels, whose suppression may be associated with high Wnt5a, increased with C10 treatment. C10 simultaneously decreased PTC proliferation and cell migration but had no effect on the growth and migration of FC, AC, or FRTL-5 cells. C10 decreases high basal phosphorylation of Tyr705 and Ser727 on Stat3 in PTC cells and inhibits IL-6-induced Stat3 phosphorylation. IL-6-induced Stat3 phosphorylation is important both in up-regulating Wnt5a levels and in cell growth. In sum, high Wnt5a levels in PTC cells may be related to high TLR3 levels and signaling; and the ability of phenylmethimazole (C10) to decrease growth and migration of PTC cells may be related to its suppressive effect on TLR3 and Wnt5a signaling, particularly Stat3 activation. PMID:17525119

  3. An extreme cytoplasmic bottleneck in the modern European cultivated potato (Solanum tuberosum) is not reflected in decreased levels of nuclear diversity

    PubMed Central

    Provan, J.; Powell, W; Dewar, H.; Bryan, G.; Machray, G. C.; Waugh, R.

    1999-01-01

    We have used the polymorphic chloroplast (cp) and nuclear simple sequence repeats (SSRs) to analyse levels of cytoplasmic and nuclear diversity in the gene pool of the European cultivated potato (Solanum tuberosum ssp. tuberosum). Primers designed from the complete chloroplast sequence of tobacco (Nicotiana tabacum) were used to amplify polymorphic products in a range of potato cultivars. Combining the data from seven polymorphic cpSSR loci gave 26 haplotypes, one of which (haplotype A) accounted for 151 out of the 178 individuals studied and corresponded to the T-type cytoplasm previously identified in cultivated potatoes using chloroplast restriction fragment length polymorphism analysis. Phylogenetic and diversity analyses of the relationships between cpSSR haplotypes confirmed much higher levels of cytoplasmic diversity outwith the T-type group. Diversity levels at eight nuclear SSR loci, however, were not significantly different between cytoplasmic groups, suggesting a severe maternal bottleneck in the evolution of the modern cultivated potato. These results highlight the importance in quantifying levels of cytoplasmic as well as nuclear diversity and confirm the need for a change in breeding practices to increase levels of non-T-type cytoplasm in the cultivated gene pool, thus helping reduce problems associated with pollen sterility. This may be facilitated by germplasm analysis using cpSSRs, which will allow efficient selection of diverse cytoplasm donors.

  4. Association of decreased variation of R-R interval and elevated serum C-reactive protein level in a general population in Japan.

    PubMed

    Kon, Hisashi; Nagano, Masahide; Tanaka, Fumitaka; Satoh, Kenyu; Segawa, Toshie; Nakamura, Motoyuki

    2006-11-01

    Several studies have suggested that an increased high sensitivity C-reactive protein (hsCRP) level is a strong independent predictor of increased risk for atherosclerotic cardiovascular mortality and morbidity. Reduced heart rate variability (HRV) has also been reported to predict cardiovascular events such as sudden death and myocardial infarction in apparently healthy subjects. The aim of this cross-sectional study was to test the possible correlation between variation of the R-R interval as one of the markers of HRV and serum hsCRP levels in a general population in Japan. Resting, supine, 2-minute, beat-to-beat heart rate data were collected in 823 randomly selected participants enrolled in our cohort study. The coefficient of variation of the R-R interval (CVrr) was obtained as a parameter of HRV. To determine which factors predict the presence of low CVrr (below the 5 percentile) in this group, we performed a multivariate logistic regression analysis using cardiovascular risk factors and an elevated hsCRP level as independent variables. The lowest CVrr group showed significantly higher hsCRP levels compared to those of other quartiles (P < 0.01). After adjustment for confounding factors such as age, heart rate, obesity, hypercholesterolemia, and hypertension by multivariate logistic analysis, an elevated hsCRP level (OR = 3.11, 95%CI; 1.27-7.60: P < 0.02) was a significant independent predictor of low CVrr. The results of the present study indicate that an increased serum hsCRP level is significantly associated with reduced CVrr in this general population. It is conceivable that the parasympathetic nerve withdrawal and inflammation could interact with each other, resulting in the progression of atherosclerotic cardiovascular disease. PMID:17268121

  5. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI.

  6. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI. PMID:27597810

  7. Low-level repeated exposure to diazinon and chlorpyrifos decrease anxiety-like behaviour in adult male rats as assessed by marble burying behaviour.

    PubMed

    Savy, Claire Y; Fitchett, Ann E; McQuade, Richard; Gartside, Sarah E; Morris, Christopher M; Blain, Peter G; Judge, Sarah J

    2015-09-01

    Occupational exposure to organophosphate (OPs) pesticides is reported to increase in the risk of developing anxiety and depression. Preclinical studies using OP levels, which inhibit acetylcholinesterase activity, support the clinical observations, but little is known of the effects of exposure below this threshold. We examined the effects of low level OP exposure on behaviours and neurochemistry associated with affective disorders. Adult rats were administered either diazinon (1 mg/kg i.p.) which is present in sheep dip and flea collars, chlorpyrifos (1 mg/kg i.p.) which is present in crop sprays, or vehicle for 5 days. OP exposure did not affect acetylcholinesterase activity (blood, cerebellum, caudate putamen, hippocampus, prefrontal cortex), anhedonia-like behaviour (sucrose preference), working memory (novel object recognition), locomotor activity or anxiety-like behaviour in the open field arena. In contrast OP exposure attenuated marble burying behaviour, an ethological measure of anxiety. The diazinon-induced reduction in marble burying persisted after exposure cessation. In comparison to vehicle, dopamine levels were lowered by chlorpyrifos, but not diazinon. 5-HT levels and turnover were unaffected by OP exposure. However, 5-HT transporter expression was reduced by diazinon suggesting subtle changes in 5-HT transmission. These data indicate exposure to occupational and domestic OPs, below the threshold to inhibit acetylcholinesterase, can subtly alter behaviour and neurochemistry.

  8. The Activation Effects of Low Level Isopropyl Alcohol Exposure on Arterial Blood Pressures Are Associated with Decreased 5-Hydroxyindole Acetic Acid in Urine

    PubMed Central

    Zhao, Zhiqiang; Liu, Xinxia; Xing, Xiumei; Lu, Yao; Sun, Yi; Ou, Xiaoyan; Su, Xiaolin; Jiang, Jun; Yang, Yarui; Chen, Jingli; Shen, Biling; He, Yun

    2016-01-01

    Purposes The objectives of this paper are to study the impact of low level isopropyl alcohol exposure on blood pressure and to explore its potential mechanism. Methods This cross-sectional study was based on a prospective occupational cohort in south China, which focusing on occupational risk factors related cardiovascular health problems. A total of 283 participants (200 low isopropyl alcohol exposed workers and 83 controls) was finally enrolled in this study. Linear regression models were used to analyze the relationship between arterial blood pressures and low level isopropyl alcohol exposure. We used mediation method to explore possible mediated roles of neurogenic factors. Results Systolic blood pressure (SBP, 123±10 vs. 118±11), diastolic blood pressure (DBP, 79±7 vs. 74±7) and mean blood pressure (MBP, 93±8 vs. 89±9) were different between the exposed group and the control group (p < 0.01). After adjusting for covariates, the difference was still significant. Besides, isopropyl alcohol and smoking had an interactive effect on DBP and MBP (p < 0.05). Furthermore, we observed a mediated effect of 5-hydroxyindole acetic acid (5-HIAA) on isopropyl alcohol exposure induced arterial blood pressure increase, which accounted for about 25%. Conclusions Our results suggest that low level isopropyl alcohol exposure is a potential risk factor for the increased arterial blood pressure and 5-HIAA partly mediates the association between low level isopropyl alcohol exposure and arterial blood pressures. PMID:27622502

  9. Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice

    PubMed Central

    Mody, Nimesh; Graham, Timothy E.; Tsuji, Yuki; Yang, Qin; Kahn, Barbara B.

    2009-01-01

    Serum retinol-binding protein (RBP4) is secreted by liver and adipocytes and is implicated in systemic insulin resistance in rodents and humans. RBP4 normally binds to the larger transthyretin (TTR) homotetramer, forming a protein complex that reduces renal clearance of RBP4. To determine whether alterations in RBP4-TTR binding contribute to elevated plasma RBP4 levels in insulin-resistant states, we investigated RBP4-TTR interactions in leptin-deficient ob/ob mice and high-fat-fed obese mice (HFD). Gel filtration chromatography of plasma showed that 88–94% of RBP4 is contained within the RBP4-TTR complex in ob/ob and lean mice. Coimmunoprecipitation with an RBP4 antibody brought down stoichiometrically equal amounts of TTR and RBP4, indicating that TTR was not more saturated with RBP4 in ob/ob mice than in controls. However, plasma TTR levels were elevated approximately fourfold in ob/ob mice vs. controls. RBP4 injected intravenously in lean mice cleared rapidly, whereas the t1/2 for disappearance was approximately twofold longer in ob/ob plasma. Urinary fractional excretion of RBP4 was reduced in ob/ob mice, consistent with increased retention. In HFD mice, plasma TTR levels and clearance of injected RBP4 were similar to chow-fed controls. Hepatic TTR mRNA levels were elevated approximately twofold in ob/ob but not in HFD mice. Since elevated circulating RBP4 causes insulin resistance and glucose intolerance in mice, these findings suggest that increased TTR or alterations in RBP4-TTR binding may contribute to insulin resistance by stabilizing RBP4 at higher steady-state concentrations in circulation. Lowering TTR levels or interfering with RBP4-TTR binding may enhance insulin sensitivity in obesity and type 2 diabetes. PMID:18285525

  10. Screening of Miners and Millers at Decreasing Levels of Asbestos Exposure: Comparison of Chest Radiography and Thin-Section Computed Tomography

    PubMed Central

    Terra-Filho, Mario; Bagatin, Ericson; Nery, Luiz Eduardo; Nápolis, Lara Maris; Neder, José Alberto; de Souza Portes Meirelles, Gustavo; Silva, C. Isabela; Muller, Nestor L.

    2015-01-01

    Background Chest radiography (CXR) is inferior to Thin-section computed tomography in the detection of asbestos related interstitial and pleural abnormalities. It remains unclear, however, whether these limitations are large enough to impair CXR´s ability in detecting the expected reduction in the frequency of these asbestos-related abnormalities (ARA) as exposure decreases. Methods Clinical evaluation, CXR, Thin-section CT and spirometry were obtained in 1418 miners and millers who were exposed to progressively lower airborne concentrations of asbestos. They were separated into four groups according to the type, period and measurements of exposure and/or procedures for controlling exposure: Group I (1940–1966/tremolite and chrysotile, without measurements of exposure and procedures for controlling exposure); Group II (1967–1976/chrysotile only, without measurements of exposure and procedures for controlling exposure); Group III (1977–1980/chrysotile only, initiated measurements of exposure and procedures for controlling exposure) and Group IV (after 1981/chrysotile only, implemented measurements of exposure and a comprehensive procedures for controlling exposure). Results In all groups, CXR suggested more frequently interstitial abnormalities and less frequently pleural plaques than observed on Thin-section CT (p<0.050). The odds for asbestosis in groups of decreasing exposure diminished to greater extent at Thin-section CT than on CXR. Lung function was reduced in subjects who had pleural plaques evident only on Thin-section CT (p<0.050). In a longitudinal evaluation of 301 subjects without interstitial and pleural abnormalities on CXR and Thin-section CT in a previous evaluation, only Thin-section CT indicated that these ARA reduced as exposure decreased. Conclusions CXR compared to Thin-section CT was associated with false-positives for interstitial abnormalities and false-negatives for pleural plaques, regardless of the intensity of asbestos exposure

  11. Rapid N2O fluxes at high level of nitrate nitrogen addition during freeze-thaw events in boreal peatlands of Northeast China

    NASA Astrophysics Data System (ADS)

    Cui, Qian; Song, Changchun; Wang, Xianwei; Shi, Fuxi; Wang, Lili; Guo, Yuedong

    2016-06-01

    Freeze-thaw (FT) events and increasing nitrogen (N) availability may alter N turnover and nitrous oxide (N2O) emissions in permafrost peatlands. However, the responses of N2O emissions to different N levels and additions during FT events are far from clear. We conducted an incubation study to investigate the impacts of different N addition levels (LN: 0.07 mg N g-1, HN: 0.14 mg N g-1) and N addition forms (AC: ammonium chloride, NS: sodium nitrate) on the emissions of N2O under FT and non-freeze-thaw (NFT) conditions in boreal peatlands of Northeast China. Results indicated that the FT condition significantly increased N2O emissions compared with the NFT condition and peaks occurred during thawing. Compared with AC treatments, NS treatments significantly elevated the accumulation of N2O emissions under the FT condition, exhibiting significant differences in different NS levels. N2O emissions were also positively dependent on soil NO3- concentrations to supply nitrate for denitrification. Nitrate-N addition was mainly responsible for the burst of N2O with denitrification as the main process during FT events. Therefore, these results suggest that N2O emissions potentially increase during FT events with increasing nitrate-N deposition in permafrost peatlands, which would contribute to global climate warming.

  12. Decreased food intake rather than zinc deficiency is associated with changes in plasma leptin, metabolic rate, and activity levels in zinc deficient rats( small star, filled).

    PubMed

    Gaetke, Lisa M.; Frederich, Robert C.; Oz, Helieh S.; McClain, Craig J.

    2002-04-01

    This study investigated the hypothesis that the reduced food intake and poor weight gain in zinc deficient rats is due to: increased plasma leptin concentration, increased physical activity and/or increased metabolic rate. Weanling rats were assigned to three groups: controls fed ad libitum (C), zinc deficient (ZD), and pair-fed controls (PF), and tested in a metabolic chamber and activity monitor at baseline and weekly for four weeks. At the end of the study, all groups were compared for differences in plasma leptin concentrations. ZD and PF animals had markedly reduced food intake and weight gain. ZD had reduced stereotypic and locomotor activity compared to PF animals and both groups demonstrated an abolished peri-nocturnal activity spike and were much less active than controls. This was associated with a reduced total metabolic rate by day 30: ZD (0.73 +/- 0.07 kcal/hr, p = 0.0001) and PF (0.83 +/- 0.06 kcal/hr, p = 0.0001) groups vs. controls (1.82 +/- 0.09 kcal/hr). Plasma leptin concentrations in ZD (1.55 +/- 0.06 &mgr;g/L) were lower than controls (2.01 +/- 0.18 &mgr;g/L, p < 0.03), but neither ZD nor controls were statistically different from PF (1.68 +/- 0.05 &mgr;g/L). Both low leptin concentrations and low metabolic rates in the ZD and PF rats were associated with decreased food intake rather than zinc deficiency. The reduced food intake and poor weight gain observed in zinc deficient rats could not be explained by elevated leptin concentrations, hypermetabolism, or increased activity. Low serum leptin concentrations, hypometabolism, and decreased activity are more likely the result of the anorexia of zinc deficiency.

  13. Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.

    PubMed

    Ahn, Min-Soo; Yoo, Byung-Su; Lee, Ji Hyun; Lee, Jun-Won; Youn, Young Jin; Ahn, Sung Gyun; Kim, Jang-Young; Lee, Seung-Hwan; Yoon, Junghan; Park, Jong-Ku; Ahn, Song Vogue; Choi, Eunhee

    2015-04-01

    The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.

  14. A therapeutic combination of metyrapone and oxazepam increases brain levels of GABA-active neurosteroids and decreases cocaine self-administration in male rats.

    PubMed

    Schmoutz, Christopher D; Guerin, Glenn F; Runyon, Scott P; Dhungana, Suraj; Goeders, Nicholas E

    2015-09-15

    In rodents, the behavioral and neurochemical effects resulting from the pharmacological blockade of the hypothalamo-pituitary-adrenal (HPA) axis are unclear. Metyrapone, a corticosterone synthesis inhibitor, has been demonstrated to reduce cocaine-related behaviors, especially in a low-dose combination with oxazepam, a benzodiazepine. Although this combination therapy (MET/OX) also reduces drug-taking and drug-seeking behaviors in both rodents and cocaine-dependent humans, these effects are not correlated with plasma glucocorticoid levels. In this brief report, we present data demonstrating that this MET/OX combination enhances brain levels of the GABA-active steroid metabolites, tetrahydrodeoxycorticosterone (THDOC) and allopregnanolone. Male rats, trained to self-administer cocaine or that received yoked-saline infusions, were pretreated with MET/OX, at doses that reduced cocaine-motivated responding, or vehicle. Allopregnanolone and THDOC were measured using liquid chromatography-mass spectroscopy (LC-MS/MS) in the prefrontal cortex and amygdala in the brains from these rats. THDOC levels were enhanced following MET/OX pretreatment in both brain regions, regardless of cocaine self-administration experience. However, allopregnanolone was selectively enhanced in the rats that self-administered cocaine, but not in rats in the yoked-saline group. Thus, the MET/OX combination increased neurosteroid content in brain regions important for drug addiction. These neurosteroids have been shown to reduce cocaine-related behaviors and may contribute to the behavioral effects of MET/OX combination therapy. PMID:26003946

  15. Decreased cerebrospinal fluid levels of L-carnitine in non-apolipoprotein E4 carriers at early stages of Alzheimer's disease.

    PubMed

    Lodeiro, María; Ibáñez, Clara; Cifuentes, Alejandro; Simó, Carolina; Cedazo-Mínguez, Ángel

    2014-01-01

    Increasing evidence suggest that Alzheimer's disease (AD) is a heterogeneous disorder that includes several subtypes with different etiology and progression. Cerebrospinal fluid (CSF) is being used to find new biomarkers reflecting the complexity of the pathological pathways within this disease. We used CSF and clinical data from patients to investigate the status of asymmetric dimethyl-L-arginine, creatine, suberylglycine, and L-carnitine along AD progression. These molecules play important roles in mitochondrial function and dysfunction in mitochondrial metabolism are involved in AD pathology. We found that non-APOE4 carriers show lower levels of L-carnitine in CSF early in AD. L-carnitine levels correlate with amyloid-β (Aβ) levels and Mini-Mental State Examination score, but do not add to the specificity or sensitivity of the classical AD CSF biomarkers, Aβ42, phospho-tau, and total-tau. Our results suggest APOE genotype-dependent differences in L-carnitine synthesis or metabolism along AD, and insinuate that L-carnitine treatments would be more beneficial for AD patients not carrying the APOE4 isoform.

  16. High levels of dietary unsaturated fat decrease alpha-tocopherol content of whole body, liver, and plasma of chickens without variations in intestinal apparent absorption.

    PubMed

    Villaverde, C; Baucells, M D; Manzanilla, E G; Barroeta, A C

    2008-03-01

    An experiment was designed to assess the effect of dietary unsaturated fat inclusion level on alpha-tocopherol apparent absorption and deposition in broiler chickens at 2 ages (20 and 39 d). The dietary fat was a mixture of linseed and fish oil, rich in polyunsaturated fatty acids (PUFA). The experimental treatments were the result of 4 levels of supplementation with alpha-tocopheryl acetate (0, 100, 200, and 400 mg/kg; E0, E100, E200, and E400 treatments, respectively) and 4 dietary oil inclusion levels (2, 4, 6, and 8%; O2, O4, O6, and O8 treatments respectively). Almond husk was used as an energy dilutor in the high-fat diets. Apparent absorption of total fatty acids was high in all treatments averaging 88% and was higher with high fat dietary inclusion level. alpha-Tocopheryl acetate hydrolysis and apparent absorption of alpha-tocopherol were similar in both ages and were not affected by fat inclusion level, except for a reduction of the absorption in the low-fat diet (O2) in the E100 treatment at 20 d of age. Despite this lack of differences in hydrolysis and absorption, higher-fat PUFA diets induced lower concentrations of free alpha-tocopherol in the excreta, at high alpha-tocopherol doses, suggesting an increase in the destruction of alpha-tocopherol by lipid oxidation in the gastrointestinal tract. Similarly, total and hepatic alpha-tocopherol deposition was lower in the birds fed high-PUFA diets in the E200- and E400-supplemented birds, possibly due to a destruction of vitamin E when protecting these PUFA from lipid peroxidation. alpha-Tocopherol concentration in liver and, to a lesser extent, in plasma was a useful indicator of the degree of response of this vitamin to different factors that can affect its bioavailability; however, in the present experiment, CV were too high to use liver and plasma concentrations as estimators of total body vitamin E. PMID:18281576

  17. The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction

    PubMed Central

    Wang, Shu-Jin; Qu, Zhong-Sen; Zhang, Qing-De; Li, Liang; Wang, Feng; Zhang, Bin; Wu, Bang-Li; Zhao, Yu-Wu

    2015-01-01

    To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease. PMID:26550224

  18. Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species

    PubMed Central

    Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes

    2015-01-01

    Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury. PMID:25649993

  19. Protection of hypoglycemia-induced neuronal death by β-hydroxybutyrate involves the preservation of energy levels and decreased production of reactive oxygen species.

    PubMed

    Julio-Amilpas, Alberto; Montiel, Teresa; Soto-Tinoco, Eva; Gerónimo-Olvera, Cristian; Massieu, Lourdes

    2015-05-01

    Glucose is the main energy substrate in brain but in certain circumstances such as prolonged fasting and the suckling period alternative substrates can be used such as the ketone bodies (KB), beta-hydroxybutyrate (BHB), and acetoacetate. It has been shown that KB prevent neuronal death induced during energy limiting conditions and excitotoxicity. The protective effect of KB has been mainly attributed to the improvement of mitochondrial function. In the present study, we have investigated the protective effect of D-BHB against neuronal death induced by severe noncoma hypoglycemia in the rat in vivo and by glucose deprivation (GD) in cortical cultures. Results show that systemic administration of D-BHB reduces reactive oxygen species (ROS) production in distinct cortical areas and subregions of the hippocampus and efficiently prevents neuronal death in the cortex of hypoglycemic animals. In vitro results show that D-BHB stimulates ATP production and reduces ROS levels, while the nonphysiologic isomer of BHB, L-BHB, has no effect on energy production but reduces ROS levels. Data suggest that protection by BHB, not only results from its metabolic action but is also related to its capability to reduce ROS, rendering this KB as a suitable candidate for the treatment of ischemic and traumatic injury.

  20. Neuropeptide Kyotorphin (Tyrosyl-Arginine) has Decreased Levels in the Cerebro-Spinal Fluid of Alzheimer’s Disease Patients: Potential Diagnostic and Pharmacological Implications

    PubMed Central

    Santos, Sara Matos; Garcia-Nimo, Laura; Sá Santos, Sónia; Tavares, Isaura; Cocho, José A.; Castanho, Miguel A. R. B.

    2013-01-01

    In Alzheimer’s disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endogenous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible correlation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured. We found a statistically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection. PMID:24198785

  1. Neuropeptide Kyotorphin (Tyrosyl-Arginine) has Decreased Levels in the Cerebro-Spinal Fluid of Alzheimer's Disease Patients: Potential Diagnostic and Pharmacological Implications.

    PubMed

    Santos, Sara Matos; Garcia-Nimo, Laura; Sá Santos, Sónia; Tavares, Isaura; Cocho, José A; Castanho, Miguel A R B

    2013-01-01

    In Alzheimer's disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endogenous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible correlation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured. We found a statistically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection.

  2. Muscimol prevents long-lasting potentiation of dorsal horn field potentials in rats with chronic constriction injury exhibiting decreased levels of the GABA transporter GAT-1.

    PubMed

    Miletic, Gordana; Draganic, Pero; Pankratz, Matthew T; Miletic, Vjekoslav

    2003-09-01

    The inhibitory activity of gamma-aminobutyric acid (GABA) is considered critical in setting the conditions for synaptic plasticity, and many studies support an important role of GABA in the suppression of nociceptive transmission in the dorsal horn. Consequently, any injury-induced modification of the GABA action has the potential to critically modify spinal synaptic plasticity. We have previously reported that chronic constriction injury of the sciatic nerve was accompanied by long-lasting potentiation of superficial spinal dorsal horn field potentials following high-frequency tetanus. In this study we examined whether the GABA-A receptor agonist muscimol would modify post-tetanic responses in rats with chronic constriction injury. In animals exhibiting maximal thermal hyperalgesia as one sign of neuropathic pain 7 days after loose ligation of the sciatic nerve, spinal application of muscimol (5, 10 or 20 microg) before the high-frequency (50 Hz) tetanus produced a long-lasting depression (rather than potentiation) of spinal dorsal horn field potentials. In separate but related Western immunoblot experiments, we also established that the chronic constriction injury was accompanied by significant decreases in the content of the GABA transporter GAT-1. These data demonstrated that GABA-A receptor agonists may effectively influence the expression of long-lasting synaptic plasticity in the spinal dorsal horn, and that an injury-induced loss in GABA transporter content may have contributed to a depletion of GABA from its terminals within the spinal dorsal horn. These data lent further support to the notion that the loss of GABA inhibition may have important consequences for the development of neuropathic pain. PMID:14499453

  3. Maternal separation enhances conditioned fear and decreases the mRNA levels of the neurotensin receptor 1 gene with hypermethylation of this gene in the rat amygdala.

    PubMed

    Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

    2014-01-01

    Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such "programmed" effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood. PMID:24831231

  4. Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

    PubMed Central

    Toda, Hiroyuki; Boku, Shuken; Nakagawa, Shin; Inoue, Takeshi; Kato, Akiko; Takamura, Naoki; Song, Ning; Nibuya, Masashi; Koyama, Tsukasa; Kusumi, Ichiro

    2014-01-01

    Stress during postnatal development is associated with an increased risk for depression, anxiety disorders, and substance abuse later in life, almost as if mental illness is able to be programed by early life stressors. Recent studies suggest that such “programmed” effects can be caused by epigenetic regulation. With respect to conditioned fear, previous studies have indicated that early life stress influences its development in adulthood, whereas no potential role of epigenetic regulation has been reported. Neurotensin (NTS) is an endogenous neuropeptide that has receptors densely located in the amygdala and hippocampus. Recently, NTS systems have constituted an emerging target for the treatment of anxiety. The aim of the present work is to clarify whether the NTS system is involved in the disturbance of conditioned fear in rats stressed by maternal separation (MS). The results showed that MS enhanced freezing behaviors in fear-conditioned stress and reduced the gene expression of NTS receptor (NTSR) 1 but not of NTS or NTSR2 in the amygdalas of adult rats. The microinjection of a NTSR1 antagonist into the amygdala increased the percentage of freezing in conditioned fear, whereas the microinjection of NTSR1 agonist decreased freezing. These results suggest that NTSR1 in the amygdala may play a role in the effects of MS on conditioned fear stress in adult rats. Moreover, MS increased DNA methylation in the promoter region of NTSR1 in the amygdala. Taken together, MS may leave epigenetic marks in the NTSR1 gene in the amygdala, which may enhance conditioned fear in adulthood. The MS-induced alternations of DNA methylation in the promoter region of NTSR1 in the amygdala may be associated with vulnerability to the development of anxiety disorders and depression in adulthood. PMID:24831231

  5. Supermolecular structure of cellulose: stepwise decrease in LODP and particle size of cellulose hydrolyzed after chemical treatment. [Leveling-off degree of polymerization

    SciTech Connect

    Yachi, T.; Hayashi, J.; Takai, M.; Shimizu, Y.

    1983-01-01

    It was observed by electron microscopy that rayons hydrolyzed with 2.4 N HCl at 100/sup 0/C for 2 h, followed by ultrasonic treatment were split into homogeneous particles having a size of about 200 A(2000A). In the previous work with rayons, crystallite length, long period, and chain length calculated from their LODP were all about 200 A(2000A), regardless of the type of rayon. The agreement between particle size and length suggested strongly that a rayon microfibril has a periodic structure along its axis at intervals of about A(2000A). Celluloses II, III, and IV and cellulose regenerated from its esters were derived both from native cellulose and rayons in the fibrous state. After hydrolysis, all the modifications derived from native cellulose showed an LODP of about 80 and rod-like fragments which showed a maximum at 400 A(2000A) in the frequency distribution of their lengths. All of the modifications, except mercerized native cellulose, showed a meridional small-angle reflection corresponding to 400 A(2000A). All the modifications from rayons showed an LODP of about 40. The esters derived from native cellulose were recrystallized by heat treatment and then saponified into cellulose II. After hydrolysis, they showed an LODP of about 40 (200 A(2000A) in chain length), a meridional reflection showing a long period of about 200 A(2000A), and a particle-like fragment having a size of about 200 A(2000A). For native cellulose, after chemical and physical treatments, the LODP, the long period, and the fragment length all decreased stepwise and by the same amounts. The steps were an integral multiple of 200 A(2000A), which is the value of the crystallite length obtained for the native and all other celluloses. The results suggest that native cellulose has a periodic structure at intervals of 200 A(2000A) in length. 40 references, 14 figures, 5 tables.

  6. Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer.

    PubMed

    Pang, Li; Wang, Jing; Jiang, Yanwen; Chen, Liangan

    2013-08-01

    Diagnostic tools capable of predicting early responses to chemotherapy are required to improve the individual management of cancer patients. The present study aimed to evaluate the prognostic significance of the serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A total of 276 patients with postoperative stage I-IV NSCLC were retrospectively reviewed. The five tumor markers were measured before and after at least two cycles of chemotherapy using an electrochemiluminescent assay. Multivariate analysis revealed that performance status, age, postoperative stage and surgery were significantly associated with the response to chemotherapy. High baseline CYFRA 21-1 and CA 19-9 levels were associated with poor effectiveness of chemotherapy. Significant reductions in CYFRA 21-1 levels were associated with a positive response to various chemotherapy regimens. CEA, CA 125 and CA 19-9 expression was only associated with a positive response in patients receiving paclitaxel, docetaxel, pemetrexed and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). NSE expression was only associated with a positive response to gemcitabine. Receiver operating characteristic (ROC) curve analysis indicated that CYFRA 21-1 is the most sensitive of the tumor markers in predicting the response to chemotherapy. Serum CYFRA 21-1 is a useful surrogate marker for predicting the response to different chemotherapy regimens used to treat NSCLC and is a more sensitive marker than CEA, CA125, CA19-9 and NSE. PMID:24137188

  7. Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis.

    PubMed

    Novati, A; Hulshof, H J; Koolhaas, J M; Lucassen, P J; Meerlo, P

    2011-09-01

    Sleep loss strongly affects brain function and may even predispose susceptible individuals to psychiatric disorders. Since a recurrent lack of sleep frequently occurs during adolescence, it has been implicated in the rise in depression incidence during this particular period of life. One mechanism through which sleep loss may contribute to depressive symptomatology is by affecting hippocampal function. In this study, we examined the effects of sleep loss on hippocampal integrity at young age by subjecting adolescent male rats to chronic sleep restriction (SR) for 1 month from postnatal day 30 to 61. They were placed in slowly rotating drums for 20 h per day and were allowed 4 h of rest per day at the beginning of the light phase. Anxiety was measured using an open field and elevated plus maze test, while saccharine preference was used as an indication of anhedonia. All tests were performed after 1 and 4 weeks of SR. We further studied effects of SR on hypothalamic-pituitary-adrenal (HPA) axis activity, and at the end of the experiment, brains were collected to measure hippocampal volume and neurogenesis. Behavior of the SR animals was not affected, except for a transient suppression of saccharine preference after 1 week of SR. Hippocampal volume was significantly reduced in SR rats compared to home cage and forced activity controls. This volume reduction was not paralleled by reduced levels of hippocampal neurogenesis and could neither be explained by elevated levels of glucocorticoids. Thus, our results indicate that insufficient sleep may be a causal factor in the reductions of hippocampal volume that have been reported in human sleep disorders and mood disorders. Since changes in HPA activity or neurogenesis are not causally implicated, sleep disturbance may affect hippocampal volume by other, possibly more direct mechanisms.

  8. Decreasing the Level of Ethyl Acetate in Ethanolic Fermentation Broths of Escherichia coli KO11 by Expression of Pseudomonas putida estZ Esterase†

    PubMed Central

    Hasona, Adnan; York, S. W.; Yomano, L. P.; Ingram, L. O.; Shanmugam, K. T.

    2002-01-01

    During the fermentation of sugars to ethanol relatively high levels of an undesirable coproduct, ethyl acetate, are also produced. With ethanologenic Escherichia coli strain KO11 as the biocatalyst, the level of ethyl acetate in beer containing 4.8% ethanol was 192 mg liter−1. Although the E. coli genome encodes several proteins with esterase activity, neither wild-type strains nor KO11 contained significant ethyl acetate esterase activity. A simple method was developed to rapidly screen bacterial colonies for the presence of esterases which hydrolyze ethyl acetate based on pH change. This method allowed identification of Pseudomonas putida NRRL B-18435 as a source of this activity and the cloning of a new esterase gene, estZ. Recombinant EstZ esterase was purified to near homogeneity and characterized. It belongs to family IV of lipolytic enzymes and contains the conserved catalytic triad of serine, aspartic acid, and histidine. As expected, this serine esterase was inhibited by phenylmethylsulfonyl fluoride and the histidine reagent diethylpyrocarbonate. The native and subunit molecular weights of the recombinant protein were 36,000, indicating that the enzyme exists as a monomer. By using α-naphthyl acetate as a model substrate, optimal activity was observed at pH 7.5 and 40°C. The Km and Vmax for α-naphthyl acetate were 18 μM and 48.1 μmol · min−1 · mg of protein−1, respectively. Among the aliphatic esters tested, the highest activity was obtained with propyl acetate (96 μmol · min−1 · mg of protein−1), followed by ethyl acetate (66 μmol · min−1 · mg of protein−1). Expression of estZ in E. coli KO11 reduced the concentration of ethyl acetate in fermentation broth (4.8% ethanol) to less than 20 mg liter−1. PMID:12039716

  9. Additional Financial Resources for Education.

    ERIC Educational Resources Information Center

    Hubbard, Ben C.

    This paper discusses the continuing need for additional educational funds and suggests that the only way to gain these funds is through concerted and persistent political efforts by supporters of education at both the federal and state levels. The author first points out that for many reasons declining enrollment may not decrease operating costs…

  10. The anti-fibrotic effect of liver growth factor is associated with decreased intrahepatic levels of matrix metalloproteinases 2 and 9 and transforming growth factor beta 1 in bile duct-ligated rats.

    PubMed

    Díaz-Gil, Juan J; García-Monzón, Carmelo; Rúa, Carmen; Martín-Sanz, Paloma; Cereceda, Rosa M; Miquilena-Colina, María E; Machín, Celia; Fernández-Martínez, Amalia; García-Cañero, Rarael

    2008-05-01

    Liver growth factor (LGF), a mitogen for liver cells, behaves as an anti-fibrotic agent even in extrahepatic sites, but its mechanistic basis is unknown. We aimed to determine the intrahepatic expression pattern of key modulators of liver fibrosis in bile duct-ligated rats (BDL) after injection of LGF. BDL rats received either LGF (4.5 microg/ratXdose, two doses/week, at time 0 or 2 or 5w after operation, depending on the group (BDL+LGF groups, n=20) or saline (BDL+S groups, n=20). Groups were compared in terms of fibrosis (histomorphometry), liver function (aminopyrine breath test), matrix metalloproteinases MMP-2 and MMP-9, transforming growth factor beta 1 (TGF-beta1) and liver endoglin content (Western blotting), and serum tissue inhibitor of metalloproteinases 1 (TIMP-1) levels (ELISA). In BDL+LGF rats, the fibrotic index was significantly lower at 5w, p=0.006, and at 8w, p=0.04, than in BDL+S rats. Liver function values in BDL+LGF rats were higher than those obtained in BDL+S rats (80% at 5w and 79% at 8w, versus 38% and 29%, p<0.01, taking healthy controls as 100%). Notably, in BDL+LGF rats the intrahepatic expression levels of both MMPs were lower at 2w (MMP-2, p=0.03; MMP-9, p=0.05) and 5w (MMP-2, p=0.05, MMP-9, p=0.04). In addition, the hepatic TGF-beta1 level in BDL+LGF rats was lower at 2w (36%, p=0.008), 5w (50%) and 8wk (37%), whereas intrahepatic endoglin expression remained constant in all BDL rats studied. LGF ameliorates liver fibrosis and improves liver function in BDL rats. The LGF-induced anti-fibrotic effect is associated with a decreased hepatic level of MMP-2, MMP-9 and TGF-beta1 in fibrotic rats.

  11. A Citrus bergamia Extract Decreases Adipogenesis and Increases Lipolysis by Modulating PPAR Levels in Mesenchymal Stem Cells from Human Adipose Tissue

    PubMed Central

    Lo Furno, Debora; Avola, Rosanna; Bonina, Francesco; Mannino, Giuliana

    2016-01-01

    The aim of this research was to assess the impact of a well-characterized extract from Citrus bergamia juice on adipogenesis and/or lipolysis using mesenchymal stem cells from human adipose tissue as a cell model. To evaluate the effects on adipogenesis, some cell cultures were treated with adipogenic medium plus 10 or 100 μg/mL of extract. To determine the properties on lipolysis, additional mesenchymal stem cells were cultured with adipogenic medium for 14 days and after this time added with Citrus bergamia for further 14 days. To verify adipogenic differentiation, oil red O staining at 7, 14, 21, and 28 days was performed. Moreover, the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), adipocytes fatty acid-binding protein (A-FABP), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), monoglyceride lipase (MGL), 5′-adenosine monophosphate-activated protein kinase (AMPK)α1/2, and pAMPKα1/2 was evaluated by Western blot analysis and the release of glycerol by colorimetric assay. Citrus bergamia extract suppressed the accumulation of intracellular lipids in mesenchymal stem cells during adipogenic differentiation and promoted lipolysis by repressing the expression of adipogenic genes and activating lipolytic genes. Citrus bergamia extract could be a useful natural product for improving adipose mobilization in obesity-related disorders. PMID:27403151

  12. Decreased levels of physical activity in adolescents with down syndrome are related with low bone mineral density: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Down syndrome (DS) has been described as one of the main contributors for low bone mineral density (BMD). Physical activity (PA) is a key factor in skeletal health and thus, PA levels might be associated to the risk of developing osteoporosis. Therefore, the aims were (1) to describe PA patterns in adolescents with DS compared to their counterparts and (2) to determine the relationships between PA and the risk of having low bone mass in adolescents with DS. Methods Nineteen adolescents (10 girls) with DS and 14 without disabilities (7 girls) participated in the study. Minutes in different PA intensities were objectively assessed with accelerometers (ActiTrainer). Moreover adolescents with DS were classified into PA tertiles taking into account the amount of total minutes of PA at any intensity, resulting in those performing low, medium or high of PA (lowPA, medPA and highPA). BMD was measured at the whole body, hip and lumbar spine with dual-energy X-ray absorptiometry and the BMD Z-score was calculated for each region taking into account age- and sex-matched reference data. Student’s unpaired t-tests and analysis of covariance were used to compare variables between different conditions (DS vs. control) and PA levels (low, medium and high). Results None of the adolescents with DS achieved the minimum of 60 min of daily moderate to vigorous PA (VPA) intensity recommended by PA guidelines; adolescents with DS group spent less time in sedentary and in VPA and more time in light PA than those without DS (p < 0.05). Adolescents with DS showed lower BMD Z-score values than those without (p < 0.05). Those adolescents with DS allocated in the lowPA tertile showed significant lower BMD Z-score at the hip and a general tendency towards lower BMD Z-score was found at whole body and lumbar spine compared to those in highPA tertile and (p < 0.05). Conclusions Adolescents with DS in the highPA tertile showed lower risk of developing future osteoporosis by having

  13. Does addition of low-level laser therapy (LLLT) in conservative care of knee arthritis successfully postpone the need for joint replacement?

    PubMed

    Ip, David

    2015-12-01

    The current study evaluates whether the addition of low-level laser therapy into standard conventional physical therapy in elderly with bilateral symptomatic tri-compartmental knee arthritis can successfully postpone the need for joint replacement surgery. A prospective randomized cohort study of 100 consecutive unselected elderly patients with bilateral symptomatic knee arthritis with each knee randomized to receive either treatment protocol A consisting of conventional physical therapy or protocol B which is the same as protocol A with added low-level laser therapy. The mean follow-up was 6 years. Treatment failure was defined as breakthrough pain which necessitated joint replacement surgery. After a follow-up of 6 years, patients clearly benefited from treatment with protocol B as only one knee needed joint replacement surgery, while nine patients treated with protocol A needed surgery (p < 0.05). We conclude low-level laser therapy should be incorporated into standard conservative treatment protocol for symptomatic knee arthritis.

  14. Severe South American ocular toxoplasmosis is associated with decreased Ifn-γ/Il-17a and increased Il-6/Il-13 intraocular levels.

    PubMed

    de-la-Torre, Alejandra; Sauer, Arnaud; Pfaff, Alexander W; Bourcier, Tristan; Brunet, Julie; Speeg-Schatz, Claude; Ballonzoli, Laurent; Villard, Odile; Ajzenberg, Daniel; Sundar, Natarajan; Grigg, Michael E; Gomez-Marin, Jorge E; Candolfi, Ermanno

    2013-11-01

    In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecting strain was characterized by genotyping when intraocular Toxoplasma DNA was detectable, as well as by peptide-specific serotyping for each patient. To characterize the immune response, we assessed Toxoplasma protein recognition patterns by intraocular antibodies and the intraocular profile of cytokines, chemokines and growth factors. Significant differences were found for size of active lesions, unilateral macular involvement, unilateral visual impairment, vitreous inflammation, synechiae, and vasculitis, with higher values observed throughout for Colombian patients. Multilocus PCR-DNA sequence genotyping was only successful in three Colombian patients revealing one type I and two atypical strains. The Colombian OT patients possessed heterogeneous atypical serotypes whereas the French were uniformly reactive to type II strain peptides. The protein patterns recognized by intraocular antibodies and the cytokine patterns were strikingly different between the two populations. Intraocular IFN-γ and IL-17 expression was lower, while higher levels of IL-13 and IL-6 were detected in aqueous humor of Colombian patients. Our results are consistent with the hypothesis that South American strains may cause more severe OT due to an inhibition of the protective effect of IFN-γ. PMID:24278490

  15. Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase

    PubMed Central

    De Groef, Lies; Salinas-Navarro, Manuel; Van Imschoot, Griet; Libert, Claude; Vandenbroucke, Roosmarijn E.; Moons, Lieve

    2015-01-01

    Matrix metalloproteinases (MMPs) have been designated as both friend and foe in the central nervous system (CNS): while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Müller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novel in vivo function for MMP-2, as an activating sheddase of tumor necrosis factor (TNF). Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS. PMID:26451076

  16. Exposure to soil, house dust and decaying plants increases gut microbial diversity and decreases serum immunoglobulin E levels in BALB/c mice.

    PubMed

    Zhou, Dongrui; Zhang, Honglin; Bai, Zhimao; Zhang, Aidi; Bai, Futian; Luo, Xing; Hou, Yue; Ding, Xiao; Sun, Beili; Sun, Xiao; Ma, Ning; Wang, Cuifen; Dai, Xiaoniu; Lu, Zuhong

    2016-05-01

    To assess the impact of sanitation of a living environment on gut microbiota and development of the immune system, we raised BALB/c mice under three distinct environmental conditions: a specific pathogen-free animal room (SPF), a general animal room (XZ) and a farmhouse (JD). All other variables like diet, age, genetic background, physiological status and original gut microbiota were controlled for in the three groups. Using high-throughput sequencing of the 16S rRNA gene, we found that each mouse group had a specific structure of the gut microbial community. Groups JD and XZ harboured a significantly more diverse and richer gut microbiota than did group SPF. Bacteroidetes were significantly more abundant in groups XZ and JD than in group SPF, whereas Firmicutes showed the inverse pattern. Total serum immunoglobulin E (IgE) levels were significantly lower in groups XZ and JD than in group SPF. There were no significant differences in gut microbiota diversity and serum IgE concentration between groups JD and XZ, but we found higher abundance of dominant genera in the gut microflora of group JD. We conclude that exposure to soil, house dust and decaying plant material enhances gut microbial diversity and innate immunity. Our results seem to provide new evidence supporting the hygiene hypothesis.

  17. Amyloid-β and α-Synuclein Decrease the Level of Metal-Catalyzed Reactive Oxygen Species by Radical Scavenging and Redox Silencing.

    PubMed

    Pedersen, Jeppe T; Chen, Serene W; Borg, Christian B; Ness, Samuel; Bahl, Justyna M; Heegaard, Niels H H; Dobson, Christopher M; Hemmingsen, Lars; Cremades, Nunilo; Teilum, Kaare

    2016-03-30

    The formation of reactive oxygen species (ROS) is linked to the pathogenesis of neurodegenerative diseases. Here we have investigated the effect of soluble and aggregated amyloid-β (Aβ) and α-synuclein (αS), associated with Alzheimer's and Parkinson's diseases, respectively, on the Cu(2+)-catalyzed formation of ROS in vitro in the presence of a biological reductant. We find that the levels of ROS, and the rate by which ROS is generated, are significantly reduced when Cu(2+) is bound to Aβ or αS, particularly when they are in their oligomeric or fibrillar forms. This effect is attributed to a combination of radical scavenging and redox silencing mechanisms. Our findings suggest that the increase in ROS associated with the accumulation of aggregated Aβ or αS does not result from a particularly ROS-active form of these peptides, but rather from either a local increase of Cu(2+) and other ROS-active metal ions in the aggregates or as a downstream consequence of the formation of the pathological amyloid structures.

  18. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels.

    PubMed

    Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wortwein, G; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A

    2016-01-01

    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID:27187231

  19. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels

    PubMed Central

    Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wortwein, G; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A

    2016-01-01

    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA. PMID:27187231

  20. The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level

    PubMed Central

    Zucal, Chiara; Latorre, Elisa; D'Agostino, Vito; Bauer, Inga; Pancher, Michael; Ballestrero, Alberto; Feldmann, Georg; Nencioni, Alessio; Provenzani, Alessandro

    2016-01-01

    The Yes-associated protein, YAP, is a transcriptional co-activator, mediating the Epithelial to Mesenchymal Transition program in pancreatic ductal adenocarcinoma (PDAC). With the aim to identify compounds that can specifically modulate YAP functionality in PDAC cell lines, we performed a small scale, drug-based screening experiment using YAP cell localization as the read-out. We identified erlotinib as an inducer of YAP cytoplasmic localization, an inhibitor of the TEA luciferase reporter system and the expression of the bona fide YAP target gene, Connective Tissue Growth Factor CTGF. On the other hand, BIS I, an inhibitor of PKCδ and GSK3β, caused YAP accumulation into the nucleus. Activation of β-catenin reporter and interfering experiments show that inhibition of the PKCδ/GSK3β pathway triggers YAP nuclear accumulation inducing YAP/TEAD transcriptional response. Inhibition of GSK3β by BIS I reduced the expression levels of SMADs protein and reduced YAP contribution to EMT. Notably, BIS I reduced proliferation, migration and clonogenicity of PDAC cells in vitro, phenocopying YAP genetic down-regulation. As shown by chromatin immunoprecipitation experiments and YAP over-expressing rescue experiments, BIS I reverted YAP-dependent EMT program by modulating the expression of the YAP target genes E-cadherin, vimentin, CTGF and of the newly identified target, CD133. In conclusion, we identified two different molecules, erlotinib and BIS I, modulating YAP functionality although via different mechanisms of action, with the second one specifically inhibiting the YAP-dependent EMT program in PDAC cell lines. PMID:27034169

  1. Obesity decreases both whole muscle and fascicle strength in young females but only exacerbates the aging‐related whole muscle level asthenia

    PubMed Central

    Tomlinson, David J.; Erskine, Robert M.; Winwood, Keith; Morse, Christopher Ian; Onambélé, Gladys L.

    2014-01-01

    Abstract Obesity has previously been associated with greater muscle strength. Aging, on the other hand, reduces muscle specific force (the force per unit physiological cross‐sectional area [PCSA] of muscle). However, neither the effect of obesity on skeletal muscle specific force nor the combined effects of aging and obesity on this parameter are known. This study aimed to describe the interplay between body mass index (BMI)/adiposity, aging, and skeletal muscle specific force. Ninety‐four untrained healthy women categorized by age into young (Y; mean ± SD: 25.5 ± 9.0 years) versus old (O; 64.8 ± 7.2 years) were assessed for body composition, gastrocnemius medialis (GM) muscle volume (V), net maximum voluntary contraction (nMVC), and specific force (SF). The young obese, while demonstrating 71% and 29% (P < 0.001) higher V and nMVC compared to normal BMI individuals, were in fact 26% (P = 0.007) weaker than these, where V was used to scale nMVC (i.e., nMVC/V). The weakness associated with obesity was further exemplified in the 34% (P < 0.001) lower SF relative to normal BMI individuals. Similarly, ≥40% body fat was associated with 60% and 27% (P < 0.001) higher V and nMVC, but 11% and 25% (P < 0.01) lower nMVC/V and SF than <40% body fat. The aging‐related rates of decline in V (−2 cm3/year P < 0.05) and nMVC (−1.2 cm3/year P < 0.05) were highest in obesity defined by BMI. This effect was also seen when segregating by >40% adiposity. Interestingly, however, obesity appeared advantageous to the aging‐related changes in nMVC/V (P < 0.001) and SF (P < 0.001). Unlike previous reports of greater strength in the obese compared with leaner age‐matched counterparts, we in fact demonstrate that the young sedentary obese, are substantially weaker, where the volume of skeletal muscle is used to scale the maximal torque output, or forces are quantified at the fascicular level. The seemingly positive impact of obesity on rate of aging, however, is complex and

  2. Serum FGF-21 levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa

    PubMed Central

    Fazeli, Pouneh K.; Faje, Alexander T.; Cross, Ela J.; Lee, Hang; Rosen, Clifford J.; Bouxsein, Mary L.; Klibanski, Anne

    2015-01-01

    BACKGROUND Anorexia nervosa (AN) is a psychiatric disorder characterized by self-induced starvation and low body weight. Women with AN have impaired bone formation, low bone mass and an increased risk of fracture. FGF-21 is a hormone secreted by the liver in starvation and FGF-21 transgenic mice have significant bone loss due to an uncoupling of bone resorption and bone formation. We hypothesized that FGF-21 may contribute to the low bone mass state of AN. SUBJECTS AND METHODS We studied 46 women: 20 with AN (median age [interquartile range]: 27.5 [25, 30.75] years) and 26 normal-weight controls (NWC) of similar age (25 [24, 28.5] years). We investigated associations between serum FGF-21 and 1) aBMD measured by dual energy X-ray absorptiometry, 2) parameters of bone microarchitecture in the distal radius and tibia measured by high-resolution peripheral quantitative CT and 3) bone strength, estimated by microfinite element analysis. RESULTS FGF-21 levels were similar in AN and NWC (AN: 33.1 [18.1, 117.0] pg/ml vs NWC: 57.4 [23.8, 107.1] pg/ml; p=0.54). There was a significant inverse association between log FGF-21 and trabecular number in the radius in both AN (R= -0.57, p<0.01) and NWC (R= -0.53, p<0.01) and a significant positive association between log FGF-21 and trabecular separation in the radius in AN (R=0.50, p<0.03) and NWC (R=0.52, p<0.01). Estimates of radial bone strength were inversely associated with log FGF-21 in AN (R= -0.50, p<0.03 for both stiffness and failure load). There were no associations between FGF-21 and aBMD, cortical parameters or tibial parameters in the AN or NWC groups. CONCLUSIONS FGF-21 may be an important determinant of trabecular skeletal homeostasis in AN. PMID:25868802

  3. Increased expression of tumor necrosis factor-alpha and decreased expression of thyroglobulin and thyroid peroxidase mRNA levels in the thyroids of iodide-treated BB/Wor rats.

    PubMed

    Mori, K; Mori, M; Stone, S; Braverman, L E; DeVito, W J

    1998-11-01

    Several lines of evidence suggest that tumor necrosis factor-alpha (TNFalpha) may contribute to the pathogenesis of autoimmune thyroid disease. It is not known, however, whether increased thyroidal TNFalpha levels are associated with changes in thyroid function. The purpose of the present study was to utilize in situ hybridization histochemistry and immunohistochemistry to determine if the expression of TNF-alpha in the thyroid is associated with a decrease in thyroglobulin (Tg) and thyroid peroxidase (TPO) mRNA levels. Lymphocytic thyroiditis was induced in BB/Wor rats by iodide administration, and thyroidal Tg and TPO mRNA levels were assessed by Northern blot analysis and in situ hybridization, and TNFalpha expression by Northern blot analysis and immunohistochemistry. Thyroids were obtained before and 1 and 2 months after iodide administration. Hematoxylin and eosin staining revealed that there was a progressive increase in mononuclear cells in the thyroids of BB/Wor rats ingesting iodide for 1 and 2 months. Northern blot analysis revealed that during the same time course there was a progressive increase in TNFalpha mRNA levels and a progressive decrease in Tg and TPO mRNA levels in the thyroids. In situ hybridization histochemistry was performed to determine if the decrease in Tg and TPO mRNA levels was associated with thyroid follicular cells in contact with infiltrating mononuclear cells. In rats treated with iodide for 1 month, there was a modest decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. After 2 months of iodide treatment there was clearly a localized decrease in Tg and TPO mRNA levels in follicular cells in contact with infiltrating mononuclear cells. Immunohistochemical analysis did not detect TNFalpha in the thyroids from control rats or from rats treated with iodide for 1 month. In contrast, after 2 months of treatment, TNFalpha was easily detected in infiltrating mononuclear cells and in some

  4. Investigation of the extent of surface coating via mechanofusion with varying additive levels and the influences on bulk powder flow properties.

    PubMed

    Zhou, Qi Tony; Qu, Li; Gengenbach, Thomas; Denman, John A; Larson, Ian; Stewart, Peter J; Morton, David A V

    2011-07-15

    The objective of this study was to investigate if the coating extent created by a mechanofusion process corresponded with observed changes in bulk powder properties. A fine lactose powder (approximate median diameter 20 μm) was dry coated with magnesium stearate using from 0.1 to 5% (w/w) content. An ultra-thin coating layer of magnesium stearate was anticipated, but previous attempts to determine such thin layers on these fine particles have had limited success, with poor resolution. In this study, the surface coating was examined using the state-of-the-art XPS and ToF-SIMS systems. The powder flow was characterized by Carr index and shear cell testing. XPS was successfully applied to demonstrate variations in surface coverage, as a function of additive levels, and indicated near complete coating coverage at additive levels of 1% (w/w) and above. ToF-SIMS results supported such coating coverage assessment, and indicated coating uniformly across the fine particle surfaces. The flow metrics employed could then be related to the coating coverage metrics. The mechanofusion process also modified the apparent surface roughness observed by SEM and BET. It was suggested that the changes in the surface chemical composition exerted a more evident and direct impact on the powder cohesion and flow characteristics than the changes in the surface morphological properties after the mechanofusion in this study.

  5. Decreased fibrinolytic activity in juvenile chronic arthritis.

    PubMed

    Mussoni, L; Pintucci, G; Romano, G; De Benedetti, F; Massa, M; Martini, A

    1990-12-01

    The basal fibrinolytic activity in 17 children with active juvenile chronic arthritis (JCA) was investigated. It was found that patients with JCA, and particularly those with the systemic form, show decreased plasma fibrinolytic activity and a marked increase in plasminogen activator inhibitor. Additionally, it was found that patients with systemic JCA, but not those with the polyarticular or pauciarticular form, have increased circulating levels of tissue-type plasminogen activator, and endothelial cell protein, suggesting possible endothelial cell participation in systemic JCA.

  6. Role of amino acids as additives on sperm motility, plasma membrane integrity and lipid peroxidation levels at pre-freeze and post-thawed ram semen.

    PubMed

    Sangeeta, Sharon; Arangasamy, A; Kulkarni, S; Selvaraju, S

    2015-10-01

    The possibility of including amino acids for cryopreservation of ram semen to improve the quality of frozen semen was exp