Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

PubMed Central

Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P.; De Geest, Bart

2017-01-01

Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001) was decreased, interstitial fibrosis was 1.88-fold (p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy. PMID:28718833

Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

PubMed

Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

2017-07-18

Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher ( p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold ( p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density ( p < 0.001) was decreased, interstitial fibrosis was 1.88-fold ( p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold ( p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower ( p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

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

PubMed

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

2016-04-01

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

Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

PubMed

Botticelli, G; Bacchi Modena, A; Bresciani, D; Villa, P; Aguzzoli, L; Florio, P; Nappi, R E; Petraglia, F; Genazzani, A R

1992-12-01

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of di(n-butyl) phthalate on testicular oxidative damage and antioxidant enzymes in hyperthyroid rats.

PubMed

Lee, Ena; Ahn, Mee Young; Kim, Hee Jin; Kim, In Young; Han, Soon Young; Kang, Tae Seok; Hong, Jin Hwan; Park, Kui Lea; Lee, Byung Mu; Kim, Hyung Sik

2007-06-01

This study compared the effects of di(n-butyl) phthalate (DBP) on the oxidative damage and antioxidant enzymes activity in testes of hyperthyroid rats. Hyperthyroidism was induced in pubertal male rats by intraperitoneal injection of triiodothyronine (T3, 10 microg/kg body weight) for 30 days. An oral dose of DBP (750 mg/kg) was administered simultaneously to normal or hyperthyroid (T3) rats over a 30-day period. No changes in body weight were observed in the hyperthyroid groups (T3, T3 + DBP) compared with controls. There were significantly higher serum T3 levels observed in the hyperthyroid rats than in the control, but the serum thyroid stimulating hormone levels were markedly lower in the hyperthyroid rats. DBP significantly decreased the weight of the testes in the normal (DBP) and hyperthyroid (T3 + DBP) groups. The serum testosterone concentrations were significantly lower in only DBP group. DBP significantly increased the 8-hydroxy-2-deoxyguanosine (8-OHdG) level in the testes, whereas the DBP-induced 8-OHdG levels were slightly higher in T3 + DBP group. Superoxide dismutase and glutathione peroxidase activities were significantly higher in the testes of the DBP or T3 + DBP groups. Catalase (CAT) activity was significantly higher in the DBP treatment group, but the T3 + DBP group showed slightly lower DBP-induced CAT activity. The testicular expression of thyroid hormone receptor alpha-1 (TRalpha-1) was significantly higher in the DBP groups, and androgen receptor (AR) expression was not detected in the DBP treatment group. In addition, DBP significantly increased the peroxisome proliferator-activated receptor-r (PPAR-r) levels in the testis. These results suggest that hyperthyroidism can cause a change in the expression level of PPAR-r in testes, and may increase the levels of oxidative damage induced by the metabolic activation of DBP.

Exogenous Cushing syndrome

MedlinePlus

Cushing syndrome - corticosteroid induced; Corticosteroid-induced Cushing syndrome; Iatrogenic Cushing syndrome ... Cushing syndrome is a disorder that occurs when your body has a higher than normal level of the hormone ...

Concorde noise-induced building vibrations, Sully Plantation - Report no. 2, Chantilly, Virginia

NASA Technical Reports Server (NTRS)

1976-01-01

Noise-induced building vibrations associated with Concorde operations were studied. The approach is to record the levels of induced vibrations and associated indoor/outdoor noise levels in selected homes, historic and other buildings near Dulles International Airport. Representative data are presented which were recorded at Sully Plantation, Chantilly, Virginia during the periods of May 20 through May 28, 1976, and June 14 through June 17, 1976. Recorded data provide relationships between the vibration levels of windows, walls, floors, and the noise associated with Concorde operations, other aircraft, and nonaircraft events. The results presented are drawn from the combined May-June data base which is considerably larger than the May data base covered. The levels of window, wall and floor vibratory response resulting from Concorde operations are higher than the vibratory levels associated with conventional aircraft. Furthermore, the vibratory responses of the windows are considerably higher than those of the walls and floors. The window response is higher for aircraft than recorded nonaircraft events and exhibits a linear response relationship with the overall sound pressure level. For a given sound pressure level, the Concorde may cause more vibration than a conventional aircraft due to spectral or other differences. However, the responses associated with Concorde appear to be much more dependent upon sound pressure level than spectral or other characteristics of the noise.

N-acetylcysteine modulates doxorubicin-induced oxidative stress and antioxidant vitamin concentrations in liver of rats.

PubMed

Koçkar, M Cem; Nazıroğlu, Mustafa; Celik, Omer; Tola, H Tahsin; Bayram, Dilek; Koyu, Ahmet

2010-12-02

Doxorubicin (DOX) is a chemotherapeutic agent, and is widely used in cancer treatment. The most common side effect of DOX was indicated on cardiovascular system by experimental studies. There are some studies suggesting oxidative stress-induced toxic changes on liver related to DOX administration. The aim of the present study was to evaluate whether antioxidant N-acetylcysteine (NAC) relieves oxidative stress in DOX- induced liver injury in rat. Twenty-four male rats were equally divided into three groups. First group was used as a control. Second group received single dose of DOX. NAC for 10 days was given to constituting the third group after giving one dose of DOX. After 10 days of the experiment, liver tissues were taken from all animals. Lipid peroxidation (LP) levels were higher in the DOX group than in control whereas LP levels were lower in the DOX+NAC group than in control. Vitamin C and vitamin E levels were lower in the DOX group than in control whereas vitamin C and vitamin E levels were higher in the DOX+NAC group than in the DOX group. Reduced glutathione levels were higher in the DOX+NAC group than in control and DOX group. Glutathione peroxidase, vitamin A and β-carotene values were not changed in the three groups by DOX and NAC administrations. In histopathological evaluation of DOX group, there were mononuclear cell infiltrations, vacuolar degeneration, hepatocytes with basophilic nucleus and sinusoidal dilatations. The findings were totally recovered by NAC administration. In conclusion, N-acetylcysteine induced modulator effects on the doxorubicin-induced hepatoxicity by inhibiting free radical production and supporting the antioxidant vitamin levels. Copyright © 2010 John Wiley & Sons, Ltd.

Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment.

PubMed

Frieling, J T; Mulder, J A; Hendriks, T; Curfs, J H; van der Linden, C J; Sauerwein, R W

1997-07-01

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model

PubMed Central

Kim, Chea-Ha

2015-01-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level. PMID:25792867

Intracerebroventricular Kainic Acid-Induced Damage Affects Blood Glucose Level in d-glucose-fed Mouse Model.

PubMed

Kim, Chea-Ha; Hong, Jae-Seung

2015-03-01

We have previously reported that the intracerebroventricular (i.c.v.) administration of kainic acid (KA) results in significant neuronal damage on the hippocampal CA3 region. In this study, we examined possible changes in the blood glucose level after i.c.v. pretreatment with KA. The blood glucose level was elevated at 30 min, began to decrease at 60 min and returned to normal at 120 min after D-glucose-feeding. We found that the blood glucose level in the KA-pretreated group was higher than in the saline-pretreated group. The up-regulation of the blood glucose level in the KA-pretreated group was still present even after 1~4 weeks. The plasma corticosterone and insulin levels were slightly higher in the KA-treated group. Corticosterone levels decreased whereas insulin levels were elevated when mice were fed with D-glucose. The i.c.v. pretreatment with KA for 24 hr caused a significant reversal of D-glucose-induced down-regulation of corticosterone level. However, the insulin level was enhanced in the KA-pretreated group compared to the vehicle-treated group when mice were fed with D-glucose. These results suggest that KA-induced alterations of the blood glucose level are related to cell death in the CA3 region whereas the up-regulation of blood glucose level in the KA-pretreated group appears to be due to a reversal of D-glucose feeding-induced down-regulation of corticosterone level.

Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage.

PubMed

Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori

2011-12-01

We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

Population-based estimates of still birth, induced abortion and miscarriage in the Indian state of Bihar.

PubMed

Kochar, Priyanka S; Dandona, Rakhi; Kumar, G Anil; Dandona, Lalit

2014-12-17

We report population-based data on still birth, induced abortion and miscarriage from the Indian state of Bihar to assess the magnitude of the problem and to inform corrective action. A representative sample of women from all districts of Bihar with a pregnancy outcome in the last 12 months was obtained through multistage sampling in early 2012. Still birth rate was calculated as fetuses born with no sign of life at 7 or more months of gestation per 1,000 births. Induced abortion and miscarriage rates were defined as expulsion of dead fetuses at less than 7 months of gestation induced by any means or without inducement, respectively, per 1000 pregnancies that had an outcome. Multiple regression models were used to explore possible associations with stillbirths, induced abortions and miscarriages. Multi-level models were developed for the relatively less developed north zone and for the south zone of Bihar to examine contextual factors associated with still births, induced abortions and miscarriages. Still birth rate was estimated as 20 per 1,000 births (95% CI 15.6-24.5), and induced abortion and miscarriage rates as 8.6 (6.6-10.6), and 46 (40.8-51.3) per 1,000 pregnancies with outcome, respectively. The odds of induced abortion and miscarriage were significantly higher in the south zone (odds ratio 2.53 [95% CI 1.79-3.57] and 1.27 [95% CI 1.10-1.47], respectively). In the multi-level model for the north zone, the odds of induced abortion were higher for women with husband's having mean years of education higher than the state mean (2.62; 95% CI 1.47-4.69). Among the nine divisions of Bihar, comprising of groups of districts, higher induced abortion rate was associated with lower neonatal mortality rate (R(2) = 0.68, p = 0.01). These population-based data show a significant burden of still births in Bihar, suggesting that addressing these must become an important part of maternal and child health initiatives. The higher induced abortion in the more developed districts, and the inverse trend between induced abortion and neonatal mortality rates, have programmatic implications.

EMI induced by HUT (Helsinki University of Technology) aircraft

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

Valmu, H.; Nikulainen, M.; Bagge, R.

1996-10-01

The different EMI behaviors of typical turboprop and piston engine aircraft were measured. As expected the level of EMI induced by piston engines were found significantly higher than the interferences induced by turboprop engines and interferences were detected in the whole band covered in the measurements (100-1000 MHz). Finally the interferences induced by the HUT remote sensing aircraft, Short SC7 Skyvan (turboprop), were analyzed and disturbances were found only in a narrow band below 100 MHz and the level of these interferences were significantly lower than the EMI induced by piston engines. 2 figs.

Induced expression of hepatic N-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen.

PubMed

Nemoto, Kiyomitsu; Ikeda, Ayaka; Hikida, Tokihiro; Kojima, Misaki; Degawa, Masakuni

2013-02-01

We previously demonstrated the super-induced expression of the Grin2c gene encoding the N-methyl-D-aspartate receptor 2C subunit during the development of liver enlargement with hepatocellular hypertrophy induced by phenobarbital, clofibrate, or piperonyl butoxide. In the present study, we assessed whether or not Grin2c gene expression was induced during the development of chemically induced liver enlargement with hyperplasia. Male Sprague-Dawley (SD) rats, stroke-prone spontaneously hypertensive rats (SHRSPs), and SHRSP's normotensive control, Wistar-Kyoto (WKY) rats, were administered lead nitrate (LN) (0.1 mmol/kg, single i.v.), a direct inducer of liver hyperplasia, and changes in the level of Grin2c mRNA in the liver were assessed by real-time RT-PCR. The level of hepatic Grin2c mRNA was significantly higher 6-48 hr after the injection in SD rats (about 30~40- and 70-fold over the control at 6~24 hr and 48 hr, respectively) and in WKY rats (about 20-fold over the control only at 12 hr), but was not significantly higher in SHRSPs. Such differences in LN-induced levels of Grin2c mRNA among SD rats, WKY rats, and SHRSPs were closely correlated with those in the previously reported increase in liver weight 48 hr after LN administration. The present findings suggest that the increase in the level of hepatic Grin2c mRNA relates to development of chemically induced liver enlargement with hyperplasia.

Muscle Damage following Maximal Eccentric Knee Extensions in Males and Females

PubMed Central

2016-01-01

Aim To investigate whether there is a sex difference in exercise induced muscle damage. Materials and Method Vastus Lateralis and patella tendon properties were measured in males and females using ultrasonography. During maximal voluntary eccentric knee extensions (12 reps x 6 sets), Vastus Lateralis fascicle lengthening and maximal voluntary eccentric knee extensions torque were recorded every 10° of knee joint angle (20–90°). Isometric torque, Creatine Kinase and muscle soreness were measured pre, post, 48, 96 and 168 hours post damage as markers of exercise induced muscle damage. Results Patella tendon stiffness and Vastus Lateralis fascicle lengthening were significantly higher in males compared to females (p<0.05). There was no sex difference in isometric torque loss and muscle soreness post exercise induced muscle damage (p>0.05). Creatine Kinase levels post exercise induced muscle damage were higher in males compared to females (p<0.05), and remained higher when maximal voluntary eccentric knee extension torque, relative to estimated quadriceps anatomical cross sectional area, was taken as a covariate (p<0.05). Conclusion Based on isometric torque loss, there is no sex difference in exercise induced muscle damage. The higher Creatine Kinase in males could not be explained by differences in maximal voluntary eccentric knee extension torque, Vastus Lateralis fascicle lengthening and patella tendon stiffness. Further research is required to understand the significant sex differences in Creatine Kinase levels following exercise induced muscle damage. PMID:26986066

IL-23 plasma level is strongly associated with CMV status and reactivation of CMV in renal transplant recipients.

PubMed

Sadeghi, Mahmoud; Lahdou, Imad; Opelz, Gerhard; Mehrabi, Arianeb; Zeier, Martin; Schnitzler, Paul; Daniel, Volker

2016-10-03

Cytomegalovirus seropositivity is an independent risk factor for atherosclerosis in patients with ESRD. Donor CMV seropositivity is associated with higher graft loss. Dendritic cells, macrophages and Th17 lymphocytes are defined as producers of IL-23. IL-23 is thought to be involved in the promotion of Th17 cell polarization. Latent CMV-induced Th17 might be involved in the pathogenesis of CMV infection in patients with ESRD. We aimed to evaluate associations of Th17-dependent cytokines with ESRD, CMV status and post-transplant outcome in kidney transplantation. IL-21 plasma levels were similar in patients and healthy controls (p = 0.47), whereas IL-9 (p = 0.02) and IL-23 (p < 0.0001) levels were significantly higher in ESRD patients. CMV-seronegative (p = 0.002) and -seropositive (p < 0.001) patients had significantly higher IL-23 plasma levels than controls. CMV-seropositive patients showed excessively higher IL-23 (p < 0.001) plasma levels than CMV-seronegative patients. Patients with post-transplant CMV reactivation had higher IL-23 plasma levels than patients without CMV reactivation (p = 0.025). Our results indicate that latent CMV induces IL-23. IL-23 might be an inflammatory mediator of latent CMV infection in patients with ESRD and predisposes patients for post-transplant CMV reactivation.

Penicillium sp. mitigates Fusarium-induced biotic stress in sesame plants.

PubMed

Radhakrishnan, Ramalingam; Pae, Suk-Bok; Shim, Kang-Bo; Baek, In-Youl

2013-07-01

Fusarium-infected sesame plants have significantly higher contents of amino acids (Asp, Thr, Ser, Asn, Glu, Gly, Ala, Val, Met, Ile, Leu, Tyr, Phe, Lys, His, Try, Arg, and Pro), compared with their respective levels in the healthy control. These higher levels of amino acids induced by Fusarium infection were decreased when Penicillium was co-inoculated with Fusarium. Compared with the control, Fusarium-infected plants showed higher contents of palmitic (8%), stearic (8%), oleic (7%), and linolenic acids (4%), and lower contents of oil (4%) and linoleic acid (11%). Co-inoculation with Penicillium mitigated the Fusarium-induced changes in fatty acids. The total chlorophyll content was lower in Fusarium- and Penicillium-infected plants than in the healthy control. The accumulation of carotenoids and γ-amino butyric acid in Fusarium-infected plants was slightly decreased by co-inoculation with Penicillium. Sesamin and sesamolin contents were higher in Penicillium- and Fusarium- infected plants than in the control. To clarify the mechanism of the biocontrol effect of Penicillium against Fusarium by evaluating changes in primary and secondary metabolite contents in sesame plants.

Prevention of hyperphagia prevents ovariectomy-induced triacylglycerol accumulation in liver, but not plasma.

PubMed

Kitson, Alex P; Marks, Kristin A; Aristizabal Henao, Juan J; Tupling, A Russell; Stark, Ken D

2015-12-01

Menopause is associated with higher plasma and liver triacylglycerol (TAG) and increased risk for cardiovascular disease. Lowering TAG in menopause may be beneficial; however, the mechanism underlying menopause-induced TAG accumulation is not clear. Ovariectomy is a model for menopause and is associated with metabolic alterations and hyperphagia. This study investigated the role of hyperphagia in ovariectomy-induced increases in blood and tissue TAG, as well as differences in lipid metabolism enzymes and resting metabolic measures. It was hypothesized that prevention of hyperphagia would restore blood and tissue TAG, enzyme expression, and metabolic measures to eugonadal levels. Ovariectomized rats were fed ad libitum (OVX + AL) or pair-fed (OVX + PF) relative to sham-operated rats (SHAM) to prevent hyperphagia. OVX + AL had higher TAG concentrations in liver and plasma than SHAM (60% and 50%, respectively), and prevention of hyperphagia in OVX + PF normalized TAG concentrations to SHAM levels in liver, but not plasma. OVX + AL also had 141% higher hepatic stearoyl-CoA desaturase 1 which was almost completely normalized to SHAM levels by pair-feeding, suggesting normalization of hepatic lipid storage. In contrast, skeletal muscle carnitine palmitoyl transferase 1 was 40% lower in OVX + AL than SHAM and was intermediate in OVX + PF, suggesting lower muscle fatty acid oxidation that may underlie the higher plasma TAG in OVX. No differences were seen in energy expenditure, VO2, or VCO2. Overall, this study indicates that prevention of hyperphagia resulting from ovarian hormone withdrawal normalizes hepatic TAG to eugonadal levels but has no effect on ovariectomy-induced increases in plasma TAG. Copyright © 2015 Elsevier Inc. All rights reserved.

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges.

PubMed

Fowler, Mark I; Weller, Roy O; Heckels, John E; Christodoulides, Myron

2004-06-01

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling

PubMed Central

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-01-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our home-made device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)-1β expression, and downregulating IL-10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen I and III were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)-13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP-1 and TIMP-2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD-induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue. PMID:28290607

BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity.

PubMed

Jin, Yong Jun; Cao, Peng Juan; Bian, Wei Hua; Li, Ming E; Zhou, Rong; Zhang, Ling Yun; Yang, Mei Zi

2015-01-01

To observe the expression of brain-derived neurotrophic factor (BDNF) in hypothalamic and adipose tissue in mice with monosodium glutamate (MSG)-induced obesity. The effects of hypothalamic lesions, specifically arcuate nucleus (ARC) lesions, induced by MSG injection were studied in male ICR mice at the neonatal stage. The following parameters were compared: body weight, body length, Lee's index, food intake, body temperature, fat weight, and levels of total cholesterol (CHOL), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and blood glucose (GLU). The BDNF expression levels in hypothalamic and adipose tissue were measured using western blotting. Results Compared with the control group, the model group body had significantly higher weight, Lee's index, food intake, fat weight, CHOL, TG, LDL, HDL, and GLU levels. BDNF expression levels in hypothalamic and adipose tissue were markedly down-regulated in the model group. BDNF may be closely associated with MSG-induced hypothalamic obesity.

Ultrafine particles from diesel vehicle emissions at different driving cycles induce differential vascular pro-inflammatory responses: Implication of chemical components and NF-κB signaling

PubMed Central

2010-01-01

Background Epidemiological evidence supports the association between exposure to ambient particulate matter (PM) and cardiovascular diseases. Chronic exposure to ultrafine particles (UFP; Dp <100 nm) is reported to promote atherosclerosis in ApoE knockout mice. Atherogenesis-prone factors induce endothelial dysfunction that contributes to the initiation and progression of atherosclerosis. We previously demonstrated that UFP induced oxidative stress via c-Jun N-terminal Kinases (JNK) activation in endothelial cells. In this study, we investigated pro-inflammatory responses of human aortic endothelial cells (HAEC) exposed to UFP emitted from a diesel truck under an idling mode (UFP1) and an urban dynamometer driving schedule (UFP2), respectively. We hypothesize that UFP1 and UFP2 with distinct chemical compositions induce differential pro-inflammatory responses in endothelial cells. Results UFP2 contained a higher level of redox active organic compounds and metals on a per PM mass basis than UFP1. While both UFP1 and UFP2 induced superoxide production and up-regulated stress response genes such as heme oxygenease-1 (HO-1), OKL38, and tissue factor (TF), only UFP2 induced the expression of pro-inflammatory genes such as IL-8 (2.8 ± 0.3-fold), MCP-1 (3.9 ± 0.4-fold), and VCAM (6.5 ± 1.1-fold) (n = 3, P < 0.05). UFP2-exposed HAEC also bound to a higher number of monocytes than UFP1-exposed HAEC (Control = 70 ± 7.5, UFP1 = 106.7 ± 12.5, UFP2 = 137.0 ± 8.0, n = 3, P < 0.05). Adenovirus NF-κB Luciferase reporter assays revealed that UFP2, but not UFP1, significantly induced NF-κB activities. NF-κB inhibitor, CAY10512, significantly abrogated UFP2-induced pro-inflammatory gene expression and monocyte binding. Conclusion While UFP1 induced higher level of oxidative stress and stress response gene expression, only UFP2, with higher levels of redox active organic compounds and metals, induced pro-inflammatory responses via NF-κB signaling. Thus, UFP with distinct chemical compositions caused differential response patterns in endothelial cells. PMID:20307321

Interspecific- and acclimation-induced variation in levels of heat-shock proteins 70 (hsp70) and 90 (hsp90) and heat-shock transcription factor-1 (HSF1) in congeneric marine snails (genus Tegula): implications for regulation of hsp gene expression.

PubMed

Tomanek, Lars; Somero, George N

2002-03-01

In our previous studies of heat-shock protein (hsp) expression in congeneric marine gastropods of the genus Tegula, we observed interspecific and acclimation-induced variation in the temperatures at which heat-shock gene expression is induced (T(on)). To investigate the factors responsible for these inter- and intraspecific differences in T(on), we tested the predictions of the 'cellular thermometer' model for the transcriptional regulation of hsp expression. According to this model, hsps not active in chaperoning unfolded proteins bind to a transcription factor, heat-shock factor-1 (HSF1), thereby reducing the levels of free HSF1 that are available to bind to the heat-shock element, a regulatory element upstream of hsp genes. Under stress, hsps bind to denatured proteins, releasing HSF1, which can now activate hsp gene transcription. Thus, elevated levels of heat-shock proteins of the 40, 70 and 90 kDa families (hsp 40, hsp70 and hsp90, respectively) would be predicted to elevate T(on). Conversely, elevated levels of HSF1 would be predicted to decrease T(on). Following laboratory acclimation to 13, 18 and 23 degrees C, we used solid-phase immunochemistry (western analysis) to quantify endogenous levels of two hsp70 isoforms (hsp74 and hsp72), hsp90 and HSF1 in the low- to mid-intertidal species Tegula funebralis and in two subtidal to low-intertidal congeners, T. brunnea and T. montereyi. We found higher endogenous levels of hsp72 (a strongly heat-induced isoform) at 13 and 18 degrees C in T. funebralis in comparison with T. brunnea and T. montereyi. However, T. funebralis also had higher levels of HSF1 than its congeners. The higher levels of HSF1 in T. funebralis cannot, within the framework of the cellular thermometer model, account for the higher T(on) observed for this species, although they may explain why T. funebralis is able to induce the heat-shock response more rapidly than T. brunnea. However, the cellular thermometer model does appear to explain the cause of the increases in T(on) that occurred during warm acclimation of the two subtidal species, in which warm acclimation was accompanied by increased levels of hsp72, hsp74 and hsp90, whereas levels of HSF1 remained stable. T. funebralis, which experiences greater heat stress than its subtidal congeners, consistently had higher ratios of hsp72 to hsp74 than its congeners, although the sum of levels of the two isoforms was similar for all three species except at the highest acclimation temperature (23 degrees C). The ratio of hsp72 to hsp74 may provide a more accurate estimate of environmental heat stress than the total concentrations of both hsp70 isoforms.

Protective effects of nicergoline against hydrogen peroxide toxicity in rat neuronal cell line.

PubMed

Iwata, E; Miyazaki, I; Asanuma, M; Iida, A; Ogawa, N

1998-07-17

We examined the effects of nicergoline on hydrogen peroxide (H2O2)-induced neurotoxicity in cultured rat neuronal cell line (B50). H2O2 induced death of B50 cells in a dose-dependent manner. The H2O2-induced neuronal cell death was significantly decreased in B50 cells maintained in the presence of nicergoline. We compared the levels of antioxidants (glutathione, catalase and superoxide dismutase) in nicergoline-treated and untreated B50 cells. Lipid peroxidation products (thiobarbituric acid reactive substances, TBARS) levels were also measured. Cultures treated with nicergoline had higher levels of catalase activity. TBARS level was significantly lower in nicergoline-treated cells than in untreated cells. Our results suggest that nicergoline may induce the up-regulation of intracellular antioxidant defences and protect the neuronal cells against oxidative stress.

Response of Saccharomyces cerevisiae to D-limonene-induced oxidative stress.

PubMed

Liu, Jidong; Zhu, Yibo; Du, Guocheng; Zhou, Jingwen; Chen, Jian

2013-07-01

In the present study, we investigated the mode of cell response induced by D-limonene in Saccharomyces cerevisiae. D-limonene treatment was found to be accompanied by intracellular accumulation of reactive oxygen species (ROS). Since ROS impair cell membranes, an engineered strain with enhanced membrane biosynthesis exhibited a higher tolerance to D-limonene. Subsequent addition of an ROS scavenger significantly reduced the ROS level and alleviated cell growth inhibition. Thus, D-limonene-induced ROS accumulation plays an important role in cell death in S. cerevisiae. In D-limonene-treated S. cerevisiae strains, higher levels of antioxidants, antioxidant enzymes, and nicotinamide adenine dinucleotide phosphate (NADPH) were synthesized. Quantitative real-time PCR results also verified that D-limonene treatment triggered upregulation of genes involved in the antioxidant system and the regeneration of NADPH at the transcription level in S. cerevisiae. These data indicate that D-limonene treatment results in intracellular ROS accumulation, an important factor in cell death, and several antioxidant mechanisms in S. cerevisiae were enhanced in response to D-limonene treatment.

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis.

PubMed

Hulshof, Henriëtte J; Novati, Arianna; Luiten, Paul G M; den Boer, Johan A; Meerlo, Peter

2012-10-01

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

PubMed

Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

2006-04-01

We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder.

PubMed

Kaneda, Takeharu; Sasaki, Noriyasu; Urakawa, Norimoto; Shimizu, Kazumasa

2018-01-01

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30-300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20-1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

PubMed

Zhang, Jifeng; Niimi, Manabu; Yang, Dongshan; Liang, Jingyan; Xu, Jie; Kimura, Tokuhide; Mathew, Anna V; Guo, Yanhong; Fan, Yanbo; Zhu, Tianqing; Song, Jun; Ackermann, Rose; Koike, Yui; Schwendeman, Anna; Lai, Liangxue; Pennathur, Subramaniam; Garcia-Barrio, Minerva; Fan, Jianglin; Chen, Y Eugene

2017-06-01

CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B-containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α-induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet-induced atherosclerosis in rabbits. © 2017 American Heart Association, Inc.

Genetic regulation of cold-induced albinism in the maize inbred line A661

PubMed Central

Rodríguez, Víctor M.; Velasco, Pablo; Garrido, José L.; Revilla, Pedro; Ordás, Amando; Butrón, Ana

2013-01-01

In spite of multiple studies elucidating the regulatory pathways controlling chlorophyll biosynthesis and photosynthetic activity, little is known about the molecular mechanism regulating cold-induced chlorosis in higher plants. Herein the characterization of the maize inbred line A661 which shows a cold-induced albino phenotype is reported. The data show that exposure of seedlings to low temperatures during early leaf biogenesis led to chlorophyll losses in this inbred. A661 shows a high plasticity, recovering resting levels of photosynthesis activity when exposed to optimal temperatures. Biochemical and transcriptome data indicate that at suboptimal temperatures chlorophyll could not be fully accommodated in the photosynthetic antenna in A661, remaining free in the chloroplast. The accumulation of free chlorophyll activates the expression of an early light inducible protein (elip) gene which binds chlorophyll to avoid cross-reactions that could lead to the generation of harmful reactive oxygen species. Higher levels of the elip transcript were observed in plants showing a cold-induced albino phenotype. Forward genetic analysis reveals that a gene located on the short arm of chromosome 2 regulates this protective mechanism. PMID:23881393

Influence of fatigue crack wake length and state of stress on crack closure

NASA Technical Reports Server (NTRS)

Telesman, J.; Fisher, D. M.

1986-01-01

The location of crack closure with respect to crack wake and specimen thickness under different loading conditions was determined. The rate of increase of K sub CL in the crack wake was found to be significantly higher for plasticity induced closure in comparison to roughness induced closure. Roughness induced closure was uniform throughout the thickness of the specimen while plasticity induced closure levels were 50 percent higher in the near surface region than in the midthickness. The influence of state of stress on low-high load interaction effects was also examined. Load interaction effects differed depending upon the state of stress and were explained in terms of delta K sub eff.

Influence of fatigue crack wake length and state of stress on crack closure

NASA Technical Reports Server (NTRS)

Telesman, Jack; Fisher, Douglas M.

1988-01-01

The location of crack closure with respect to crack wake and specimen thickness under different loading conditions was determined. The rate of increase of K sub CL in the crack wake was found to be significantly higher for plasticity induced closure in comparison to roughness induced closure. Roughness induced closure was uniform throughout the thickness of the specimen while plasticity induced closure levels were 50 percent higher in the near surface region than in the midthickness. The influence of state of stress on low-high load interaction effects was also examined. Load interaction effects differed depending upon the state of stress and were explained in terms of delta K sub eff.

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

2000-01-01

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

[Relationship between G6PD deficiency and hand-foot-mouth disease induced by enterovirus 71].

PubMed

Ou, Jun-Bin; Zhang, Cui-Mei; Fu, Si-Mao; Huang, Xiang; Huang, Lian-Hong

2013-09-01

To study the influence of glucose-6-phosphate dehydrogenase (G6PD) deficiency on hand-foot-mouth disease (HFMD) induced by enterovirus 71 (EV71) , and possible mechanisms. A total of 220 boys with HFMD induced by EV71 were classified into two groups based on disease severity: mild/moderate (n=145) and severe HFMD groups (n=75), and 132 healthy boys were selected as the control group. The activity of G6PD and levels of reduced glutathione (GSH) and malonaldehyde (MDA) in blood were measured using the automatic biochemical analyzer. The percentage of G6PD deficiency cases in the severe HFMD group was significantly higher than in the control group (P<0.0125). In the severe HFMD group, the durations of fever, mental abnormality, limb trembling and hospital stay were significantly longer in children with G6PD deficiency than in those with normal G6PD activity (P<0.05). In the acute and recovery stages, patients in the mild/moderate and severe HFMD groups had significantly lower GSH levels and G6PD activity and significantly higher MDA levels compared with those in the control group (P<0.05). In the acute stage, children in the mild/moderate and severe HFMD groups with G6PD deficiency had significantly lower GSH levels and significantly higher MDA levels compared with those with normal G6PD activity (P<0.01). In the acute and recovery stages, GSH level in children with HFMD was positively correlated with G6PD activity (r=0.61, P<0.01; r=0.58, P<0.01), and in the acute stage, MDA level was negatively correlated with G6PD activity (r=-0.29, P<0.01). G6PD deficiency is probably a predisposing factor for HFMD induced by EV71 and may aggravate the patient's condition. Its mechanism might be related to oxidative stress.

Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

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

Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn; Zhang, Dong-Mei; Yu, Xiao-Jing

The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiacmore » atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced hypertension and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced imbalance of PVN neurotransmitters. • PVN inhibition of ACE attenuates ANG II-induced imbalance of cytokines in the PVN. • PVN blockade of AT1-R attenuates ANG II-induced imbalance of cytokines in the PVN.« less

Habitat quality affects stress responses and survival in a bird wintering under extremely low ambient temperatures

NASA Astrophysics Data System (ADS)

Cīrule, Dina; Krama, Tatjana; Krams, Ronalds; Elferts, Didzis; Kaasik, Ants; Rantala, Markus J.; Mierauskas, Pranas; Luoto, Severi; Krams, Indrikis A.

2017-12-01

Animals normally respond to stressful environmental stimuli by releasing glucocorticoid hormones. We investigated whether baseline corticosterone (CORT), handling-induced corticosterone concentration(s), and body condition indices of members of willow tit ( Poecile montanus) groups differed while wintering in old growth forests and managed young forests in mild weather conditions and during cold spells. Willow tits spend the winter season in non-kin groups in which dominant individuals typically claim their priority to access resources, while subordinate individuals may experience greater levels of stress and higher mortality, especially during cold spells. We captured birds to measure baseline CORT and levels of handling-induced CORT secretion after 20 min of capture. Willow tits in the young forests had higher baseline CORT and a smaller increase in CORT in response to capture than individuals in the old forests. Baseline CORT was higher in females and juvenile birds compared to adult males, whereas handling-induced CORT secretion did not differ between birds of different ages. During cold spells, baseline CORT of willow tits increased and handling-induced CORT secretion decreased, especially in birds in young forests. Willow tits' survival was higher in the old forests, with dominant individuals surviving better than subordinates. Our results show that changes in CORT secretion reflect responses to habitat quality and climate harshness, indicating young managed coniferous forests as a suboptimal habitat for the willow tit.

Comparative levels of macrophage migration inhibitory factor, procalcitonin, osteoprotegerin, interleukin-8, hs-C reactive protein, D-dimer in febrile neutropenia, newly diagnosed cancer patients, and infectious fever.

PubMed

Bilgir, Oktay; Bilgir, Ferda; Kebapcilar, Levent; Bozkaya, Giray; Çalan, Mehmet; Kırbıyık, Halil; Avci, Meltem; Sari, İsmail; Yuksel, Arif; Isikyakar, Tolgay

2012-02-01

The purpose of this study is to determine the levels of procalcitonin (PCT), IL-8 (interleukin-8), MIF (macrophage migration inhibitory factor), osteoprotegerin (OPG), hs-CRP and D-dimer during fever above 38.3°C due to various causes. Blood samples taken from a total of consecutive 65 hospitalized patients during fever were prospectively tested for hsCRP, PCT, IL-8, OPG, MIF and D-dimer. Of these patients, there were 26 patients presenting with chemotherapy-induced neutropenia who had no infectious agents found; 23 patients, who had a malignancy with a febrile episode which was neither a microbiologically documented infection nor a chemotherapy-induced neutropenia, and 16 patients who did not have a malignancy and were considered to have a clinically and microbiologically documented infection. IL-8 and D-dimer levels were higher in patients with febrile neutropenia than in the other two groups. Although MIF and OPG were higher in patients with newly diagnosed cancers, there were no differences among the three groups regarding PCT and hs-CRP values. High serum IL-8 and D-dimer levels can be useful markers to identify hospitalized chemotherapy-induced neutropenia patients. MIF and OPG were found to be higher in patients with newly diagnosed cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ca2+ influx in the endothelial cells is required for the bradykinin-induced endothelium-dependent contraction in the porcine interlobar renal artery

PubMed Central

Ihara, Eikichi; Derkach, Dmitry N; Hirano, Katsuya; Nishimura, Junji; Nawata, Hajime; Kanaide, Hideo

2001-01-01

To determine the mechanism of bradykinin-induced production of endothelium-derived contracting factors, we monitored the changes in cytosolic Ca2+ concentration ([Ca2+]i) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca2+]i of smooth muscle cells and force in porcine interlobar renal arterial strips using front-surface fluorometry of fura-2. In the presence of Nω-nitro-l-arginine methyl ester, bradykinin caused an endothelium-dependent transient elevation of [Ca2+]i and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H2/thromboxane A2 receptor antagonist. In the absence of extracellular Ca2+, bradykinin failed to induce contraction. However, replenishing extracellular Ca2+ to 0.75 mm and higher induced an instantaneous contraction. However, replenishing Ca2+per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10−5m 1-(β-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF96365) or 0.2 mm Ni2+ abolished the contraction induced by bradykinin in the presence of extracellular Ca2+. Treatment with 10−5m indomethacin completely inhibited the contractile response induced by Ca2+ replenishment, regardless of the timing of its application, before or after the application of bradykinin. In endothelial cells in the valvular strips, bradykinin caused a transient [Ca2+]i elevation in the presence of 1.25 mm extracellular Ca2+, but [Ca2+]i returned to the resting level within 10 min. Neither 10−5m SKF96365 nor 0.2 mm Ni2+ had any effect on the peak [Ca2+]i elevation, but decreased [Ca2+]i in the declining phase. In the absence of extracellular Ca2+, bradykinin induced a transient [Ca2+]i elevation to a level similar to that seen in the presence of 1.25 mm extracellular Ca2+. However, [Ca2+]i then rapidly returned to the prestimulation level within 5 min. Subsequent Ca2+ replenishment to 0.75 mm and higher in the presence of bradykinin elevated [Ca2+]i to significantly higher levels than the resting level seen in the media containing 1.25 mm Ca2+. In conclusion, Ca2+ influx in the endothelial cells is essential for bradykinin to induce endothelium-dependent contraction in the porcine interlobar renal artery. PMID:11483701

Effect of Prolonged Exposure to Elevated Carbon Monoxide and Carbon Dioxide Levels on Red Blood Cell Parameters during Submarine Patrols

DTIC Science & Technology

1975-12-01

rise in Hb, Hct. and red cells, to compensate for the anoxic stress induced by higher carboxyhemoglobin levels (HbCO). Inhalation of CO2 in higher...expected to cause an equilibrium value of 8-50% carboxyhemoglobin (HbCO). Under these conditions, Schulte (1961) did not find any gross changes in...according to Stewart (1974). Carboxyhemoglobin levels of 1-5% cause an increased blood Cow to vital organs, which compensates for the loss of oxygen

ICE1 of Pyrus ussuriensis functions in cold tolerance by enhancing PuDREBa transcriptional levels through interacting with PuHHP1

NASA Astrophysics Data System (ADS)

Huang, Xiaosan; Li, Kongqing; Jin, Cong; Zhang, Shaoling

2015-12-01

ICE1 transcription factor plays an important role in plant cold stress via regulating the expression of stress-responsive genes. In this study, a PuICE1 gene isolated from Pyrus ussuriensis was characterized for its function in cold tolerance. The expression levels of the PuICE1 were induced by cold, dehydration and salt, with the greatest induction under cold conditions. PuICE1 was localized in the nucleus and could bind specifically to the MYC element in the PuDREBa promoter. The PuICE1 fused to the GAL4 DNA-binding domain to have transcriptional activation activity. Ectopic expression of the PuICE1 in tomato conferred enhanced tolerance to cold stress at cold temperatures, less electrolyte leakage, less MDA content, higher chlorophyll content, higher survival rate, higher proline content, higher activities of enzymes. In additon, steady-state mRNA levels of six stress-responsive genes coding for either functional or regulatory genes were induced to higher levels in the transgenic lines by cold stress. Yeast two-hybrid, transient assay, split luciferase complementation and BiFC assays all revealed that PuHHP1 protein can physically interact with PuICE1. Taken together, these results demonstrated that PuICE1 plays a positive role in cold tolerance, which may be due to enhancement of PuDREBa transcriptional levels through interacting with the PuHHP1.

Selective breeding of mice for different susceptibilities to high fat diet-induced glucose intolerance: Development of two novel mouse lines, Selectively bred Diet-induced Glucose intolerance-Prone and -Resistant.

PubMed

Nagao, Mototsugu; Asai, Akira; Kawahara, Momoyo; Nakajima, Yasushi; Sato, Yuki; Tanimura, Kyoko; Okajima, Fumitaka; Takaya, Makiyo; Sudo, Mariko; Takemitsu, Shuji; Harada, Taro; Sugihara, Hitoshi; Oikawa, Shinichi

2012-06-06

Aims/Introduction:  The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet-induced diabetes, we performed selective breeding for differences in high fat diet (HFD)-induced glucose intolerance.   Selective breeding was performed using hybrid mice of C57BL/6J, C3H/HeJ and AKR/N backgrounds. After 5-week HFD feeding, mice showing high and low 2-h blood glucose levels in an oral glucose tolerance test (OGTT) were selected and bred over 14 generations to produce lines prone and resistant to diet-induced glucose intolerance (designated Selectively bred Diet-induced Glucose intolerance-Prone [SDG-P] and -Resistant [SDG-R]).   At 5 weeks of age (pre HFD feeding), SDG-P mice showed higher blood glucose levels both in the OGTT and insulin tolerance test as compared to SDG-R mice. After receiving HFD, the glucose intolerance of SDG-P mice became more evident without hyper insulin secretion. In addition, SDG-P mice had greater body weight gain and lower HDL-cholesterol levels as compared to SDG-R mice. In comparison with C57BL/6J, a well-known strain prone to HFD-induced glucose intolerance, SDG-P mice showed significantly higher glucose levels in OGTT after the 5-week HFD feeding.   Susceptibility to HFD-induced glucose intolerance was transmitted over generations and was intensified by selective breeding. The newly established mouse lines, SDG-P and SDG-R, may be useful in investigating the pathophysiology of type 2 diabetes through elucidating the crucial factors for determining the susceptibility to HFD-induced glucose intolerance. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00175.x, 2011).

Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression.

PubMed

Costa, Elísio; Fernandes, João; Ribeiro, Sandra; Sereno, José; Garrido, Patrícia; Rocha-Pereira, Petronila; Coimbra, Susana; Catarino, Cristina; Belo, Luís; Bronze-da-Rocha, Elsa; Vala, Helena; Alves, Rui; Reis, Flávio; Santos-Silva, Alice

2014-12-01

Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.

DNA adducts and oxidative DNA damage induced by organic extracts from PM2.5 in an acellular assay.

PubMed

Topinka, Jan; Rossner, Pavel; Milcova, Alena; Schmuczerova, Jana; Svecova, Vlasta; Sram, Radim J

2011-05-10

The genotoxic activities of complex mixtures of organic extracts from the urban air particles collected in various localities of the Czech Republic, which differed in the extent and sources of air pollution, were compared. For this purpose, PM2.5 particles were collected by high volume samplers in the most polluted area of the Czech Republic--Ostrava region (localities Bartovice, Poruba and Karvina) and in the locality exhibiting a low level of air pollution--Trebon--a small town in the non-industrial region of Southern Bohemia. To prepare extractable organic matter (EOM), PM2.5 particles were extracted by dichloromethane and c-PAHs contents in the EOMs were determined. As markers of genotoxic potential, DNA adduct levels and oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG, levels) induced by EOMs in an acellular assay of calf thymus DNA coupled with ³²P-postlabeling (DNA adducts) and ELISA (8-oxodG) in the presence and absence of microsomal S9 fraction were employed. Twofold higher DNA adduct levels (17.20 adducts/10⁸ nucleotides/m³ vs. 8.49 adducts/10⁸ nucleotides/m³) were induced by EOM from Ostrava-Bartovice (immediate proximity of heavy industry) compared with that from Ostrava-Poruba (mostly traffic emissions). Oxidative DNA damage induced by EOM from Ostrava-Bartovice was more than fourfold higher than damage induced by EOM from Trebon (8-oxodG/10⁸ dG/m³: 0.131 vs. 0.030 for Ostrava-Bartovice vs. Trebon, respectively). Since PM2.5 particles collected in various localities differ with respect to their c-PAHs content, and c-PAHs significantly contribute to genotoxicity (DNA adduct levels), we suggest that monitoring of PM2.5 levels is not a sufficient basis to assess genotoxicity of respirable aerosols. It seems likely that the industrial emissions prevailing in Ostrava-Bartovice represent a substantially higher genotoxic risk than mostly traffic-related emissions in Ostrava-Poruba. B[a]P and c-PAH contents in EOMs are the most important factors relating to their genotoxic potential. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

HSP90 gene expression induced by aspirin is associated with damage remission in a chicken myocardial cell culture exposed to heat stress.

PubMed

Zhang, X; Qian, Z; Zhu, H; Tang, S; Wu, D; Zhang, M; Kemper, N; Hartung, J; Bao, E

2016-08-01

To understand the potential protection of heat shock protein 90 (HSP90) induced by aspirin against heat stress damage in chicken myocardial cells, enzyme activities related to stress damage, cytopathological changes, the expression and distribution of HSP90, and HSP90 mRNA levels in the myocardial cells exposed to heat stress (42°C) for different durations with or without aspirin administration (1 mg/ml, 2 h prior) in vitro were investigated. Significant increase of enzyme levels in the supernatant of heat-stressed myocardial cells and cellular lesions characterised by acute degeneration, karyopyknosis and karyorrhexis were observed, compared to non-treated cells. However, the lesions of cells treated with aspirin were milder, characterised by earlier recovery of enzyme levels to the control levels and no obvious heat stress-related cellular necrosis. Stronger positive signals in the cytoplasm and longer retention of HSP90 signal in nuclei were observed in aspirin-treated myocardial cells than those of only heat-stressed cells. HSP90 level in the aspirin-treated myocardial cells was 11.1-fold higher than that in non-treated cells, and remained at a high level at the early stage of heat stress, whereas it was just 4.1-fold higher in only heat-stressed cells and returned rapidly to a low level. Overexpression of HSP90 mRNA in aspirin-treated cells was observed throughout the experiment, whereas HSP90 mRNA decreased significantly only in heat-stressed cells. The early higher HSP90 expression induced by aspirin during heat stress was accompanied by decreased heat stress damage, suggesting that aspirin might play an important role in preventing myocardial cells from heat stress damage in vitro.

Ketamine potentiates oxidative stress and influences behavior and inflammation in response to lipolysaccharide (LPS) exposure in early life.

PubMed

Réus, Gislaine Z; Simões, Lutiana R; Colpo, Gabriela D; Scaini, Giselli; Oses, Jean P; Generoso, Jaqueline S; Prossin, Alan R; Kaddurah-Daouk, Rima; Quevedo, João; Barichello, Tatiana

2017-06-14

Immune activation (IA) during the early neonatal period is a risk factor for the development of schizophrenia. Lipopolysaccharide (LPS) injected in neonates lead to behavioral and brain changes that persist to adult life. We investigated oxidative stress, levels of cytokines, and the locomotor activity of IA in a schizophrenia animal model in which neonatal male Wistar rats were administered with an injection of LPS (50μg/kg) on postnatal day 3 and different doses of ketamine (5, 15 and 25mg/kg) for 7days during adulthood. Rats LPS-induced did not have locomotor activity alterations. Locomotor activity was elevated in neonatally saline-injected in the higher dose ketamine-treated animals. Carbonyl protein in the prefrontal cortex (PFC), hippocampus and striatum were increased in the LPS- and saline-induced in the ketamine (25mg/kg)-treated animals. Lipid damage occurred in the PFC, striatum and hippocampus in the LPS- and saline-induced in the ketamine (15 and 25mg/kg) -treated animals. In the hippocampus the superoxide dismutase (SOD) was decreased in the LPS- and saline-induced in the ketamine-treated with the dose of 25mg/kg. In the PFC SOD was reduced in the LPS-induced in the ketamine (25mg/kg)-treated animals. Catalase in the PFC and hippocampus was reduced in the LPS- and saline-induced in the ketamine (25mg/kg)-treated animals. Pro- and anti-inflammatory cytokines were lower in the brains of LPS-induced in the higher dose ketamine-treated rats. IA influences the locomotor activity and cytokine levels induced by ketamine, and it has a negative effect in potentiating the oxidative stress by higher doses of ketamine in the brain. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Anti-diabetic activity of Vaccinium bracteatum Thunb. leaves' polysaccharide in STZ-induced diabetic mice.

PubMed

Wang, Li; Zhang, Ying; Xu, Maochao; Wang, Yingyao; Cheng, Sujiao; Liebrecht, Alex; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

2013-10-01

Vaccinium bracteatum Thunb. (VBT) is a traditional Chinese herbal medicine. The anti-diabetic activity of VBT leaves' polysaccharide (VBTLP) is studied in this paper. The results indicated VBTLP had a dose-dependent decrease on the blood glucose (BG) level, and the time effect of VBTLP on BG level was also significant. The insulin level of high dose group (HDG) was significantly higher (p<0.05) than that of model control (MC) group. Compared to MC, HDG and lose dose group (LDG) had significantly lower (p<0.05) TC and LDL-C levels, however, TG and HDL-C levels are similar. Compared to non-diabetic control (NC), HDG and LDG had similar plasma lipid levels except for higher LDL-C level. Although body weights of LDG and HDG were significant lower (p<0.05) than that of NC from week 2 to week 6, they were similar to that of PC. The results indicate VBTLP possesses a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright © 2013 Elsevier B.V. All rights reserved.

Induced Insecurity: Understanding the Potential Pitfalls in Developing Theater Campaign Plans

DTIC Science & Technology

2015-06-11

effective partnerships that meet outlined in higher- level strategic guidance . 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. UMITATION OF... effective partnerships that meet the desired end states outlined in higher-level strategic guidance. DEDICATION To the millions of men and women who...and draw conclusions, it does not always prove to be an effective means of predicting the outcome of current or future events. In addition, the

Homemade-device-induced negative pressure promotes wound healing more efficiently than VSD-induced positive pressure by regulating inflammation, proliferation and remodeling.

PubMed

Liu, Jinyan; Hu, Feng; Tang, Jintian; Tang, Shijie; Xia, Kun; Wu, Song; Yin, Chaoqi; Wang, Shaohua; He, Quanyong; Xie, Huiqing; Zhou, Jianda

2017-04-01

Vacuum sealing drainage (VSD) is an effective technique used to promote wound healing. However, recent studies have shown that it exerts positive pressure (PP) rather than negative pressure (NP) on skin. In this study, we created a homemade device that could maintain NP on the wound, and compared the therapeutic effects of VSD-induced PP to those of our homemade device which induced NP on wound healing. The NP induced by our device required less time for wound healing and decreased the wound area more efficiently than the PP induced by VSD. NP and PP both promoted the inflammatory response by upregulating neutrophil infiltration and interleukin (IL)‑1β expression, and downregulating IL‑10 expression. Higher levels of epidermal growth factor (EGF), transforming growth factor (TGF)‑β and platelet-derived growth factor (PDGF), and lower levels of basic fibroblast growth factor (bFGF) were observed in the wound tissue treated with NP compared to the wound tissue exposed to PP. Proliferation in the wound tissue exposed to NP on day 10 was significantly higher than that in wound tissue exposed to PP. NP generated more fibroblasts, keratinized stratified epithelium, and less epithelia with stemness than PP. The levels of ccollagen Ⅰ and Ⅲ were both decreased in both the NP and PP groups. NP induced a statistically significant increase in the expression of fibronectin (FN) on days 3 and 10 compared to PP. Furthermore, the level of matrix metalloproteinase (MMP)‑13 increased in the NP group, but decreased in the PP group on day 3. NP also induced a decrease in the levels of tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 during the early stages of wound healing, which was significantly different from the increasing effect of PP on TIMP‑1 and TIMP‑2 levels at the corresponding time points. On the whole, our data indicate that our homemade device which induced NP, was more efficient than VSD‑induced PP on wound healing by regulating inflammation, secretion, proliferation and the distribution of different cells in wound tissue.

Investigation of the role of α-lipoic acid on fatty acids profile, some minerals (zinc, copper, iron) and antioxidant activity against aluminum-induced oxidative stress in the liver of male rats.

PubMed

Sahin, Zafer; Ozkaya, Ahmet; Yilmaz, Okkes; Yuce, Abdurrauf; Gunes, Mehmet

2017-07-26

We have investigated the effects of α-lipoic acid (LA), a powerful antioxidant, on the fatty acid (FA) profiles, aluminum accumulation, antioxidant activity and some minerals such as zinc, copper and iron against aluminum chloride (AlCl3)-induced oxidative stress in rat liver. Twenty-eight male Wistar rats were divided into four groups as control, LA, AlCl3 and LA+AlCl3. For 30 days, LA was intraperitoneally administrated (50 mg/kg) and AlCl3 was given via orogastric gavage (1600 ppm) every other day. AlCl3-treated animals exhibited higher hepatic malondialdehyde concentration and lower glutathione peroxidase and catalase activity, whereas these alterations were restored by the LA supplementation. Total saturated FA of the AlCl3-treated group was higher than the LA supplementation groups. Moreover, total unsaturated FA level of the LA+AlCl3 group was higher than the AlCl3-treated group. Hepatic zinc level of the AlCl3-treated group was lower than the control group, whereas it was higher in the LA and the LA+AlCl3 groups. Hepatic copper levels did not significantly change in the experimental groups. Iron level was lower in the LA and LA+AlCl3 groups compared with the AlCl3-treated group. Moreover, the liver Al concentration was found to be lower in the LA and LA+AlCl3 groups compared to the AlCl3 group. These results indicate that AlCl3 treatment can induce oxidative stress in the liver. LA supplementation has a beneficial effect on the AlCl3-induced alterations such as high lipid peroxidation, Al accumulation, FA profile ratios and mineral concentrations.

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Influence of Arsenic on Global Levels of Histone Posttranslational Modifications: a Review of the Literature and Challenges in the Field.

PubMed

Howe, Caitlin G; Gamble, Mary V

2016-09-01

Arsenic is a human carcinogen and also increases the risk for non-cancer outcomes. Arsenic-induced epigenetic dysregulation may contribute to arsenic toxicity. Although there are several reviews on arsenic and epigenetics, these have largely focused on DNA methylation. Here, we review investigations of the effects of arsenic on global levels of histone posttranslational modifications (PTMs). Multiple studies have observed that arsenic induces higher levels of H3 lysine 9 dimethylation (H3K9me2) and also higher levels of H3 serine 10 phosphorylation (H3S10ph), which regulate chromosome segregation. In contrast, arsenic causes a global loss of H4K16ac, a histone PTM that is a hallmark of human cancers. Although the findings for other histone PTMs have not been entirely consistent across studies, we discuss biological factors which may contribute to these inconsistencies, including differences in the dose, duration, and type of arsenic species examined; the tissue or cell line evaluated; differences by sex; and exposure timing. We also discuss two important considerations for the measurement of histone PTMs: proteolytic cleavage of histones and arsenic-induced alterations in histone expression.

Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

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

Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu

2005-09-01

Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-{alpha} and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-{alpha}-induced responses, in this study we examined the TNF-{alpha}-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-{alpha} (rTNF-{alpha}) was significantly higher than those from ALmore » cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5{sup +} or sIgM{sup +} cells and these cells showed resistance to TNF-{alpha}-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-{alpha}-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection.« less

Hair Trace Element and Electrolyte Content in Women with Natural and In Vitro Fertilization-Induced Pregnancy.

PubMed

Skalny, Anatoly V; Tinkov, Alexey A; Voronina, Irina; Terekhina, Olga; Skalnaya, Margarita G; Kovas, Yulia

2018-01-01

The objective of the present study was to perform comparative analysis of hair trace element content in women with natural and in vitro fertilization (IVF)-induced pregnancy. Hair trace element content in 33 women with IVF-induced pregnancy and 99 age- and body mass index-matched control pregnant women (natural pregnancy) was assessed using inductively coupled plasma mass spectrometry. The results demonstrated that IVF-pregnant women are characterized by significantly lower hair levels of Cu, Fe, Si, Zn, Ca, Mg, and Ba at p < 0.05 or lower. Comparison of the individual levels with the national reference values demonstrated higher incidence of Fe and Cu deficiency in IVF-pregnant women in comparison to that of the controls. IVF pregnancy was also associated with higher hair As levels (p < 0.05). Multiple regression analysis revealed a significant interrelation between IVF pregnancy and hair Cu, Fe, Si, and As content. Hair Cu levels were also influenced by vitamin/mineral supplementation and the number of pregnancies, whereas hair Zn content was dependent on prepregnancy anthropometric parameters. In turn, planning of pregnancy had a significant impact on Mg levels in scalp hair. Generally, the obtained data demonstrate an elevated risk of copper, iron, zinc, calcium, and magnesium deficiency and arsenic overload in women with IVF-induced pregnancy. The obtained data indicate the necessity of regular monitoring of micronutrient status in IVF-pregnant women in order to prevent potential deleterious effects of altered mineral homeostasis.

Human H7N9 virus induces a more pronounced pro-inflammatory cytokine but an attenuated interferon response in human bronchial epithelial cells when compared with an epidemiologically-linked chicken H7N9 virus.

PubMed

To, Kelvin K W; Lau, Candy C Y; Woo, Patrick C Y; Lau, Susanna K P; Chan, Jasper F W; Chan, Kwok-Hung; Zhang, Anna J X; Chen, Honglin; Yuen, Kwok-Yung

2016-03-15

Avian influenza virus H7N9 has jumped species barrier, causing sporadic human infections since 2013. We have previously isolated an H7N9 virus from a patient, and an H7N9 virus from a chicken in a live poultry market where the patient visited during the incubation period. These two viruses were genetically highly similar. This study sought to use a human bronchial epithelial cell line model to infer the virulence of these H7N9 viruses in humans. Human bronchial epithelial cell line Calu-3 was infected with two H7N9 viruses (human H7N9-HU and chicken H7N9-CK), a human H5N1 virus and a human 2009 pandemic H1N1 virus. The infected cell lysate was collected at different time points post-infection for the determination of the levels of pro-inflammatory cytokines (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]), anti-inflammatory cytokines (interleukin 10 [IL-10] and transforming growth factor beta [TGF-β]), chemokines (interleukin 8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]), and interferons (interferon β [IFN-β] and interferon lambda 1 [IFNL1]). The viral load in the cell lysate was also measured. Comparison of the human and chicken H7N9 viruses showed that H7N9-HU induced significantly higher levels of TNF-α at 12 h post-infection, and significantly higher levels of IL-8 from 12 to 48 h post-infection than those of H7N9-CK. However, the level of IFNL1 was lower for H7N9-HU than that of H7N9-CK at 48 h post-infection (P < 0.001). H7N9-HU had significantly higher viral loads than H7N9-CK at 3 and 6 h post-infection. H5N1 induced significantly higher levels of TNF-α, IL-6, IL-8, IL-10 and MCP-1 than those of H7N9 viruses at 48 h post-infection. Conversely, H1N1 induced lower levels of TNF-α, IL-10, MCP-1, IFNL1 and IFN-β when compared with H7N9 viruses at the same time point. H7N9-HU induced higher levels of pro-inflammatory IL-6 and IL-8 and exhibited a more rapid viral replication than H7N9-CK. However, the level of antiviral IFNL1 was lower for H7N9-HU than H7N9-CK. Our results suggest that the gained properties in modulating human innate immunity by H7N9-HU transformed it to be a more virulent virus in humans than H7N9-CK.

Gender Differences in Emotional Response: Inconsistency between Experience and Expressivity.

PubMed

Deng, Yaling; Chang, Lei; Yang, Meng; Huo, Meng; Zhou, Renlai

2016-01-01

The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception-women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence.

Gender Differences in Emotional Response: Inconsistency between Experience and Expressivity

PubMed Central

Deng, Yaling; Chang, Lei; Yang, Meng; Huo, Meng

2016-01-01

The present study investigated gender differences in both emotional experience and expressivity. Heart rate (HR) was recorded as an indicator of emotional experience while the participants watched 16 video clips that induced eight types of emotion (sadness, anger, horror, disgust, neutrality, amusement, surprise, and pleasure). We also asked the participants to report valence, arousal, and motivation as indicators of emotional expressivity. Overall, the results revealed gender differences in emotional experience and emotional expressivity. When watching videos that induced anger, amusement, and pleasure, men showed larger decreases in HR, whereas women reported higher levels of arousal. There was no gender difference in HR when the participants watched videos that induced horror and disgust, but women reported lower valence, higher arousal, and stronger avoidance motivation than did men. Finally, no gender difference was observed in sadness or surprise, although there was one exception—women reported higher arousal when watching videos that induced sadness. The findings suggest that, when watching videos that induce an emotional response, men often have more intense emotional experiences, whereas women have higher emotional expressivity, particularly for negative emotions. In addition, gender differences depend on the specific emotion type but not the valence. PMID:27362361

Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence

PubMed Central

Benanti, Jennifer A.; Galloway, Denise A.

2004-01-01

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated β-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS. PMID:15024073

Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

PubMed

Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

2013-11-01

High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, p<0.01) while ursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation.

PubMed

Xiong, Xi; Ren, Yuqian; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

2017-12-01

Cholestasis, as a main manifestation, induces liver injury during sepsis. The farnesoid X receptor (FXR) plays an important role in regulating bile acid homeostasis. Whether FXR activation by its agonist obeticholic acid (OCA) is contributed to improve sepsis-induced liver injury remains unknown. The aim of the present study was to investigate the effect of OCA on lipopolysaccharide (LPS)-induced acute liver injury in mice. 8-week old male C57BL/6J mice were randomly divided into control group, LPS group, oral OCA group and LPS plus oral OCA (LPS + OCA) group. The serum and livers were collected for further analysis. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA) and total bilirubin (TBIL) were measured at indicated time after LPS administration. Liver sections were stained with hematoxylin & eosin (H&E). Orally OCA pretreatment stimulated the expression of FXR and BSEP in livers and protected mice from LPS-induced hepatocyte apoptosis and inflammatory infiltration. Consistently, LPS-induced higher serum levels of ALT, AST, TBA and TBIL were significantly reversed by OCA administration. Meanwhile, the mRNA levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-6 were decreased in livers of mice in LPS + OCA group compared with LPS group. Further investigation indicated that the higher expression of ATF4 and LC3II/I were associated with the protective effect of OCA on LPS-induced liver injury. Orally OCA pretreatment protects mice from LPS-induced liver injury possibly contributed by improved bile acid homeostasis, decreased inflammatory factors and ATF4-mediated autophagy activity in hepatocytes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

PubMed Central

Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

2015-01-01

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15th day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase (P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue iNOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups (P < 0.05). CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model, possibly via reduction of MPO, TNF-α, and iNOS levels. PMID:26676086

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

PubMed

Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

2015-12-14

To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase (P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue iNOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups (P < 0.05). Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model, possibly via reduction of MPO, TNF-α, and iNOS levels.

Effects of near-ultraviolet light on mutations, intragenic and intergenic recombinations in Saccharomyces cerevisiae.

PubMed

Machida, I; Saeki, T; Nakai, S

1986-03-01

The effects of far (254 nm) and near (290-350 nm) ultraviolet (UV) light on mutations, intragenic and intergenic recombinations were compared in diploid strains of Saccharomyces cerevisiae. At equivalent survival levels there was not much difference in the induction of nonsense and missense mutations between far- and near-UV radiations. However, frameshift mutations were induced more frequently by near-UV than by far-UV radiation. Near-UV radiation induced intragenic recombination (gene conversion) as efficiently as far-UV radiation and the induced levels were similar in both radiations at equitoxic doses. A strikingly higher frequency was observed for the intergenic recombination induced by near-UV radiation than by far-UV radiation when compared at equivalent survival levels. Photoreactivation reduced the frequency only slightly in far-UV induced intergenic recombination and not at all in near-UV induction. These results indicate that near-UV damage involves strand breakage in addition to pyrimidine dimers and other lesions induced, whereas far-UV damage consists largely of photoreactivable lesions, pyrimidine dimers, and near-UV induced damage is more efficient for the induction of crossing-over.

Comparative in vitro toll-like receptor ligand induced cytokine profiles of Toda and Murrah buffaloes-Identification of tumour necrosis factor alpha promoter polymorphism.

PubMed

Vignesh, A R; Dhinakar Raj, G; Dhanasekaran, S; Tirumurugaan, K G; Raja, A

2012-12-15

The objective of this study was to assess cytokine production upon activation of pattern recognition receptors responsible for sensing bacterial and viral pathogen associated molecular patterns in two genetically diverse buffalo breeds, Toda and Murrah. A very limited molecular-epidemiological analysis showed a higher prevalence of Anaplasma and Theileria in Murrah than Toda buffaloes. Toda buffalo peripheral blood mononuclear cells (PBMC) produced significantly higher levels of IFN γ and/or TNF α mRNAs in response to peptidoglycan, poly I:C, lipopolysaccharide, imiquimod and CpG. Flagellin stimulation did not result in any significant differences in the expression levels of the cytokines tested between these breeds. The levels of ligand induced IFN γ and TNF α mRNA and proteins also correlated except when induced with CpG. The proximal promoter region of TNF α across these two breeds were also sequenced to detect SNPs and promoter assay performed to determine their role in altering the transcriptional activity. Two polymorphisms were identified at -737 (T/A) and -1092 (G/T) positions in Toda buffalo TNF α promoter and promoter assay revealed higher transcription activity in Toda buffalos than in Murrah. This suggests that disease tolerance of these buffalo breeds could be due to the differences in their cytokine transcription levels in response to the respective PAMPs that may be at least in part determined by polymorphisms in the cytokine promoter regions. Copyright © 2012 Elsevier B.V. All rights reserved.

Methionine sulfoxide reductase A protects hepatocytes against acetaminophen-induced toxicity via regulation of thioredoxin reductase 1 expression.

PubMed

Singh, Mahendra Pratap; Kwak, Geun-Hee; Kim, Ki Young; Kim, Hwa-Young

2017-06-03

Thioredoxin reductase 1 (TXNRD1) is associated with susceptibility to acetaminophen (APAP)-induced liver damage. Methionine sulfoxide reductase A (MsrA) is an antioxidant and protein repair enzyme that specifically catalyzes the reduction of methionine S-sulfoxide residues. We have previously shown that MsrA deficiency exacerbates acute liver injury induced by APAP. In this study, we used primary hepatocytes to investigate the underlying mechanism of the protective effect of MsrA against APAP-induced hepatotoxicity. MsrA gene-deleted (MsrA -/- ) hepatocytes showed higher susceptibility to APAP-induced cytotoxicity than wild-type (MsrA +/+ ) cells, consistent with our previous in vivo results. MsrA deficiency increased APAP-induced glutathione depletion and reactive oxygen species production. APAP treatment increased Nrf2 activation more profoundly in MsrA -/- than in MsrA +/+ hepatocytes. Basal TXNRD1 levels were significantly higher in MsrA -/- than in MsrA +/+ hepatocytes, while TXNRD1 depletion in both MsrA -/- and MsrA +/+ cells resulted in increased resistance to APAP-induced cytotoxicity. In addition, APAP treatment significantly increased TXNRD1 expression in MsrA -/- hepatocytes, while no significant change was observed in MsrA +/+ cells. Overexpression of MsrA reduced APAP-induced cytotoxicity and TXNRD1 expression levels in APAP-treated MsrA -/- hepatocytes. Collectively, our results suggest that MsrA protects hepatocytes from APAP-induced cytotoxicity through the modulation of TXNRD1 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Protein tyrosine phosphatase 1B is a mediator of cyclic ADP ribose-induced Ca2+ signaling in ventricular myocytes.

PubMed

Park, Seon-Ah; Hong, Bing-Zhe; Ha, Ki-Chan; Kim, Uh-Hyun; Han, Myung-Kwan; Kwak, Yong-Geun

2017-06-02

Cyclic ADP-ribose (cADPR) releases Ca 2+ from ryanodine receptor (RyR)-sensitive calcium pools in various cell types. In cardiac myocytes, the physiological levels of cADPR transiently increase the amplitude and frequency of Ca 2+ (that is, a rapid increase and decrease of calcium within one second) during the cardiac action potential. In this study, we demonstrated that cADPR levels higher than physiological levels induce a slow and gradual increase in the resting intracellular Ca 2+ ([Ca 2+ ] i ) level over 10 min by inhibiting the sarcoendoplasmic reticulum Ca 2+ ATPase (SERCA). Higher cADPR levels mediate the tyrosine-dephosphorylation of α-actin by protein tyrosine phosphatase 1B (PTP1B) present in the endoplasmic reticulum. The tyrosine dephosphorylation of α-actin dissociates phospholamban, the key regulator of SERCA, from α-actin and results in SERCA inhibition. The disruption of the integrity of α-actin by cytochalasin B and the inhibition of α-actin tyrosine dephosphorylation by a PTP1B inhibitor block cADPR-mediated Ca 2+ increase. Our results suggest that levels of cADPR that are relatively higher than normal physiological levels modify calcium homeostasis through the dephosphorylation of α-actin by PTB1B and the subsequent inhibition of SERCA in cardiac myocytes.

Herbivore-induced plant volatiles accurately predict history of coexistence, diet breadth, and feeding mode of herbivores

USDA-ARS?s Scientific Manuscript database

Herbivore induced plant volatiles (HIPVs) serve as specific cues to higher trophic levels. Novel, exotic herbivores entering foodwebs with a common co-existence history may disrupt the native infochemical network due to changes in HIPV profiles. Here we analyzed HIPV blends of native Brassica rapa p...

USE OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS TO ASSESS POLLUTANT-INDUCED LUNG CHANGES IN AN ANIMAL MODEL OF CARDIOVASCULAR (CV) DISEASE.

EPA Science Inventory

Animal models of coronary heart disease (e.g., hyperlipidemic rabbits) are being used to investigate epidemiologic associations between higher levels of air pollution and adverse CV consequences. Mechanisms by which pollutant-induced lung or systemic inflammation leads to acute C...

Development of inducer-free expression plasmids based on IPTG-inducible promoters for Bacillus subtilis.

PubMed

Tran, Dinh Thi Minh; Phan, Trang Thi Phuong; Huynh, Thanh Kieu; Dang, Ngan Thi Kim; Huynh, Phuong Thi Kim; Nguyen, Tri Minh; Truong, Tuom Thi Tinh; Tran, Thuoc Linh; Schumann, Wolfgang; Nguyen, Hoang Duc

2017-07-25

Besides Escherichia coli, Bacillus subtilis is an important bacterial species for the production of recombinant proteins. Recombinant genes are inserted into shuttle expression vectors which replicate in both E. coli and in B. subtilis. The ligation products are first transformed into E. coli cells, analyzed for correct insertions, and the correct recombinant plasmids are then transformed into B. subtilis. A major problem using E. coli cells can be the strong basal level of expression of the recombinant protein which may interfere with the stability of the cells. To minimize this problem, we developed strong expression vectors being repressed in E. coli and inducer-free in B. subtilis. In general, induction of IPTG-inducible expression vectors is determined by the regulatory lacI gene encoding the LacI repressor in combination with the lacO operator on the promoter. To investigate the inducer-free properties of the vectors, we constructed inducer-free expression plasmids by removing the lacI gene and characterized their properties. First, we examined the ability to repress a reporter gene in E. coli, which is a prominent property facilitating the construction of the expression vectors carrying a target gene. The β-galactosidase (bgaB gene) basal levels expressed from Pgrac01-bgaB could be repressed at least twice in the E. coli cloning strain. Second, the inducer-free production of BgaB from four different plasmids with the Pgrac01 promoter in B. subtilis was investigated. As expected, BgaB expression levels of inducer-free constructs are at least 37 times higher than that of the inducible constructs in the absence of IPTG, and comparable to those in the presence of the inducer. Third, using efficient IPTG-inducible expression vectors containing the strong promoter Pgrac100, we could convert them into inducer-free expression plasmids. The BgaB production levels from the inducer-free plasmid in the absence of the inducer were at least 4.5 times higher than that of the inducible vector using the same promoter. Finally, we used gfp as a reporter gene in combination with the two promoters Pgrac01 and Pgrac100 to test the new vector types. The GFP expression levels could be repressed at least 1.5 times for the Pgrac01-gfp+ inducer-free construct in E. coli. The inducer-free constructs Pgrac01-gfp+ and Pgrac100-gfp+ allowed GFP expression at high levels from 23 × 10 4 to 32 × 10 4 RFU units and 9-13% of total intracellular proteins. We could reconfirm the two major advantages of the new inducer-free expression plasmids: (1) Strong repression of the target gene expression in the E. coli cloning strain, and (2) production of the target protein at high levels in B. subtilis in the absence of the inducer. We propose a general strategy to generate inducer-free expression vector by using IPTG-inducible vectors, and more specifically we developed inducer-free expression plasmids using IPTG-inducible promoters in the absence of the LacI repressor. These plasmids could be an excellent choice for high-level production of recombinant proteins in B. subtilis without the addition of inducer and at the same time maintaining a low basal level of the recombinant proteins in E. coli. The repression of the recombinant gene expression would facilitate cloning of genes that potentially inhibit the growth of E. coli cloning strains. The inducer-free expression plasmids will be extended versions of the current available IPTG-inducible expression vectors for B. subtilis, in which all these vectors use the same cognate promoters. These inducer-free and previously developed IPTG-inducible expression plasmids will be a useful cassette to study gene expression at a small scale up to a larger scale up for the production of recombinant proteins.

Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism

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

Fang Cheng; Behr, Melissa; Xie Fang

2008-02-15

Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dosemore » of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.« less

Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

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

Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu; Pratheeshkumar, Poyil; Budhraja, Amit

Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROSmore » levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.« less

Immune responses induced by co-infection with Capillaria hepatica in Clonorchis sinensis-infected rats.

PubMed

Moon, E-K; Lee, S-H; Goo, T W; Quan, F-S

2018-07-01

Clonorchis sinensis and Capillaria hepatica are zoonotic parasites that mainly infect the liver and cause serious liver disorders. However, immunological parameters induced by co-infection with these parasites remain unknown. In this study, for the first time, we investigated immunological profiles induced by co-infection with C. hepatica (CH) in C. sinensis (CS)-infected rats (Sprague-Dawley). Rats were infected primarily with 50 metacercariae of C. sinensis; 4 weeks later, they were subsequently infected with 1000 infective C. hepatica eggs. Significantly higher levels of C. sinensis- or C. hepatica-specific IgG antibodies were found in the sera of rats. Interestingly, no cross-reacting antibody was observed between C. sinensis and C. hepatica infections. Significantly raised eosinophil levels were found in the blood of C. sinensis/C. hepatica co-infected rats (CS + CH) compared to the blood of rats infected singly with C. sinensis. Co-infected rats showed significantly higher levels of lymphocyte proliferation and cytokine production compared to a single C. sinensis infection. The worm burden of C. sinensis was significantly reduced in co-infected rats compared to the single C. sinensis infection. These results indicate that the eosinophils, lymphocyte proliferation and cytokine production induced by subsequent infection with C. hepatica in C. sinensis-infected rats might contribute to the observed C. sinensis worm reduction.

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

PubMed

Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

2016-07-01

To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

Differential screening-selected gene aberrative in neuroblastoma (DAN) is increased in the CSF of patients with MS and may be induced by therapy with interferon-β.

PubMed

Mausner-Fainberg, Karin; Kolb, Hadar; Penn, Moran; Regev, Keren; Vaknin-Dembinsky, Adi; Gadoth, Avi; Kestenbaum, Meir; Karni, Arnon

2016-03-15

Bone morphogenic proteins (BMPs) signaling blockade induce neurogenesis and oligodendrogenesis. Differential screening-selected gene aberrative in neuroblastoma (DAN) is a glycoprotein that antagonizes BMPs. We found that DAN levels were higher in CSF compared to serum in all participants. CSF-DAN levels were elevated in RR-and progresssive MS patients compared to controls. Moreover, serum-DAN levels were reduced in those patients, but elevated in IFN-β1a treated patients. The main source of DAN is apparently CNS- resident cells. The enhanced levels of CSF-DAN in MS patients suggest a tendency to induce neurogenesis/oligodendrogenesis in the patients CNS. Our results suggest an unreported mode of action of IFN-β1a. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of purified compared with nonpurified diet on bone changes induced by hindlimb suspension of female rats

NASA Technical Reports Server (NTRS)

Tou, Janet C L.; Arnaud, Sara B.; Grindeland, Richard; Wade, Charles

2005-01-01

The purpose of this study was to compare the bone changes induced by unloading in rats fed different diets, because space flight studies use a semipurified diet, whereas space flight simulation studies typically use nonpurified diets. Female Sprague-Dawley rats were fed a purified American Institute of Nutrition (AIN) 93G diet or a standard nonpurified diet and kept ambulatory or subjected to unloading by hindlimb suspension (HLS) for 38 days. Bone mineral content (BMC), mechanical strength, and factors related to the diet that affect bone (i.e., urinary calcium excretion, estradiol, and corticosterone) were measured. Average food intakes (grams per day) differed for diets, but caloric intake (kilocalories per day) and the final body masses of treatment groups were similar. The HLS-induced decrease in femoral BMC was not statistically different for rats fed a nonpurified diet (-8.6%) compared with a purified AIN-93G diet (-11.4%). The HLS-induced decrease in femoral mechanical strength was not statistically different for rats fed a nonpurified diet (-24%) compared with a purified AIN-93G diet (-31%). However, bone lengths were decreased (P < 0.05) in rats fed a nonpurified diet compared with a purified diet. Plasma estradiol levels were lower (P < 0.05) in the HLS/AIN-93G group but similar in the HLS and ambulatory rats fed a nonpurified diet. Plasma estradiol was related to femoral BMC (r = 0.85, P < 0.01). Urinary calcium excretion was higher (P < 0.05) in rats fed a nonpurified diet than those fed a purified AIN-93G diet, which is consistent with the higher level of calcium in the nonpurified diet. Urinary corticosterone levels were higher (P < 0.05) in rats fed a nonpurified diet than rats fed the AIN-93G diet. Although the osteopenia induced by unloading was similar in both diet groups, there were differences in longitudinal bone growth, calcium excretion, plasma estradiol levels, and urinary corticosterone levels. Results indicate that the type of standard diet used is an important factor to consider when measuring bone end points.

Overexpression of alpha(1)-acid glycoprotein in transgenic mice leads to sensitisation to acute colitis.

PubMed

Hochepied, T; Wullaert, A; Berger, F G; Baumann, H; Brouckaert, P; Steidler, L; Libert, C

2002-09-01

alpha(1)-Acid glycoprotein (alpha(1)-AGP) is an acute phase protein in most mammalian species whose concentration rises 2-5-fold during an acute phase reaction. Its serum concentration has often been used as a marker of disease, including inflammatory bowel disease (IBD). High alpha(1)-AGP levels were found to have a prognostic value for an increased risk of relapse in IBD. To investigate a possible role for increased serum levels of alpha(1)-AGP in the development of IBD. Dextran sodium sulphate (DSS) 2% was added to the drinking water of transgenic mice, overexpressing the rat alpha(1)-AGP gene, to induce acute colitis, thus mimicking the conditions of relapse. Clinical parameters, inflammatory parameters, and histological analyses on colon sections were performed. Homozygous alpha(1)-AGP-transgenic mice started losing weight and showed rectal bleeding significantly earlier than heterozygous transgenic or wild-type mice. Survival time of homozygous transgenic mice was significantly shorter compared with heterozygous and wild-type mice. The higher susceptibility of homozygous alpha(1)-AGP-transgenic mice to DSS induced acute colitis was also reflected in higher local myeloperoxidase levels, higher inflammation scores of the colon, and higher systemic levels of interleukin 6 and serum amyloid P component. Local inflammatory parameters were also significantly different in heterozygous transgenic mice compared with wild-type mice, indicating a local dosage effect. In homozygous transgenic mice, significantly higher amounts of bacteria were found in organs but IgA levels were only slightly lower than those of control mice. Sufficiently high serum levels of alpha(1)-AGP result in a more aggressive development of acute colitis.

Effect of stress during handling, seawater acclimation, confinement, and induced spawning on plasma ion levels and somatolactin-expressing cells in mature female Liza ramada.

PubMed

Khalil, Noha A; Hashem, Amal M; Ibrahim, Amal A E; Mousa, Mostafa A

2012-08-01

The present experiments were designed to determine the effect of different stress factors; handling, seawater acclimation, confinement, and induced spawning on plasma cortisol, hydro mineral balance as well as changes in size, number and integrated intensity of somatolactin (SL)-expressing cells in Liza ramada mature females confined to fresh water ponds. The plasma levels of cortisol, PO(4)(3-), Na(+), and K(+) were higher, while Ca(2+) and Mg(2+) were lower than controls during transportation without anesthesia. By using clove oil (5 mg L(-1)) as an anesthetic during transportation, the plasma cortisol, PO(4) (3-), Na(+), and K(+) were similar to controls, while Ca(2+) and Mg(2+) were higher. During seawater acclimation, the plasma cortisol and minerals were significantly higher except Na(+) which was lower than controls. In addition, during induction of spawning, the plasma levels of cortisol, PO(4)(3-), Na(+), K(+), and Mg(2+) were significantly higher than controls. The SL-producing cells are located in the pars intermedia (PI) bordering the neurohypophysis. The stress affected the number, size, and immunostaining of SL-expressing cells. During seawater acclimation, the size and the integrated intensity of SL immunoreactivity were lower, but the number of these cells was higher than controls. Furthermore, the number, size, and the integrated intensity of SL immunoreactivity were significantly lower than controls during handling and after spawning, which was opposite to confinement. The response of SL-expressing cells in PI in parallel with changes in cortisol and hydro mineral balance induced by stress support the possible role of SL in the adaptive response of fish to stress. © 2012 WILEY PERIODICALS, INC.

Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection

PubMed Central

Grebely, Jason; Feld, Jordan J.; Applegate, Tanya; Matthews, Gail V.; Hellard, Margaret; Sherker, Alana; Petoumenos, Kathy; Zang, Geng; Shaw, Ineke; Yeung, Barbara; George, Jacob; Teutsch, Suzy; Kaldor, John M.; Cherepanov, Vera; Bruneau, Julie; Shoukry, Naglaa H.; Lloyd, Andrew R.; Dore, Gregory J.

2013-01-01

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic HCV. In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 300 individuals, 245 (181 male, 47 HIV+) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV co-infection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n=137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248±32 vs. 142±22 pg/mL, P=0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P=0.048) and 16% (27 of 165) and in those in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favourable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance. PMID:23325615

Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model.

PubMed

Sarukhani, Mohammad Reza; Haghdoost-Yazdi, Hashem; Khandan-Chelarci, Gilda

2018-05-01

Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson's disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.

[Evolution of voluntary interruption of pregnancy in Italy from its legalization until today].

PubMed

Spinelli, A; Boccuzzo, G; Grandolfo, M E; Buratta, V; Pediconi, M; Donati, S; Frova, L; Timperi, F

1999-01-01

Induced abortion was legalized in Italy in 1978. After an initial increase in the incidence, from 187,631 in 1979 to 234,801 in 1983, induced abortion has steadily decreased to 140,398 in 1996. Analysis of the abortion rates has shown that the main decrease has been among married women aged 25-35, while there has been an increase among unmarried women. Women with lower levels of education tend to have higher rates and housewives have higher rates than women in paid work. Programmes for the prevention of induced abortion should be directed at directed at easily accessible groups: women who have just delivered a baby, couples who marry, teenagers in school and women who have already had an induced abortion. In any case, the need for rationalisation of the procedure to obtain an induced abortion is urgent.

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

PubMed

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

2011-04-01

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

mRNA expression levels of hypoxia-induced and stem cell-associated genes in human glioblastoma.

PubMed

Bache, Matthias; Rot, Swetlana; Keßler, Jacqueline; Güttler, Antje; Wichmann, Henri; Greither, Thomas; Wach, Sven; Taubert, Helge; Söling, Ariane; Bilkenroth, Udo; Kappler, Matthias; Vordermark, Dirk

2015-06-01

The roles of hypoxia-induced and stem cell-associated genes in the development of malignancy and tumour progression are well known. However, there are a limited number of studies analysing the impact of mRNA expression levels of hypoxia-induced and stem cell-associated genes in the tissues of brain tumours and glioblastoma patients. In this study, tumour tissues from patients with glioblastoma multiforme and tumour adjacent tissues were analysed. We investigated mRNA expression levels of hypoxia-inducible factor-1α (HIF-1α), hypoxia-inducible factor-2α (HIF-2α), carbonic anhydrase 9 (CA9), vascular endothelial growth factor (VEGF), glucose transporter-1 (GLUT-1) and osteopontin (OPN), and stem cell-associated genes survivin, epidermal growth factor receptor (EGFR), human telomerase reverse transcriptase (hTERT), Nanog and octamer binding transcription factor 4 (OCT4) using quantitative real-time polymerase chain reaction (qRT-PCR). Our data revealed higher mRNA expression levels of hypoxia-induced and stem cell-associated genes in tumour tissue than levels in the tumour adjacent tissues in patients with glioblastoma multiforme. A strong positive correlation between the mRNA expression levels of HIF-2α, CA9, VEGF, GLUT-1 and OPN suggests a specific hypoxia-associated profile of mRNA expression in glioblastoma multiforme. Additionally, the results indicate the role of stem-cell-related genes in tumour hypoxia. Kaplan-Maier analysis revealed that high mRNA expression levels of hypoxia-induced markers showed a trend towards shorter overall survival in glioblastoma patients (P=0.061). Our data suggest that mRNA expression levels of hypoxia-induced genes are important tumour markers in patients with glioblastoma multiforme.

Antioxidant treatment prevents the development of fructose-induced abdominal adipose tissue dysfunction.

PubMed

Fariña, Juan Pablo; García, María Elisa; Alzamendi, Ana; Giovambattista, Andrés; Marra, Carlos Alberto; Spinedi, Eduardo; Gagliardino, Juan José

2013-07-01

In the present study, we tested the effect of OS (oxidative stress) inhibition in rats fed on an FRD [fructose-rich diet; 10% (w/v) in drinking water] for 3 weeks. Normal adult male rats received a standard CD (commercial diet) or an FRD without or with an inhibitor of NADPH oxidase, APO (apocynin; 5 mM in drinking water; CD-APO and FRD-APO). We thereafter measured plasma OS and metabolic-endocrine markers, AAT (abdominal adipose tissue) mass and cell size, FA (fatty acid) composition (content and release), OS status, LEP (leptin) and IRS (insulin receptor substrate)-1/IRS-2 mRNAs, ROS (reactive oxygen species) production, NADPH oxidase activity and LEP release by isolated AAT adipocytes. FRD-fed rats had larger AAT mass without changes in body weight, and higher plasma levels of TAG (triacylglycerol), FAs, TBARS (thiobarbituric acid-reactive substance) and LEP. Although no significant changes in glucose and insulin plasma levels were observed in these animals, their HOMA-IR (homoeostasis model assessment of insulin resistance) values were significantly higher than those of CD. The AAT from FRD-fed rats had larger adipocytes, higher saturated FA content, higher NADPH oxidase activity, greater ROS production, a distorted FA content/release pattern, lower insulin sensitivity together with higher and lower mRNA content of LEP and IRS-1-/2 respectively, and released a larger amount of LEP. The development of all the clinical, OS, metabolic, endocrine and molecular changes induced by the FRD were significantly prevented by APO co-administration. The fact that APO treatment prevented both changes in NADPH oxidase activity and the development of all the FRD-induced AAT dysfunctions in normal rats strongly suggests that OS plays an important role in the FRD-induced MS (metabolic syndrome) phenotype.

Object Substitution Masking Induced by Illusory Masks: Evidence for Higher Object-Level Locus of Interference

ERIC Educational Resources Information Center

Hirose, Nobuyuki; Osaka, Naoyuki

2009-01-01

A briefly presented target can be rendered invisible by a lingering sparse mask that does not even touch it. This form of visual backward masking, called object substitution masking, is thought to occur at the object level of processing. However, it remains unclear whether object-level interference alone produces substitution masking because…

The Effect of IQ Level on the Degree of Cognitive Deterioration Experienced during Acute Hypoglycemia in Normal Humans.

ERIC Educational Resources Information Center

Gold, Ann E.; And Others

1995-01-01

Whether IQ level exerts a differential effect on the impairment of cognitive performance induced during acute hypoglycemia was studied for 24 nondiabetic adults. At various levels of hypoglycemia, no overall effect of IQ on deterioration was noted. Higher IQ did not apparently protect against adverse effects. (SLD)

Lower Oncogenic Potential of Human Mesenchymal Stem Cells Derived from Cord Blood Compared to Induced Pluripotent Stem Cells

PubMed Central

Foroutan, T.; Najmi, M.; Kazemi, N.; Hasanlou, M.; Pedram, A.

2015-01-01

Background: In regenerative medicine, use of each of the mesenchymal stem cells derived from bone marrow, cord blood, and adipose tissue, has several cons and pros. Mesenchymal stem cells derived from cord blood have been considered the best source for precursor transplantation. Direct reprogramming of a somatic cell into induced pluripotent stem cells by over-expression of 6 transcription factors Oct4, Sox2, Klf4, lin28, Nanog, and c-Myc has great potential for regenerative medicine, eliminating the ethical issues of embryonic stem cells and the rejection problems of using non-autologous cells. Objective: To compare reprogramming and pluripotent markers OCT4, Sox-2, c-Myc, Klf4, Nanog, and lin28 in mesenchymal stem cells derived from cord blood and induced pluripotent stem cells. Methods: We analyzed the expression level of OCT4, Sox-2, c-Myc, Klf4, Nanog and lin28 genes in human mesenchymal stem cells derived from cord blood and induced pluripotent stem cells by cell culture and RT-PCR. Results: The expression level of pluripotent genes OCT4 and Sox-2, Nanog and lin28 in mesenchymal stem cells derived from cord blood were significantly higher than those in induced pluripotent stem cells. In contrast to OCT-4A and Sox-2, Nanog and lin28, the expression level of oncogenic factors c-Myc and Klf4 were significantly higher in induced pluripotent stem cells than in mesenchymal stem cells derived from cord blood. Conclusion: It could be concluded that mesenchymal stem cells derived from human cord blood have lower oncogenic potential compared to induced pluripotent stem cells. PMID:26306155

Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

PubMed

Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

2014-02-01

Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes.

PubMed

Stjernholm, Theresa; Ommen, Pernille; Langkilde, Ane; Johansen, Claus; Iversen, Lars; Rosada, Cecilia; Stenderup, Karin

2017-04-01

Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Catheter-Based Renal Sympathetic Denervation Significantly Inhibits Atrial Fibrillation Induced by Electrical Stimulation of the Left Stellate Ganglion and Rapid Atrial Pacing

PubMed Central

Po, Sunny S.; Wang, Huan; Zhang, Ling; Zhang, Feng; Wang, Kun; Zhou, Qina

2013-01-01

Background Sympathetic activity involves the pathogenesis of atrial fibrillation (AF). Renal sympathetic denervation (RSD) decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive. The aim of this study was to identify the effects of RSD on AF inducibility induced by hyper-sympathetic activity in a canine model. Methods To establish a hyper-sympathetic tone canine model of AF, sixteen dogs were subjected to stimulation of left stellate ganglion (LSG) and rapid atrial pacing (RAP) for 3 hours. Then animals in the RSD group (n = 8) underwent radiofrequency ablation of the renal sympathetic nerve. The control group (n = 8) underwent the same procedure except for ablation. AF inducibility, effective refractory period (ERP), ERP dispersion, heart rate variability and plasma norepinephrine levels were measured at baseline, after stimulation and after ablation. Results LSG stimulation combined RAP significantly induced higher AF induction rate, shorter ERP, larger ERP dispersion at all sites examined and higher plasma norepinephrine levels (P<0.05 in all values), compared to baseline. The increased AF induction rate, shortened ERP, increased ERP dispersion and elevated plasma norepinephrine levels can be almost reversed by RSD, compared to the control group (P<0.05). LSG stimulation combined RAP markedly shortened RR-interval and standard deviation of all RR-intervals (SDNN), Low-frequency (LF), high-frequency (HF) and LF/HF ratio (P<0.05). These changes can be reversed by RSD, compared to the control group (P<0.05). Conclusions RSD significantly reduced AF inducibility and reversed the atrial electrophysiological changes induced by hyper-sympathetic activity. PMID:24223140

Oxygen transmittance correction for solar-induced chlorophyll fluorescence measured on proximal sensing: application to the NASA-GSFC fusion tower

USDA-ARS?s Scientific Manuscript database

Since oxygen (O2) absorption of light becomes more pronounced at higher pressure levels, even a few meters distance between the target and the sensor can strongly affect canopy leaving Solar-Induced chlorophyll Fluorescence (SIF) retrievals. This study was conducted to quantify the consequent error ...

A sexually dimorphic hypothalamic response to chronic high-fat diet consumption.

PubMed

Morselli, E; Frank, A P; Palmer, B F; Rodriguez-Navas, C; Criollo, A; Clegg, D J

2016-02-01

In this review, we discuss the observations that, following chronic high-fat diet (HFD) exposure, male mice have higher levels of saturated fatty acids (FAs) and total sphingolipids, whereas lower amounts of polyunsaturated FAs in the central nervous system (CNS) than females. Furthermore, males, when compared with female mice, have higher levels of inflammatory markers in the hypothalamus following exposure to HFD. The increase in markers of inflammation in male mice is possibly due to the reductions in proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and estrogen receptor alpha (ERα), which is not recapitulated in female mice. Consistently, hypothalamic inflammation is induced both in male and female ERα total-body knockout mice when exposed to a HFD, thus confirming the key role of ERα in the regulation of HFD-induced hypothalamic inflammation. Finally, the HFD-induced depletion of hypothalamic ERα is associated with dysregulation in metabolic homeostasis, as evidenced by reductions in glucose tolerance and decrements in myocardial function.

Cell Proliferation, Reactive Oxygen and Cellular Glutathione

PubMed Central

Day, Regina M.; Suzuki, Yuichiro J.

2005-01-01

A variety of cellular activities, including metabolism, growth, and death, are regulated and modulated by the redox status of the environment. A biphasic effect has been demonstrated on cellular proliferation with reactive oxygen species (ROS)—especially hydrogen peroxide and superoxide—in which low levels (usually submicromolar concentrations) induce growth but higher concentrations (usually >10–30 micromolar) induce apoptosis or necrosis. This phenomenon has been demonstrated for primary, immortalized and transformed cell types. However, the mechanism of the proliferative response to low levels of ROS is not well understood. Much of the work examining the signal transduction by ROS, including H2O2, has been performed using doses in the lethal range. Although use of higher ROS doses have allowed the identification of important signal transduction pathways, these pathways may be activated by cells only in association with ROS-induced apoptosis and necrosis, and may not utilize the same pathways activated by lower doses of ROS associated with increased cell growth. Recent data has shown that low levels of exogenous H2O2 up-regulate intracellular glutathione and activate the DNA binding activity toward antioxidant response element. The modulation of the cellular redox environment, through the regulation of cellular glutathione levels, may be a part of the hormetic effect shown by ROS on cell growth. PMID:18648617

Corticosterone profiles in northern cardinals (Cardinalis cardinalis): Do levels vary through life history stages?

PubMed

Duckworth, Benjamin M; Jawor, Jodie M

2018-07-01

As animals move through life history stages, energy requirements for each stage will vary. Both daily and annual variation in the glucocoriticoid hormones (specifically corticosterone, or CORT, in birds) helps provide the variable energy needed through life history stages. In many bird species, CORT is higher in the breeding season when energy demands can be quite high and is often lower in the non-breeding season. Additionally, CORT has a role to play in the response to stressful stimuli and the level to which CORT is elevated following stressful events can vary through the annual cycle as well. Here we report on baseline and stress-induced CORT levels in both sexes of northern cardinals, Cardinalis cardinalis, a non-migrating, year-round territorial species across life history stages. Corticosterone is overall higher in the non-breeding season than the breeding season in both sexes. Males tend to have higher levels of stress-induced CORT than females, although the observed patterns are complex. Our findings differ from one of the more common profile reported in songbirds where breeding season CORT tends to be higher than non-breeding levels. A strong influence may be the prolonged breeding season seen in cardinals; lower levels of CORT during breeding may guard against adverse maternal effects, interruptions in breeding behaviors, or egg production. Additional investigation of species with similar ecologies to northern cardinals, and more populations of cardinals, may show that annual glucocorticoid profiles are more labile than previously appreciated. Copyright © 2018 Elsevier Inc. All rights reserved.

De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

PubMed

Gebert, Dorothea; Auer, Matthias K; Stieg, Mareike R; Freitag, Martin T; Lahne, Madlén; Fuss, Johannes; Schilbach, Katharina; Schopohl, Jochen; Stalla, Günter K; Kopczak, Anna

2018-02-01

Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline oxytocin levels and stimulated OT-responses might have different effects on affective function, which should be considered in future substitution paradigms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Understanding Demonstration-based Training: A Definition, Conceptual Framework, and Some Initial Guidelines

DTIC Science & Technology

2009-11-01

promoting learning by inducing deeper levels of transfer appropriate processing in the observer ( Craik & Lockhart , 1972; Bransford et al., 1977). We...Vicarious learning from dialogue and discourse. Instructional science, 27, 431-458. Craik , F., & Lockhart , R. (1972). Levels of processing : A...attention, retention and production processes are driven by levels of motivation. Higher levels of motivation will lead to more focused attention

The Indirect Effect of UV: Some Good News for Microbes?

NASA Technical Reports Server (NTRS)

Rothschild, Lynn J.; Purcell, Diane; Rogoff, Dana; Wilson, Cindy; Brass, James A. (Technical Monitor)

2002-01-01

Ultraviolet (UV) radiation is of great concern because its biological effects are predominantly harmful. UV damage may be direct or indirect, the latter mediated through the photochemical production of reactive oxygen species such as hydrogen peroxide. We measured the effect of H2O2 on various microbes both in the lab and in nature. At our study site in Yellowstone National Park, there is a UV-induced diurnal fluctuation of H2O2 extending up to one micron. Levels of DNA synthesis resulting from exposure to H2O2 were measured in several algal mats. Within naturally-occurring concentrations of H2O2, DNA synthesis increased. Laboratory studies showed that similar concentrations of H2O2 induce mitosis. We hypothesize that the low levels of H2O2 encountered in nature are inducing mitotic division. At higher levels of H2O2 a second peak in DNA synthesis was found which we interpret to represent DNA damage repair. These experiments suggest that in nature, the low levels of H2O2 produced may have a mitogenic rather than damaging effect. Assuming early levels of UV radiation were substantially higher at the time protists evolved, differential mitogenic effects could have influenced protistan evolution. With H2O2 likely to be present on such bodies as Mars and Europa, the response of organisms will be concentration-dependent and not linear.

Antibiotic tigecycline enhances cisplatin activity against human hepatocellular carcinoma through inducing mitochondrial dysfunction and oxidative damage

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

Tan, Jun; Song, Meijun; Zhou, Mi

Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo. Mechanistically, tigecycline specifically inhibits mitochondrial translation as shown by the decreased protein levels of Cox-1 and -2 but not Cox-4 or Grp78, and increased mRNA levels of Cox-1more » and -2 but not Cox-4 in HCC cells exposed to tigecycline. In addition, tigecycline significantly induces mitochondrial dysfunction in HCC cells via decreasing mitochondrial membrane potential, complex I and IV activities, mitochondrial respiration and ATP levels. Tigecycline also increases levels of mitochondrial superoxide, hydrogen peroxide and ROS levels. Consistent with oxidative stress, oxidative damage on DNA, protein and lipid are also observed in tigecycline-treated cells. Importantly, antioxidant N-acetyl-L-cysteine (NAC) reverses the effects of tigecycline, suggesting that oxidative stress is required for the action of tigecycline in HCC cells. We further show that HCC cells have higher level of mitochondrial biogenesis than normal liver cells which might explain the different sensitivity to tigecycline between HCC and normal liver cells. Our work is the first to demonstrate that tigecycline is a promising candidate for HCC treatment and highlight the therapeutic value of targeting mitochondrial metabolism in HCC. - Highlights: • Tigecycline selectively targets HCC in vitro and in vivo. • Tigecycline enhances HCC cell response to chemotherapeutic drug. • Tigecycline inhibits mitochondrial translation and functions in HCC cells. • Tigecycline induces oxidative stress and damage in HCC cells. • Mitochondrial biogenesis and respiration is higher in HCC than normal liver cells.« less

Effect of peroxisome proliferator-activated receptor alpha activators on tumor necrosis factor expression in mice during endotoxemia.

PubMed

Hill, M R; Clarke, S; Rodgers, K; Thornhill, B; Peters, J M; Gonzalez, F J; Gimble, J M

1999-07-01

Inflammatory mediators orchestrate the host immune and metabolic response to acute bacterial infections and mediate the events leading to septic shock. Tumor necrosis factor (TNF) has long been identified as one of the proximal mediators of endotoxin action. Recent studies have implicated peroxisome proliferator-activated receptor alpha (PPARalpha) as a potential target to modulate regulation of the immune response. Since PPARalpha activators, which are hypolipidemic drugs, are being prescribed for a significant population of older patients, it is important to determine the impact of these drugs on the host response to acute inflammation. Therefore, we examined the role of PPARalpha activators on the regulation of TNF expression in a mouse model of endotoxemia. CD-1 mice treated with dietary fenofibrate or Wy-14,643 had fivefold-higher lipopolysaccharide (LPS)-induced TNF plasma levels than LPS-treated control-fed animals. Higher LPS-induced TNF levels in drug-fed animals were reflected physiologically in significantly lower glucose levels in plasma and a significantly lower 50% lethal dose than those in LPS-treated control-fed animals. Utilizing PPARalpha wild-type (WT) and knockout (KO) mice, we showed that the effect of fenofibrate on LPS-induced TNF expression was indeed mediated by PPARalpha. PPARalpha WT mice fed fenofibrate also had a fivefold increase in LPS-induced TNF levels in plasma compared to control-fed animals. However, LPS-induced TNF levels were significantly decreased and glucose levels in plasma were significantly increased in PPARalpha KO mice fed fenofibrate compared to those in control-fed animals. Data from peritoneal macrophage studies indicate that Wy-14,643 modestly decreased TNF expression in vitro. Similarly, overexpression of PPARalpha in 293T cells decreased activity of a human TNF promoter-luciferase construct. The results from these studies suggest that any anti-inflammatory activity of PPARalpha in vivo can be masked by other systemic effects of PPARalpha activators.

Molecular basis of sodium butyrate-dependent proapoptotic activity in cancer cells.

PubMed

Pajak, B; Orzechowski, A; Gajkowska, B

2007-01-01

This review outlines the molecular events that accompany the antitumor action of sodium butyrate (NaBt). Butyrate, a low-molecular weight four-carbon chain volatile fatty acid (VFA) has been previously shown to withdraw cells from cell cycle or to promote cell differentiation, and finally to induce programmed cell death. Recent advances in molecular biology indicate, that this product of large bowel microbial fermentation of dietary fiber, might evoke the above-mentioned effects by indirect action on genes. NaBt was shown to inhibit histone deacetylase activity, allowing DNA binding of several transcription factors. Higher genomic activity leads to the higher expression of proapoptotic genes, higher level of their protein products and elevated sensitivity to death ligand-induced apoptosis. Cancer cells might be arrested in G1 phase of cell cycle in a p21-dependent manner. Proapoptotic activity of NaBt includes higher expression of membrane death receptors (DR4/5), higher level and activation of Smad3 protein in TGF-beta-dependent apoptotic pathway, lower level of antiapoptotic proteins (cFLIP, XIAP) and activation ofproapoptotic tBid protein. Thus, both intrinsic and extrinsic apoptotic pathways are stimulated to ampify the apoptotic signals. These effects are specific for tumor but not for regular cells. Unique properties of NaBt make this agent a promising metabolic inhibitor to retard tumorigenesis to suppress tumor growth.

Dietary fructose augments ethanol-induced liver pathology.

PubMed

Thomes, Paul G; Benbow, Jennifer H; Brandon-Warner, Elizabeth; Thompson, Kyle J; Jacobs, Carl; Donohue, Terrence M; Schrum, Laura W

2017-05-01

Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

PubMed

Sowjanya, A Pavani; Rao, Meera; Vedantham, Haripriya; Kalpana, Basany; Poli, Usha Rani; Marks, Morgan A; Sujatha, M

2016-01-30

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer. Copyright © 2015. Published by Elsevier Inc.

Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats

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

Pal, Subhashis; Khan, Kainat; China, Shyamsundar Pal

The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks)more » bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH){sub 2} vitamin D{sub 3} (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. - Highlights: • Theophylline induced osteoblast apoptosis by cAMP-induced ROS generation. • Theophylline levels in bone marrow were much higher than blood. • Theophylline diminished bone regeneration at the fracture site and caused osteopenia. • Theophylline caused hypo-vitaminosis D, and altered calciotropic hormones. • Vitamin D treatment prevented theophylline-induced changes in bone metabolism.« less

Permethrin Induces Overexpression of Cytochrome c Oxidase Subunit 3 in Aedes aegypti

USDA-ARS?s Scientific Manuscript database

Using quantitative PCR (QPCR), the relative transcriptional levels of cytochrome c oxidase subunit 3 (CO3) were studied in Aedes aegypti (L.) in response to treatments with acetone, permethrin, or fipronil. The transcriptional levels of CO3 were significantly (p <0.05) higher in acetone-treated Ae. ...

Effects of hyperthyroidism induced by L-thyroxin administration on lipid peroxidation in various rat tissues.

PubMed

Mogulkoc, R; Baltaci, A Kasim; Oztekin, Esma; Sivrikaya, A; Aydin, Leyla

2006-06-01

Thyroid dysfunctions are associated with many pathological signs in the body. One of these is lipid peroxidation that develops due to over- or under-secretion of thyroid hormones. The present study was conducted to determine lipid peroxidation that develops in different tissues including the brain, liver and heart of rats in experimental hyperthyroidism induced by L-thyroxin. The study was carried out on 30 male Sprague-Dawley rats. They were divided into three groups as control, sham hyperthyroidism and hyperthyroidism. Malondialdehyde (MDA) and glutathione (GSH) levels in rat tissues were determined at the end of a 3-weeks period of L-thyroxin administration. It was observed that MDA levels in the hyperthyroidism group were significantly higher in the cerebral cortex, liver and ventriculer tissue of heart (p < 0.001) than in the control and in sham hyperthyroidism groups. GSH levels were higher in the hyperthyroidism group than in control and sham hyperthyroidism groups in all tissues (p < 0.001). Results demonstrate that hyperthyroidism induced by L-thyroxin activates both oxidant and antioxidant systems in cerebral, hepatic and cardiac tissues. However, the increase in antioxidant activity cannot adequately prevent oxidative damage.

Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3-nitropropionic acid-induced oxidative stress and neurotoxicity in rats: behavioural and biochemical evidence.

PubMed

K M, Denny Joseph; Muralidhara

2014-04-01

The beneficial effects of fish oil (FO) supplements on the central nervous system have been adequately demonstrated. However, FO supplementation at higher doses for longer duration is likely to cause oxidative stress in vivo. To overcome this, attempts have been made to enrich FO with known antioxidants/phytochemicals. In the present study, we examined the hypothesis that a combination of FO with ferulic acid (FA), a naturally occurring phenolic compound, is likely to provide higher degree of neuroprotection. This was examined by employing 3-nitropropionic acid (NPA), a well-known neurotoxin used to mimic behavioural and neurochemical features of Huntington's disease. Growing male rats administered with NPA (25 mg/kg of body weight (bw) for 4 days) were provided with either FO (2 mL/kg bw), FA (50 mg/kg bw) or FO+FA for 2 weeks. Interestingly, FO+FA not only offered significant protection against NPA-induced behavioural impairments, but also markedly attenuated oxidative stress in brain regions (striatum/cerebellum) as evidenced by the reduction in reactive species, malondialdehyde, hydroperoxides and nitric oxide (NO) levels. Further, FO+FA combination restored the activities of various antioxidant enzymes and the levels of cytosolic calcium. In striatum, activity levels of acetylcholinesterase enzyme and dopamine levels were markedly restored among FO+FA rats. Interestingly, NPA-induced mitochondrial dysfunctions were also attenuated among FO+FA rats. Collectively, our findings suggest the advantage of co-treatment of FO with known antioxidants to achieve a higher therapeutic benefit in the treatment of oxidative stress-mediated neurodegenerative conditions.

Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner

PubMed Central

Peter, Mirjam E.; Sevinc Ok, Ebru; Celenk, Fatma Gul; Yilmaz, Mumtaz; Steppan, Sonja; Asci, Gulay; Ok, Ercan; Passlick-Deetjen, Jutta

2012-01-01

Background. Vascular calcification (VC), mainly due to elevated phosphate levels, is one major problem in patients suffering from chronic kidney disease. In clinical studies, an inverse relationship between serum magnesium and VC has been reported. However, there is only few information about the influence of magnesium on calcification on a cellular level available. Therefore, we investigated the effect of magnesium on calcification induced by β-glycerophosphate (BGP) in bovine vascular smooth muscle cells (BVSMCs). Methods. BVSMCs were incubated with calcification media for 14 days while simultaneously increasing the magnesium concentration. Calcium deposition, transdifferentiation of cells and apoptosis were measured applying quantification of calcium, von Kossa and Alizarin red staining, real-time reverse transcription–polymerase chain reaction and annexin V staining, respectively. Results. Calcium deposition in the cells dramatically increased with addition of BGP and could be mostly prevented by co-incubation with magnesium. Higher magnesium levels led to inhibition of BGP-induced alkaline phosphatase activity as well as to a decreased expression of genes associated with the process of transdifferentiation of BVSMCs into osteoblast-like cells. Furthermore, estimated calcium entry into the cells decreased with increasing magnesium concentrations in the media. In addition, higher magnesium concentrations prevented cell damage (apoptosis) induced by BGP as well as progression of already established calcification. Conclusions. Higher magnesium levels prevented BVSMC calcification, inhibited expression of osteogenic proteins, apoptosis and further progression of already established calcification. Thus, magnesium is influencing molecular processes associated with VC and may have the potential to play a role for VC also in clinical situations. PMID:21750166

The predictive value of drug-induced sleep endoscopy for CPAP titration in OSA patients.

PubMed

Lan, Ming-Chin; Hsu, Yen-Bin; Lan, Ming-Ying; Huang, Yun-Chen; Kao, Ming-Chang; Huang, Tung-Tsun; Chiu, Tsan-Jen; Yang, Mei-Chen

2017-12-15

The aim of this study was to identify possible upper airway obstructions causing a higher continuous positive airway pressure (CPAP) titration level, utilizing drug-induced sleep endoscopy (DISE). A total of 76 patients with obstructive sleep apnea (OSA) underwent CPAP titration and DISE. DISE findings were recorded using the VOTE classification system. Polysomnographic (PSG) data, anthropometric variables, and patterns of airway collapse during DISE were analyzed with CPAP titration levels. A significant association was found between the CPAP titration level and BMI, oxygen desaturation index (ODI), apnea-hypopnea index (AHI), and neck circumference (NC) (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively, by Spearman correlation). Patients with concentric collapse of the velum or lateral oropharyngeal collapse were associated with a significantly higher CPAP titration level (P < 0.001 and P = 0.043, respectively, by nonparametric Mann-Whitney U test; P < 0.001 and P = 0.004, respectively, by Spearman correlation). No significant association was found between the CPAP titration level and any other collapse at the tongue base or epiglottis. By analyzing PSG data, anthropometric variables, and DISE results with CPAP titration levels, we can better understand possible mechanisms resulting in a higher CPAP titration level. We believe that the role of DISE can be expanded as a tool to identify the possible anatomical structures that may be corrected by oral appliance therapy or surgical intervention to improve CPAP compliance.

Comparison of tissue deterioration of ripening banana fruit (Musa spp., AAA group, Cavendish subgroup) under chilling and non-chilling temperatures.

PubMed

Ramírez-Sánchez, Maricruz; Huber, Donald J; Vallejos, Carlos E

2018-03-08

In fleshy fruits, induced programmed cell death (PCD) has been observed in heat-treated tomato, and in ethylene-treated and low-temperature exposure in immature cucumber. No other fleshy fruit has been evaluated for chilling-injury-induced PCD, especially mature fruit with full ripening capacity. The purpose of this research was to identify and evaluate the presence of PCD processes during the development of low-temperature-induced physiopathy of banana fruit. Exposure of fruit to 5 °C for 4 days induced degradative processes similar to those occurring during ripening and overripening of non-chilled fruit. Nuclease from banana peel showed activity in both DNA substrates and RNA substrates. No exclusive low-temperature-induced proteases and nucleases were observed. DNA of chilled peel showed earlier signs of degradation and higher levels of DNA tailing during overripening. This study shows that exposure to low temperatures did not induce a pattern of degradative processes that differed from that occurring during ripening and overripening of non-chilled fruit. DNA showed earlier signs of degradation and higher levels of DNA tailing. Nuclease activity analysis showed bifunctionality in both chilled and non-chilled tissue and no chilling-exclusive protease and nuclease. Fleshy fruit might use their available resources on degradative processes and adjust them depending on environmental conditions. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

[Comparative analysis on the biological basis of blood stasis syndrome induced by qi-stagnation and qi-deficiency in patients with unstable angina pectoris].

PubMed

Ren, Jian-xun; Liu, Jian-xun; Lin, Cheng-ren

2010-04-01

To comparatively analyse the objective characteristics of different syndrome types of qi-disturbance-induced blood stasis syndrome (QDBS) in the pathogenetic evolution of unstable angina coronary heart disease (UA-CHD). Seventy-eight patients with UA-CHD of QDBS were differentiated into 2 groups: 55 in the qi-deficiency-induced blood-stasis syndrome group (A) and 23 in the qi-stagnation-induced blood-stasis syndrome group (B). The comparative analysis on them was carried out through comparing their blood pressure, glucose and lipid metabolisms, coagulation function, thyroid function and inflammation reaction changes, etc. In the pathogenetic process of qi-disturbance induced blood stasis, the initiating age, levels of HbA1c, TSH, PT and APTT between the two groups were significantly different (P < 0.05). Levels of TNF-alpha and LN were higher and levels of sIgA lower in patients than those in healthy subjects (P < 0.05). Inflammation immune reaction may play an important role in the pathogenetic process of blood-stasis syndrome, and the functional disturbance of hypothalamus, pituitary and endocrinal secretion induced by emotional stress is possibly the essence of qi-stagnation induced blood stasis syndrome.

Induction of Resistance Mediated by an Attenuated Strain of Valsa mali var. mali Using Pathogen-Apple Callus Interaction System

PubMed Central

Zhang, Qingming; Wang, Caixia; Yong, Daojing; Li, Guifang; Dong, Xiangli; Li, Baohua

2014-01-01

To study the induced resistance in apple against Valsa mali var. mali (Vmm), a Vmm–apple callus interaction system was developed to evaluate the induced resistance of an attenuated Vmm strain LXS081501 against further infection by a virulent Vmm strain LXS080601. The infection index was up to 97.32 for apple calli inoculated with LXS080601 alone at 15 days after inoculation whereas it was only 41.84 for calli pretreated with LXS081501 followed by LXS080601 inoculation. In addition, the maximum levels of free proline, soluble sugar, and protein in calli treated with LXS081501 plus LXS080601 were 2.14 to 3.47 times higher than controls and 1.42 to 1.75 times higher than LXS080601 treatment. The activities of defense-related enzymes such as phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD), and catalase (CAT) as well as β-1,3-glucanase and chitinase in apple calli inoculated with LXS080601 alone or LXS081501 plus LXS080601 increased significantly 24 hai and peaked from 48 to 120 hpi. However, in the latter treatment, the maximum enzyme activities were much higher and the activities always maintained much higher levels than control during the experimental period. These results suggested the roles of osmotic adjustment substances and defense-related enzymes in induced resistance. PMID:25054166

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

PubMed

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

2016-02-01

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

5-hydroxytryptamine level and 5-HT2A receptor mRNA expression in the guinea pigs eyes with spectacle lens-induced myopia

PubMed Central

Yang, Ji-Wen; Xu, Yan-Chun; Sun, Lin; Tian, Xiao-Dan

2010-01-01

AIM To investigate 5-hydroxytryptamine (5-HT) function and 5-HT receptor 2A (5-HT2A) mRNA expression in the formation of lens-induced myopia (LIM). METHODS Lens-induced myopia construction method was applied to generate myopia on guinea pig right eye (LIM eye). RESULTS LIM eyes formed significant myopia with longer axial length. 5-HT level in retina, choroids and sclera from LIM eyes was significantly higher than that in control group. 5-HT2A mRNA expression was also significantly up-regulated. CONCLUSION Refraction lens could induce myopia in guinea pig and 5-HT may play an important role in the formation of myopia by binding with 5-HT2A receptor. PMID:22553578

Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke.

PubMed

Mao, Jenny T; Tashkin, Donald P; Tsu, I-Hsien; Serio, Kenneth J

2008-09-01

Leukotrienes have been implicated to play a prominent inductive role in carcinogenesis. We previously reported that bronchoalveolar lavage (BAL) cells from smokers manifested higher levels of leukotriene B4 (LTB4) production than ex-smokers. This study aims to elucidate the underlying mechanism(s). BAL cells from current and former smokers were exposed to lipopolysaccharide (LPS) for up to 7 days. LPS induced the release of LTB4 from BAL cells and down-regulated 5-lipoxygenase (5-LOX) mRNA expression in a dose-dependent manner, followed by a decrease in 5-LOX protein production and normalization of LTB4 levels. Exogenous LTB4 inhibited LPS-induced 5-LOX activity and accentuated the down-regulation of 5-LOX mRNA, whereas suppression of 5-LOX abrogated the LPS-induced changes, suggesting a negative feedback mechanism. LPS concomitantly induced expression and activity of the LTB4 metabolizing enzyme LTB4 omega-hydroxylase (LTB4OH) in ex-smokers' BAL cells, but not in smokers' BAL cells. In vitro smoke exposure of ex-smokers' BAL cells also abrogated the LPS-induced up-regulation of LTB4OH mRNA expression. Furthermore, ex-smokers' BAL cells expressed significantly higher LTB4OH mRNA levels than smokers' BAL cells. Such differential modulation of LTB4 synthesis and degradation by LPS in the setting of tobacco smoke exposure suggests that mechanisms responsible for sustained elevation of LTB4 levels in the lung microenvironment may contribute to the pathogenesis of tobacco-related respiratory diseases such as lung cancer. By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PubMed Central

2017-01-01

Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

Exogenous Methyl Jasmonate and Salicylic Acid Induce Subspecies-Specific Patterns of Glucosinolate Accumulation and Gene Expression in Brassica oleracea L.

PubMed

Yi, Go-Eun; Robin, Arif Hasan Khan; Yang, Kiwoung; Park, Jong-In; Hwang, Byung Ho; Nou, Ill-Sup

2016-10-24

Glucosinolates have anti-carcinogenic properties. In the recent decades, the genetics of glucosinolate biosynthesis has been widely studied, however, the expression of specific genes involved in glucosinolate biosynthesis under exogenous phytohormone treatment has not been explored at the subspecies level in Brassica oleracea . Such data are vital for strategies aimed at selective exploitation of glucosinolate profiles. This study quantified the expression of 38 glucosinolate biosynthesis-related genes in three B. oleracea subspecies, namely cabbage, broccoli and kale, and catalogued associations between gene expression and increased contents of individual glucosinolates under methyl jasmonate (MeJA) and salicylic acid (SA) treatments. Glucosinolate accumulation and gene expression in response to phytohormone elicitation was subspecies specific. For instance, cabbage leaves showed enhanced accumulation of the aliphatic glucoiberin, progoitrin, sinigrin and indolic neoglucobrassicin under both MeJA and SA treatment. MeJA treatment induced strikingly higher accumulation of glucobrassicin (GBS) in cabbage and kale and of neoglucobrassicin (NGBS) in broccoli compared to controls. Notably higher expression of ST5a (Bol026200), CYP81F1 (Bol028913, Bol028914) and CYP81F4 genes was associated with significantly higher GBS accumulation under MeJA treatment compared to controls in all three subspecies. CYP81F4 genes, trans-activated by MYB34 genes, were expressed at remarkably high levels in all three subspecies under MeJA treatment, which also induced in higher indolic NGBS accumulation in all three subspecies. Remarkably higher expression of MYB28 (Bol036286), ST5b , ST5c , AOP2 , FMOGS-OX5 (Bol031350) and GSL-OH (Bol033373) was associated with much higher contents of aliphatic glucosinolates in kale leaves compared to the other two subspecies. The genes expressed highly could be utilized in strategies to selectively increase glucosinolate compounds in B. oleracea subspecies. These results promote efforts to develop genotypes of B. oleracea and other species with enhanced levels of desired glucosinolates.

Cocaine effects on pulsatile secretion of anterior pituitary, gonadal, and adrenal hormones.

PubMed

Mendelson, J H; Mello, N K; Teoh, S K; Ellingboe, J; Cochin, J

1989-12-01

Pulse frequency analysis of LH, PRL, testosterone, and cortisol was carried out with the Cluster Analysis Program in eight male cocaine abusers and eight aged-matched normal men. Four of the eight cocaine abusers had hyperprolactinemia (range, 22.08-44.65 micrograms/L). Cocaine users as a group had significantly higher mean peak height (P less than 0.02) than control subjects. Cocaine users with hyperprolactinemia had higher mean peak height than control subjects or cocaine users with normal PRL levels (P less than 0.01). Cocaine users with hyperprolactinemia also had higher mean amplitude increments than control subjects (P less than 0.02). Cocaine users with hyperprolactinemia had a higher mean valley than controls (P less than 0.01) and cocaine users with normal PRL levels (P less than 0.03). However, there were no significant differences in PRL peak frequency, peak duration, or interpulse intervals between cocaine users with or without hyperprolactinemia and control subjects. There were minimal differences between cocaine users and control subjects in pulse frequency analysis of LH parameters; the small differences in mean LH levels and average interpulse interval were not in the abnormal range and were probably not biologically significant. No differences between cocaine users and controls were detected for pulse frequency analysis of testosterone or cortisol. Cocaine-induced hyperprolactinemia may contribute to disorders of sexual and reproductive function in men who abuse the drug, and recent reports that PRL modulates immune function suggest that cocaine-induced derangements of PRL secretion may also contribute to cocaine-related comorbidity in infectious disease. Since cocaine users with hyperprolactinemia had a higher mean valley as well as a higher peak pulse PRL height than control subjects, but did not have greater PRL pulse frequencies, we conclude that hyperprolactinemia in these men may be due to a cocaine-induced derangement of dopaminergic inhibition of basal PRL secretion.

Salt stress-induced transcription of σB- and CtsR-regulated genes in persistent and non-persistent Listeria monocytogenes strains from food processing plants.

PubMed

Ringus, Daina L; Ivy, Reid A; Wiedmann, Martin; Boor, Kathryn J

2012-03-01

Listeria monocytogenes is a foodborne pathogen that can persist in food processing environments. Six persistent and six non-persistent strains from fish processing plants and one persistent strain from a meat plant were selected to determine if expression of genes in the regulons of two stress response regulators, σ(B) and CtsR, under salt stress conditions is associated with the ability of L. monocytogenes to persist in food processing environments. Subtype data were also used to categorize the strains into genetic lineages I or II. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to measure transcript levels for two σ(B)-regulated genes, inlA and gadD3, and two CtsR-regulated genes, lmo1138 and clpB, before and after (t=10 min) salt shock (i.e., exposure of exponential phase cells to BHI+6% NaCl for 10 min at 37°C). Exposure to salt stress induced higher transcript levels relative to levels under non-stress conditions for all four stress and virulence genes across all wildtype strains tested. Analysis of variance (ANOVA) of induction data revealed that transcript levels for one gene (clpB) were induced at significantly higher levels in non-persistent strains compared to persistent strains (p=0.020; two-way ANOVA). Significantly higher transcript levels of gadD3 (p=0.024; two-way ANOVA) and clpB (p=0.053; two-way ANOVA) were observed after salt shock in lineage I strains compared to lineage II strains. No clear association between stress gene transcript levels and persistence was detected. Our data are consistent with an emerging model that proposes that establishment of L. monocytogenes persistence in a specific environment occurs as a random, stochastic event, rather than as a consequence of specific bacterial strain characteristics.

Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children.

PubMed

Contreras, J Paola; Ly, Ngoc P; Gold, Diane R; He, Hongzhen; Wand, Mathew; Weiss, Scott T; Perkins, David L; Platts-Mills, Thomas A E; Finn, Patricia W

2003-12-01

The early childhood allergen-induced immune responses associated with atopic disease and IgE production in early life are not well understood. We assessed the relationship of allergen-induced cytokine production by PBMCs to both atopic disease and to IgE increase in a cohort of children with a parental history of allergy or asthma (n = 112) at a median of 2 years of age. We examined cockroach (Bla g 1)-induced, house dust mite (Der f 1)-induced, and cat (Fel d 1)-induced cytokine secretion, including secretion of IFN-gamma, IL-13, IL-10, and TNF-alpha. We investigated whether distinct cytokine patterns associated with atopic disease can be detected in immune responses of children. PBMCs were isolated, and allergen-induced cytokine secretion was analyzed by means of ELISA. Atopic disease was defined as physician- or nurse-diagnosed eczema or hay fever. Increased IgE was defined as an IgE level of greater than 35 U/mL to dust mite, cockroach, cat, and egg white or a total IgE level of 60 U/mL or greater. Compared with children without atopic disease, children with atopic disease had lower Der f 1 (P =.005) and Bla g 2 (P =.03) allergen-induced IFN-gamma levels. Compared with children without increased IgE (n = 95), those with increased IgE (n = 16) had higher Der f 1-induced (P =.006) and Fel d 1-induced (P =.005) IL-13 levels and lower Bla g 2-induced (P =.03) IFN-gamma levels. Compared with children with neither atopic disease nor repeated wheeze, children with both atopic disease and repeated wheeze had lower levels of allergen-induced IFN-gamma (P =.01 for Der f 1 and P =.02 for Bla g 2) cytokine secretion. In young children at risk for asthma or allergy, decreased allergen-induced IFN-gamma secretion is associated with atopic disease and, in some cases, with increased IgE levels. Increased allergen-induced IL-13 secretion is most strongly associated with early life increase of IgE.

Structural recovery of the retina in a retinoschisin-deficient mouse after gene replacement therapy by solid lipid nanoparticles.

PubMed

Apaolaza, P S; Del Pozo-Rodríguez, A; Solinís, M A; Rodríguez, J M; Friedrich, U; Torrecilla, J; Weber, B H F; Rodríguez-Gascón, A

2016-06-01

X-linked juvenile retinoschisis (XLRS) is a retinal degenerative disorder caused by mutations in the RS1 gene encoding a protein termed retinoschisin. The disease is an excellent candidate for gene replacement therapy as the majority of mutations have been shown to lead to a complete deficiency of the secreted protein in the retinal structures. In this work, we have studied the ability of non-viral vectors based on solid lipid nanoparticles (SLN) to induce the expression of retinoschisin in photoreceptors (PR) after intravitreal administration to Rs1h-deficient mice. We designed two vectors prepared with SLN, protamine, and dextran (DX) or hyaluronic acid (HA), bearing a plasmid containing the human RS1 gene under the control of the murin opsin promoter (mOPS). In vitro, the nanocarriers were able to induce the expression of retinoschisin in a PR cell line. After injection into the murine vitreous, the formulation prepared with HA induced a higher transfection level in PR than the formulation prepared with DX. Moreover, the level of retinoschisin in the inner nuclear layer (INL), where bipolar cells are located, was also higher. Two weeks after vitreal administration into Rs1h-deficient mice, both formulations showed significant improvement of the retinal structure by inducing a decrease of cavities and PR loss, and an increase of retinal and outer nuclear layer (ONL) thickness. HA-SLN resulted in a significant higher increase in the thickness of both retina and ONL, which can be explained by the higher transfection level of PR. In conclusion, we have shown the structural improvement of the retina of Rs1h-deficient mice with PR specific expression of the RS1 gene driven by the specific promoter mOPS, after successful delivery via SLN-based non-viral vectors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cordyceps sinensis increases hypoxia tolerance by inducing heme oxygenase-1 and metallothionein via Nrf2 activation in human lung epithelial cells.

PubMed

Singh, Mrinalini; Tulsawani, Rajkumar; Koganti, Praveen; Chauhan, Amitabh; Manickam, Manimaran; Misra, Kshipra

2013-01-01

Cordyceps sinensis, an edible mushroom growing in Himalayan regions, is widely recognized in traditional system of medicine. In the present study, we report the efficacy of Cordyceps sinensis in facilitating tolerance to hypoxia using A549 cell line as a model system. Treatment with aqueous extract of Cordyceps sinensis appreciably attenuated hypoxia induced ROS generation, oxidation of lipids and proteins and maintained antioxidant status similar to that of controls via induction of antioxidant gene HO1 (heme oxygenase-1), MT (metallothionein) and Nrf2 (nuclear factor erythroid-derived 2-like 2). In contrast, lower level of NF κ B (nuclear factor kappaB) and tumor necrosis factor- α observed which might be due to higher levels of HO1, MT and transforming growth factor- β . Further, increase in HIF1 (hypoxia inducible factor-1) and its regulated genes; erythropoietin, vascular endothelial growth factor, and glucose transporter-1 was observed. Interestingly, Cordyceps sinensis treatment under normoxia did not regulate the expression HIF1, NF κ B and their regulated genes evidencing that Cordyceps sinensis per se did not have an effect on these transcription factors. Overall, Cordyceps sinensis treatment inhibited hypoxia induced oxidative stress by maintaining higher cellular Nrf2, HIF1 and lowering NF κ B levels. These findings provide a basis for possible use of Cordyceps sinensis in tolerating hypoxia.

Cordyceps sinensis Increases Hypoxia Tolerance by Inducing Heme Oxygenase-1 and Metallothionein via Nrf2 Activation in Human Lung Epithelial Cells

PubMed Central

Manickam, Manimaran; Misra, Kshipra

2013-01-01

Cordyceps sinensis, an edible mushroom growing in Himalayan regions, is widely recognized in traditional system of medicine. In the present study, we report the efficacy of Cordyceps sinensis in facilitating tolerance to hypoxia using A549 cell line as a model system. Treatment with aqueous extract of Cordyceps sinensis appreciably attenuated hypoxia induced ROS generation, oxidation of lipids and proteins and maintained antioxidant status similar to that of controls via induction of antioxidant gene HO1 (heme oxygenase-1), MT (metallothionein) and Nrf2 (nuclear factor erythroid-derived 2-like 2). In contrast, lower level of NFκB (nuclear factor kappaB) and tumor necrosis factor-α observed which might be due to higher levels of HO1, MT and transforming growth factor-β. Further, increase in HIF1 (hypoxia inducible factor-1) and its regulated genes; erythropoietin, vascular endothelial growth factor, and glucose transporter-1 was observed. Interestingly, Cordyceps sinensis treatment under normoxia did not regulate the expression HIF1, NFκB and their regulated genes evidencing that Cordyceps sinensis per se did not have an effect on these transcription factors. Overall, Cordyceps sinensis treatment inhibited hypoxia induced oxidative stress by maintaining higher cellular Nrf2, HIF1 and lowering NFκB levels. These findings provide a basis for possible use of Cordyceps sinensis in tolerating hypoxia. PMID:24063008

Early-developmental stress, repeatability, and canalization in a suite of physiological and behavioral traits in female zebra finches.

PubMed

Careau, Vincent; Buttemer, William A; Buchanan, Katherine L

2014-10-01

Adaptive developmental plasticity allows individuals experiencing poor environmental conditions in early life to adjust their life-history strategy in order to prioritize short-term fitness benefits and maximize reproductive output in challenging environments. Much research has been conducted to test whether such adoption of a "faster" life-history strategy is accompanied by concordant changes in behavior and physiology, with mixed results. As research in this field has focused on comparison of mean-level responses of treatment groups, few studies include repeated measures of response variables and the effect that developmental stress may have on repeatability per se. We investigated how early-developmental stress affects the mean expression of (and repeatability in) a variety of behavioral and physiological traits in female zebra finches. We predicted that: (1) individuals subjected to nutritional restriction in the nestling phase would have higher feeding and activity rates, with associated increases in hematocrit and basal metabolic rates (BMRs), (2) nutritional restriction in early life would alter adults' stress-induced corticosterone level, and (3) developmental stress would, respectively, influence the amount of among-individual and within-individual variation in behavioral and physiological traits, hence affecting the repeatability of these traits. In comparison to control females, stressed females did not differ in activity rate or stress-induced corticosterone level, but they did have higher levels of feeding, hematocrit, and BMR. Among-individual variance and repeatability were generally higher in stressed females than in controls. Finally, we found that developmental dietary restriction significantly reduced the amount of within-individual variance both in activity rate in the novel environment and in stress-induced corticosterone level. Our results not only confirm previous findings on the effect of early-developmental stress on BMR, but also extend its effect to feeding rate and hematocrit, suggesting that developmental plasticity in these traits is ontogenetically linked. Early-developmental stress may disable particular genetic canalizing processes, which would release cryptic genetic variation and explain why repeatability and among-individual variance were generally higher in the stressed groups than in controls. For activity rate in the novel environment and with stress-induced corticosterone level, however, early-developmental stress significantly reduced within-individual variance, which may be a consequence of increased canalization of these traits at the micro-environmental level. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Oleic acid-induced ANGPTL4 enhances head and neck squamous cell carcinoma anoikis resistance and metastasis via up-regulation of fibronectin.

PubMed

Shen, Chih-Jie; Chan, Shih-Hung; Lee, Chung-Ta; Huang, Wan-Chen; Tsai, Jhih-Peng; Chen, Ben-Kuen

2017-02-01

Obese patients have higher levels of free fatty acids (FFAs) in their plasma and a higher risk of cancer than their non-obese counterparts. However, the mechanisms involved in the regulation of cancer metastasis by FFAs remain unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4 (ANGPTL4) protein expression and secretion and conferred anoikis resistance to head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA-induced ANGPTL4 further promoted HNSCC migration and invasion. In addition, the expression of peroxisome proliferator-activated receptor (PPAR) was essential for the OA-induced ANGPTL4 expression and invasion. The levels of OA-induced epithelial-mesenchymal transition markers, such as vimentin, MMP-9, and fibronectin and its downstream effectors Rac1/Cdc42, were significantly reduced in ANGPTL4-depleted cells. Knocking down fibronectin inhibited the expression of MMP-9 and repressed OA- and recombinant ANGPTL4-induced HNSCC invasion. On the other hand, ANGPTL4 siRNA inhibited OA-induced MMP-9 expression, which was reversed in fibronectin-overexpressing cells. Furthermore, the depletion of ANGPTL4 impeded the OA-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that OA enhances HNSCC metastasis through the ANGPTL4/fibronectin/Rac1/Cdc42 and ANGPTL4/fibronectin/MMP-9 signaling axes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of amino acid infusion on anesthesia-induced hypothermia in muscle atrophy model rats.

PubMed

Kanazawa, Masahiro; Ando, Satoko; Tsuda, Michio; Suzuki, Toshiyasu

2010-01-01

An infusion of amino acids stimulates heat production in skeletal muscle and then attenuates the anesthesia-induced hypothermia. However, in a clinical setting, some patients have atrophic skeletal muscle caused by various factors. The present study was therefore conducted to investigate the effect of amino acids on the anesthesia-induced hypothermia in the state of muscle atrophy. As the muscle atrophy model, Sprague-Dawley rats were subjected to hindlimb immobilization for 2 wk. Normal rats and atrophy model rats were randomly assigned to one of the two treatment groups: saline or amino acids (n=8 for each group). Test solutions were administered intravenously to the rats under sevoflurane anesthesia for 180 min, and the rectal temperature was measured. Plasma samples were collected for measurement of insulin, blood glucose, and free amino acids. The rectal temperature was significantly higher in the normal-amino acid group than in the muscle atrophy-amino acid group from 75 to 180 min. The plasma insulin level was significantly higher in the rats given amino acids than in the rats given saline in both normal and model groups. In the rats given amino acids, plasma total free amino acid concentration was higher in the model group than in the normal group. These results indicate that skeletal muscle plays an important role in changes in body temperature during anesthesia and the effect of amino acids on anesthesia-induced hypothermia decreases in the muscle atrophy state. In addition, intravenous amino acids administration during anesthesia induces an increase in the plasma insulin level.

Protective effects of radon inhalation on carrageenan-induced inflammatory paw edema in mice.

PubMed

Kataoka, Takahiro; Teraoka, Junichi; Sakoda, Akihiro; Nishiyama, Yuichi; Yamato, Keiko; Monden, Mayuko; Ishimori, Yuu; Nomura, Takaharu; Taguchi, Takehito; Yamaoka, Kiyonori

2012-04-01

We assessed whether radon inhalation inhibited carrageenan-induced inflammation in mice. Carrageenan (1% v/v) was injected subcutaneously into paws of mice that had or had not inhaled approximately 2,000 Bq/m(3) of radon for 24 h. Radon inhalation significantly increased superoxide dismutase (SOD) and catalase activities and significantly decreased lipid peroxide levels in mouse paws, indicating that radon inhalation activates antioxidative functions. Carrageenan administration induced paw edema and significantly increased tumor necrosis factor-alpha (TNF-α) and nitric oxide in serum. However, radon inhalation significantly reduced carrageenan-induced paw edema. Serum TNF-α levels were lower in the radon-treated mice than in sham-treated mice. In addition, SOD and catalase activities in paws were significantly higher in the radon-treated mice than in the sham-treated mice. These findings indicated that radon inhalation had anti-inflammatory effects and inhibited carrageenan-induced inflammatory paw edema.

SOCIOECONOMIC VARIATIONS IN INDUCED ABORTION IN TURKEY.

PubMed

Ankara, Hasan Giray

2017-01-01

This study aimed to identify the levels of, and socioeconomic variations in, income-related inequality in induced abortion among Turkish women. The study included 15,480 ever-married women of reproductive age (15-49) from the 2003 and 2008 waves of the Turkish Demographic and Health Survey. The measured inequalities in abortion levels and their changes over time were decomposed into the percentage contributions of selected socioeconomic factors using ordinary least square analysis and concentration indices were calculated. The inequalities and their first difference (difference in inequalities between 2003 and 2008) were decomposed using the approaches of Wagstaff et al. (2003). Higher socioeconomic characteristics (such as higher levels of wealth and education and better neighbourhood) were found to be associated with higher rates of abortion. Inequality analyses indicated that although deprived women become more familiar with abortion over time, abortion was still more concentrated among affluent women in the 2008 survey. The decomposition analyses suggested that wealth, age, education and level of regional development were the most important contributors to income-related inequality in abortion. Therefore policies that (i) increase the level of wealth and education of deprived women, (ii) develop deprived regions of Turkey, (iii) improve knowledge about family planning and, especially (iv) enhance the accessibility of family planning services for deprived and/or rural women, may be beneficial for reducing socioeconomic variations in abortion in the country.

The possible protective effect of L-carnitine on tilmicosin-induced cardiotoxicity in mice.

PubMed

Kart, A; Yapar, K; Karapehlivan, M; Citil, M

2007-04-01

The protective effect of L-carnitine was investigated against tilmicosin-induced cardiotoxic effects including blood creatine kinase (CK), CK-MB, total sialic acid as well as the alterations in glutathione and malondialdehyde concentrations in mice. Thirty-two Balb/C mice were divided into four groups including group 1 (control), group 2 (L-carnitine, s.c., 500 mg/kg for 5 days), group 3 (tilmicosin, s.c., single dose of 75 mg/kg) and group 4 (L-carnitine plus tilmicosin). Serum CK, CK-MB and malondialdehyde (MDA) levels were significantly (P < 0.05) higher in group 3 compared with those of other groups. Total sialic acid level in group 3 was found to be significantly (P < 0.05) higher than that in groups 1 and 2, as well. Contrary to these results, glutathione level in group 3 was found to be significantly (P < 0.05) lower than that in groups 1 and 2. In group 4, serum CK, CK-MB, MDA and total sialic acid levels were found to be significantly (P < 0.05) lower than those in group 3. These results suggest that tilmicosin is cardiotoxic in mice as evidenced by higher total sialic acid, CK and CK-MB. In addition, tilmicosin caused the decrease in glutathione and increase in MDA levels. However, administration of L-carnitine could ameliorate these adverse toxic effects of tilmicosin in mice.

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men

PubMed Central

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-01-01

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12–15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally. PMID:29671767

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men.

PubMed

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-04-19

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats.

PubMed

Kim, Jong Whi; Chae, Junghyun; Nam, Sung Min; Kim, Yo Na; Yoo, Dae Young; Choi, Jung Hoon; Jung, Hyo Young; Song, Wook; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

2015-01-01

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.

Proteome Analyses of Staphylococcus aureus Biofilm at Elevated Levels of NaCl

PubMed Central

Islam, Nazrul; Ross, Julia M; Marten, Mark R

2016-01-01

Our studies demonstrate that sodium chloride (NaCl) induces changes in biofilm, mediated by increased production of polysaccharides intercellular adhesion (PIA). We identified 12 proteins that showed higher abundance in increased level of NaCl. This includes one important protein (IsaA) known to be associated with biofilm stability. In addition, we also found higher abundance of a cold shock protein, CspA, at higher NaCl. We have also identified several other proteins that are differentially expressed to the elevated levels of NaCl and mapped them in the regulatory pathways of PIA. The majority of proteins are involved with various aspects bacterial metabolic function. Our results demonstrated that NaCl influences gene regulatory networks controlling exopolysaccharide expression. PMID:26973848

Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation.

PubMed

d'Avila, Joana Costa; Siqueira, Luciana Domett; Mazeraud, Aurélien; Azevedo, Estefania Pereira; Foguel, Debora; Castro-Faria-Neto, Hugo Caire; Sharshar, Tarek; Chrétien, Fabrice; Bozza, Fernando Augusto

2018-01-30

Microglia function is essential to maintain the brain homeostasis. Evidence shows that aged microglia are primed and show exaggerated response to acute inflammatory challenge. Systemic inflammation signals to the brain inducing changes that impact cognitive function. However, the mechanisms involved in age-related cognitive decline associated to episodic systemic inflammation are not completely understood. The aim of this study was to identify neuropathological features associated to age-related cognitive decline in a mouse model of episodic systemic inflammation. Young and aged Swiss mice were injected with low doses of LPS once a week for 6 weeks to induce episodic systemic inflammation. Sickness behavior, inflammatory markers, and neuroinflammation were assessed in different phases of systemic inflammation in young and aged mice. Behavior was evaluated long term after episodic systemic inflammation by open field, forced swimming, object recognition, and water maze tests. Episodic systemic inflammation induced systemic inflammation and sickness behavior mainly in aged mice. Systemic inflammation induced depressive-like behavior in both young and aged mice. Memory and learning were significantly affected in aged mice that presented lower exploratory activity and deficits in episodic and spatial memories, compared to aged controls and to young after episodic systemic inflammation. Systemic inflammation induced acute microglia activation in young mice that returned to base levels long term after episodic systemic inflammation. Aged mice presented dystrophic microglia in the hippocampus and entorhinal cortex at basal level and did not change morphology in the acute response to SI. Regardless of their dystrophic microglia, aged mice produced higher levels of pro-inflammatory (IL-1β and IL-6) as well as pro-resolution (IL-10 and IL-4) cytokines in the brain. Also, higher levels of Nox2 expression, oxidized proteins and lower antioxidant defenses were found in the aged brains compared to the young after episodic systemic inflammation. Our data show that aged mice have increased susceptibility to episodic systemic inflammation. Aged mice that showed cognitive impairments also presented higher oxidative stress and abnormal production of cytokines in their brains. These results indicate that a neuroinflammation and oxidative stress are pathophysiological mechanisms of age-related cognitive impairments.

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2015-01-01

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

The intake of high fat diet with different trans fatty acid levels differentially induces oxidative stress and non alcoholic fatty liver disease (NAFLD) in rats

PubMed Central

2011-01-01

Background Trans-fatty acids (TFA) are known as a risk factor for coronary artery diseases, insulin resistance and obesity accompanied by systemic inflammation, the features of metabolic syndrome. Little is known about the effects on the liver induced by lipids and also few studies are focused on the effect of foods rich in TFAs on hepatic functions and oxidative stress. This study investigates whether high-fat diets with different TFA levels induce oxidative stress and liver dysfunction in rats. Methods Male Wistar rats were divided randomly into four groups (n = 12/group): C receiving standard-chow; Experimental groups that were fed high-fat diet included 20% fresh soybean oil diet (FSO), 20% oxidized soybean oil diet (OSO) and 20% margarine diet (MG). Each group was kept on the treatment for 4 weeks. Results A liver damage was observed in rats fed with high-fat diet via increase of liver lipid peroxidation and decreased hepatic antioxidant enzyme activities (superoxide dismutase, catalase and glutathione peroxidase). The intake of oxidized oil led to higher levels of lipid peroxidation and a lower concentration of plasma antioxidants in comparison to rats fed with FSO. The higher inflammatory response in the liver was induced by MG diet. Liver histopathology from OSO and MG groups showed respectively moderate to severe cytoplasm vacuolation, hypatocyte hypertrophy, hepatocyte ballooning, and necroinflammation. Conclusion It seems that a strong relationship exists between the consumption of TFA in the oxidized oils and lipid peroxidation and non alcoholic fatty liver disease (NAFLD). The extent of the peroxidative events in liver was also different depending on the fat source suggesting that feeding margarine with higher TFA levels may represent a direct source of oxidative stress for the organism. The present study provides evidence for a direct effect of TFA on NAFLD. PMID:21943357

Corticosterone stress response in tree swallows nesting near polychlorinated biphenyl- and dioxin-contaminated rivers

USGS Publications Warehouse

Franceschini, M.D.; Custer, Christine M.; Custer, T.W.; Reed, J.M.; Romero, L.M.

2008-01-01

We assayed baseline and stress-induced corticosterone concentrations from adult female and nestling tree swallows, Tachycineta bicolor, from New England, USA, sites with different levels of contamination with polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Corticosterone was compared over 2 years from a highly contaminated PCB site along the Housatonic River (Berkshire County, MA, USA), a midrange contaminated site upstream, and a reference site. Adult females (n = 29), sampled only in 2003, showed an inverted-U association with PCBs, with higher stress-induced corticosterone with midrange contamination than at the high-contamination site. In nestlings, stress-induced corticosterone was highest for the highly contaminated site compared with the other sites in 2003 (n = 53, 29 nests), with no difference among sites in 2004 (n = 93, 27 nests). In 2004, we began testing mechanisms underlying these changes in nestlings at the high- and low-PCB sites. Corticosterone response to dexamethasone injection (used to test negative feedback) was not different between sites, but stress-induced corticosterone was reduced at the contaminated site after adrenocorticotropin hormone injection (used to test adrenal responsiveness), suggesting an inhibited ability to mount a stress response. We also compared nestlings from a stretch of the Woonasquatucket River, Rhode Island, USA, heavily contaminated with TCDD (n = 80, 43 nests) with nestlings from an upstream site that had lower levels of TCDD and the Berkshire County reference site. Although there were no stress-induced differences, baseline corticosterone was lower at the higher TCDD site than at the reference site. Altogether these findings suggest that tree swallows chronically exposed to high PCB and TCDD levels exhibit altered baseline and stress-induced corticosterone responses, but the patterns of alteration might not be predictable. ?? 2008 SETAC.

Gender differences in alcohol-induced neurotoxicity and brain damage.

PubMed

Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

2013-09-06

Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Asphyxia by Drowning Induces Massive Bleeding Due To Hyperfibrinolytic Disseminated Intravascular Coagulation.

PubMed

Schwameis, Michael; Schober, Andreas; Schörgenhofer, Christian; Sperr, Wolfgang Reinhard; Schöchl, Herbert; Janata-Schwatczek, Karin; Kürkciyan, Erol Istepan; Sterz, Fritz; Jilma, Bernd

2015-11-01

To date, no study has systematically investigated the impact of drowning-induced asphyxia on hemostasis. Our objective was to test the hypothesis that asphyxia induces bleeding by hyperfibrinolytic disseminated intravascular coagulation. Observational study. A 2,100-bed tertiary care facility in Vienna, Austria, Europe. All cases of drowning-induced asphyxia (n=49) were compared with other patients with cardiopulmonary resuscitation (n=116) and to patients with acute promyelocytic leukemia (n=83). Six drowning victims were investigated prospectively. To study the mechanism, a forearm-ischemia model was used in 20 volunteers to investigate whether hypoxia releases tissue plasminogen activator. None. Eighty percent of patients with drowning-induced asphyxia developed overt disseminated intravascular coagulation within 24 hours. When compared with nondrowning cardiac arrest patients, drowning patients had a 13 times higher prevalence of overt disseminated intravascular coagulation at admission (55% vs 4%; p<0.001). Despite comparable disseminated intravascular coagulation scores, acute promyelocytic leukemia patients had higher fibrinogen but lower d-dimer levels and platelet counts than drowning patients (p<0.001). Drowning victims had a three-fold longer activated partial thromboplastin time (124 s; p<0.001) than both nondrowning cardiac arrest and acute promyelocytic leukemia patients. Hyperfibrinolysis was reflected by up to 1,000-fold increased d-dimer levels, greater than 5-fold elevated plasmin antiplasmin levels, and a complete absence of thrombelastometric clotting patterns, which was reversed by antifibrinolytics and heparinase. Thirty minutes of forearm-ischemia increased tissue plasminogen activator 31-fold (p<0.001). The vast majority of drowning patients develops overt hyperfibrinolytic disseminated intravascular coagulation, partly caused by hypoxia induced tissue plasminogen activator release. Antifibrinolytics and heparinase partially reverse the abnormal clotting patterns. Severe activated partial thromboplastin time prolongation may be a marker of combined hyperfibrinolytic afibrinogenemia and autoheparinization in drowning-related asphyxia.

Rose oil (from Rosa × damascena Mill.) vapor attenuates depression-induced oxidative toxicity in rat brain.

PubMed

Nazıroğlu, Mustafa; Kozlu, Süleyman; Yorgancıgil, Emre; Uğuz, Abdülhadi Cihangir; Karakuş, Kadir

2013-01-01

Oxidative stress is a critical route of damage in various physiological stress-induced disorders, including depression. Rose oil may be a useful treatment for depression because it contains flavonoids which include free radical antioxidant compounds such as rutin and quercetin. We investigated the effects of absolute rose oil (from Rosa × damascena Mill.) and experimental depression on lipid peroxidation and antioxidant levels in the cerebral cortex of rats. Thirty-two male rats were randomly divided into four groups. The first group was used as control, while depression was induced in the second group using chronic mild stress (CMS). Oral (1.5 ml/kg) and vapor (0.15 ml/kg) rose oil were given for 28 days to CMS depression-induced rats, constituting the third and fourth groups, respectively. The sucrose preference test was used weekly to identify depression-like phenotypes during the experiment. At the end of the experiment, cerebral cortex samples were taken from all groups. The lipid peroxidation levels in the cerebral cortex in the CMS group were higher than in control whereas their levels were decreased by rose oil vapor exposure. The vitamin A, vitamin E, vitamin C and β-carotene concentrations in the cerebral cortex were lower in the CMS group than in the control group whereas their concentrations were higher in the rose oil vapor plus CMS group. The CMS-induced antioxidant vitamin changes were not modulated by oral treatment. Glutathione peroxidase activity and reduced glutathione did not change statistically in the four groups following CMS or either treatment. In conclusion, experimental depression is associated with elevated oxidative stress while treatment with rose oil vapor induced protective effects on oxidative stress in depression.

Efficient programming of human eye conjunctiva-derived induced pluripotent stem (ECiPS) cells into definitive endoderm-like cells.

PubMed

Massumi, Mohammad; Hoveizi, Elham; Baktash, Parvaneh; Hooti, Abdollah; Ghazizadeh, Leili; Nadri, Samad; Pourasgari, Farzaneh; Hajarizadeh, Athena; Soleimani, Masoud; Nabiuni, Mohammad; Khorramizadeh, Mohammad R

2014-03-10

Due to pluripotency of induced pluripotent stem (iPS) cells, and the lack of immunological incompatibility and ethical issues, iPS cells have been considered as an invaluable cell source for future cell replacement therapy. This study was aimed first at establishment of novel iPS cells, ECiPS, which directly reprogrammed from human Eye Conjunctiva-derived Mesenchymal Stem Cells (EC-MSCs); second, comparing the inductive effects of Wnt3a/Activin A biomolecules to IDE1 small molecule in derivation of definitive endoderm (DE) from the ECiPS cells. To that end, first, the EC-MSCs were transduced by SOKM-expressing lentiviruses and characterized for endogenous expression of embryonic markers Then the established ECiPS cells were induced to DE formation by Wnt3a/Activin A or IDE1. Quantification of GSC, Sox17 and Foxa2 expression, as DE-specific markers, in both mRNA and protein levels revealed that induction of ECiPS cells by either Wnt3a/Activin A or IDE1 could enhance the expression level of the genes; however the levels of increase were higher in Wnt3a/Activin A induced ECiPS-EBs than IDE1 induced cells. Furthermore, the flow cytometry analyses showed no synergistic effect between Activin A and Wnt3a to derive DE-like cells from ECiPS cells. The comparative findings suggest that although both Wnt3a/Activin A signaling and IDE1 molecule could be used for differentiation of iPS into DE cells, the DE-inducing effect of Wnt3a/Activin A was statistically higher than IDE1. Copyright © 2014 Elsevier Inc. All rights reserved.

Alpha-ketoglutarate enhances freeze-thaw tolerance and prevents carbohydrate-induced cell death of the yeast Saccharomyces cerevisiae.

PubMed

Bayliak, Maria M; Hrynkiv, Olha V; Knyhynytska, Roksolana V; Lushchak, Volodymyr I

2018-01-01

Stress resistance and fermentative capability are important quality characteristics of baker's yeast. In the present study, we examined protective effects of exogenous alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle and amino acid metabolism, against freeze-thaw and carbohydrate-induced stresses in the yeast Saccharomyces cerevisiae. Growth on AKG-supplemented medium prevented a loss of viability and improved fermentative capacity of yeast cells after freeze-thaw treatment. The cells grown in the presence of AKG had higher levels of amino acids (e.g., proline), higher metabolic activity and total antioxidant capacity, and higher activities of catalase, NADP-dependent glutamate dehydrogenase and glutamine synthase compared to control ones. Both synthesis of amino acids and enhancement of antioxidant system capacity could be involved in AKG-improved freeze-thaw tolerance in S. cerevisiae. Cell viability dramatically decreased under incubation of stationary-phase yeast cells in 2% glucose or fructose solutions (in the absence of the other nutrients) as compared with incubation in distilled water or in 10 mM AKG solution. The decrease in cell viability was accompanied by acidification of the medium, and decrease in cellular respiration, aconitase activity, and levels of total protein and free amino acids. The supplementation with 10 mM AKG effectively prevented carbohydrate-induced yeast death. Protective mechanisms of AKG could be associated with the intensification of respiration and prevention of decreasing protein level as well as with direct antioxidant AKG action.

The effect of diffusion induced lattice stress on the open-circuit voltage in silicon solar cells

NASA Technical Reports Server (NTRS)

Weizer, V. G.; Godlewski, M. P.

1984-01-01

It is demonstrated that diffusion induced stresses in low resistivity silicon solar cells can significantly reduce both the open-circuit voltage and collection efficiency. The degradation mechanism involves stress induced changes in both the minority carrier mobility and the diffusion length. Thermal recovery characteristics indicate that the stresses are relieved at higher temperatures by divacancy flow (silicon self diffusion). The level of residual stress in as-fabricated cells was found to be negligible in the cells tested.

Protective effect of Moringa oleifera oil against HgCl2-induced hepato- and nephro-toxicity in rats.

PubMed

Abarikwu, Sunny O; Benjamin, Sussan; Ebah, Sunday Godspower; Obilor, Godbless; Agbam, Goodluck

2017-07-26

Various parts of the Moringa oleifera (M. oleifera) tree are widely accepted to have ameliorative effects against metal toxicity. In the present study, M. oleifeira oil (MO) was tested against HgCl2-induced tissue pathologies and oxidative stress. Male Wistar rats were administered MO (1.798 mg/kg p.o.) or HgCl2 (5 mg/kg body wt) alone or in combination (5 mg/kg HgCl2+1.798 mg/kg MO p.o.) three times per week for 21 days. After exposure and treatment periods, rats were sacrificed; blood collected and the oxidative status of the liver and kidney homogenates were evaluated. In the liver, malondialdehyde (MDA) level, glutathione (GSH), and superoxide dismutase (SOD) activities were higher whereas catalase (CAT) activity was lower in the HgCl2 group than in the control group. In the kidney, MDA level, SOD, and CAT activities were higher whereas GSH activity was unchanged in the HgCl2 group compared to the control group. In the liver, MDA level, SOD, and CAT activities were lower in the HgCl2+MO group than in the HgCl2 group. In the kidney, MDA level, SOD and CAT activities were lower in the HgCl2+MO than in the HgCl2 group. Furthermore, Hg-induced increases in creatinine and bilirubin levels as well as the increase in γ-glutamyl transferase, lactate dehydrogenase, and alkaline phosphatase activities were attenuated in the combine exposure group and the animals showed improvement in the histology of the liver and kidney. MO decreased the negative effects of Hg-induced oxidative stress in rats.

17β-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway.

PubMed

Hoffmann, Marta; Fiedor, Elżbieta; Ptak, Anna

2016-11-01

Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17β-estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17β-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17β-estradiol and leptin, we observed antagonistic effects of 17β-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17β-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR + /ER + , 17β-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. © The Author(s) 2016.

Effects of BDNF receptor antagonist on the severity of physical and psychological dependence, morphine-induced locomotor sensitization and the ventral tegmental area-nucleus accumbens BDNF levels in morphine- dependent and withdrawn rats.

PubMed

Khalil-Khalili, Masoumeh; Rashidy-Pour, Ali; Bandegi, Ahmad Reza; Yousefi, Behpoor; Jorjani, Hassan; Miladi-Gorji, Hossein

2018-03-06

This study examined the effects of systemic administration of the TrkB receptor antagonist (ANA-12) on the severity of physical and psychological dependence and morphine-induced locomotor sensitization, the ventral tegmental area (VTA)-nucleus accumbens (NAc) BDNF levels in morphine-dependent and withdrawn rats. Rats were injected with bi-daily doses (10 mg/kg, at 12 h intervals) of morphine for 10 days. Then, rats were tested for naloxone-precipitated morphine withdrawal signs, the anxiety (the elevated plus maze-EPM) after the last morphine injection and injection of ANA12 (ip). Also, morphine-induced locomotor sensitization was evaluated after morphine challenge followed by an injection of ANA-12 in morphine-withdrawn rats. The VTA-NAc BDNF levels were assessed in morphine-dependent and withdrawn rats. The overall Gellert-Holtzman score was significantly higher in morphine-dependent rats receiving ANA-12 than in those receiving saline. Also, the percentage of time spent in the open arms in control and morphine-dependent rats receiving ANA-12 were higher compared to the Cont/Sal and D/Sal rats, respectively. There was no significant difference in the locomotor activity and the VTA-NAc BDNF levels between D/Sal/morphine and D/ANA-12/morphine groups after morphine withdrawal. We conclude that the systemic administration of ANA-12 exacerbates the severity of physical dependence on morphine and partially attenuates the anxiety-like behavior in morphine-dependent rats. However, ANA-12 did not affect morphine-induced locomotor sensitization and the VTA-NAc BDNF levels in morphine-dependent and withdrawn rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Cigarette smoking and hyperglycemia increase renal response to low levels of cadmium in welders: cystatin C as a sensitive marker.

PubMed

Harisa, Gamaleldin I; Attia, Sabry M; Ashour, Abdelkader E; Abdallah, Gamil M; Omran, Gamal A; Touliabah, Hussein E

2014-06-01

The present study was undertaken to investigate the utility of cystatin C (CysC) as an early biomarker of cadmium (Cd)-induced renal injury. The study was carried out on 50 adult male individuals divided into five groups of 10 individuals as follows: control, welders, smoker welders, diabetic welders, and smoker diabetic welders. The results indicated that plasma levels of CysC, creatinine, urea, and uric acid were significantly higher in welders compared to control individuals. In addition, the levels of whole blood Cd, lipid peroxidation, and protein oxidation products as well as erythrocyte osmotic fragility were significantly higher in welders compared to control individuals. In contrast, the levels of plasma albumin and whole blood glutathione were significantly decreased in welders compared to control individuals. The alterations of the measured parameters were enhanced in the presence of smoking and hyperglycemia besides exposure to welding fumes. These results suggest that CysC can be used as a sensitive biomarker of the early stages of Cd-induced renal injury.

Differential Responses of Polyamines and Antioxidants to Drought in a Centipedegrass Mutant in Comparison to Its Wild Type Plants

PubMed Central

Liu, Mingxi; Chen, Jingjing; Guo, Zhenfei; Lu, Shaoyun

2017-01-01

Centipedegrass (Eremochloa ophiuroides [Munro] Hack.) is an important warm-season turfgrass species with low turf maintenance requirements. However, our knowledge on physiological adaptation of centipedegrass to drought stress is limited. Physiological responses to drought in a gamma-ray-induced mutant 22-1 as compared with two wild type (WT) lines were analyzed for understanding of drought tolerance mechanism of centipedegrass. The mutant showed an elevated drought tolerance with higher levels of relative water content, net photosynthetic rate (A) and stomatal conductance (gs) and lower levels of ion leakage and malondialdehyde (MDA) under drought stress as compared with WT plants. A showed significant correlation with gs and MDA. Higher levels of antioxidant enzymes activities, non-enzyme antioxidants, and polyamines including putrescine (Put), spermidine (Spd), and spermine (Spm) were maintained in 22-1 than in WT plants. Superoxide dismutase (SOD), catalase (CAT), ascorbate-peroxidase (APX), and glutathione reductase (GR) activities and ascorbic acid (AsA) content were significantly correlated with both Put and Spd levels, and reduced glutathione level was correlated with Put during drought stress. Exogenous application of Put, Spd, and Spm increased drought tolerance and activities of SOD, CAT, APX, and GR in WT plants. The results suggest that higher levels of polyamines and antioxidant defense system are associated with the elevated drought tolerance in 22-1, which may improve protection on photosynthesis against drought induced oxidative damage. PMID:28559909

Clusterin and Pycr1 alterations associate with strain and model differences in susceptibility to experimental pancreatitis.

PubMed

Iyer, Sapna; Park, Min-Jung; Moons, David; Kwan, Raymond; Liao, Jian; Liu, Li; Omary, M Bishr

2017-01-22

Acute pancreatitis has several underlying etiologies, and results in consequences ranging from mild to complex multi-organ failure. The wide range of pathology suggests a genetic predisposition for progression. We compared the susceptibility to acute pancreatitis in BALB/c and FVB/N mice, coupled with proteomic analysis, in order to identify potential protein associations with pancreatitis progression. Pancreatitis was induced in BALB/c and FVB/N mice by administration of cerulein or feeding a choline-deficient, ethionine-supplemented (CDE) diet. Histology and changes in serum amylase were examined. Proteome profiling in cerulein-treated mice was performed using 2-dimensional differential in gel electrophoresis (2D-DIGE) followed by mass spectrometry analysis and biochemical validation. Male and female FVB/N mice manifested more severe cerulein-induced pancreatitis as compared with BALB/c mice, but both strains were similarly susceptible to CDE-induced pancreatitis. Few of the 2D-DIGE alterations were validated by immunoblotting. Clusterin was markedly up-regulated after cerulein-induced pancreatitis in FVB/N but less-so in BALB/c mice. Pyrroline-5-carboxylate reductase (Pycr1), an enzyme involved in proline biosynthesis, had higher basal levels in FVB/N male and female mouse pancreata compared with BALB/c pancreata, and was relatively more resistant to degradation in FVB/N pancreata. However, serum and pancreas tissue proline levels were similar in the two strains. FVB/N is more susceptible than BALB/c mice to cerulein-induced but not CDE-induced pancreatitis. Most of the 2D-DIGE alterations in the two strains likely relate to posttranslational modifications rather than protein level differences. Clusterin levels increase dramatically in association with pancreatitis severity, while Pycr1 is higher in FVB/N versus BALB/c pancreata basally and after induction of pancreatitis. Changes in proline metabolism may represent a novel potential genetic modifier in the context of pancreatitis. Published by Elsevier Inc.

Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression.

PubMed

Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M; Essex, Marilyn J

2014-09-01

Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary fructose enhances the incidence of precancerous hepatocytes induced by administration of diethylnitrosamine in rat

PubMed Central

2013-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is a risk for hepatocellular carcinoma (HCC), but the association between a high-fructose diet and HCC is not fully understood. In this study, we investigated whether a high-fructose diet affects hepatocarcinogenesis induced by administration of diethylnitrosamine (DEN). Methods Seven-week-old male Sprague–Dawley rats were fed standard chow (controls), a high-fat diet (54% fat), or a high-fructose diet (66% fructose) for 8 weeks. All rats were given DEN at 50 μg/L in drinking water during the same period. Precancerous hepatocytes were detected by immunostaining of the placental form of glutathione-S-transferase (GST-P). The number of GST-P-positive hepatocytes was assessed in liver specimens. Results Serum levels of total cholesterol were similar among the three groups, but serum triglyceride, fasting blood glucose, and insulin levels were higher in the high-fructose group compared to the high-fat group. In contrast, hepatic steatosis was more severe in the high-fat group compared with the high-fructose and control groups, but the incidence of GST-P-positive specimens was significantly higher in the high-fructose group compared to the other two groups. The average number of GST-P-positive hepatocytes in GST-P positive specimens in the high-fructose group was also higher than those in the other two groups. This high prevalence of GST-P-positive hepatocytes was accompanied by higher levels of 8-hydroxydeoxyguanosine in serum and liver tissue. Conclusions These results indicate that dietary fructose, rather than dietary fat, increases the incidence of precancerous hepatocytes induced by administration of DEN via insulin resistance and oxidative stress in rat. Thus, excessive fructose intake may be a potential risk factor for hepatocarcinogenesis. PMID:24321741

Expression of Shiga toxin 2 (Stx2) in highly virulent Stx-producing Escherichia coli (STEC) carrying different anti-terminator (q) genes.

PubMed

Olavesen, Kristoffer K; Lindstedt, Bjørn-Arne; Løbersli, Inger; Brandal, Lin T

2016-08-01

Shiga toxins (Stx) are key virulence factors of Shiga toxin-producing Escherichia coli (STEC) during development of haemolytic uremic syndrome (HUS). It has been suggested that not only specific stx2 subtypes, but also the amount of Stx2 expressed might be essential for STEC pathogenicity. We aimed to investigate if various anti-terminator (q) genes might influence the expression level of Stx2 in highly virulent STEC. A multiplex PCR detecting q933, q21, and qO111 was run on 20 stx2a-positive STEC strains, of which 18 were HUS associated serotypes (HAS) and two non-HAS. Relative expression of Stx2 mRNA was assessed for all strains, both in non-induced and induced (mitomycin C) state. The HAS STEC carried either q933 (n = 8), qO111 (n = 8), or both (n = 2). In basal state, no STEC strains showed higher expression of Stx2 mRNA than the calibrator EDL933 (non-sorbitol fermenting (NSF) O157:H7carrying q933). Variations among strains were not associated with different q genes present, but rather related to specific serogroups. In induced state, O104:H4 strains (q933) showed higher Stx2 mRNA level than EDL933, whereas sorbitol fermenting (SF) O157:H- (qO111) and O121:H? (q933) STEC showed levels comparable with EDL933. An association between the presence of q933 and higher Stx2 level was seen within some HAS, but not all. Interestingly, the O103:H25 STEC strains, responsible for a HUS outbreak in Norway, carried both q933 and qO111. However, the Stx2 mRNA level in these strains was significantly lower than EDL933 in both states, indicating that other factors than the level of Stx2 might explain the aggressiveness of these bacteria. The two non-HAS STEC did not carry any of the examined q genes. In induced state, these bacteria showed the lowest Stx2 mRNA level compared to EDL933. One of the non-HAS STEC was not induced by mitomycin C, suggesting that stx2a might be located on a defect bacteriophage. No association between specific q genes and Stx2 mRNA expression level was revealed in stx2a-positive HAS STEC. Our results suggest that other factor(s) than specific q genes might influence the level of Stx2 produced in highly virulent STEC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes.

PubMed

Song, Changjie; Hsu, Kenneth; Yamen, Eric; Yan, Weixing; Fock, Jianyi; Witting, Paul K; Geczy, Carolyn L; Freedman, S Ben

2009-12-01

Serum amyloid A (SAA) is a biomarker of inflammation. Elevated blood levels in cardiovascular disease and local deposition in atheroma implies a role of SAA as a mediator rather than just a marker of inflammation. This study explored SAA-induced cytokine production and secretion by mononuclear cells. RT-PCR showed that SAA time-dependently induced cytokine mRNAs in peripheral blood mononuclear cells (PBMC) and THP-1 monocytoid cells, and dramatically increased IL-1beta, MCP-1, IL-6, IL-8, IL-10, GM-CSF, TNF, and MIP-1alpha secretion by PBMC to levels 28 to 25,000 fold above baseline, as measured with Bio-Plex kits; monocytes were the principle source. SAA induction of cytokines in monocyte-derived macrophages (MDM) was significantly higher than from monocytes from the same donors. SAA time-dependently induced transient and significant upregulation of NF-kappaB1 mRNA; inhibitor studies indicate that activation of NF-kappaB through the ERK1/2, p38 and JNK MAPKs and the PI3K pathway was involved. PBMC from 10 patients with coronary artery disease (CAD) spontaneously secreted higher levels of IL-6 and MIP-1alpha after 24h incubation than PBMC from normal controls, whereas SAA-induced levels of all cytokines were similar to controls. Aortic and coronary sinus sampling in 23 CAD patients indicated significant SAA release into the coronary circulation, not evident in 11 controls. SAA can increase monocyte and macrophage cytokine production, possibly at sites of atherosclerosis, thereby contributing to the pro-inflammatory state in coronary artery disease.

Vitamin E supplementation does not prevent ethanol-reduced hepatic retinoic acid levels in rats

PubMed Central

Chung, Jayong; Veeramachaneni, Sudipta; Liu, Chun; Mernitz, Heather; Russell, Robert M.; Wang, Xiang-Dong

2009-01-01

Chronic, excessive ethanol intake can increase retinoic acid (RA) catabolism by inducing cytochrome P450 2E1 (CYP2E1). Vitamin E (VE) is an antioxidant implicated in CYP2E1 inhibition. In the current study, we hypothesized that VE supplementation inhibits CYP2E1 and decreases RA catabolism, thereby preventing ethanol-induced hepatocyte hyperproliferation. For 1 month, four groups of Sprague-Dawley rats were fed a Lieber-DeCarli liquid ethanol (36% of the total calories) diet as follows: either ethanol alone (Alc group) or ethanol in combination with 0.1 mg/kg body wt of all-trans RA (Alc+RA group), 2 mg/kg body wt of VE (Alc+VE group), or both together (Alc+RA+VE group). Control rats were pair-fed a liquid diet with an isocaloric amount of maltodextrin instead of ethanol. The ethanol-fed groups had three-fold higher hepatic CYP2E1 levels, 50% lower hepatic RA levels, and significantly increased hepatocyte proliferation when compared with the controls. The ethanol-fed rats given VE had more than four-fold higher hepatic VE concentrations than did ethanol-fed rats without VE, but this did not prevent ethanol induction of CYP2E1, lower hepatic retinoid levels, or hepatocellular hyperproliferation. Further, VE supplementation could not prevent RA catabolism in liver microsomal fractions of the ethanol-fed rats in vitro. These results show that VE supplementation can neither inhibit ethanol-induced changes in RA catabolism nor prevent ethanol-induced hepatocyte hyperproliferation in the rat liver. PMID:19854382

PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling

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

Petriello, Michael C.; University of Kentucky Superfund Research Center, Lexington, KY 40536; Han, Sung Gu

2014-06-01

Environmental toxicants such as polychlorinated biphenyls (PCBs) have been implicated in the promotion of multiple inflammatory disorders including cardiovascular disease, but information regarding mechanisms of toxicity and cross-talk between relevant cell signaling pathways is lacking. To examine the hypothesis that cross-talk between membrane domains called caveolae and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathways alters PCB-induced inflammation, caveolin-1 was silenced in vascular endothelial cells, resulting in a decreased PCB-induced inflammatory response. Cav-1 silencing (siRNA treatment) also increased levels of Nrf2-ARE transcriptional binding, resulting in higher mRNA levels of the antioxidant genes glutathione s-transferase and NADPH dehydrogenase quinone-1 in both vehiclemore » and PCB-treated systems. Along with this upregulated antioxidant response, Cav-1 siRNA treated cells exhibited decreased mRNA levels of the Nrf2 inhibitory protein Keap1 in both vehicle and PCB-treated samples. Silencing Cav-1 also decreased protein levels of Nrf2 inhibitory proteins Keap1 and Fyn kinase, especially in PCB-treated cells. Further, endothelial cells from wildtype and Cav-1 −/− mice were isolated and treated with PCB to better elucidate the role of functional caveolae in PCB-induced endothelial inflammation. Cav-1 −/− endothelial cells were protected from PCB-induced cellular dysfunction as evidenced by decreased vascular cell adhesion molecule (VCAM-1) protein induction. Compared to wildtype cells, Cav-1 −/− endothelial cells also allowed for a more effective antioxidant response, as observed by higher levels of the antioxidant genes. These data demonstrate novel cross-talk mechanisms between Cav-1 and Nrf2 and implicate the reduction of Cav-1 as a protective mechanism for PCB-induced cellular dysfunction and inflammation. - Highlights: • Reduction of caveolin-1 protein protects against polychlorinated biphenyl toxicity. • Decreasing caveolin-1 levels increases the Nrf2 antioxidant response. • Reducing caveolin-1 levels decreases expression of Nrf2 inhibitory proteins. • Caveolin-1/Nrf2 cross-talk is evident in mouse, human, and porcine endothelial cells.« less

Substance P Inhibits the Collagen Synthesis of Rat Myocardial Fibroblasts Induced by Ang II.

PubMed

Yang, Zhiyong; Zhang, Xinzhong; Guo, Naipeng; Li, Bin; Zhao, Sheng

2016-12-16

BACKGROUND The aim of this study was to explore the regulating effects of Substance P (SP) on the collagen synthesis of rat myocardial fibroblasts (CFBs) induced by angiotensin II (Ang II) and its potential mechanism. MATERIAL AND METHODS The CFBs of a neonatal SD rat were separately cultured and divided into the control group, Ang II treatment group, and treatment groups with different concentrations of SP, Ang II +; each group was given corresponding treatment respectively. RESULTS Ang II successfully induced the collagen synthesis of CFBs. Compared with the control group, the phosphorylation levels of TGF-β, erk, and smad2/3 were higher (p<0.05). Different concentrations of SP had an effect on Ang II-induced CFBs, reduced the collagen synthesis of CFBs, and increased the expressions of SP receptors, accompanied by lowering TGF-β protein, erk protein phosphorylation level, and smad2/3 protein phosphorylation level (p<0.05). Moreover, the higher the concentrations of SP, the more obvious of an effect it exerted. Treating the Ang II + SP group with aprepitant reduced the inhibiting effects of SP on collagen synthesis. The expression changes of collagen I and collagen III detected by immunocytochemistry were exactly in accordance with the results of qPCR and Western blotting. CONCLUSIONS SP can inhibit collagen synthesis of CFBs after Ang II inducing which may adjust the downstream signaling pathways associated protein including TGF-β, erk and smad2/3. SP can block the progress of myocardial fibrosis and is dose dependent, which is expected to be a promising target for the treatment of myocardial fibrosis.

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic

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

Hossain, Ekhtear; Islam, Khairul; Yeasmin, Fouzia

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nailsmore » were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose–response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions. -- Highlights: ► Plasma Big ET-1 is an indicator of endothelial damage. ► Plasma Big ET-1 level increases dose-dependently in arsenic exposed individuals. ► Study subjects in arsenic-endemic areas with hypertension have elevated Big ET-1 levels. ► Study subjects with arsenic-induced skin lesions show elevated plasma Big ET-1 levels. ► Arsenic-induced hypertension and skin lesions may be linked to plasma Big ET-1 levels.« less

Limited Interactions between Streptococcus Suis and Haemophilus Parasuis in In Vitro Co-Infection Studies

PubMed Central

Mathieu-Denoncourt, Annabelle; Letendre, Corinne; Auger, Jean-Philippe; Segura, Mariela; Aragon, Virginia; Lacouture, Sonia; Gottschalk, Marcelo

2018-01-01

Streptococcus suis and Haemophilus parasuis are normal inhabitants of the porcine upper respiratory tract but are also among the most frequent causes of disease in weaned piglets worldwide, causing inflammatory diseases such as septicemia, meningitis and pneumonia. Using an in vitro model of infection with tracheal epithelial cells or primary alveolar macrophages (PAMs), it was possible to determine the interaction between S. suis serotype 2 and H. parasuis strains with different level of virulence. Within H. parasuis strains, the low-virulence F9 strain showed higher adhesion levels to respiratory epithelial cells and greater association levels to PAMs than the high-virulence Nagasaki strain. Accordingly, the low-virulence F9 strain induced, in general, higher levels of pro-inflammatory cytokines than the virulent Nagasaki strain from both cell types. In general, S. suis adhesion levels to respiratory epithelial cells were similar to H. parasuis Nagasaki strain. Yet, S. suis strains induced a significantly lower level of pro-inflammatory cytokine expression from epithelial cells and PAMs than those observed with both H. parasuis strains. Finally, this study has shown that, overall and under the conditions used in the present study, S. suis and H. parasuis have limited in vitro interactions between them and use probably different host receptors, regardless to their level of virulence. PMID:29316613

Hepatoprotective activity of Psidium guajava Linn. leaf extract.

PubMed

Roy, Chanchal K; Kamath, Jagadish V; Asad, Mohammed

2006-04-01

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.

Circulating exosomes from patients with systemic lupus erythematosus induce an proinflammatory immune response.

PubMed

Lee, Joo Youn; Park, Jin Kyun; Lee, Eun Young; Lee, Eun Bong; Song, Yeong Wook

2016-11-16

Exosomes are involved in intercellular communication. The aim of this study was to investigate whether circulating exosomes effectively contribute to the inflammatory response in systemic lupus erythematosus (SLE). Exosomes were purified from SLE patients and healthy controls (HCs). Healthy peripheral blood mononuclear cells (PBMCs) were stimulated with exosomes isolated from SLE patients and HCs in the presence or absence of Toll-like receptor (TLR) inhibitors. Production of interferon (IFN)-α, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured. Correlation between exosome levels and SLE disease activity was examined. The serum exosomes levels were significantly higher in SLE patients than in HCs. SLE exosomes induced a higher production of IFN-α, TNF-α, IL-1β, and IL-6 compared to healthy exosomes. SLE serum that was depleted of exosomes and SLE exosomes that were mechanically disrupted failed to induce any significant cytokine production. Exosome-mediated production of TNF-α, IL-1β, and IL-6 was decreased by the TLR4 antagonist, whereas that of IFN-α was suppressed by the TLR1/2, TLR7, and TLR9 antagonists. Exosome levels correlated with disease activity in SLE patients (rho = 0.846, p = 0.008). The circulating exosomes are immunologically active and their levels correlate with disease activity in SLE patients. The circulating exosomes might serve as novel biomarkers of SLE disease activity.

Elevated O-GlcNAcylation promotes colonic inflammation and tumorigenesis by modulating NF-κB signaling.

PubMed

Yang, Yong Ryoul; Kim, Dae Hyun; Seo, Young-Kyo; Park, Dohyun; Jang, Hyun-Jun; Choi, Soo Youn; Lee, Yong Hwa; Lee, Gyun Hui; Nakajima, Kazuki; Taniguchi, Naoyuki; Kim, Jung-Min; Choi, Eun-Jeong; Moon, Hyo Youl; Kim, Il Shin; Choi, Jang Hyun; Lee, Ho; Ryu, Sung Ho; Cocco, Lucio; Suh, Pann-Ghill

2015-05-20

O-GlcNAcylation is a reversible post-translational modification. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. More recent evidence indicates that regulation of O-GlcNAcylation is important for inflammatory diseases and tumorigenesis. In this study, we revealed that O-GlcNAcylation was increased in the colonic tissues of dextran sodium sulfate (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) animal models. Moreover, the O-GlcNAcylation level was elevated in human CAC tissues compared with matched normal counterparts. To investigate the functional role of O-GlcNAcylation in colitis, we used OGA heterozygote mice, which have an increased level of O-GlcNAcylation. OGA(+/-) mice have higher susceptibility to DSS-induced colitis than OGA(+/+) mice. OGA(+/-) mice exhibited a higher incidence of colon tumors than OGA(+/+) mice. In molecular studies, elevated O-GlcNAc levels were shown to enhance the activation of NF-κB signaling through increasing the binding of RelA/p65 to its target promoters. We also found that Thr-322 and Thr352 in the p65-O-GlcNAcylation sites are critical for p65 promoter binding. These results suggest that the elevated O-GlcNAcylation level in colonic tissues contributes to the development of colitis and CAC by disrupting regulation of NF-κB-dependent transcriptional activity.

Liver damage, proliferation, and progenitor cell markers in experimental necrotizing enterocolitis.

PubMed

Miyake, Hiromu; Li, Bo; Lee, Carol; Koike, Yuhki; Chen, Yong; Seo, Shogo; Pierro, Agostino

2018-05-01

Necrotizing enterocolitis (NEC) is a disease known to cause injury to multiple organs including the liver. Liver regeneration is essential for the recovery after NEC-induced liver injury. Our aim was to investigate hepatic proliferation and progenitor cell marker expression in experimental NEC. Following ethical approval (#32238), NEC was induced in mice by hypoxia, gavage feeding of hyperosmolar formula, and lipopolysaccharide. Breastfed pups were used as control. We analyzed serum ALT level, liver inflammatory cytokines, liver proliferation markers, and progenitor cell marker expression. Comparison was made between NEC and controls. Serum ALT level was higher in NEC (p<0.05). The mRNA expression of inflammatory cytokines in the liver was also higher in NEC (IL6: p<0.05, TNF-α: p<0.01). Conversely, mRNA expression of proliferation markers in the liver was lower in NEC (Ki67; p<0.01, PCNA: p<0.01). LGR5 expression was also significantly decreased in NEC as demonstrated by mRNA (p<0.05) and protein (p<0.01) levels. Inflammatory injury was present in the liver during experimental NEC. Proliferation and LGR5 expression were impaired in the NEC liver. Modulation of progenitor cell expressing LGR5 may result in stimulation of liver regeneration in NEC-induced liver injury and improved clinical outcome. Level IV. Copyright © 2018. Published by Elsevier Inc.

Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

PubMed

Shah, N S; Gulati, O D

1984-01-01

Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

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

Ruiz-Ramos, Ruben; Departamento de Toxicologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, 07360 Mexico D.F.; Lopez-Carrillo, Lizbeth

There is limited available information on the effects of arsenic on enzymes participating in the folate cycle. Therefore, our aim was to evaluate the effects of sodium arsenite on the protein levels of methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) and its further relationship with the expression MT1/2 and c-myc in MCF-7 cells. Arsenite treatment (0-10 muM) for 4 h decreased MTHFR levels in a concentration-dependent fashion without significant effects on DHFR. The effects on MTHFR were observed at arsenite concentrations not significantly affecting cell viability. We also observed an increase in S-phase recruitment at all concentrations probed. Lower concentrationsmore » (< 5 muM) induced cell proliferation, showing a high proportion of BrdU-stained cells, indicating a higher DNA synthesis rate. However, higher concentrations (>= 5 muM) or longer treatment periods induced apoptosis. Arsenite also induced dose-dependent increases in MT1/2 and c-Myc protein levels. The levels of MTHFR were inversely correlated to MT1/2 and c-Myc overexpression and increased S-phase recruitment. Our findings indicate that breast epithelial cells are responsive to arsenite and suggest that exposure may pose a risk for breast cancer. The reductions in MTHFR protein levels contribute to understand the mechanisms underlying the induction of genes influencing growth regulation, such as c-myc and MT1/2. However, further research is needed to ascertain if the effects here reported following short-time and high-dose exposure are relevant for human populations chronically exposed to low arsenic concentrations.« less

Chromatic Perceptual Learning but No Category Effects without Linguistic Input.

PubMed

Grandison, Alexandra; Sowden, Paul T; Drivonikou, Vicky G; Notman, Leslie A; Alexander, Iona; Davies, Ian R L

2016-01-01

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest.

Effects of 810 nm laser on mouse primary cortical neurons

NASA Astrophysics Data System (ADS)

Kharkwal, Gitika B.; Sharma, Sulbha K.; Huang, Ying-Ying; De Taboada, Luis; McCarthy, Thomas; Hamblin, Michael R.

2011-03-01

In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from mouse embryonic brains. Neurons were irradiated with light dose of 0.03, 0.3, 3, 10 and 30 J/cm2 and intracellular levels of reactive oxygen species, nitric oxide and calcium were measured. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluence. ROS was induced significantly by light at all light doses. Nitric oxide levels also showed an increase on treatment with light. The results of the present study suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling process which in turn may be responsible for the biomodulatory effects of the low level laser. At higher fluences beneficial mediators are reduced but potentially harmful mediators are increased thus offering an explanation for the biphasic dose response.

Up regulation of serum tumor necrosis factor-related apoptosis inducing ligand in juvenile-onset systemic lupus erythematosus: relations with disease activity, antibodies to double -stranded DNA, nephritis and neutropenia.

PubMed

Ezzat, Mohamed H M; El-Gammasy, Tarek M A; Shaheen, Kareem Y A; El-Mezdawi, Ramzi A M; Youssef, Mervat S M

2013-06-01

Apoptosis is induced by binding of death receptor ligands, members of the tumor necrosis factor (TNF) superfamily, to their cognate receptors. It is suggested that TNF-related apoptosis inducing ligand (TRAIL) is involved in pathogenesis of juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to assess TRAIL concentrations in sera of JSLE children and to determine their potential relationship with disease activity, anti-double-stranded DNA (anti-dsDNA) levels, neutropenia and renal involvement. Circulating levels of TRAIL were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 40 JSLE patients (20 with active and 20 with inactive disease) and 20 controls. The mean (SEM) serum TRAIL concentration in JSLE was 1750.7 (440.2) pg/mL. Serum TRAIL concentrations in patients were higher than those in controls (P < 0.01). Serum TRAIL concentrations for children with inactive disease (1854.8 [485.4] pg/mL) and those with activity (1646.6 [390.6] pg/mL) were statistically comparable. JSLE children with positive anti-dsDNA antibodies had significantly higher TRAIL levels (mean = 1846 [456] vs. 1455 [325] pg/mL; P < 0.05). Serum TRAIL concentrations were significantly higher in classes III and IV nephritis compared to classes I and II nephritis (1970 [512] vs. 1330 [331] pg/mL; P < 0.01). Serum TRAIL concentrations in patients with neutropenia were higher than those without neutropenia (1805 [505] vs. 1516 [400] pg/mL; P = 0.042) and in controls (P = 0.024). Our data indicate that an increased level of TRAIL is a feature of JSLE that correlates with disease activity, anti-dsDNA titers neutropenia and lupus nephritis. © 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

DOSE-RESPONSE RELATIONSHIPS FOR MOLECULAR ALTERATIONS INDUCED BY B[ A ]P IN STRAIN A/J MOUSE LUNG

EPA Science Inventory

Benzo[a]pyrene (B[a]P) induces tumors in rodents at doses much higher than those found in the environment. Current cancer risk assessment of B[a]P assumes that the risk posed by low level exposure to B[a]P is linear with respect to dose. We have measur...

Abundance of Cysteine Endopeptidase Dionain in Digestive Fluid of Venus Flytrap (Dionaea muscipula Ellis) Is Regulated by Different Stimuli from Prey through Jasmonates

PubMed Central

Libiaková, Michaela; Floková, Kristýna; Novák, Ondřej; Slováková, L'udmila; Pavlovič, Andrej

2014-01-01

The trap of the carnivorous plant Venus flytrap (Dionaea muscipula) catches prey by very rapid closure of its modified leaves. After the rapid closure secures the prey, repeated mechanical stimulation of trigger hairs by struggling prey and the generation of action potentials (APs) result in secretion of digestive fluid. Once the prey's movement stops, the secretion is maintained by chemical stimuli released from digested prey. We investigated the effect of mechanical and chemical stimulation (NH4Cl, KH2PO4, further N(Cl) and P(K) stimulation) on enzyme activities in digestive fluid. Activities of β-D-glucosidases and N-acetyl-β-D-glucosaminidases were not detected. Acid phosphatase activity was higher in N(Cl) stimulated traps while proteolytic activity was higher in both chemically induced traps in comparison to mechanical stimulation. This is in accordance with higher abundance of recently described enzyme cysteine endopeptidase dionain in digestive fluid of chemically induced traps. Mechanical stimulation induced high levels of cis-12-oxophytodienoic acid (cis-OPDA) but jasmonic acid (JA) and its isoleucine conjugate (JA-Ile) accumulated to higher level after chemical stimulation. The concentration of indole-3-acetic acid (IAA), salicylic acid (SA) and abscisic acid (ABA) did not change significantly. The external application of JA bypassed the mechanical and chemical stimulation and induced a high abundance of dionain and proteolytic activity in digestive fluid. These results document the role of jasmonates in regulation of proteolytic activity in response to different stimuli from captured prey. The double trigger mechanism in protein digestion is proposed. PMID:25153528

Viral proliferation and expression of tumor-related gene in different chicken embryo fibroblasts infected with different tumorigenic phenotypes of avian leukosis virus subgroup J.

PubMed

Qu, Yajin; Liu, Litao; Niu, Yujuan; Qu, Yue; Li, Ning; Sun, Wei; Lv, Chuanwei; Wang, Pengfei; Zhang, Guihua; Liu, Sidang

2016-10-01

Subgroup J avian leukosis virus (ALV-J) causes a neoplastic disease in infected chickens. The ALV-J strain NX0101, which was isolated from broiler breeders in 2001, mainly induced formation of myeloid cell tumors. However, strain HN10PY01, which was recently isolated from laying hens, mainly induces formation of myeloid cell tumors and hemangioma. To identify the molecular pathological mechanism underlying changes in host susceptibility and tumor classification induced by these two types of ALV-J strains, chicken embryo fibroblasts derived from chickens with different genetic backgrounds (broiler breeders and laying hens) and an immortalized chicken embryo fibroblasts (DF-1) were prepared and infected with strain NX0101 or HN10PY01, respectively. The 50% tissue culture infective dose (TCID50) and levels of ALV group-specific antigen p27 and heat shock protein 70 in the supernatant collected from the ALV-J infected cells were detected. Moreover, mRNA expression levels of tumor-related genes p53, c-myc, and Bcl-2 in ALV-J-infected cells were quantified. The results indicated that the infection of ALV-J could significantly increase mRNA expression levels of p53, c-myc, and Bcl-2 Strain HN10PY01 exhibited a greater influence on the three tumor-related genes in each of the three types of cells when compared with strain NX0101, and the TCID50 and p27 levels in the supernatant collected from HN10PY01-infected cells were higher than those collected from NX0101-infected cells. These results indicate that the infection of the two ALV-J strains influenced the gene expression levels in the infected cells, while the newly isolated strain HN10PY01 showed higher replication ability in cells and induced higher expression levels of tumor-related genes in infected cells. Furthermore, virus titers and expression levels of tumor-related genes and cellular stress responses of cells with different genetic backgrounds when infected with each of the two ALV-J strain were different, indicating that genetic backgrounds influenced the capabilities of the virus to infect and proliferate. The findings of this study provide useful data to further elucidate the mechanism underlying host susceptibility and tumor classification in ALV-J-infected chickens and cells. © 2016 Poultry Science Association Inc.

Protective effect of dexpanthenol on ischemia-reperfusion-induced renal injury in rats.

PubMed

Altintas, Ramazan; Parlakpinar, Hakan; Beytur, Ali; Vardi, Nigar; Polat, Alaadin; Sagir, Mustafa; Odabas, Gul Pelin

2012-01-01

This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time. Copyright © 2012 S. Karger AG, Basel.

Sensitization with 7S globulins from peanut, hazelnut, soy or pea induces IgE with different biological activities which are modified by soy tolerance.

PubMed

Kroghsbo, Stine; Bøgh, Katrine L; Rigby, Neil M; Mills, E N Clare; Rogers, Adrian; Madsen, Charlotte B

2011-01-01

It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their 'normal' matrix. Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3 times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. The 4 related 7S globulins induced a response with an almost identical level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Although the 4 7S globulins are structurally related allergens, they induce antibodies with different antigen-binding characteristics. Peanut 7S induces IgE of a higher avidity than hazelnut and pea 7S which, again, has a higher avidity than IgE induced by soy 7S. We also show that soy tolerance influences the function of antibodies to peanut 7S. These findings may help explain how antibodies of different clinical significances can develop in different individuals sensitized to the same allergen. Copyright © 2011 S. Karger AG, Basel.

Concorde noise-induced building vibrations for Sully Plantation, Chantilly, Virginia

NASA Technical Reports Server (NTRS)

Mayes, W. H.; Scholl, H. F.; Stephens, D. G.; Holliday, B. G.; Deloach, R.; Holmes, H. K.; Lewis, R. B.; Lynch, J. W.

1976-01-01

A study to assess the noise-induced building vibrations associated with Concorde operations is presented. The approach is to record the levels of induced vibrations and associated indoor/outdoor noise levels in selected homes, historic and other buildings near Dulles and Kennedy International Airports. Presented is a small, representative sample of data recorded at Sully Plantation, Chantilly, Virginia during the period of May 20 through May 28, 1976. Recorded data provide relationships between the vibration levels of walls, floors, windows, and the noise associated with Concorde operations (2 landings and 3 takeoffs), other aircraft, nonaircraft sources, and normal household activities. Results suggest that building vibrations resulting from aircraft operations were proportional to the overall sound pressure levels and relatively insensitive to spectral differences associated with the different types of aircraft. Furthermore, the maximum levels of vibratory response resulting from Concorde operations were higher than those associated with conventional aircraft. The vibrations of nonaircraft events were observed in some cases to exceed the levels resulting from aircraft operations. These nonaircraft events are currently being analyzed in greater detail.

Dexamethasone attenuates echinococcosis-induced allergic reactions via regulatory T cells in mice.

PubMed

Zhang, Qin; Ye, Jianrong; Zheng, Hong

2016-03-11

Cystic echinococcosis (CE), caused by infection with Echinococcus granulosus larvae, is a potentially life-threatening disease in humans. Anaphylactic shock caused by CE is very dangerous, and is highly prevalent during surgery. Dexamethasone (DEX) is used clinically before operations to prevent allergic reactions; Regulatory T cells (Treg cells) are believed to be associated with negative immune response, which play an important role in alleviating allergic reactions. However, the association of Treg cells with DEX remains unknown. In this study, C57BL/6 mice were divided into uninfected group, untreated group and DEX group which were inoculated with protoscoleces from E. granulosus and sensitized using a cyst fluid suspension to induce anaphylactic shock. In addition, the mice in DEX group were treated with 10 mg/kg DEX by intraperitoneal injection 30 min before being sensitized. It was found that 93.75 % of all sensitized mice experienced allergic symptoms. The levels of IgE, IgE/IgG, and IgE/IgG1 were significantly higher in both untreated group and DEX group. The proportion of CD4 + CD25 + FOXP3 + Treg cells relative to CD4+ Treg cells, and the levels of interleukin-10 (IL-10) and tumor growth factor-β (TGF-β1) were significantly higher in DEX group. The level of IL-13 was significantly higher in the sensitized mice than in the other groups. These cells may play a key role in alleviating the immune response in CE-induced anaphylactic shock. The protective effect of DEX may be due to Treg cell upregulating IL-10 and TGF-β1 levels, and inhibiting helper T cell 2 cytokines.

Sphere formation of adipose stem cell engineered by poly-2-hydroxyethyl methacrylate induces in vitro angiogenesis through fibroblast growth factor 2.

PubMed

Kim, Jong-Ho; Lim, I-Rang; Joo, Hyung Joon; Choi, Seung-Cheol; Choi, Ji-Hyun; Cui, Long-Hui; Im, Lisa; Hong, Soon Jun; Lim, Do-Sun

A number of researchers have been reporting a wide range of in vitro and in vivo studies of cell engraftment to enhance angiogenesis using stem cells. Despite these efforts, studies involving three-dimensional (3D) culture method that mimics in vivo environment have not reached its peak yet. In this study, we investigated the change and effects on cellular angiogenic growth factors through sphere formation of adipose stem cell (ASC) which is engineered by poly-2-hydroxyethyl methacrylate (Poly-HEMA). First of all, we successfully induced sphere formation of ASC (sph-ASC) on Poly-HEMA coated plates. sph-ASC represented significantly higher expression levels of anti-apoptotic and hypoxic factors compared to monolayer adherent ASC (adh-ASC). Interestingly, sph-ASC showed higher mRNA levels of the following genes; CD31, CD144, vWF, IGF-2, MCP-1, PDGF-A, VEGF-A, VEGF-C, and FGF-2. In addition, mRNA expressions of angiogenic growth factor receptors such as Flk1, FGFR1, FGFR2, and Tie2 were elevated in sph-ASC. In protein level, Cytokine/Chemokines antibody array revealed a significant increase of FGF-2 in sph-ASC (3.17-fold) compared to adh-ASC. To investigate the effects of FGF-2 on sph-ASC, Matrigel angiogenic invasion assay showed significant reduced level of FGF-2 in FGF-2 siRNA transfected sph-ASC (2.27-fold) compared to negative control siRNA transfected sph-ASC. These findings suggest that Poly-HEMA coated plates induce sphere formation of ASC which has significantly higher expression of FGF-2, and plays a critical role as a major regulating growth factor of in vitro angiogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

PubMed

Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-07-01

Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. © 2014 by the Society for the Study of Reproduction, Inc.

Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

PubMed Central

Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

2014-01-01

ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

Subclinical herpesvirus shedding among HIV-1-infected men on antiretroviral therapy.

PubMed

Agudelo-Hernandez, Arcadio; Chen, Yue; Bullotta, Arlene; Buchanan, William G; Klamar-Blain, Cynthia R; Borowski, Luann; Riddler, Sharon A; Rinaldo, Charles R; Macatangay, Bernard J C

2017-09-24

We evaluated the subclinical shedding of six different herpesviruses in antiretroviral drug-treated HIV-positive [HIV(+)] MSM, and determined how this is associated with markers of inflammation and immune activation. We obtained blood, semen, throat washing, urine, and stool from 15 antiretroviral-treated HIV-1-infected MSM with CD4 T-cell reconstitution, and 12 age-matched HIV-negative [HIV (-)] MSM from the Multicenter AIDS Cohort Study at four timepoints over 24 weeks to measure DNA levels of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 and 2, human herpesvirus 6 (HHV6), and HHV8. T-cell activation and plasma levels of soluble markers of inflammation and activation were also measured at the corresponding timepoints. HIV(+) participants had a trend for higher total herpesvirus shedding rate. HIV(+) participants also had a significantly higher rate of shedding EBV and CMV compared with the HIV(-) group. Herpesvirus shedding was mostly seen in throat washings. In the HIV(+) group, herpesvirus shedding rate inversely correlated with plasma levels of interferon γ-induced protein 10 and soluble CD163. CMV DNA levels negatively correlated with levels of T-cell activation. There was a trend for a positive correlation between EBV shedding rate and plasma soluble CD14. HHV6 shedding rate negatively correlated with plasma levels of interleukin-6, soluble CD163, and interferon gamma-induced protein 10. Correlations were not observed among HIV(-) individuals. Among treated HIV-infected MSM, there are higher subclinical shedding rates of some herpesviruses that occur in different body compartments and negatively correlate with levels of inflammation and immune activation.

[Sucrose reward promotes rats' motivation for cocaine].

PubMed

Li, Yan-Qing; LE, Qiu-Min; Yu, Xiang-Chen; Ma, Lan; Wang, Fei-Fei

2016-06-25

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

Nuclear thioredoxin-1 is required to suppress cisplatin-mediated apoptosis of MCF-7 cells

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

Chen, Xiao-Ping; Liu, Shou; Tang, Wen-Xin

2007-09-21

Different cell line with increased thioredoxin-1 (Trx-1) showed a decreased or increased sensitivity to cell killing by cisplatin. Recently, several studies found that the subcellular localization of Trx-1 is closely associated with its functions. In this study, we explored the association of the nuclear Trx-1 with the cisplatin-mediated apoptosis of breast cancer cells MCF-7. Firstly, we found that higher total Trx-1 accompanied by no change of nuclear Trx-1 can not influence apoptosis induced by cisplatin in MCF-7 cells transferred with Trx-1 cDNA. Secondly, higher nuclear Trx-1 accompanied by no change of total Trx-1 can protect cells from apoptosis induced bymore » cisplatin. Thirdly, high nuclear Trx-1 involves in the cisplatin-resistance in cisplatin-resistive cells. Meanwhile, we found that the mRNA level of p53 is closely correlated with the level of nuclear Trx-1. In summary, we concluded that the nuclear Trx-1 is required to resist apoptosis of MCF-7 cells induced by cisplatin, probably through up-regulating the anti-apoptotic gene, p53.« less

Extracellular adenosine triphosphate affects systemic and kidney immune cell populations in pregnant rats.

PubMed

Spaans, Floor; Melgert, Barbro N; Borghuis, Theo; Klok, Pieter A; de Vos, Paul; Bakker, Winston W; van Goor, Harry; Faas, Marijke M

2014-09-01

Changes in the systemic immune response are found in preeclampsia. This may be related to high extracellular adenosine triphosphate (ATP) levels. The question arose whether ATP could affect immune responses in pregnancy. Previously, we investigated whether ATP affected monocyte activation and subpopulations. Here, we investigated ATP-induced changes in other immune cell populations in pregnant rats, systemically and in the kidney, an affected organ in preeclampsia. Using flow cytometry or immunohistochemistry, blood and kidney leukocytes were studied in pregnant and non-pregnant rats at different intervals after ATP or saline infusion. Adenosine triphosphate (ATP) infusion induced increased peripheral blood non-classical monocytes and decreased T lymphocyte subsets in pregnant rats only, higher glomerular macrophage and T lymphocyte numbers in non-pregnant animals 1 day after infusion, and higher glomerular macrophage numbers in pregnant rats 6 days after infusion. Adenosine triphosphate (ATP) infusion in pregnant rats induced a pregnancy-specific inflammatory response. Increased ATP levels could potentially contribute to development of the inflammatory response of preeclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-intensity high-volume swimming induces more robust signaling through PGC-1α and AMPK activation than sprint interval swimming in m. triceps brachii

PubMed Central

Plaza-Díaz, Julio; Ruiz-Ojeda, Francisco J.; Aragón-Vela, Jerónimo; Robles-Sanchez, Cándido; Nordsborg, Nikolai B.; Hebberecht, Marina; Salmeron, Luis M.; Huertas, Jesus R.

2017-01-01

We aimed to test whether high-intensity high-volume training (HIHVT) swimming would induce more robust signaling than sprint interval training (SIT) swimming within the m. triceps brachii due to lower metabolic and oxidation. Nine well-trained swimmers performed the two training procedures on separate randomized days. Muscle biopsies from m. triceps brachii and blood samples were collected at three different time points: a) before the intervention (pre), b) immediately after the swimming procedures (post) and c) after 3 h of rest (3 h). Hydroperoxides, creatine kinase (CK), and lactate dehydrogenase (LDH) were quantified from blood samples, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the AMPKpTHR172/AMPK ratio were quantified by Western blot analysis. PGC-1α, sirtuin 3 (SIRT3), superoxide-dismutase 2 (SOD2), and vascular endothelial growth factor (VEGF) mRNA levels were also quantified. SIT induced a higher release of LDH (p < 0.01 at all time points) and CK (p < 0.01 at post) than HIHVT, but neither SIT nor HIHVT altered systemic hydroperoxides. Additionally, neither SIRT3 nor SOD2 mRNA levels increased, while PGC-1α transcription increased at 3 h after SIT (p < 0.01) and after HIHVT (p < 0.001). However, PGC-1α protein was higher after HIHVT than after SIT (p < 0.05). Moreover, the AMPKpTHR172/AMPK ratio increased at post after SIT (p < 0.05), whereas this effect was delayed after HIHVT as it increased after 3 h (p < 0.05). In addition, VEGF transcription was higher in response to HIHVT (p < 0.05). In conclusion, SIT induces higher muscular stress than HIHVT without increasing systemic oxidation. In addition, HIHVT may induce more robust oxidative adaptations through PGC-1α and AMPK. PMID:28973039

High-intensity high-volume swimming induces more robust signaling through PGC-1α and AMPK activation than sprint interval swimming in m. triceps brachii.

PubMed

Casuso, Rafael A; Plaza-Díaz, Julio; Ruiz-Ojeda, Francisco J; Aragón-Vela, Jerónimo; Robles-Sanchez, Cándido; Nordsborg, Nikolai B; Hebberecht, Marina; Salmeron, Luis M; Huertas, Jesus R

2017-01-01

We aimed to test whether high-intensity high-volume training (HIHVT) swimming would induce more robust signaling than sprint interval training (SIT) swimming within the m. triceps brachii due to lower metabolic and oxidation. Nine well-trained swimmers performed the two training procedures on separate randomized days. Muscle biopsies from m. triceps brachii and blood samples were collected at three different time points: a) before the intervention (pre), b) immediately after the swimming procedures (post) and c) after 3 h of rest (3 h). Hydroperoxides, creatine kinase (CK), and lactate dehydrogenase (LDH) were quantified from blood samples, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the AMPKpTHR172/AMPK ratio were quantified by Western blot analysis. PGC-1α, sirtuin 3 (SIRT3), superoxide-dismutase 2 (SOD2), and vascular endothelial growth factor (VEGF) mRNA levels were also quantified. SIT induced a higher release of LDH (p < 0.01 at all time points) and CK (p < 0.01 at post) than HIHVT, but neither SIT nor HIHVT altered systemic hydroperoxides. Additionally, neither SIRT3 nor SOD2 mRNA levels increased, while PGC-1α transcription increased at 3 h after SIT (p < 0.01) and after HIHVT (p < 0.001). However, PGC-1α protein was higher after HIHVT than after SIT (p < 0.05). Moreover, the AMPKpTHR172/AMPK ratio increased at post after SIT (p < 0.05), whereas this effect was delayed after HIHVT as it increased after 3 h (p < 0.05). In addition, VEGF transcription was higher in response to HIHVT (p < 0.05). In conclusion, SIT induces higher muscular stress than HIHVT without increasing systemic oxidation. In addition, HIHVT may induce more robust oxidative adaptations through PGC-1α and AMPK.

Avionics electromagnetic interference immunity and environment

NASA Technical Reports Server (NTRS)

Clarke, C. A.

1986-01-01

Aircraft electromagnetic spectrum and radio frequency (RF) field strengths are charted, profiling the higher levels of electromagnetic voltages encountered by the commercial aircraft wiring. Selected military, urban, and rural electromagnetic field levels are plotted and provide a comparison of radiation amplitudes. Low frequency magnetic fields and electric fields from 400 H(Z) power systems are charted versus frequency and wire separation to indicate induced voltages on adjacent or neighboring circuits. Induced EMI levels and attenuation characteristics of electric, magnetic, RF fields, and transients are plotted and graphed for common types of wire circuits. The significance of wire circuit returns and shielding is emphasized to highlight the techniques that help block the paths of electromagnetic interference and maintain avionic interface signal quality.

Diethylnitrosamine-induced hepatocarcinogenesis is suppressed in lecithin:retinol acyltransferase-deficient mice primarily through retinoid actions immediately after carcinogen administration.

PubMed

Shirakami, Yohei; Gottesman, Max E; Blaner, William S

2012-02-01

Loss of retinoid-containing lipid droplets upon hepatic stellate cell (HSC) activation is one of the first events in the development of liver disease leading to hepatocellular carcinoma. Although retinoid stores are progressively lost from HSCs during the development of hepatic disease, how this affects hepatocarcinogenesis is unclear. To investigate this, we used diethylnitrosamine (DEN) to induce hepatic tumorigenesis in matched wild-type (WT) and lecithin:retinol acyltransferase (LRAT) knockout (KO) mice, which lack stored retinoid and HSC lipid droplets. Male 15-day-old WT or Lrat KO mice were given intraperitoneal injections of DEN (25 mg/kg body wt). Eight months later, Lrat KO mice showed significantly less liver tumor development compared with WT mice, characterized by less liver tumor incidence and smaller tumor size. Two days after DEN injection, lower serum levels of alanine aminotransferase and decreased hepatic levels of cyclin D1 were observed in Lrat KO mice. Lrat KO mice also exhibited increased levels of retinoic acid-responsive genes, including p21, lower levels of cytochrome P450 enzymes required for DEN bioactivation and higher levels of the DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), both before and after DEN treatment. Our results indicate that Lrat KO mice are less susceptible to DEN-induced hepatocarcinogenesis due to increased retinoid signaling and higher expression of p21, which is accompanied by altered hepatic levels of DEN-activating enzymes and MGMT in Lrat KO mice also contribute to decreased cancer initiation and suppressed liver tumor development.

Hemoglobin extravasation in the brain of rats exchange-transfused with hemoglobin-based oxygen carriers.

PubMed

Terraneo, Laura; Bianciardi, Paola; Malavalli, Ashok; Mkrtchyan, Gnel; Spann, Stephanie N; Lohman, Jeff; Samaja, Michele; Vandegriff, Kim D

2017-06-01

Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb. Animals were sacrificed 2 h after transfusion, brain tissue was harvested and processed for double-staining immunofluorescence, whereby Hb ? chain and NeuN (a neuron protein) were stained and quantitated. Whereas Hextend did not induce Hb extravasation, in both MP4OX and ??Hb brains Hb molecules were detected outside neurons. The level of extravasated Hb chains was > 3-fold higher in Hb compared to MP4OX. Western blot analysis revealed that the expression levels of protein related to redox imbalance (e.g., Nrf2, iNOS and ERK phosphorylation) were higher in ααHb than MP4OX. In conclusions, higher Hb extravasation in ααHb than MP4OX induces redox imbalance, which causes higher anti-oxidant response. Whereas Nrf2 response may be considered protective, iNOS response appears damaging.

Plant volatiles induced by herbivore egg deposition affect insects of different trophic levels.

PubMed

Fatouros, Nina E; Lucas-Barbosa, Dani; Weldegergis, Berhane T; Pashalidou, Foteini G; van Loon, Joop J A; Dicke, Marcel; Harvey, Jeffrey A; Gols, Rieta; Huigens, Martinus E

2012-01-01

Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant's volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels.

Gene Expression Signature in Adipose Tissue of Acromegaly Patients

PubMed Central

Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

2015-01-01

To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

Glutamine deprivation induces interleukin-8 expression in ataxia telangiectasia fibroblasts.

PubMed

Kim, Min-Hyun; Kim, Aryung; Yu, Ji Hoon; Lim, Joo Weon; Kim, Hyeyoung

2014-05-01

To investigate whether glutamine deprivation induces expression of inflammatory cytokine interleukin-8 (IL-8) by determining NF-κB activity and levels of oxidative indices (ROS, reactive oxygen species; hydrogen peroxide; GSH, glutathione) in fibroblasts isolated from patients with ataxia telangiectasia (A-T). We used A-T fibroblasts stably transfected with empty vector (Mock) or with human full-length ataxia telangiectasia mutated (ATM) cDNA (YZ5) and mouse embryonic fibroblasts (MEFs) transiently transfected with ATM small interfering RNA (siRNA) or with non-specific control siRNA. The cells were cultured with or without glutamine or GSH. ROS levels were determined using a fluorescence reader and confocal microscopy. IL-8 or murine IL-8 homolog, keratinocyte chemoattractant (KC), and hydrogen peroxide levels in the medium were determined by enzyme-linked immunosorbent assay and colorimetric assay. GSH level was assessed by enzymatic assay, while IL-8 (KC) mRNA level was measured by reverse transcription-polymerase chain reaction (RT-PCR) and/or quantitative real-time PCR. NF-κB DNA-binding activity was determined by electrophoretic mobility shift assay. Catalase activity and ATM protein levels were determined by O2 generation and Western blotting. While glutamine deprivation induced IL-8 expression and increased NF-κB DNA-binding activity in Mock cells, both processes were decreased by treatment of cells with glutamine or GSH or both glutamine and GSH. Glutamine deprivation had no effect on IL-8 expression or NF-κB DNA-binding activity in YZ5 cells. Glutamine-deprived Mock cells had higher oxidative stress indices (increases in ROS and hydrogen peroxide, reduction in GSH) than glutamine-deprived YZ5 cells. In Mock cells, glutamine deprivation-induced oxidative stress indices were suppressed by treatment with glutamine or GSH or both glutamine and GSH. GSH levels and catalase activity were lower in Mock cells than YZ5 cells. MEFs transfected with ATM siRNA and cultured without glutamine showed higher levels of ROS and IL-8 than those transfected with negative control siRNA; increased levels of ROS and IL-8 were suppressed by the treatment of glutamine. Glutamine deprivation induces ROS production, NF-κB activation, and IL-8 expression as well as a reduction in GSH in A-T fibroblasts, all of which are attenuated by glutamine supplementation.

Alterations in circadian and meal-induced gut peptide levels in lean and obese rats.

PubMed

Moghadam, Alexander A; Moran, Timothy H; Dailey, Megan J

2017-12-01

Alterations in gut hormone signaling are a likely contributing factor to the metabolic disturbances associated with overweight/obesity as they coordinate the timing of feeding behavior, absorption, and utilization of nutrients. These hormones are released in response to food intake, or follow a circadian or anticipatory pattern of secretion that is independent of nutrient stimulation. The aim of this study was to identify the degree to which high-fat diet-induced obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced levels in the middle of the light or dark cycle. Male Sprague-Dawley rats were fed a high-fat diet (OBESE) or chow (LEAN), implanted with jugular catheters, and blood samples were taken every 2 h throughout the light/dark cycle while freely feeding or after an Ensure liquid meal. We found that even when OBESE and LEAN animals ate the same kcals and have a similar pattern of food intake, there is a difference in both the levels and rhythm of plasma gut peptides. GLP-1 and PYY are higher during the light cycle in LEAN animals and AMY is higher in the OBESE group throughout the light/dark cycle. There was also a differential response of plasma gut signals after the Ensure meal, even though the composition and amount of intake of the meal were the same in both groups. These changes occur prior to the high-fat diet induced loss of glycemic control and may be a target for early intervention. Impact statement The aim of this study was to test if obesity would alter the daily rhythm of gut peptides or meal-induced levels in the middle of the light or dark cycle. We found that even when animals are eating the same amount (in kcal) of food that the obese animals have altered daily rhythms and meal-induced gut peptide levels. In particular, we are the first to show that obesity induces increases in peptide YY levels during the light cycle and amylin remains high throughout the light and dark cycle in obese animals. These changes occurred prior to a loss of glycemic control. Thus, the rhythm of gut peptides could be used as an early indicator of later and more serious metabolic disturbances and may be a target for early intervention.

Effect of clot aging and cholesterol content on ultrasound-assisted thrombolysis.

PubMed

Zhou, Yufeng; Murugappan, Suresh Kanna; Sharma, Vijay Kumar

2014-10-01

Exposure to 2-MHz transcranial diagnostic ultrasound enhances the thrombolytic activity of intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (sonothrombolysis). However, rates of arterial recanalization vary widely, depending upon the clot burden, its location, and stroke subtype. We evaluated the influence of age and cholesterol level of the blood clots on sonothrombolysis in an in vitro model. To "age" the clots, serum was replaced by fresh blood periodically. We increased the cholesterol content of the clots by adding cholesterin to the blood. The clots were lysed by tPA and/or transcranial Doppler ultrasound sonication for 1 h. The extent of thrombolysis induced by various treatment protocols (controls, sonication, tPA, and sonothrombolysis) was evaluated with relative changes in the clot weights and in the clot structure by scanning electron microscopy (SEM) at end of the experiment. Sonothrombolysis induced significantly higher weight reduction in fresh clots (37.3 % in 2-h old clots versus 24.8 % in 10-h ones, p < 0.005) as well as the clots with higher cholesterol levels (41.7 versus 30.6 % in normal cholesterol clots, p < 0.005). SEM demonstrated patterns of clot dissolution among various treatment modalities. Sonothrombolysis induced better clot lysis in fresh thrombi with high cholesterol levels.

Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice.

PubMed

Ishida, Naoyuki; Ishihara, Yuichi; Ishida, Kazuto; Tada, Hiroyuki; Funaki-Kato, Yoshiko; Hagiwara, Makoto; Ferdous, Taslima; Abdullah, Mohammad; Mitani, Akio; Michikawa, Makoto; Matsushita, Kenji

2017-01-01

Periodontitis is a localized infectious disease caused by periodontopathic bacteria, such as Porphyromonas gingivalis . Recently, it has been suggested that bacterial infections may contribute to the onset and the progression of Alzheimer's disease (AD). However, we do not have any evidence about a causative relationship between periodontitis and AD. In this study, we investigated by using a transgenic mouse model of AD whether periodontitis evoked by P. gingivalis modulates the pathological features of AD. Cognitive function was significantly impaired in periodontitis-induced APP-Tg mice, compared to that in control APP-Tg mice. Levels of Amiloid β (Aβ) deposition, Aβ40, and Aβ42 in both the hippocampus and cortex were higher in inoculated APP-Tg mice than in control APP-Tg mice. Furthermore, levels of IL-1β and TNF-α in the brain were higher in inoculated mice than in control mice. The levels of LPS were increased in the serum and brain of P. gingivalis -inoculated mice. P. gingivalis LPS-induced production of Aβ40 and Aβ42 in neural cell cultures and strongly enhanced TNF-α and IL-1β production in a culture of microglial cells primed with Aβ. Periodontitis evoked by P. gingivalis may exacerbate brain Aβ deposition, leading to enhanced cognitive impairments, by a mechanism that involves triggering brain inflammation.

Genetically obese (ob/ob) mice are resistant to the lethal effects of thioacetamide hepatotoxicity

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

Won, Young-Suk; Song, Ji-Won; Lim, Jong-Hwan

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels ofmore » malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [{sup 14}C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects. - Highlights: • ob/ob mice are resistant to lethal doses of thioacetamide, compared to ob/+ mice. • ob/ob mice show reduced oxidative stress and enhanced antioxidant enzyme activity. • ob/ob mice exhibit diminished bioactivation of thioacetamide.« less

Sildenafil reduces polyuria in rats with lithium-induced NDI.

PubMed

Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

2012-01-01

Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

Responses to salinity in invasive cordgrass hybrids and their parental species (Spartina) in a scenario of sea level rise and climate change

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods: Salinity is one of the main abiotic factors in salt marshes. Studies rooted to analyzed salinity tolerance of halophytes may help to relate their physiological tolerances with distribution limits in the field. Climate change-induced sea level rise and higher temperatures...

The effects of roflumilast on the pancreas and remote organs in a cerulein-induced experimental acute pancreatitis model in rats.

PubMed

Uslukaya, Omer; Turkoglu, Ahmet; Yazgan, Umit Can; Kaplan, Ibrahim; Ibiloglu, Ibrahim; Kapan, Murat; Gumus, Metehan

2016-12-01

Systemic damage in acute pancreatitis (AP) can be characterized by oxidative stress and the release of pro-inflammatory cytokines. Roflumilast has been shown to be a potent anti-inflammatory and antioxidant agent. In the present study, we aimed to investigate the effect of roflumilast in cerulein-induced AP. Thirty-two male rats were divided into four groups: group 1 (sham), group 2 (Roflumilast), group 3 (AP), and group 4 (AP + Roflumilast). AP was induced by injecting 4 × 75 μg/kg of body weight at an interval of 1 h. Rats were killed after 12 h following the last cerulein administration. AP was confirmed by measuring the serum amylase level and inflammatory features. Morphological changes were observed in the pancreas. Amylase levels were higher in the AP and AP + Roflumilast groups than the sham and Roflumilast groups. The serum levels of TNF-α, IL-1β, and IL-6 increased in the AP group, whereas they decreased in the Roflumilast group. The total oxidant activity (TOA) was higher and the total antioxidant capacity (TAC) was lower in the AP group. The administration of roflumilast decreased the TOA and increased the TAC in comparison with the AP group (p < 0.05 for both). Roflumilast significantly decreases oxidative stress and inflammatory mediators in the plasma, pancreas, and lung in cerulein-induced AP rats.

Cross-Resistance and Resistance Longevity as Induced by Bean Leaf Beetle, Cerotoma trifurcata and Soybean Looper, Pseudoplusia includens herbivory on Soybean

PubMed Central

Srinivas, P.; Danielson, Stephen D.; Smith, C. Michael; Foster, John E.

2001-01-01

Cross-resistance, and longevity of resistance, induced by the bean leaf beetle, Cerotoma trifurcata, was studied IN the soybean PI 227687 that exhibited induced response in earlier studies. Bean leaf beetle adults and soybean looper, Pseudoplusia includens, larvae were used to induce resistance and to determine beetle feeding preference. Beetles were collected from soybean fields 2 to 5 days prior to the feeding preference test. The level of cross-resistance induced by soybean looper herbivory to subsequent bean leaf beetle feeding was higher when compared to cross-resistance induced by bean leaf beetle herbivory against subsequent feeding by soybean looper. Further, herbivory by the bean leaf beetle also induced resistance against soybean looper feeding. In the longevity study, leaflets from treated plants were collected 5, 10, 12, 14, 16, 20 and 25 days after initiation of feeding. Pairwise comparisons of leaflets from plants treated by bean leaf beetle herbivory with untreated plants revealed that induced responses were highest 14 and lowest 25 days after initiation of feeding. On other sampling days, levels of induced response varied with the sampling day. PMID:15455065

Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

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

Tavintharan, S.; Ong, C.N.; Jeyaseelan, K.

2007-09-01

Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ{sub 10}). In HepG2 cells, simvastatin decreased mitochondrial CoQ{sub 10} levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ{sub 10}, reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ{sub 10} deficiency plays an important role in statin-induced hepatopathy, and that CoQ{sub 10} supplementation protectsmore » HepG2 cells from this complication.« less

CXC ligand 9 response to malaria during pregnancy is associated with low-birth-weight deliveries.

PubMed

Dong, Shu; Kurtis, Jonathan D; Pond-Tor, Sunthorn; Kabyemela, Edward; Duffy, Patrick E; Fried, Michal

2012-09-01

Placental infection with Plasmodium falciparum is associated with increased levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), and previous studies have associated increased levels of these cytokines with low birth weight (LBW), especially for malaria-infected primigravidae. To define the contribution of TNF-α and IFN-γ networks to placental-malaria-associated LBW, we measured chemokines induced by TNF-α and IFN-γ and related them to birth weight in a birth cohort of 782 mother-infant pairs residing in an area of P. falciparum holoendemicity in Tanzania. Among primigravidae, levels of CCL2, CXC ligand 9 (CXCL9), and CXCL13 were significantly higher during malaria infection in both the placenta and peripheral blood. Placental CXCL9 and CXCL13 levels were also higher in placental blood from secundigravidae and multigravidae. In multivariate analyses adjusted for known predictors of birth weight, malaria-infected primigravidae with placental CXCL9 levels in the lowest tertile gave birth to babies who weighed 610 g more than babies born to mothers with high CXCL9 levels. CXCL9 expression is induced by IFN-γ, and the strong association between birth weight and placental CXCL9 is consistent with previous observations relating IFN-γ to poor pregnancy outcomes.

Expression of activation-induced cytidine deaminase gene in B lymphocytes of patients with common variable immunodeficiency.

PubMed

Abolhassani, Hassan; Farrokhi, Amir Salek; Pourhamdi, Shabnam; Mohammadinejad, Payam; Sadeghi, Bamdad; Moazzeni, Seyed-Mohammad; Aghamohammadi, Asghar

2013-08-01

Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination (CSR) as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase (AID) protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells (PBMC) of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients (230.95±103.04 ng/ml) rather than controls (210.00±44.72 ng/ml; P=0.5). CVID cases with lower level of AID had decreased total level of IgE (P=0.04) and stimulated IgE production (P=0.02); while cases with increased level of AID presented higher level of IgA (P=0.04) and numbers of B cells (P=0.02) and autoimmune disease (P=0.02). Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients.

Jasmonic Acid Is a Key Regulator of Spider Mite-Induced Volatile Terpenoid and Methyl Salicylate Emission in Tomato1[w

PubMed Central

Ament, Kai; Kant, Merijn R.; Sabelis, Maurice W.; Haring, Michel A.; Schuurink, Robert C.

2004-01-01

The tomato (Lycopersicon esculentum) mutant def-1, which is deficient in induced jasmonic acid (JA) accumulation upon wounding or herbivory, was used to study the role of JA in the direct and indirect defense responses to phytophagous mites (Tetranychus urticae). In contrast to earlier reports, spider mites laid as many eggs and caused as much damage on def-1 as on wild-type plants, even though def-1 lacked induction of proteinase inhibitor activity. However, the hatching-rate of eggs on def-1 was significantly higher, suggesting that JA-dependent direct defenses enhanced egg mortality or increased the time needed for embryonic development. As to gene expression, def-1 had lower levels of JA-related transcripts but higher levels of salicylic acid (SA) related transcripts after 1 d of spider mite infestation. Furthermore, the indirect defense response was absent in def-1, since the five typical spider mite-induced tomato-volatiles (methyl salicylate [MeSA], 4,8,12-trimethyltrideca-1,3,7,11-tetraene [TMTT], linalool, trans-nerolidol, and trans-β-ocimene) were not induced and the predatory mite Phytoseiulus persimilis did not discriminate between infested and uninfested def-1 tomatoes as it did with wild-type tomatoes. Similarly, the expression of the MeSA biosynthetic gene salicylic acid methyltransferase (SAMT) was induced by spider mites in wild type but not in def-1. Exogenous application of JA to def-1 induced the accumulation of SAMT and putative geranylgeranyl diphosphate synthase transcripts and restored MeSA- and TMTT-emission upon herbivory. JA is therefore necessary to induce the enzymatic conversion of SA into MeSA. We conclude that JA is essential for establishing the spider mite-induced indirect defense response in tomato. PMID:15310835

Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats.

PubMed

Maddirala, Yasaswi; Tobwala, Shakila; Karacal, Humeyra; Ercal, Nuran

2017-04-26

The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups. Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Cataracts were evaluated at the end of week 2 (postpartum day 14) when the rat pups opened their eyes. N-acetylcysteine amide eye drops were administered beginning on week 3 until the end of week 4 (postpartum days 15 to 30), and the rats were sacrificed at the end of week 4. Lenses were isolated and examined for oxidative stress parameters such as glutathione, lipid peroxidation, and calcium levels along with the glutathione reductase and thioltransferase enzyme activities. Casein zymography and Western blot of m-calpain were performed using the water soluble fraction of lens proteins. Morphological examination of the lenses in the NACA-treated group indicated that NACA was able to reverse the cataract grade. In addition, glutathione level, thioltransferase activity, m-calpain activity, and m-calpain level (as assessed by Western blot) were all significantly higher in the NACA-treated group than in the sodium selenite-induced cataract group. Furthermore, sodium selenite- injected rat pups had significantly higher levels of malondialdehyde, glutathione reductase enzyme activity, and calcium levels, which were reduced to control levels upon treatment with NACA. The data suggest that NACA has the potential to significantly improve vision and decrease the burden of cataract-related loss of function. Prevention and reversal of cataract formation could have a global impact. Development of pharmacological agents like NACA may eventually prevent cataract formation in high-risk populations and may prevent progression of early-stage cataracts. This brings a paradigm shift from expensive surgical treatment of cataracts to relatively inexpensive prevention of vision loss.

Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac hypertrophy partially via Type 1 Angiotensin II receptor.

PubMed

Diniz, Gabriela Placoná; Lino, Caroline Antunes; Guedes, Elaine Castilho; Moreira, Luana do Nascimento; Barreto-Chaves, Maria Luiza Morais

2015-09-01

Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of cardiac homeostasis, and miR-133 has been shown to be involved in cardiac hypertrophy. However, the potential role of miR-133 in cardiac growth induced by TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as its potential role in cardiac hypertrophy in response to TH. Wistar rats were subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum levels were assessed to confirm the hyperthyroid status. TH induced cardiac hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and α-actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was decreased in TH-induced cardiac hypertrophy in part through the AT1R. Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin were increased in hyperthyroidism partially via AT1R, as evaluated by real-time RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte hypertrophy in vitro. However, a gain-of-function study revealed that miR-133 mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our data indicate that miR-133 expression is reduced in TH-induced cardiac hypertrophy partially by the AT1R and that miR-133 mimic prevents the cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new insights regarding the mechanisms involved in the cardiac growth mediated by TH, suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.

Response of tobacco to the Pseudomonas syringae pv. Tomato DC3000 is mainly dependent on salicylic acid signaling pathway.

PubMed

Liu, Yang; Wang, Li; Cai, Guohua; Jiang, Shanshan; Sun, Liping; Li, Dequan

2013-07-01

Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000) was the first pathogen to be demonstrated to infect Arabidopsis and to cause disease symptoms in the laboratory setting. However, the defense response to Pst DC3000 was unclear in tobacco. In this report, the expression profiles of twelve defense response-related genes were analyzed after treatment with salicylic acid (SA), jasmonic acid (JA), and pathogen Pst DC3000 by qRT-PCR. According to our results, it could be presented that the genes primarily induced by SA were also induced to higher levels after Pst DC3000 infection. SA accumulation could be induced to a higher level than that of JA after Pst DC3000 infection. In addition, SA could result in hypersensitive response (HR), which did not completely depend on accumulation of reactive oxygen species. These results indicated that tobacco mainly depended on SA signaling pathway rather than on JA signaling pathway in response to Pst DC3000. Further study demonstrated that JA could significantly inhibit the accumulation of SA and the generation of the HR induced by Pst DC3000. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Amplified and persistent immune responses generated by single-cycle replicating adenovirus vaccines.

PubMed

Crosby, Catherine M; Nehete, Pramod; Sastry, K Jagannadha; Barry, Michael A

2015-01-01

Replication-competent adenoviral (RC-Ad) vectors generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common replication-defective Ad (RD-Ad) vectors with deletions of E1 avoid this risk but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered "single-cycle" adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower-seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes at levels hundreds of times higher than that of RD-Ad. Surprisingly, SC-Ad, but not RC-Ad, generated higher levels of transgene-specific antibody than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher gamma interferon (IFN-γ) responses and higher transgene-specific serum antibody levels. These data suggest that SC-Ad vectors may have utility as mucosal vaccines. This work illustrates the utility of our recently developed single-cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication-defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows that replicating SC-Ad6 produces higher levels of luciferase and induces higher levels of green fluorescent protein (GFP)-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication-competent (RC-Ad6) vector produces more luciferase than SC-Ad6, it does not elicit comparable levels of anti-GFP antibodies in permissive hamsters. When tested in the larger rhesus macaque model, SC-Ad6 induces higher transgene-specific antibody and T cell responses. Together, these data suggest that SC-Ad6 could be a more effective platform for developing vaccines against more relevant antigens. This could be especially beneficial for developing vaccines for pathogens for which traditional replication-defective adenovirus vectors have not been effective. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparison of heat induced damage at the saphenofemoral junction after ablation with 1,470 nm laser or radiofrequency.

PubMed

Ozcinar, Evren; Cakici, Mehmet; Korun, Oktay; Han, Unsal; Kiziltepe, Ugursay

2017-03-01

The aim of this study was to evaluate the heat induced damage at the saphenofemoral junction level according to histopathological changes after radiofrequency or 1,470 nm radial tip laser ablation. Varicose vein segments of 6-10 mm in diameter were exposed to radiofrequency (Closure Fast catheter, 7 cm heat segment, one cycle, 15 seconds, 10 Watt, 120 °C) or laser ablation (1,470 nm radial tip, continuous wave, vein diameter: 6 cm/8 cm/10 cm-power: 10 Watt-pullback speed: 2.2 mm/s, 1.7 mm/s, 1.3 mm/s-LEED: 45J/cm, 60J/cm, 75J/cm-EFE 25J/cm 2 , respectively). Approximate 2 cm segments of the vein were left untreated, then histopathological examinations of the untouched segments (5 slices: level 1 - furthest segment, level 2 - nearest segment) for heat induced damage were performed. A total damage scoring system was established, including the presence of endothelial swelling, intimal thickening, cellular vacuolisation in the muscle layer, oedema in the tunica media, and extent of necrosis. At level 1, the furthest segment of the specimen, there was no significant difference between the laser and control group, while the total damage score of the radiofrequency group was significantly higher than the control group (p < 0.01). Radiofrequency group had higher total damage score compared to the laser group at level 1 (p < 0.01), 2 (p < 0.01), and 5 (p < 0.01); while no significant difference was observed at level 3 (p = 0.46) and 4 (p = 0.13). Significant heat induced damage may be seen even if the 2 cm segment of the vessel is left unablated. Radiofrequency ablation seems to cause more histological damage than laser ablation in this ex vivo study. Further in vivo studies are necessary, in order to validate these findings.

Trends in Inequalities in Induced Abortion According to Educational Level among Urban Women

PubMed Central

García-Subirats, Irene; Rodríguez-Sanz, Maica; Díez, Elia; Borrell, Carme

2010-01-01

This study aims to describe trends in inequalities by women’s socioeconomic position and age in induced abortion in Barcelona (Spain) over 1992–1996 and 2000–2004. Induced abortions occurring in residents in Barcelona aged 20 and 44 years in the study period are included. Variables are age, educational level, and time periods. Induced abortion rates per 1,000 women and absolute differences for educational level, age, and time period are calculated. Poisson regression models are fitted to obtain the relative risk (RR) for trends. Induced abortion rates increased from 10.1 to 14.6 per 1,000 women aged 20–44 (RR = 1.44; 95% confidence interval (CI) 1.41–1.47) between 1992–1996 and 2000–2004. The abortion rate was highest among women aged 20–24 and 25–34 and changed little among women aged 35–44. Among women aged 20–24 and 25–34, those with a primary education or less had higher rates of induced abortion in the second period. Induced abortion rates also grew in those women with secondary education. In the 35–44 age group, the induced abortion rate declined among women with a secondary education (RR = 0.66; 95% CI 0.60–0.73) and slightly among those with a greater level of education. Induced abortion is rising most among women in poor socioeconomic positions. This study reveals deep inequalities in induced abortion in Barcelona, Spain. The trends identified in this study suggest that policy efforts to reduce unintended pregnancies are failing in Spain. Our study fills an important gap in literature on recent trends in Southern Europe. PMID:20229107

Efficient removal of cyclobutane pyrimidine dimers in barley: differential contribution of light-dependent and dark DNA repair pathways.

PubMed

Manova, Vasilissa; Georgieva, Ralitsa; Borisov, Borislav; Stoilov, Lubomir

2016-10-01

Barley stress response to ultraviolet radiation (UV) has been intensively studied at both the physiological and morphological level. However, the ability of barley genome to repair UV-induced lesions at the DNA level is far less characterized. In this study, we have investigated the relative contribution of light-dependent and dark DNA repair pathways for the efficient elimination of cyclobutane pyrimidine dimers (CPDs) from the genomic DNA of barley leaf seedlings. The transcriptional activity of barley CPD photolyase gene in respect to the light-growth conditions and UV-C irradiation of the plants has also been analyzed. Our results show that CPDs induced in the primary barley leaf at frequencies potentially damaging DNA at the single-gene level are removed efficiently and exclusively by photorepair pathway, whereas dark repair is hardly detectable, even at higher CPD frequency. A decrease of initially induced CPDs under dark is observed but only after prolonged incubation, suggesting the activation of light-independent DNA damage repair and/or tolerance mechanisms. The green barley seedlings possess greater capacity for CPD photorepair than the etiolated ones, with efficiency of CPD removal dependent on the intensity and quality of recovering light. The higher repair rate of CPDs measured in the green leaves correlates with the higher transcriptional activity of barley CPD photolyase gene. Visible light and UV-C radiation affect differentially the expression of CPD photolyase gene particularly in the etiolated leaves. We propose that the CPD repair potential of barley young seedlings may influence their response to UV-stress. © 2016 Scandinavian Plant Physiology Society.

Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.

PubMed

Sotomayor-Zárate, Ramón; Abarca, Jorge; Araya, Katherine A; Renard, Georgina M; Andrés, María E; Gysling, Katia

2015-11-01

A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lactobacillus fermentum ZYL0401 Attenuates Lipopolysaccharide-Induced Hepatic TNF-α Expression and Liver Injury via an IL-10- and PGE2-EP4-Dependent Mechanism

PubMed Central

Lv, Longxian; Yang, Jianzhuan; Lu, Haifeng; Li, Lanjuan

2015-01-01

Lipopolysaccharide (LPS) has essential role in the pathogenesis of D-galactosamine-sensitized animal models and alcoholic liver diseases of humans, by stimulating release of pro-inflammatory mediators that cause hepatic damage and intestinal barrier impairment. Oral pretreatment of probiotics has been shown to attenuate LPS-induced hepatic injury, but it is unclear whether the effect is direct or due to improvement in the intestinal barrier. The present study tested the hypothesis that pretreatment with probiotics enables the liver to withstand directly LPS-induced hepatic injury and inflammation. In a mouse model of LPS-induced hepatic injury, the levels of hepatic tumor necrosis factor-alpha (TNF-α) and serum alanine aminotransferase (ALT) of mice with depleted intestinal commensal bacteria were not significantly different from that of the control models. Pre-feeding mice for 10 days with Lactobacillus fermentum ZYL0401 (LF41), significantly alleviated LPS-induced hepatic TNF-α expression and liver damage. After LF41 pretreatment, mice had dramatically more L.fermentum-specific DNA in the ileum, significantly higher levels of ileal cyclooxygenase (COX)-2 and interleukin 10 (IL-10) and hepatic prostaglandin E2 (PGE2). However, hepatic COX-1, COX-2, and IL-10 protein levels were not changed after the pretreatment. There were also higher hepatic IL-10 protein levels after LPS challenge in LF41-pretreaed mice than in the control mice. Attenuation of hepatic TNF-α was mediated via the PGE2/E prostanoid 4 (EP4) pathway, and serum ALT levels were attenuated in an IL-10-dependent manner. A COX-2 blockade abolished the increase in hepatic PGE2 and IL-10 associated with LF41. In LF41-pretreated mice, a blockade of IL-10 caused COX-2-dependent promotion of hepatic PGE2, without affecting hepatic COX-2levels. In LF41-pretreated mice, COX2 prevented enhancing TNF-α expression in both hepatic mononuclear cells and the ileum, and averted TNF-α-mediated increase in intestinal permeability. Together, we demonstrated that LF41 pre-feeding enabled the liver to alleviate LPS-induced hepatic TNF-α expression and injury via a PGE2-EP4- and IL-10-dependent mechanism. PMID:25978374

Analysis of obstruction site in obstructive sleep apnea syndrome patients by drug induced sleep endoscopy.

PubMed

Koo, Soo Kweon; Choi, Jang Won; Myung, Nam Suk; Lee, Hyoung Ju; Kim, Yang Jae; Kim, Young Joong

2013-01-01

We analyzed site, pattern and degree of obstruction in Korean male obstructive sleep apnea syndrome (OSAS) patients by drug-induced sleep endoscopy (DISE). We also investigated possible links between BMI, AHI and DISE findings. Sixty-nine male patients underwent DISE. DISE findings were reported using our classification system in which modified 'VOTE classification' - obstruction type, site of obstruction, degree of obstruction and anatomical site contributing obstruction - was reported. Associations were analyzed among the results of the polysomnography, patients' characteristics and DISE finding. Multilevel airway obstruction was found in 84.06% of patients and 15.94% had a unilevel obstruction. Among those with unilevel obstruction, 90.90% had retropalatal level obstruction and 9.10% had retrolingual level obstruction. Palate with lateral pharyngeal wall obstruction (49.28%) is the most common obstruction type of the retropalatal level and tongue with lateral pharyngeal wall (37.68%) is the most common obstruction type of the retrolingual level. Examining the relation between obstruction site according to body mass index (BMI) and severity of OSAS (apnea hypopnea index, AHI), the lateral pharyngeal wall had an increasing tendency associated with higher BMI and higher AHI. But the lateral pharyngeal wall of both levels was statistically significant associated with higher AHI. The majority of the Korean male OSAS patients have multilevel obstruction and according to BMI and AHI, the DISE findings indicate that the lateral pharyngeal wall is the most important anatomical site contributing to obstruction regardless of the level at which the obstruction lies. © 2013 Elsevier Inc. All rights reserved.

Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence

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

Cote, Marceline; Miller, A. Dusty; Liu, Shan-Lu

2007-08-17

The RON receptor tyrosine kinase is a member of the MET proto-oncogene family and is important for cell proliferation, differentiation, and cancer development. Here, we created a series of Madin-Darby canine kidney (MDCK) epithelial cell clones that express different levels of RON, and have investigated their biological properties. While low levels of RON correlated with little morphological change in MDCK cells, high levels of RON expression constitutively led to morphological scattering or complete and stabilized epithelial-to-mesenchymal transition (EMT). Unexpectedly, MDCK clones expressing higher levels of RON exhibited retarded proliferation and senescence, despite increased motility and invasiveness. RON was constitutively tyrosine-phosphorylatedmore » in MDCK cells expressing high levels of RON and undergoing EMT, and the MAPK signaling pathway was activated. This study reveals for the first time that RON alone is sufficient to induce complete and stabilized EMT in MDCK cells, and overexpression of RON does not cause cell transformation but rather induces cell cycle arrest and senescence, leading to impaired cell proliferation.« less

Significance of the DNA-Histone Complex Level as a Predictor of Major Adverse Cardiovascular Events in Hemodialysis Patients: The Effect of Uremic Toxin on DNA-Histone Complex Formation.

PubMed

Jeong, Jong Cheol; Kim, Ji-Eun; Gu, Ja-Yoon; Yoo, Hyun Ju; Ryu, Ji Won; Kim, Dong Ki; Joo, Kwon Wook; Kim, Hyun Kyung

2016-01-01

Neutrophils can release the DNA-histone complex into circulation following exposure to inflammatory stimuli. This prospective study investigated whether the DNA-histone complex and other biomarkers could predict major cardiovascular adverse events (MACEs) in hemodialysis (HD) patients. The levels of circulating DNA-histone complexes, cell-free DNA, interleukin (IL)-6, and neutrophil elastase were measured in 60 HD patients and 28 healthy controls. MACE was assessed at 24 months. Uremic toxin-induced neutrophil released contents were measured in vitro. Compared with controls, HD patients showed higher levels of DNA-histone complexes and IL-6. The DNA-histone complex level was inversely associated with the Kt/V. In a multivariable Cox analysis, the high level of DNA-histone complexes was a significant independent predictor of MACE. The uremic toxins induced DNA-histone complex formation in normal neutrophils in vitro. The DNA-histone complex is a potentially useful marker to predict MACE in HD patients. Uremic toxins induced DNA-histone complex formation in vitro. © 2015 S. Karger AG, Basel.

MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

PubMed

Di Pasqua, Laura G; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Croce, Anna Cleta; Vairetti, Mariapia; Ferrigno, Andrea

2016-08-01

Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH.

Chloride-dependency of amyloid beta protein-induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons.

PubMed

Zhang, Nan-Yan; Kitagawa, Kaori; Wu, Bo; Xiong, Zheng-Mei; Otani, Hitomi; Inagaki, Chiyoko

2006-05-15

In our previous studies, pathophysiological concentrations of amyloid-beta (Abeta) proteins increased intracellular Cl(-) concentration ([Cl(-)]i) and enhanced glutamate neurotoxicity in primary cultured neurons, suggesting Cl(-)-dependent changes in glutamate signaling. To test this possibility, we examined the effects of isethionate-replaced low Cl(-) medium on the Abeta-induced enhancement of glutamate neurotoxicity in the primary cultured rat hippocampal neurons. In a normal Cl(-) (135 mM) medium, treatment with 10 nM Abeta25-35 for 2 days increased neuronal [Cl(-)]i to a level three times higher than that of control as assayed using a Cl(-)-sensitive fluorescent dye, while in a low Cl(-) (16 mM) medium such an Abeta25-35-induced increase in [Cl(-)]i was not observed. The Abeta treatment aggravated glutamate neurotoxicity in a normal Cl(-) medium as measured by mitochondrial reducing activity and lactate dehydrogenase (LDH) release, while in a low Cl(-) medium the Abeta treatment did not enhance glutamate toxicity. Upon such Abeta plus glutamate treatment under a normal Cl(-) condition, activated anti-apoptotic molecule Akt (Akt-pS473) level monitored by Western blot significantly decreased to 74% of control. Under a low Cl(-) condition, a resting Akt-pS473 level was higher than that under a normal Cl(-) condition and did not significantly change upon Abeta plus glutamate treatment. Tyrosine phosphorylation levels of 110 and 60 kDa proteins (pp110 and pp60) increased upon Abeta plus glutamate treatment under a normal Cl(-), but not low Cl(-), condition. These findings indicated that Abeta-induced enhancement of glutamate neurotoxicity is Cl(-)-dependent. Chloride-sensitive Akt pathway and tyrosine phosphorylation of proteins (pp110 and pp60) may be involved in this process.

Different mechanisms of Trichoderma virens-mediated resistance in tomato against Fusarium wilt involve the jasmonic and salicylic acid pathways.

PubMed

Jogaiah, Sudisha; Abdelrahman, Mostafa; Tran, Lam-Son Phan; Ito, Shin-Ichi

2018-04-01

In the present study, we investigated the role of Trichoderma virens (TriV_JSB100) spores or cell-free culture filtrate in the regulation of growth and activation of the defence responses of tomato (Solanum lycopersicum) plants against Fusarium oxysporum f. sp. lycopersici by the development of a biocontrol-plant-pathogen interaction system. Two-week-old tomato seedlings primed with TriV_JSB100 spores cultured on barley grains (BGS) or with cell-free culture filtrate (CF) were inoculated with Fusarium pathogen under glasshouse conditions; this resulted in significantly lower disease incidence in tomato Oogata-Fukuju plants treated with BGS than in those treated with CF. To dissect the pathways associated with this response, jasmonic acid (JA) and salicylic acid (SA) signalling in BGS- and CF-induced resistance was evaluated using JA- and SA-impaired tomato lines. We observed that JA-deficient mutant def1 plants were susceptible to Fusarium pathogen when they were treated with BGS. However, wild-type (WT) BGS-treated tomato plants showed a higher JA level and significantly lower disease incidence. SA-deficient mutant NahG plants treated with CF were also found to be susceptible to Fusarium pathogen and displayed low SA levels, whereas WT CF-treated tomato plants exhibited moderately lower disease levels and substantially higher SA levels. Expression of the JA-responsive defensin gene PDF1 was induced in WT tomato plants treated with BGS, whereas the SA-inducible pathogenesis-related protein 1 acidic (PR1a) gene was up-regulated in WT tomato plants treated with CF. These results suggest that TriV_JSB100 BGS and CF differentially induce JA and SA signalling cascades for the elicitation of Fusarium oxysporum resistance in tomato. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Cardiac ACE2/angiotensin 1–7/Mas receptor axis is activated in thyroid hormone-induced cardiac hypertrophy

PubMed Central

Diniz, Gabriela P.; Senger, Nathalia; Carneiro-Ramos, Marcela S.; Santos, Robson A. S.; Barreto-Chaves, Maria Luiza M.

2015-01-01

Objectives: Thyroid hormone (TH) promotes marked effects on the cardiovascular system, including the development of cardiac hypertrophy. Some studies have demonstrated that the renin–angiotensin system (RAS) is a key mediator of the cardiac growth in response to elevated TH levels. Although some of the main RAS components are changed in cardiac tissue on hyperthyroid state, the potential modulation of the counter regulatory components of the RAS, such as angiotensin-converting enzyme type 2 (ACE2), angiotensin 1–7 (Ang 1–7) levels and Mas receptor induced by hyperthyroidism is unknown. The aim of this study was to investigate the effect of hyperthyroidism on cardiac Ang 1–7, ACE2 and Mas receptor levels. Methods: Hyperthyroidism was induced in Wistar rats by daily intraperitoneal injections of T4 for 14 days. Results: Although plasma Ang 1–7 levels were unchanged by hyperthyroidism, cardiac Ang 1–7 levels were increased in TH-induced cardiac hypertrophy. ACE2 enzymatic activity was significantly increased in hearts from hyperthyroid animals, which may be contributing to the higher Ang 1–7 levels observed in the T4 group. Furthermore, elevated cardiac levels of Ang 1–7 levels were accompanied by increased Mas receptor protein levels. Conclusion: The counter-regulatory components of the RAS are activated in hyperthyroidism and may be contributing to modulate the cardiac hypertrophy in response to TH. PMID:26715125

The transgenic cloned pig population with integrated and controllable GH expression that has higher feed efficiency and meat production

PubMed Central

Ju, Huiming; Zhang, Jiaqing; Bai, Lijing; Mu, Yulian; Du, Yutao; Yang, Wenxian; Li, Yong; Sheng, Anzhi; Li, Kui

2015-01-01

Sustained expression of the GH gene has been shown to have detrimental effects on the health of animals. In the current study, transgenic founder pigs, with controllable pig growth hormone (pGH) expression, were cloned via the handmade cloning method (HMC), and pGH expression levels were examined at the cellular and organismal levels. The serum pGH levels in 3 founder male pigs were found to be significantly higher after induction with intramuscular injection of doxycycline (DOX) compared to baseline. A daily dose of DOX was administered via feed to these animals for a period of 65 to 155 days. The growth rate, feed efficiency and pGH serum concentration increased in the DOX-induced transgenic group compared with the other groups. 8 numbers of animals were euthanized and the dressing percentage, loin muscle and lean meat percentage were significantly higher in the DOX-induced F1 transgenic group compared with the other groups. In this study a large population of transgenic pigs, with integrated controllable expression of a transgene, was obtained. The transgenic pigs were healthy and normal in terms of reproductive capability. At the same time, feed efficiency was improved, production processes were accelerated and meat yield was increased. PMID:25959098

The transgenic cloned pig population with integrated and controllable GH expression that has higher feed efficiency and meat production.

PubMed

Ju, Huiming; Zhang, Jiaqing; Bai, Lijing; Mu, Yulian; Du, Yutao; Yang, Wenxian; Li, Yong; Sheng, Anzhi; Li, Kui

2015-05-11

Sustained expression of the GH gene has been shown to have detrimental effects on the health of animals. In the current study, transgenic founder pigs, with controllable pig growth hormone (pGH) expression, were cloned via the handmade cloning method (HMC), and pGH expression levels were examined at the cellular and organismal levels. The serum pGH levels in 3 founder male pigs were found to be significantly higher after induction with intramuscular injection of doxycycline (DOX) compared to baseline. A daily dose of DOX was administered via feed to these animals for a period of 65 to 155 days. The growth rate, feed efficiency and pGH serum concentration increased in the DOX-induced transgenic group compared with the other groups. 8 numbers of animals were euthanized and the dressing percentage, loin muscle and lean meat percentage were significantly higher in the DOX-induced F1 transgenic group compared with the other groups. In this study a large population of transgenic pigs, with integrated controllable expression of a transgene, was obtained. The transgenic pigs were healthy and normal in terms of reproductive capability. At the same time, feed efficiency was improved, production processes were accelerated and meat yield was increased.

Plasma homocysteine involved in methylation and expression of thrombomodulin in cerebral infarction.

PubMed

Yang, Zhifu; Wang, Lizhen; Zhang, Wei; Wang, Xinxin; Zhou, Shengnian

2016-05-13

Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X(2) = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = -0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Properdin Levels in Individuals with Chemotherapy-Induced Neutropenia.

PubMed

Tsyrkunou, Artsiom; Agarwal, Sarika; Koirala, Bibek; Finberg, Robert W; Nath, Rajneesh; Barton, Bruce; Levitz, Stuart M; Wang, Jennifer P; Ram, Sanjay

2017-01-01

Neutrophils produce and carry key components of the alternative pathway (AP) of complement, including properdin (P). The effect of chemotherapy-induced absolute neutropenia on circulating P levels and AP function has not been previously established. We prospectively measured free P levels in serum from 27 individuals expected to develop neutropenia after administration of chemotherapy for hematological malignancies in preparation for hematopoietic stem cell transplantation and here describe the relationship between serum P levels and the neutrophil count over time. When the absolute neutrophil count (ANC) was >500 cells/mm 3 pre-chemotherapy, P levels were significantly higher than P levels associated with an ANC ≤500 cells/mm 3 (median values 8392 ng/mL and 6355 ng/mL, respectively; P = .001). Pairwise comparison between pre-chemotherapy P levels and P levels at initial or last documented neutropenia before recovery showed a significant decline ( P < .0001). No correlation was observed between P levels during neutropenia and after recovery of neutropenia in 20 subjects for which postneutropenia samples were obtained. A small but significant ( P = .02) decrease in AP hemolytic activity was noted between baseline (preneutropenia) and samples obtained at the onset of neutropenia, but only with low (6.25%) and not higher (12.5 or 25%) serum concentrations. A decline in P levels and AP activity could contribute to the increased risk of infection in neutropenic patients and warrants further study. © The Author 2016. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Lifetime Induced Abortion: A Comparison between Women Living and Not Living with HIV

PubMed Central

Pilecco, Flávia Bulegon; Teixeira, Luciana Barcellos; Vigo, Álvaro; Dewey, Michael E.; Knauth, Daniela Riva

2014-01-01

Background Studies aimed at understanding the association between induced abortion and HIV are scarce and differ on the direction of the association. This paper aims to show the prevalence of induced abortion in a sample of pregnancies of women living and not living with HIV/Aids, determining variables associated with pregnancy termination and linked to the life course of women and to the specific context of the pregnancy. Methods Data came from a cross-sectional study, using interviewer-administered questionnaire, developed with women that attended public health services in Porto Alegre, Brazil. A generalized estimating equation model with logit link measured the association between determinants and abortion. Findings The final sample was composed of 684 women living with HIV/Aids (2,039 pregnancies) and 639 women not living with HIV/Aids (1,539 pregnancies). The prevalence of induced abortion among pregnancies in women living with HIV/Aids was 6.5%, while in women not living with HIV/Aids was 2.9%. Among women living with HIV/Aids, the following were associated with induced abortion in the multivariable analysis: being older, having a higher education level, having had more sexual partners (i.e., variables linked to the life course of women), having had children prior to the index pregnancy and living with a sexual partner during pregnancy (i.e., variables linked to the context of each pregnancy). On the other hand, among women not living with HIV/Aids, only having a higher education level and having had more sexual partners (i.e., determinants linked to the life course of women) were associated with voluntary pregnancy termination in multivariable analysis. Conclusion Although determinants are similar between women living and not living with HIV/Aids, prevalence of induced abortion is higher among pregnancies in women living with HIV/Aids, pointing to their greater social vulnerability and to the need for public policy to address prevention and treatment of HIV associated with reproductive issues. PMID:24752119

Lifetime induced abortion: a comparison between women living and not living with HIV.

PubMed

Pilecco, Flávia Bulegon; Teixeira, Luciana Barcellos; Vigo, Alvaro; Dewey, Michael E; Knauth, Daniela Riva

2014-01-01

Studies aimed at understanding the association between induced abortion and HIV are scarce and differ on the direction of the association. This paper aims to show the prevalence of induced abortion in a sample of pregnancies of women living and not living with HIV/Aids, determining variables associated with pregnancy termination and linked to the life course of women and to the specific context of the pregnancy. Data came from a cross-sectional study, using interviewer-administered questionnaire, developed with women that attended public health services in Porto Alegre, Brazil. A generalized estimating equation model with logit link measured the association between determinants and abortion. The final sample was composed of 684 women living with HIV/Aids (2,039 pregnancies) and 639 women not living with HIV/Aids (1,539 pregnancies). The prevalence of induced abortion among pregnancies in women living with HIV/Aids was 6.5%, while in women not living with HIV/Aids was 2.9%. Among women living with HIV/Aids, the following were associated with induced abortion in the multivariable analysis: being older, having a higher education level, having had more sexual partners (i.e., variables linked to the life course of women), having had children prior to the index pregnancy and living with a sexual partner during pregnancy (i.e., variables linked to the context of each pregnancy). On the other hand, among women not living with HIV/Aids, only having a higher education level and having had more sexual partners (i.e., determinants linked to the life course of women) were associated with voluntary pregnancy termination in multivariable analysis. Although determinants are similar between women living and not living with HIV/Aids, prevalence of induced abortion is higher among pregnancies in women living with HIV/Aids, pointing to their greater social vulnerability and to the need for public policy to address prevention and treatment of HIV associated with reproductive issues.

Involvement of indole-3-acetic acid produced by Azospirillum brasilense in accumulating intracellular ammonium in Chlorella vulgaris.

PubMed

Meza, Beatriz; de-Bashan, Luz E; Bashan, Yoav

2015-01-01

Accumulation of intracellular ammonium and activities of the enzymes glutamine synthetase (GS) and glutamate dehydrogenase (GDH) were measured when the microalgae Chlorella vulgaris was immobilized in alginate with either of two wild type strains of Azospirillum brasilense or their corresponding indole-3-acetic acid (IAA)-attenuated mutants. After 48 h of immobilization, both wild types induced higher levels of intracellular ammonium in the microalgae than their respective mutants; the more IAA produced, the higher the intracellular ammonium accumulated. Accumulation of intracellular ammonium in the cells of C. vulgaris followed application of four levels of exogenous IAA reported for A. brasilense and its IAA-attenuated mutants, which had a similar pattern for the first 24 h. This effect was transient and disappeared after 48 h of incubation. Immobilization of C. vulgaris with any bacteria strain induced higher GS activity. The bacterial strains also had GS activity, comparable to the activity detected in C. vulgaris, but weaker than when immobilized with the bacteria. When net activity was calculated, the wild type always induced higher GS activity than IAA-attenuated mutants. GDH activity in most microalgae/bacteria interactions resembled GS activity. When complementing IAA-attenuated mutants with exogenous IAA, GS activity in co-immobilized cultures matched those of the wild type A. brasilense immobilized with the microalga. Similarity occurred when the net GS activity was measured, and was higher with greater quantities of exogenous IAA. It is proposed that IAA produced by A. brasilense is involved in ammonium uptake and later assimilation by C. vulgaris. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Hypoglycemic and Hypolipidemic Effects of the Cracked-Cap Medicinal Mushroom Phellinus rimosus (Higher Basidiomycetes) in Streptozotocin-Induced Diabetic Rats.

PubMed

Rony, Kuttikkadan A; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Phellinus rimosus is a parasitic host specific polypore mushroom with profound antioxidant, antihepatotoxic, anti-inflammatory, antitumor, and antimutagenic activities. This study investigated the hypoglycemic and hypolipidemic activities of the wood-inhabiting polypore mushroom Ph. Rimosus in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by single intraperitoneal injection of STZ (45 mg/kg) to Wistar rats. The effects of 30 days treatment with Ph. Rimosus (50 and 250 mg/ kg) and glibenclamide (0.65 mg/kg) on blood glucose level, serum insulin, serum lipid profile, liver glycogen, liver function enzymes, and non-enzymic and enzymic antioxidants activities in pancreas, liver, and kidney were evaluated in STZ-induced diabetic rats. Oral administration of Ph. Rimosus extract exhibited a significant reduction in blood glucose, triacylglycerol, total cholesterol, LDL-cholesterol, and liver function enzymes, and increased serum insulin, liver glycogen, and HDL-cholesterol levels in STZ-induced diabetic rats. Furthermore, Ph. Rimosus treatment increased antioxidant status in pancreas, liver, and kidney tissues with concomitant decreases in levels of thiobarbituric acid- reactive substances. Results of this study indicated that Ph. Rimosus possessed significant hypoglycemic and hypolipidemic activities and this effect may be related to its insulinogenic and antioxidant effect.

Physiological response of a red tide alga (Skeletonema costatum) to nitrate enrichment, with special reference to inorganic carbon acquisition.

PubMed

Gao, Guang; Xia, Jianrong; Yu, Jinlan; Zeng, Xiaopeng

2018-02-01

A classical red tide alga Skeletonema costatum was cultured under various nitrate levels to investigate its physiological response to nitrate enrichment combined with CO 2 limitation. The higher nitrate levels increased content of photosynthetic pigments (Chl a and Chl c), electron transport rate in photosystem II, photosynthetic O 2 evolution, and thus growth rate in S. costatum. On the other hand, the lower CO 2 levels (3.5-4.4 μmol kg -1 seawater) and higher pH (8.56-8.63) values in seawater were observed under higher nitrate conditions. Redox activity of plasma membrane and carbonic anhydrase in S. costatum was enhanced to address the reduced CO 2 level at higher nitrate levels. In addition, the pH compensation point was enhanced and direct HCO 3 - use was induced at higher nitrate levels. These findings indicate that nitrate enrichment would stimulate the breakout of S. costatum dominated red tides via enhancing its photosynthetic performances, and maintain a quick growth rate under CO 2 limitation conditions through improving its inorganic carbon acquisition capability. Our study sheds light on the mechanisms of S. costatum defeating CO 2 limitation during algal bloom. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Ionic mechanisms of depolarization responses induced by glutamate application to nerve cells of Helix pomatia].

PubMed

Gerasimov, V D

1982-01-01

The reversal potentials for transmembrane ionic currents induced by glutamate were measured in different D-neurons of the snail Helix pomatia. The first group of neurons had a mean reversal potential--10.6 +/- 1.2 mV and the second one--40.0 +/- 0.6 mV. Under normal conditions glutamate evoked spike discharges in the first group of neurons but not in the second one. At higher concentrations of glutamate the amplitude of D-responses in the latter group increased only to a certain level, not reaching the critical level for cell firing. Decrease in external Cl concentration led to a shift of their reversal potential in depolarizing direction. Ionic mechanisms of depolarizing responses induced by glutamate in these groups of neurons are discussed.

HOXC9-Induced Differentiation in Neuroblastoma Development

DTIC Science & Technology

2014-10-01

Neuroblastoma Development PRINCIPAL INVESTIGATOR: Han-Fei Ding RECIPIENT: Georgia Health Sciences University Research Institute, Inc... Neuroblastoma  Development   5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0613 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...role in determining the differentiation states of neuroblastoma tumors, with higher levels of HOXC9 promoting differentiation. At the cellular level

Chromatic Perceptual Learning but No Category Effects without Linguistic Input

PubMed Central

Grandison, Alexandra; Sowden, Paul T.; Drivonikou, Vicky G.; Notman, Leslie A.; Alexander, Iona; Davies, Ian R. L.

2016-01-01

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest. PMID:27252669

Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats.

PubMed

Todorova, Valentina K; Harms, Stacy A; Kaufmann, Yihong; Luo, Shaoke; Luo, Kevin Q; Babb, Kirk; Klimberg, V Suzanne

2004-12-01

Glutamine (GLN) is a non-essential amino acid that is present in nearly every biochemical pathway and is the major intraorgan nitrogen carrier. GLN via glutamate, is one of the precursors for the synthesis of glutathione (GSH), the major endogenous antioxidant in mammalian cells, which protects them from oxidative injury and cell death. Cancer cells have higher GSH levels than the surrounding normal cells, which attributes to a higher rate of cell proliferation and resistance to chemotherapy. Therefore, selective tumor depletion of GSH presents a promising strategy in cancer treatment. Experimental studies have associated decreased GSH levels with inhibition of proliferation and stimulation of apoptosis. Previous results of our laboratory have provided evidence that dietary GLN diminished tumor development in implantable as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer and elevated GSH in the host tissues. In this study we examined the effects of GLN on GSH levels in DMBA-induced mammary tumors and correlated the results with protein and mRNA expression of apoptosis-related proteins Bcl-2, Bax and caspase-3 in tumor cells. The results have shown that GLN supplementation caused a significant decrease in the tumor GSH levels and the ratio GSH/oxidized GSH (GSSG), accompanied by up-regulation of Bax and caspase-3, and down-regulation of Bcl-2. These findings suggest that dietary GLN supplementation suppresses mammary carcinogenesis by activation of apoptosis in tumor cells and this probably is a result of GSH down-regulation.

Chlorpyrifos-induced oxidative damage is reduced under warming and predation risk: Explaining antagonistic interactions with a pesticide.

PubMed

Janssens, Lizanne; Stoks, Robby

2017-07-01

Interactions with pollutants and environmental factors are poorly studied for physiological traits. Yet physiological traits are important for explaining and predicting interactions at higher levels of organization. We investigated the single and combined impact of the pesticide chlorpyrifos, predation risk and warming on endpoints related to oxidative stress in the damselfly Enallagma cyathigerum. We thereby integrated information on reactive oxygen species (ROS), antioxidant enzymes and oxidative damage. All three treatments impacted the oxidative stress levels and for most traits the pesticide interacted antagonistically with warming or predation risk. Chlorpyrifos exposure resulted in increased ROS levels, decreased antioxidant defence and increased oxidative damage compared to the control situation. Under warming, the pesticide-induced increase in oxidative stress was less strong and the investment in antioxidant defence higher. Although both the pesticide and predation risk increased oxidative damage, the effects of the pesticide on oxidative damage were less strong in the presence of predator cues (at 20 °C). Despite the weaker pesticide-induced effects under predation risk, the combination of the pesticide and predator cues consistently caused the highest ROS levels, the lowest antioxidant defence and the highest oxidative damage, indicating the importance of cumulative stressor effects for impairing fitness. Our results provide the first evidence for antagonistic interactions of warming and predation risk with a pollutant for physiological traits. We identified two general mechanisms that may generate antagonistic interactions for oxidative stress: cross-tolerance and the maximum cumulative levels of damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Metabolic profiling of muscle contraction in lean compared with obese rodents.

PubMed

Thyfault, John P; Cree, Melanie G; Tapscott, Edward B; Bell, Jill A; Koves, Timothy R; Ilkayeva, Olga; Wolfe, Robert R; Dohm, G Lynis; Muoio, Deborah M

2010-09-01

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs. Predictably, IMTG content was grossly elevated in control muscles from obese rats compared with their lean counterparts. In muscles of obese (but not lean) rats, contraction resulted in marked hydrolysis of IMTG, which was then restored to near resting levels during 25 min of recovery. Despite dramatic phenotypical differences in contraction-induced IMTG turnover, muscle levels of diacylglycerol (DAG) and long-chain acyl-CoAs (LCACoA) were surprisingly similar between groups. Tissue profiles of acylcarnitine metabolites suggested that the surfeit of IMTG in obese rats fueled higher rates of fat oxidation relative to the lean group. Muscles of the obese rats had reduced lactate levels immediately following contraction and higher glycogen resynthesis during recovery, consistent with a lipid-associated glucose-sparing effect. Together, these findings suggest that contraction-induced mobilization of local lipid reserves in obese muscles promotes beta-oxidation, while discouraging glucose utilization. Further studies are necessary to determine whether persistent oxidation of IMTG-derived fatty acids contributes to systemic glucose intolerance in other physiological settings.

Understanding heterogeneity in social anxiety disorder: dependency and self-criticism moderate fear responses to interpersonal cues.

PubMed

Kopala-Sibley, Daniel C; Zuroff, David C; Russell, Jennifer J; Moskowitz, D S

2014-06-01

This study examined how the personality traits of self-criticism and dependency moderated the effects of situational interpersonal cues on fear during interpersonal interactions among individuals with social anxiety disorder (SAD). We hypothesized that self-criticism would moderate the fear-inducing effects of situational self-consciousness and that dependency would moderate the fear-inducing effects of situational emotional insecurity. Forty SAD patients (Mage = 29.23) and matched community controls (Mage = 28.93) completed event-contingent record forms after each significant social interaction of over 5 min for a 20-day period. There were 20 female patients and 20 male patients in each group. Event-level self-consciousness was more strongly associated with elevations in fear among socially anxious patients who reported higher levels of self-criticism, while event-level emotional security was more strongly associated with decreases in fear among SAD patients who reported higher levels of dependency. These interactions were not found in the community sample. Findings support the application of personality-vulnerability models to understanding fear during social interactions in patients with SAD. Results also have implications for psychotherapeutic treatments of SAD. © 2013 The British Psychological Society.

Bradykinin-forming components in Kuwaiti patients with type 2 diabetes.

PubMed

Sharma, J N; Al-Shoumer, K A S; Matar, K M; Al-Gharee, H Y; Madathil, N V

2013-01-01

Diabetes is the most common risk factor in inducing hypertension, nephropathy and retinopathy. The bradykinin (BK)-forming system has been proposed to protect cardiovascular and renal functions. We therefore evaluated urinary active and proactive kallikrein, total kininogen, plasma tissue kallikrein, plasma creatinine, plasma glucose and plasma HbA1c in newly diagnosed untreated type 2 diabetic patients and healthy subjects. In diabetic patients, urinary and plasma tissue kallikrein concentrations were significantly increased. In addition, plasma prekallikrein levels were also significantly higher. However, urinary kininogen values were significantly reduced in diabetic patients when compared with healthy subjects. This is the first investigation among Kuwaiti Arab patients with type 2 diabetes showing abnormal activities in the BK-forming system. High levels of plasma prekallikrein may be a risk factor for developing high blood pressure as well as nephropathy. The urinary and plasma tissue kallikrein concentrations were higher in diabetic patients, which could indicate the hyperactivities of these components, and may result in increased levels of plasma glucose to induce diabetes. Furthermore, the urinary kininogen levels were reduced in diabetic patients. These alterations might reflect the utilization of urinary kininogen to form BK, a potent inflammatory agent. However, this hypothesis needs further investigation.

Induction of antioxidant enzyme activity and lipid peroxidation level in ion-beam-bombarded rice seeds

NASA Astrophysics Data System (ADS)

Semsang, Nuananong; Yu, LiangDeng

2013-07-01

Low-energy ion beam bombardment has been used to mutate a wide variety of plant species. To explore the indirect effects of low-energy ion beam on biological damage due to the free radical production in plant cells, the increase in antioxidant enzyme activities and lipid peroxidation level was investigated in ion-bombarded rice seeds. Local rice seeds were bombarded with nitrogen or argon ion beams at energies of 29-60 keV and ion fluences of 1 × 1016 ions cm-2. The activities of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST) and lipid peroxidation level were assayed in the germinated rice seeds after ion bombardment. The results showed most of the enzyme activities and lipid peroxidation levels in both the argon and nitrogen bombarded samples were higher than those in the natural control. N-ion bombardment could induce higher levels of antioxidant enzyme activities in the rice samples than the Ar-ion bombardment. Additional effects due to the vacuum condition were found to affect activities of some antioxidant enzymes and lipid peroxidation level. This study demonstrates that ion beam bombardment and vacuum condition could induce the antioxidant enzyme activity and lipid peroxidation level which might be due to free radical production in the bombarded rice seeds.

Nutritional and metabolic responses in common dentex (Dentex dentex) fed on different types and levels of carbohydrates.

PubMed

Pérez-Jiménez, Amalia; Abellán, Emilia; Arizcun, Marta; Cardenete, Gabriel; Morales, Amalia E; Hidalgo, M Carmen

2015-06-01

The present study was aimed to evaluate the capacity of common dentex (Dentex dentex) to efficiently use dietary carbohydrates. So, the effects of different type and levels of carbohydrates on growth performance, feed utilization, fish composition, plasma metabolites and key metabolic pathways in liver and white muscle of common dentex are presented. Nine isonitrogenous (43%) and isoenergetic (22 MJ kg(-1)) diets were formulated combining three types, pregelatinized starch (PS), dextrin (Dx) and maltodextrin (Mx), and three levels (12, 18 and 24%) of carbohydrates. Growth performance was not significantly influenced by treatments. The best feed utilization was observed in 18% Mx group. Higher hepatic lipid content was found in fish fed lower dietary carbohydrate levels. PS induced higher liver and white muscle hexokinase and pyruvate kinase activities compared to the lower values observed for Mx. Malic enzyme and glucose 6-phosphate dehydrogenase in liver and white muscle were lower in Mx group. The influence of dietary carbohydrates source was more noticeable than those induced by the carbohydrate level, when glycolysis and lipogenesis pathways were considered. Common dentex is able to use properly dietary carbohydrates, although optimal dietary inclusion levels are below 24%. The greater protein-sparing effect was promoted by the less complex carbohydrate (maltodextrin) and the best feed utilization indices were obtained at intermediate levels of inclusion (18%). Copyright © 2015 Elsevier Inc. All rights reserved.

Elevation of Glucose 6-Phosphate Dehydrogenase Activity Induced by Amplified Insulin Response in Low Glutathione Levels in Rat Liver

PubMed Central

Taniguchi, Misako; Mori, Nobuko; Iramina, Chizuru

2016-01-01

Weanling male Wistar rats were fed on a 10% soybean protein isolate (SPI) diet for 3 weeks with or without supplementing 0.3% sulfur-containing amino acids (SAA; methionine or cystine) to examine relationship between glutathione (GSH) levels and activities of NADPH-producing enzymes, glucose 6-phosphate dehydrogenase (G6PD) and malic enzyme (ME), in the liver. Of rats on the 10% SPI diet, GSH levels were lower and the enzyme activities were higher than of those fed on an SAA-supplemented diet. Despite the lower GSH level, γ-glutamylcysteine synthetase (γ-GCS) activity was higher in the 10% SPI group than other groups. Examination of mRNAs of G6PD and ME suggested that the GSH-suppressing effect on enzyme induction occurred prior to and/or at transcriptional levels. Gel electrophoresis of G6PD indicated that low GSH status caused a decrease in reduced form and an increase in oxidized form of the enzyme, suggesting an accelerated turnover rate of the enzyme. In primary cultured hepatocytes, insulin response to induce G6PD activity was augmented in low GSH levels manipulated in the presence of buthionine sulfoximine. These findings indicated that elevation of the G6PD activity in low GSH levels was caused by amplified insulin response for expression of the enzyme and accelerated turnover rate of the enzyme molecule. PMID:27597985

An immunoproteomic approach revealing peptides from Sporothrix brasiliensis that induce a cellular immune response in subcutaneous sporotrichosis.

PubMed

de Almeida, José Roberto Fogaça; Jannuzzi, Grasielle Pereira; Kaihami, Gilberto Hideo; Breda, Leandro Carvalho Dantas; Ferreira, Karen Spadari; de Almeida, Sandro Rogério

2018-03-08

Sporothrix brasiliensis is the most virulent fungus of the Sporothrix complex and is the main species recovered in the sporotrichosis zoonotic hyperendemic area in Rio de Janeiro. A vaccine against S. brasiliensis could improve the current sporotrichosis situation. Here, we show 3 peptides from S. brasiliensis immunogenic proteins that have a higher likelihood for engaging MHC-class II molecules. We investigated the efficiency of the peptides as vaccines for preventing subcutaneous sporotrichosis. In this study, we observed a decrease in lesion diameters in peptide-immunized mice, showing that the peptides could induce a protective immune response against subcutaneous sporotrichosis. ZR8 peptide is from the GP70 protein, the main antigen of the Sporothrix complex, and was the best potential vaccine candidate by increasing CD4 + T cells and higher levels of IFN-γ, IL-17A and IL-1β characterizing a strong cellular immune response. This immune environment induced a higher number of neutrophils in lesions that are associated with fungus clearance. These results indicated that the ZR8 peptide induces a protective immune response against subcutaneous sporotrichosis and is a vaccine candidate against S. brasiliensis infection.

Aldosterone Induced Galectin-3 Secretion In Vitro and In Vivo: From Cells to Humans

PubMed Central

Lin, Yen-Hung; Chou, Chia-Hung; Wu, Xue-Ming; Chang, Yi-Yao; Hung, Chi-Sheng; Chen, Ying-Hsien; Tzeng, Yu-Lin; Wu, Vin-Cent; Ho, Yi-Lwun; Hsieh, Fon-Jou; Wu, Kwan-Dun

2014-01-01

Context Patients with primary aldosteronism are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis. Objective To investigate whether aldosterone induces galectin-3 secretion in vitro and in vivo. Methods and Results We investigated the possible molecular mechanism of aldosterone-induced galectin-3 secretion in macrophage cell lines (THP-1 and RAW 264.7 cells). Aldosterone induced galectin-3 secretion through mineralocorticoid receptors via the PI3K/Akt and NF-κB transcription signaling pathways. In addition, aldosterone-induced galectin-3 expression enhanced fibrosis-related factor expression in fibroblasts. We observed that galectin-3 mRNA from peripheral blood mononuclear cells and serum galectin-3 levels were both significantly increased in mice implanted with aldosterone pellets on days 7 and 14. We then conducted a prospective preliminary clinical study to investigate the association between aldosterone and galectin-3. Patients with aldosterone-producing adenoma had a significantly higher plasma galectin-3 level than patients with essential hypertension. One year after adrenalectomy, the plasma galectin-3 level had decreased significantly in the patients with aldosterone-producing adenoma. Conclusion This study demonstrated that aldosterone could induce galectin-3 secretion in vitro and in vivo. PMID:25180794

Inorganic arsenite alters macrophage generation from human peripheral blood monocytes

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

Sakurai, Teruaki; Ohta, Takami; Fujiwara, Kitao

2005-03-01

Inorganic arsenite has caused severe inflammatory chronic poisoning in humans through the consumption of contaminated well water. In this study, we examined the effects of arsenite at nanomolar concentrations on the in vitro differentiation of human macrophages from peripheral blood monocytes. While arsenite was found to induce cell death in a culture system containing macrophage colony stimulating factor (M-CSF), macrophages induced by granulocyte-macrophage CSF (GM-CSF) survived the treatment, but were morphologically, phenotypically, and functionally altered. In particular, arsenite-induced cells expressed higher levels of a major histocompatibility complex (MHC) class II antigen, HLA-DR, and CD14. They were more effective at inducingmore » allogeneic or autologous T cell responses and responded more strongly to bacterial lipopolysaccharide (LPS) by inflammatory cytokine release as compared to cells induced by GM-CSF alone. On the other hand, arsenite-induced cells expressed lower levels of CD11b and CD54 and phagocytosed latex beads or zymosan particles less efficiently. We also demonstrated that the optimum amount of cellular reactive oxygen species (ROS) induced by nM arsenite might play an important role in this abnormal monocyte differentiation. This work may have implications in chronic arsenic poisoning because the total peripheral blood arsenic concentrations of these patients are at nM levels.« less

Leptin protects vital organ functions after sepsis through recovering tissue myeloperoxidase activity: an anti-inflammatory role resonating with indomethacin.

PubMed

Lin, Ji; Yan, Guang-Tao; Xue, Hui; Hao, Xiu-Hua; Zhang, Kai; Wang, Lu-Huan

2007-08-01

In this research, the role of leptin on sepsis-induced organ dysfunction was evaluated. Making use of a mice sepsis model, changes of alanine transaminase and uric acid in serum, myeloperoxidase activity, leptin levels and histological alterations in heart, lung, liver and kidney were determined. Results showed that sepsis induced significantly higher levels of serum alanine transaminase and uric acid, decreased tissue myeloperoxidase activity and leptin levels, and triggered distinct histological alterations. However, leptin and indomethacin injections reversed those impairments at 6h and/or 12h after injury. These data reveal a protective role of both leptin and indomethacin on vital organ functions after sepsis by recovering tissue myeloperoxidase activity.

Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

PubMed

Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2017-05-01

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

The expression of Apoc3 mRNA is regulated by HNF4α and COUP-TFII, but not acute retinoid treatments, in primary rat hepatocytes and hepatoma cells.

PubMed

Howell, Meredith; Li, Rui; Zhang, Rui; Li, Yang; Chen, Wei; Chen, Guoxun

2014-02-01

Vitamin A status regulates obesity development, hyperlipidemia, and hepatic lipogenic gene expression in Zucker fatty (ZF) rats. The development of hyperlipidemia in acne patients treated with retinoic acid (RA) has been attributed to the induction of apolipoprotein C-III expression. To understand the role of retinoids in the development of hyperlipidemia in ZF rats, the expression levels of several selected RA-responsive genes in the liver and isolated hepatocytes from Zucker lean (ZL) and ZF rats were compared using real-time PCR. The Rarb and Srebp-1c mRNA levels are higher in the liver and isolated hepatocytes from ZF than ZL rats. The Apoc3 mRNA level is only higher in the isolated hepatocytes from ZF than ZL rats. To determine whether dynamic RA production acutely regulates Apoc3 expression, its mRNA levels in response to retinoid treatments or adenovirus-mediated overexpression of hepatocyte nuclear factor 4 alpha (HNF4α) and chicken ovalbumin upstream-transcription factor II (COUP-TFII) were analyzed. Retinoid treatments for 2-6 h did not induce the expression of Apoc3 mRNA. The overexpression of HNF4α or COUP-TFII induced or inhibited Apoc3 expression, respectively. We conclude that short-term retinoid treatments could not induce Apoc3 mRNA expression, which is regulated by HNF4α and COUP-TFII in hepatocytes.

Prevotella intermedia Induces Severe Bacteremic Pneumococcal Pneumonia in Mice with Upregulated Platelet-Activating Factor Receptor Expression

PubMed Central

Nagaoka, Kentaro; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

2014-01-01

Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells. PMID:24478074

Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

PubMed

Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

2014-02-01

Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

Different levels of UV-B resistance in Vaccinium corymbosum cultivars reveal distinct backgrounds of phenylpropanoid metabolites.

PubMed

Luengo Escobar, Ana; Magnum de Oliveira Silva, Franklin; Acevedo, Patricio; Nunes-Nesi, Adriano; Alberdi, Miren; Reyes-Díaz, Marjorie

2017-09-01

UV-B radiation induces several physiological and biochemical effects that can influence regulatory plant processes. Vaccinium corymbosum responds differently to UV-B radiation depending on the UV-B resistance of cultivars, according to their physiological and biochemical features. In this work, the effect of two levels of UV-B radiation during long-term exposure on the phenylpropanoid biosynthesis, and the expression of genes associated with flavonoid biosynthesis as well as the absolute quantification of secondary metabolites were studied in two contrasting UV-B-resistant cultivars (Legacy, resistant and Bluegold, sensitive). Multivariate analyses were performed to understand the role of phenylpropanoids in UV-B defense mechanisms. The amount of phenylpropanoid compounds was generally higher in Legacy than in Bluegold. Different expression levels of flavonoid biosynthetic genes for both cultivars were transiently induced, showing that even in longer period of UV-B exposure; plants are still adjusting their phenylpropanoids at the transcription levels. Multivariate analysis in Legacy indicated no significant correlation between gene expression and the levels of the flavonoids and phenolic acids. By contrast, in the Bluegold cultivar higher number of correlations between secondary metabolite and transcript levels was found. Taken together, the results indicated different adjustments between the cultivars for a successful UV-B acclimation. While the sensitive cultivar depends on metabolite adjustments to respond to UV-B exposure, the resistant cultivar also possesses an intrinsically higher antioxidant and UV-B screening capacity. Thus, we conclude that UV-B resistance involves not only metabolite level adjustments during the acclimation period, but also depends on the intrinsic metabolic status of the plant and metabolic features of the phenylpropanoid compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Obstructive Sleep Apnea is Associated With Early but Possibly Modifiable Alzheimer's Disease Biomarkers Changes.

PubMed

Liguori, Claudio; Mercuri, Nicola Biagio; Izzi, Francesca; Romigi, Andrea; Cordella, Alberto; Sancesario, Giuseppe; Placidi, Fabio

2017-05-01

Obstructive sleep apnea (OSA) is a common sleep disorder. The, literature lacks studies examining sleep, cognition, and Alzheimer's Disease (AD) cerebrospinal fluid (CSF) biomarkers in OSA patients. Therefore, we first studied cognitive performances, polysomnographic sleep, and CSF β-amyloid42, tau proteins, and lactate levels in patients affected by subjective cognitive impairment (SCI) divided in three groups: OSA patients (showing an Apnea-Hypopnea Index [AHI] ≥15/hr), controls (showing an AHI < 15/hr), and patients with OSA treated by continuous positive airway pressure (CPAP). We compared results among 25 OSA, 10 OSA-CPAP, and 15 controls who underwent a protocol counting neuropsychological testing in the morning, 48-hr polysomnography followed by CSF analysis. OSA patients showed lower CSF Aβ42 concentrations, higher CSF lactate levels, and higher t-tau/Aβ42 ratio compared to controls and OSA-CPAP patients. OSA patients also showed reduced sleep quality and continuity and lower performances at memory, intelligence, and executive tests than controls and OSA-CPAP patients. We found significant relationships among higher CSF tau proteins levels, sleep impairment, and increased CSF lactate levels in the OSA group. Moreover, lower CSF Aβ42 levels correlate with memory impairment and nocturnal oxygen saturation parameters in OSA patients. We hypothesize that OSA reducing sleep quality and producing intermittent hypoxia lowers CSF Aβ42 levels, increases CSF lactate levels, and alters cognitive performances in SCI patients, thus inducing early AD clinical and neuropathological biomarkers changes. Notably, controls as well as OSA-CPAP SCI patients did not show clinical and biochemical AD markers. Therefore, OSA may induce early but possibly CPAP-modifiable AD biomarkers changes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.

PubMed

Park, Jeongho; Goergen, Craig J; HogenEsch, Harm; Kim, Chang H

2016-03-01

Short-chain fatty acids (SCFAs) are major products of gut microbial fermentation and profoundly affect host health and disease. SCFAs generate IL-10(+) regulatory T cells, which may promote immune tolerance. However, SCFAs can also induce Th1 and Th17 cells upon immunological challenges and, therefore, also have the potential to induce inflammatory responses. Because of the seemingly paradoxical SCFA activities in regulating T cells, we investigated, in depth, the impact of elevated SCFA levels on T cells and tissue inflammation in mice. Orally administered SCFAs induced effector (Th1 and Th17) and regulatory T cells in ureter and kidney tissues, and they induced T cell-mediated ureteritis, leading to kidney hydronephrosis (hereafter called acetate-induced renal disease, or C2RD). Kidney hydronephrosis in C2RD was caused by ureteral obstruction, which was, in turn, induced by SCFA-induced inflammation in the ureteropelvic junction and proximal ureter. Oral administration of all major SCFAs, such as acetate, propionate, and butyrate, induced the disease. We found that C2RD development is dependent on mammalian target of rapamycin activation, T cell-derived inflammatory cytokines such as IFN-γ and IL-17, and gut microbiota. Young or male animals were more susceptible than old or female animals, respectively. However, SCFA receptor (GPR41 or GPR43) deficiency did not affect C2RD development. Thus, SCFAs, when systemically administered at levels higher than physiological levels, cause dysregulated T cell responses and tissue inflammation in the renal system. The results provide insights into the immunological and pathological effects of chronically elevated SCFAs. Copyright © 2016 by The American Association of Immunologists, Inc.

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

PubMed

Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

2017-07-01

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

NASA Astrophysics Data System (ADS)

Schartner, Michael M.; Carhart-Harris, Robin L.; Barrett, Adam B.; Seth, Anil K.; Muthukumaraswamy, Suresh D.

2017-04-01

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

PubMed Central

Schartner, Michael M.; Carhart-Harris, Robin L.; Barrett, Adam B.; Seth, Anil K.; Muthukumaraswamy, Suresh D.

2017-01-01

What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity. PMID:28422113

Short term resistance training enhanced plasma apoA-I and FABP4 levels in Streptozotocin-induced diabetic rats.

PubMed

Safarzade, Alireza; Talebi-Garakani, Elahe

2014-03-04

Type 1 diabetes mellitus is associated with a high risk for early atherosclerotic complications. Altered lipids and lipoprotein metabolism in chronic diabetes mellitus is associated with pathogenesis of atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the effects of 4 weeks resistance training on plasma lipid profile, fatty acid binding protein (FABP) 4 and apolipoprotein (apo) A-I levels in type 1 diabetic rats. Thirty two male Wister rats (12-14 weeks old) were randomly divided into four groups: non-diabetic control; non-diabetic trained; diabetic control; diabetic trained. The rats in training groups were subjected to a resistance training program (3 days/wk, for 4 wk) consisted of climbing a ladder carrying a load suspended from the tail. Diabetic inducing increased plasma apoA-I and decreased FABP4 levels compared with non-diabetic control group (respectively, P = 0.001 & P = 0.041). After 4 weeks' resistance training, plasma levels of apoA-I and FABP4 in the diabetic trained rats were significantly higher compared with the diabetic control group (respectively, P = 0.003 & P = 0.017). Plasma HDL-C level in diabetic trained group was higher than diabetic control group (P = 0.048). Liver triglycerides concentrations were significantly lower in both trained (non-diabetic and diabetic) groups compared with their control groups (respectively, P = 0.041 and P = 0.002). These data indicated that resistance training may be an efficient intervention strategy to increase plasma apoA-I, HDL-C and FABP4 concentrations, along with decreases liver triglycerides in streptozotocin induced diabetic rats. Further research is needed to elucidate physiological significance of circulating FABP4 levels.

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

PubMed

Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Cetuximab-induced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin

PubMed Central

Satomi, Machiko; Asama, Toshiyuki; Ebisawa, Yoshiaki; Chisato, Naoyuki; Suno, Manabu; Karasaki, Hidenori; Furukawa, Hiroyuki; Matsubara, Kazuo

2010-01-01

Calcium and magnesium replacement is effective in reducing oxaliplatin-induced neurotoxicity. However, cetuximab treatment has been associated with severe hypomagnesaemia. Therefore, we retrospectively investigated whether cetuximab-induced hypomagnesaemia exacerbated oxaliplatin-induced neurotoxicity. Six patients with metastatic colorectal cancer who were previously treated with oxaliplatin-fluorouracil combination therapy were administered cetuximab in combination with irinotecan alone or irinotecan and fluorouracil as a second-line treatment. All patients had normal magnesium levels before receiving cetuximab. The Common Terminology Criteria for Adverse Events version 3.0 was used to evaluate the grade of neurotoxicity, hypomagnesaemia, hypocalcaemia, and hypokalemia every week. All six patients had grade 1 or higher hypomagnesaemia after starting cetuximab therapy. The serum calcium and potassium levels were within the normal range at the onset of hypomagnesaemia. Oxaliplatin-induced neurotoxicity occurred in all patients at the beginning of cetuximab therapy, with grade 1 neurotoxicity in five patients and grade 2 in one patient. After cetuximab administration, the neurotoxicity worsened in all six patients, and three progressed to grade 3. Among the three patients with grade 3 neurotoxicity, two required a dose reduction and one had to discontinue cetuximab therapy. A discontinuation or dose reduction in cetuximab therapy was associated with exacerbated oxaliplatin-induced neurotoxicity due to cetuximab-induced hypomagnesaemia in half of patients who had previously received oxaliplatin. Therefore, when administering cetuximab after oxaliplatin therapy, we suggest serially evaluating serum magnesium levels and neurotoxicity. PMID:22811813

Plant Volatiles Induced by Herbivore Egg Deposition Affect Insects of Different Trophic Levels

PubMed Central

Fatouros, Nina E.; Lucas-Barbosa, Dani; Weldegergis, Berhane T.; Pashalidou, Foteini G.; van Loon, Joop J. A.; Dicke, Marcel; Harvey, Jeffrey A.; Gols, Rieta; Huigens, Martinus E.

2012-01-01

Plants release volatiles induced by herbivore feeding that may affect the diversity and composition of plant-associated arthropod communities. However, the specificity and role of plant volatiles induced during the early phase of attack, i.e. egg deposition by herbivorous insects, and their consequences on insects of different trophic levels remain poorly explored. In olfactometer and wind tunnel set-ups, we investigated behavioural responses of a specialist cabbage butterfly (Pieris brassicae) and two of its parasitic wasps (Trichogramma brassicae and Cotesia glomerata) to volatiles of a wild crucifer (Brassica nigra) induced by oviposition of the specialist butterfly and an additional generalist moth (Mamestra brassicae). Gravid butterflies were repelled by volatiles from plants induced by cabbage white butterfly eggs, probably as a means of avoiding competition, whereas both parasitic wasp species were attracted. In contrast, volatiles from plants induced by eggs of the generalist moth did neither repel nor attract any of the tested community members. Analysis of the plant’s volatile metabolomic profile by gas chromatography-mass spectrometry and the structure of the plant-egg interface by scanning electron microscopy confirmed that the plant responds differently to egg deposition by the two lepidopteran species. Our findings imply that prior to actual feeding damage, egg deposition can induce specific plant responses that significantly influence various members of higher trophic levels. PMID:22912893

Serum PAI-1 and PAI-1 4G/5G Polymorphism in Hepatitis C Virus-Induced Cirrhosis and Hepatitis C Virus-Induced Hepatocellular Carcinoma Patients.

PubMed

El Edel, Rawhia H; Essa, Enas Said; Essa, Abdallah S; Hegazy, Sara A; El Rowedy, Dalia I

2016-11-01

Association between variable agent-induced hepatocellular carcinoma (HCC) and both PAI-1 4G/5G polymorphism and plasminogen activator inhibitor (PAI-1) levels compared to healthy controls have been reported in earlier studies. We aimed to assess serum PAI-1 and PAI-1 4G/5G polymorphism in hepatitis C virus (HCV)-induced HCC, HCV-induced liver cirrhosis, and viral infection-free apparently healthy control subjects. Forty nine HCC, 52 cirrhosis, and 105 controls were genotyped for PAI-1 4G/5G using an allele-specific polymerase chain reaction analysis. In addition, for 31 HCC, 24 cirrhosis, and 28 controls, serum PAI-1 level was measured by enzyme-linked immunosorbent assay (ELISA). There was no significant difference in PAI-1 4G/5G genotype distribution between cirrhosis and controls (p = 0.33, p = 0.15, and p = 0.38 for the codominant, dominant, and recessive models, respectively) or between HCC and cirrhosis (p = 0.5, p = 0.24, and p = 0.69 for the codominant, dominant, and recessive models, respectively). Serum PAI-1 was significantly higher in cirrhosis than controls and significantly lower in HCC than cirrhosis (p < 0.001 for both). Serum PAI-1 did not differ significantly among the three PAI-1 4G/5G genotypes in controls, cirrhosis, and HCC (p = 0.29, p = 0.28, and p = 0.73 respectively). We documented higher serum PAI-1 in HCV-induced HCC than viral infection-free controls, but interestingly, lower than HCV-induced liver cirrhosis patients. This was not genotype related. Further studies will be needed to clearly elucidate the underlying mechanism.

Relationships of maternal blood lead and disorders of pregnancy to neonatal birthweight.

PubMed

Kaul, P P; Srivastava, R; Srivastava, S P; Kamboj, M; Chand, S

2002-12-01

Transient complications of pregnancy (anemia, toxemia, proteinuria, arterial hypertension and hyperemesis) were studied in pregnant women from the general population reporting to local hospitals. Comparison of blood lead levels (PbB) was made between women with normal pregnancies and those with complications. Significantly higher PbB were found in women with pregnancy complications as compared to those with normal pregnancies. Increments in the PbB levels were accompanied by statistically significant decrements in neonate birthweights. Complications of pregnancy may be induced by higher PbB and may also compound the adverse effects of decrements of neonate birthweights

Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

PubMed

Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

2014-11-01

We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis.

PubMed

Cardona, Pere-Joan; Gordillo, Sergi; Díaz, Jorge; Tapia, Gustavo; Amat, Isabel; Pallarés, Angeles; Vilaplana, Cristina; Ariza, Aurelio; Ausina, Vicenç

2003-10-01

We have used the murine model of aerosol-induced experimental tuberculosis to assess the effects of four clinical isolates and a reference strain of Mycobacterium tuberculosis on resistant C57BL/6 mice and susceptible DBA/2 mice. Histological studies and detection of 25 cytokines potentially involved in the infection were carried out. DBA/2 mice showed higher concentrations of bacilli in bronchoalveolar lavage fluid and lung tissue. Furthermore, these mice evidenced a larger granulomatous infiltration in the parenchyma due to an increased rate of emigration of infected foamy macrophages from the granulomas to the neighboring pulmonary alveolar spaces. The better control of bacillary concentrations and pulmonary infiltration observed in C57BL/6 mice from week 3 postinfection could result from their higher RANTES, ICAM-1, and gamma interferon (IFN-gamma) mRNA levels. On the other hand, the higher MIP-2 and MCP-3 mRNA levels seen in DBA/2 mice would result in stronger lung recruitment of macrophages and neutrophils. Additionally, DBA/2 mice showed increased inducible nitric oxide synthase expression, induced by the larger number of foamy macrophages, at weeks 18 and 22. This increment was a consequence of phagocytosed bacillary debris, was independent of IFN-gamma expression, and could exert only a bacteriostatic effect. The results of the study suggest that DBA/2 mice are more susceptible than C57BL/6 mice to M. tuberculosis infection due to a higher bronchial dissemination of bacilli inside poorly activated foamy macrophages.

Stronger proteasomal inhibition and higher CHOP induction are responsible for more effective induction of paraptosis by dimethoxycurcumin than curcumin

PubMed Central

Yoon, M J; Kang, Y J; Lee, J A; Kim, I Y; Kim, M A; Lee, Y S; Park, J H; Lee, B Y; Kim, I A; Kim, H S; Kim, S-A; Yoon, A-R; Yun, C-O; Kim, E-Y; Lee, K; Choi, K S

2014-01-01

Although curcumin suppresses the growth of a variety of cancer cells, its poor absorption and low systemic bioavailability have limited its translation into clinics as an anticancer agent. In this study, we show that dimethoxycurcumin (DMC), a methylated, more stable analog of curcumin, is significantly more potent than curcumin in inducing cell death and reducing the clonogenicity of malignant breast cancer cells. Furthermore, DMC reduces the tumor growth of xenografted MDA-MB 435S cells more strongly than curcumin. We found that DMC induces paraptosis accompanied by excessive dilation of mitochondria and the endoplasmic reticulum (ER); this is similar to curcumin, but a much lower concentration of DMC is required to induce this process. DMC inhibits the proteasomal activity more strongly than curcumin, possibly causing severe ER stress and contributing to the observed dilation. DMC treatment upregulates the protein levels of CCAAT-enhancer-binding protein homologous protein (CHOP) and Noxa, and the small interfering RNA-mediated suppression of CHOP, but not Noxa, markedly attenuates DMC-induced ER dilation and cell death. Interestingly, DMC does not affect the viability, proteasomal activity or CHOP protein levels of human mammary epithelial cells, suggesting that DMC effectively induces paraptosis selectively in breast cancer cells, while sparing normal cells. Taken together, these results suggest that DMC triggers a stronger proteasome inhibition and higher induction of CHOP compared with curcumin, giving it more potent anticancer effects on malignant breast cancer cells. PMID:24625971

Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure.

PubMed

Rosen, Hugo R; Biggins, Scott W; Niki, Toshiro; Gralla, Jane; Hillman, Holly; Hirashima, Mitsuomi; Schilsky, Michael; Lee, William M

2016-04-01

Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells

PubMed Central

Andreo, Ursula; Elkind, Josh; Blachford, Courtney; Cederbaum, Arthur I.; Fisher, Edward A.

2011-01-01

VLDL is produced by the liver. Its major protein is apoB100. Docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid (PUFA), reduces VLDL levels and is used therapeutically for hypertriglyceridemia. In model systems, DHA lowers VLDL secretion by inducing presecretory apoB100 degradation, a process dependent on PUFA-derived lipid peroxides. We hypothesized that superoxide (SO) was a major participant in DHA-induced apoB100 degradation, given its promotion of lipid peroxidation. SO levels in a model of VLDL metabolism, rat hepatoma McArdle cells, were either decreased by a mimetic of superoxide dismutase 1 (SOD1) or by overexpressing SOD1 or increased by SOD1 siRNA. ApoB100 recovery was assessed by immunoprecipitation, SO by 2-hydroxyethidine, and lipid peroxides by thiobarbituric acid reactive substances. The SOD1 mimetic or SOD1 overexpression reduced SO and inhibited apoB100 degradation in DHA-treated cells by up to 100%. Surprisingly, silencing SOD1 did not increase DHA-induced degradation, although levels of SO were higher (+44%); those of lipid peroxides were similar, and their reduction by α-tocopherol decreased degradation by 50%. SO is required for lipid peroxidation in DHA-induced apoB100 degradation, but it is the peroxide level that has a tighter relationship to the level of degradation and the regulation of VLDL production.—Andreo, U., Elkind, J., Blachford, C., Cederbaum, A. I., Fisher, E. A. Role of superoxide radical anion in the mechanism of apoB100 degradation induced by DHA in hepatic cells. PMID:21757500

Involvement of NADPH oxidase isoforms in the production of O2− manipulated by ABA in the senescing leaves of early-senescence-leaf (esl) mutant rice (Oryza sativa)

PubMed Central

Wang, Fubiao; Zhao, Qian; Liu, Jianchao; Cheng, Fangmin

2018-01-01

In this study, the differences in reactive oxygen species (ROS) generation and abscisic acid (ABA) accumulation in senescing leaves were investigated by early-senescence-leaf (esl) mutant and its wild type, to clarify the relationship among ABA levels, ROS generation, and NADPH oxidase (Nox) in senescing leaves of rice (Oryza sativa). The temporal expression levels of OsNox isoforms in senescing leaves and their expression patterns in response to ABA treatment were determined through quantitative real-time reverse transcription PCR (qRT-PCR). Results showed that the flag leaf of the esl mutant generated more O2- concentrations and accumulated higher ABA levels than the wild-type cultivar did in the grain-filling stage. Exogenous ABA treatment induced O2- generation; however, it was depressed by diphenyleneiodonium chloride (DPI) pretreatment in the detached leaf segments. This finding suggested the involvement of NADPH oxidase in ABA-induced O2- generation. The esl mutant exhibited significantly higher expression of OsNox2, OsNox5, OsNox6, and OsNox7 in the initial of grain-filling stage, followed by sharply decrease. The transcriptional levels of OsNox1, OsNox3, and OsFR07 in the flag leaf of the esl mutant were significantly lower than those in the wild-type cultivar. The expression levels of OsNox2, OsNox5, OsNox6, and OsNox7 were significantly enhanced by exogenous ABA treatments. The enhanced expression levels of OsNox2 and OsNox6 were dependent on the duration of ABA treatment. The inducible expression levels of OsNox5 and OsNox7 were dependent on ABA concentrations. By contrast, exogenous ABA treatment severely repressed the transcripts of OsNox1, OsNox3, and OsFR07 in the detached leaf segments. Therefore, OsNox2, OsNox5, OsNox6, and OsNox7 were probably involved in the ABA-induced O2- generation in the initial stage of leaf senescence. Subsequently, other oxidases activated in deteriorating cells were associated with ROS generation and accumulation in the senescing leaves of the esl mutant. Conversely, OsNox1, OsNox3, and OsFR07 were not associated with ABA-induced O2- generation during leaf senescence. PMID:29309410

Involvement of NADPH oxidase isoforms in the production of O2- manipulated by ABA in the senescing leaves of early-senescence-leaf (esl) mutant rice (Oryza sativa).

PubMed

Li, Zhaowei; Wang, Fubiao; Zhao, Qian; Liu, Jianchao; Cheng, Fangmin

2018-01-01

In this study, the differences in reactive oxygen species (ROS) generation and abscisic acid (ABA) accumulation in senescing leaves were investigated by early-senescence-leaf (esl) mutant and its wild type, to clarify the relationship among ABA levels, ROS generation, and NADPH oxidase (Nox) in senescing leaves of rice (Oryza sativa). The temporal expression levels of OsNox isoforms in senescing leaves and their expression patterns in response to ABA treatment were determined through quantitative real-time reverse transcription PCR (qRT-PCR). Results showed that the flag leaf of the esl mutant generated more O2- concentrations and accumulated higher ABA levels than the wild-type cultivar did in the grain-filling stage. Exogenous ABA treatment induced O2- generation; however, it was depressed by diphenyleneiodonium chloride (DPI) pretreatment in the detached leaf segments. This finding suggested the involvement of NADPH oxidase in ABA-induced O2- generation. The esl mutant exhibited significantly higher expression of OsNox2, OsNox5, OsNox6, and OsNox7 in the initial of grain-filling stage, followed by sharply decrease. The transcriptional levels of OsNox1, OsNox3, and OsFR07 in the flag leaf of the esl mutant were significantly lower than those in the wild-type cultivar. The expression levels of OsNox2, OsNox5, OsNox6, and OsNox7 were significantly enhanced by exogenous ABA treatments. The enhanced expression levels of OsNox2 and OsNox6 were dependent on the duration of ABA treatment. The inducible expression levels of OsNox5 and OsNox7 were dependent on ABA concentrations. By contrast, exogenous ABA treatment severely repressed the transcripts of OsNox1, OsNox3, and OsFR07 in the detached leaf segments. Therefore, OsNox2, OsNox5, OsNox6, and OsNox7 were probably involved in the ABA-induced O2- generation in the initial stage of leaf senescence. Subsequently, other oxidases activated in deteriorating cells were associated with ROS generation and accumulation in the senescing leaves of the esl mutant. Conversely, OsNox1, OsNox3, and OsFR07 were not associated with ABA-induced O2- generation during leaf senescence.

A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet.

PubMed

Hirai, K; Ozeki, Y; Nakano, T; Takezoe, R; Nakanishi, M; Asano, Y; Higuchi, H

2001-01-01

The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p<0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p<0.05) and in the casein groups than in the soy protein groups (p<0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p<0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p<0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p<0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.

Mode of action of dopamine in inducing hyperglycemia in the fresh water edible crab, Oziothelphusa senex senex.

PubMed

Swetha, Ch; Sainath, S B; Reddy, P Sreenivasula

2014-11-01

The objective of this study was to investigate the mode of action of dopamine in regulating hemolymph sugar level in the fresh water edible crab, Oziothelphusa senex senex. Injection of dopamine produced hyperglycemia in a dose-dependent manner in intact crabs but not in eyestalkless crabs. Administration of dopamine resulted in a significant decrease in total carbohydrates and glycogen levels with a significant increase in glycogen phosphorylase activity levels in hepatopancreas and muscle of intact crabs, indicating dopamine-induced glycogenolysis resulting in hyperglycemia. Bilateral eyestalk ablation resulted in significant increase in the total carbohydrates and glycogen levels with a significant decrease in the activity levels of phosphorylase in the hepatopancreas and muscle of the crabs. Eyestalk ablation resulted in significant decrease in hemolymph hyperglycemic hormone levels. The levels of hyperglycemic hormone in the hemolymph of dopamine injected crabs were significantly higher than in control crabs. However, no significant changes in the levels of hemolymph hyperglycemic hormone and sugar and tissue carbohydrate and phosphorylase activity were observed in dopamine injected eyestalk ablated crabs when compared with eyestalk ablated crabs. These results support an earlier hypothesis in crustaceans that dopamine acts as a neurotransmitter and induces hyperglycemia by triggering the release of hyperglycemic hormone in the crab, O. senex senex. © 2014 Wiley Periodicals, Inc.

Fluid Shear Stress-Induced JNK Activity Leads to Actin Remodeling for Cell Alignment

PubMed Central

Mengistu, Meron; Brotzman, Hannah; Ghadiali, Samir; Lowe-Krentz, Linda

2012-01-01

Fluid shear stress (FSS) exerted on endothelial cell surfaces induces actin cytoskeleton remodeling through mechanotransduction. This study was designed to determine whether FSS activates Jun N-terminal kinase (JNK), to examine the spatial and temporal distribution of active JNK relative to the actin cytoskeleton in endothelial cells exposed to different FSS conditions, and to evaluate the effects of active JNK on actin realignment. Exposure to 15 and 20 dyn/cm2 FSS induced higher activity levels of JNK than the lower 2 and 4 dyn/cm2 flow conditions. At the higher FSS treatments, JNK activity increased with increasing exposure time, peaking 30 minutes after flow onset with an 8-fold activity increase compared to cells in static culture. FSS-induced phospho-JNK co-localized with actin filaments at cell peripheries, as well as with stress fibers. Pharmacologically blocking JNK activity altered FSS-induced actin structure and distribution as a response to FSS. Our results indicate that FSS-induced actin remodeling occurs in three phases, and that JNK plays a role in at least one, suggesting that this kinase activity is involved in mechanotransduction from the apical surface to the actin cytoskeleton in endothelial cells. PMID:20626006

Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL

PubMed Central

2014-01-01

Background Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage. Methods L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS. We further studied the effects of gender-influenced LDL electronegativity on aortic cellular senescence and DNA damage in leptin receptor–deficient (db/db) mice by using senescence-associated–β-galactosidase and γH2AX staining, respectively. We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL–induced senescence in cultured bovine aortic endothelial cells (BAECs). Results L5 levels were higher in MetS patients than in healthy subjects (P < 0.001), particularly in men (P = 0.001). LDL isolated from male db/db mice was more electronegative than that from male or female wild-type mice. In addition, LDL from male db/db mice contained abundantly more apolipoprotein CIII and induced more BAEC senescence than did female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type mice, we observed cellular senescence and DNA damage, and the effect was more significant in male than in female db/db mice. Pretreatment with 17β-estradiol or genistein inhibited BAEC senescence induced by male or female db/db LDL and downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor necrosis factor-alpha protein. Conclusion The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men. PMID:24666525

Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

PubMed

Takahashi, L K; Kalin, N H

1991-08-30

Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

Hydrogen saline prevents selenite-induced cataract in rats

PubMed Central

Yang, Chun-xiao; Ding, Tian-bing

2013-01-01

Purpose The aim of this study was to investigate the potential antioxidative effect and mechanism for the protective effects of hydrogen saline on selenite-induced cataract in rats. Methods Sprague-Dawley rat pups were divided into the following groups: control (Group A), selenite induced (Group B), and selenite plus hydrogen saline treated (Group C). Rat pups in Groups B and C received a single subcutaneous injection of sodium selenite (25 μmol/kg bodyweight) on postnatal day 12. Group C also received an intraperitoneal injection of H2 saline (5 ml/kg bodyweight) daily from postnatal day 8 to postnatal day 17. The development of cataract was assessed weekly by slit-lamp examination for 2 weeks. After sacrifice, extricated lenses were analyzed for activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, levels of malondialdehyde, reduced glutathione (GSH), and total sulfhydryl contents. Results The magnitude of lens opacification in Group B was significantly higher than in Group A (p<0.05), while Group C had less opacification than Group B (p<0.05). Compared with Group B, the mean activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, levels of GSH, and total sulfhydryl contents were higher, whereas the level of malondialdehyde was lower following treatment with hydrogen saline(p<0.05). Conclusions This is an initial report showing that hydrogen saline can prevent selenite-induced cataract in rats. It acts via maintaining antioxidant enzymes and GSH, protecting the sulfhydryl group, and inhibiting lipid peroxidation. PMID:23922487

Polyethylene glycol-conjugated HER2-targeted peptides as a nuclear imaging probe for HER2-overexpressed gastric cancer detection in vivo.

PubMed

Guan, Siao-Syun; Wu, Cheng-Tien; Chiu, Chen-Yuan; Luo, Tsai-Yueh; Wu, Jeng-Yih; Liao, Tse-Zung; Liu, Shing-Hwa

2018-06-19

The human epidermal growth factor receptor 2 (HER2) involved proliferation, angiogenesis, and reduced apoptosis in gastric cancer (GC), which is a common target for tumor therapy. HER2 is usually overexpressed in more than 15% GC patients, developing a reliable diagnostic tool for tumor HER2 detection is important. In this study, we attend to use polyethylene glycol (PEG) linked anti-HER2/neu peptide (AHNP-PEG) as a nuclear imaging agent probe for HER2 detection in GC xenograft animal model. The HER2 expression of human sera and tissues were detected in GC patients and normal subjects. GC cell lines NCI-N87 (high HER2 levels) and MKN45 (low HER2 levels) were treated with AHNP-PEG to assess the cell viability and HER2 binding ability. The NCI-N87 was treated with AHNP-PEG to observe the level and phosphorylation of HER2. The MKN45 and NCI-N87-induced xenograft mice were intravenous injection with fluorescence labeled AHNP-PEG for detecting in vivo fluorescence imaging properties and biodistribution. The AHNP-PEG was conjugated with diethylenetriaminopentaacetic acid (DTPA) for indium-111 labeling ( 111 In-DTPA-AHNP-PEG). The stability of was assessed in vitro. The imaging properties and biodistribution of 111 In-DTPA-AHNP-PEG were observed in NCI-N87-induced xenograft mice. The serum HER2 (sHER2) levels in GC patients were significantly higher than the normal subjects. The sHER2 levels were correlated with the tumor HER2 levels in different stages of GC patients. The AHNP-PEG inhibited the cell growth and down-regulated HER2 phosphorylation in HER2-overexpressed human GC cells (NCI-N87) via specific HER2 interaction of cell surface. In addition, the GC tumor tissues from HER2-postive xenograft mice presented higher HER2 fluorescence imaging as compared to HER2-negative group. The HER2 levels in the tumor tissues were also higher than other organs in NCI-N87-induced xenograft mice. Finally, we further observed that the 111 In-DTPA-AHNP-PEG was significantly enhanced in tumor tissues of NCI-N87-induced xenograft mice compared to control. These findings suggest that the sHER2 measurement may be as a potential tool for detecting HER2 expressions in GC patients. The radioisotope-labeled AHNP-PEG may be useful to apply in GC patients for HER2 nuclear medicine imaging.

The effects of fatigue on performance in simulated nursing work.

PubMed

Barker, Linsey M; Nussbaum, Maury A

2011-09-01

Fatigue is associated with increased rates of medical errors and healthcare worker injuries, yet existing research in this sector has not considered multiple dimensions of fatigue simultaneously. This study evaluated hypothesised causal relationships between mental and physical fatigue and performance. High and low levels of mental and physical fatigue were induced in 16 participants during simulated nursing work tasks in a laboratory setting. Task-induced changes in fatigue dimensions were quantified using both subjective and objective measures, as were changes in performance on physical and mental tasks. Completing the simulated work tasks increased total fatigue, mental fatigue and physical fatigue in all experimental conditions. Higher physical fatigue adversely affected measures of physical and mental performance, whereas higher mental fatigue had a positive effect on one measure of mental performance. Overall, these results suggest causal effects between manipulated levels of mental and physical fatigue and task-induced changes in mental and physical performance. STATEMENT OF RELEVANCE: Nurse fatigue and performance has implications for patient and provider safety. Results from this study demonstrate the importance of a multidimensional view of fatigue in understanding the causal relationships between fatigue and performance. The findings can guide future work aimed at predicting fatigue-related performance decrements and designing interventions.

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

PubMed

Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-07-26

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease

PubMed Central

Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

2016-01-01

Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease. PMID:27409675

Air pollution as a determinant of rheumatoid arthritis.

PubMed

Sigaux, Johanna; Biton, Jérôme; André, Emma; Semerano, Luca; Boissier, Marie-Christophe

2018-03-07

Pollution has long been incriminated in many cardiovascular and respiratory diseases. More recently, studies evaluated the potential role for particulate pollutants in autoimmune diseases, including rheumatoid arthritis (RA). The incidence of RA was found to be higher in urban areas. Living near air pollution emitters was associated with higher risks of developing RA and of producing RA-specific autoantibodies. Nevertheless, no strong epidemiological evidence exists to link one or more specific air pollution particles to RA. The presence in the bronchi of lymphoid satellite islands (inducible bronchus-associated lymphoid tissue, iBALT) is strongly associated with both inflammatory lung disease and RA-associated lung disease. Diesel exhaust particles can stimulate iBALT formation. The induction by air pollution of an inflammatory environment with high citrullination levels in the lung may induce iBALT formation, thereby causing a transition toward a more specific immune response via the production of anti-citrullinated peptide antibodies. Air pollution not only triggers innate immune responses at the molecular level, increasing the levels of proinflammatory cytokines and reactive oxygen species, but is also involved in adaptive immune responses. Thus, via the aryl hydrocarbon receptor (AHR), diesel exhaust particles can trigger a T-cell switch to the Th17 profile. Finally, in the murine collagen-induced arthritis model, animals whose lymphocytes lack the AHR develop milder arthritis. Copyright © 2018. Published by Elsevier SAS.

Hypothyroidism protects di(n-butyl) phthalate-induced reproductive organs damage in Sprague-Dawley male rats.

PubMed

Lee, Ena; Kim, Hee Jin; Im, Ji Young; Kim, Jeonga; Park, Hyeyoung; Ryu, Ju Young; Lee, Jaewon; Shim, Keun Aee; Jung, Kee Kyung; Han, Soon Young; Lee, Byung Mu; Kim, Seung Hee; Kim, Hyung Sik

2008-08-01

This study examined the deleterious effects of di(n-butyl) phthalate (DBP) on the male reproductive organs in hypothyroid rats. Hypothyroidism was induced in prepubertal male rats (28 days of age) by an intraperitonial (i.p.) injection of 10 mg/kg/day propylthiouracil (PTU) for 30 days. DBP (100 and 500 mg/kg/day) was administered by oral gavages to the intact or hypothyroid rats for 30 days. The body weight of the PTU-treated rats was significantly lower than the control group. The total triiodothyronine (T3) and thyroxine (T4) serum level was lower, and the thyroid-stimulating hormone (TSH) level was higher in the hypothyroid rats than in the control rats. The DBP treatment rats showed significantly lower testes, epididymides, seminal vesicles, and ventral prostate weights than the untreated rats. The hypothyroid rats had significantly higher thyroid weights and lower adrenal glands weights than the control rats. The histomorphological examination showed diffused Leydig cells hyperplasias and germ cells loss in the DBP (500 mg/kg)-treated rats, whereas these effects were mild in the DBP-treated hypothyroid rats. The serum levels of monobutyl phthalate (MBP) were significantly lower in PTU-induced hypothyroid rats than in the DBP-treated rats. This data suggests that the hypothyroid status might offer some protection from male reproductive organ toxicity caused by a disturbance in the metabolic activation of the parent compound, DBP.

Nrf2-Dependent Induction of NQO1 in Mouse Aortic Endothelial Cells Overexpressing Catalase

PubMed Central

Lin, Xinghua; Yang, Hong; Zhou, LiChun; Guo, ZhongMao

2011-01-01

Overexpression of catalase has been shown to accelerate benzo(a)pyrene (BaP) detoxification in mouse aortic endothelial cells (MAECs ). NAD(P)H:quinone oxidoreductase1 (NQO1) is an enzyme that catalyzes BaP-quinone detoxification. Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor-2 (Nrf2) are transcription factors that control NQO1 expression. Here, we investigated the effect of catalase overexpression on NQO1, Nrf2 and AhR expressions. The levels of NQO1 mRNA and protein were comparable in MAECs isolated from wild-type and transgenic mice that overexpress human catalase (hCatTg). BaP treatment increased NQO1 mRNA and protein levels in both groups, with a significantly greater induction in hCatTg MAECs than in wild-type cells. BaP-induced NQO1 promoter activity was dramatically higher in hCatTg MAECs than in wild-type cells. Our data also showed that the basal level of AhR and the BaP-induced level of Nrf2 were significantly higher in hCatTg MAECs than in wild-type cells. Inhibition of specificity protein-1 (Sp1) binding to the AhR promoter region by mithramycin A reversed the enhanced effect of catalase overexpression on AhR expression. Knockdown of AhR by RNA interference diminished BaP-induced expression of Nrf2 and NQO1. Knockdown of Nrf2 significantly decreased NQO1 mRNA and protein levels in cells with or without BaP treatment. NQO1 promoter activity was abrogated by mutation of the Nrf2-binding site in this promoter. In contrast, mutation of the AhR-binding site in NQO1 promoter did not affect the promoter activity. These results suggest that catalase overexpression upregulates BaP-induced NQO1 expression via enhancing the Sp1-AhR-Nrf2 signaling cascade. PMID:21569840

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

Accumulation of intra-cellular polyphosphate in Chlorella vulgaris cells is related to indole-3-acetic acid produced by Azospirillum brasilense.

PubMed

Meza, Beatriz; de-Bashan, Luz E; Hernandez, Juan-Pablo; Bashan, Yoav

2015-06-01

Accumulation of intra-cellular phosphate, as polyphosphate, was measured when the microalga Chlorella vulgaris was immobilized in alginate with either of two wild-type strains of the microalgae growth-promoting bacterium Azospirillum brasilense or their corresponding IAA-attenuated mutants. Wild type strains of A. brasilense induced higher amounts of intra-cellular phosphate in Chlorella than their respective mutants. Calculations comparing intra-cellular phosphate accumulation by culture or net accumulation by the cell and the amount of IAA that was produced by each of these strains revealed that higher IAA was linked to higher accumulations of intra-cellular phosphate. Application of four levels of exogenous IAA reported for A. brasilense and their IAA-attenuated mutants to cultures of C. vulgaris enhanced accumulation of intra-cellular phosphate; the higher the content of IAA per culture or per single cell, the higher was the amount of accumulated phosphate. When an IAA-attenuated mutant was complemented with exogenous IAA, accumulation of intra-cellular phosphate at the culture level was even higher than phosphate accumulation with the respective wild type strains. When calculating the net accumulation of intra-cellular phosphate in the complementation experiment, net intra-cellular phosphate induced by the IAA-attenuated mutant was completely restored and was similar to the wild strains. We propose that IAA produced by A. brasilense is linked to polyphosphate accumulation in C. vulgaris. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Retinoid Expression in Onchocercal Skin Disease: Pilot Study

PubMed Central

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA (r2 = 0.25, P = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light. PMID:29317828

Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

PubMed

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r 2  = 0.25, P  = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.

Tumor Associated Mesenchymal Stromal Cells Show Higher Immunosuppressive and Angiogenic Properties Compared to Adipose Derived MSCs.

PubMed

Langroudi, Ladan; Hassan, Zuhair Muhammad; Soleimani, Masoud; Hashemi, Seyed Mahmoud

2015-12-01

Differentiation, migratory properties and availability of Mesenchymal Stromal Cells (MSC) have become an important part of biomedical research. However, the functional heterogeneity of cells derived from different tissues has hampered providing definitive phenotypic markers for these cells. To characterize and compare the phenotype and cytokines of adipose derived MSCs (AD-MSCs) and tumoral-MSCs (T-MSCs) isolated from mammary tumors of BALB/c mice. Immunophenotyping and in vitro differentiation tests were used for MSC characterization. Cytokine and enzyme profiles were assessed using ELISA and Real-time PCR, respectively. T-MSCs expressed significantly higher levels of HLA-DR (p=0.04). Higher levels of PGE2 and COX-2 enzyme were also observed in T-MSCs (p=0.07 and p=0.00, respectively). Additionally, T-MSCs expressed higher levels of iNOS and MMP9 (p=0.01 and p=0.01, respectively). T-MSCs were also able to induce higher levels of proliferation and migration of HUVEC endothelial cells in wound scratch assay compared to AD-MSCs (p=0.015). Functional differences showed by the surface markers of MSCs, cytokine and enzyme production indicate the effect of different microenvironments on MSCs phenotype and function.

Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration

PubMed Central

Yu, Honghua; Zou, Xiulan; Peng, Lianghong; Wang, Yong; Zhang, Chu

2013-01-01

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease. PMID:24083358

Recovery from Object Substitution Masking Induced by Transient Suppression of Visual Motion Processing: A Repetitive Transcranial Magnetic Stimulation Study

ERIC Educational Resources Information Center

Hirose, Nobuyuki; Kihara, Ken; Mima, Tatsuya; Ueki, Yoshino; Fukuyama, Hidenao; Osaka, Naoyuki

2007-01-01

Object substitution masking is a form of visual backward masking in which a briefly presented target is rendered invisible by a lingering mask that is too sparse to produce lower image-level interference. Recent studies suggested the importance of an updating process in a higher object-level representation, which should rely on the processing of…

Endothelial dysfunction and metabolic control in streptozotocin-induced diabetic rats

PubMed Central

Rodríguez-Mañas, Leocadio; Angulo, Javier; Peiró, Concepción; Llergo, José L; Sánchez-Ferrer, Alberto; López-Dóriga, Pedro; Sánchez-Ferrer, Carlos F

1998-01-01

The aim of this work was to study the influence of the metabolic control, estimated by the levels of glycosylated haemoglobin in total blood samples (HbA1c), in developing vascular endothelial dysfunction in streptozotocin-induced diabetic rats. Four groups of animals with different levels of insulin treatment were established, by determining HbA1c values in 5.5 to 7.4%, 7.5 to 9.4%, 9.5 to 12% and >12%, respectively.The parameters analysed were: (1) the endothelium-dependent relaxations to acetylcholine (ACh) in isolated aorta and mesenteric microvessels; (2) the vasodilator responses to exogenous nitric oxide (NO) in aorta; and (3) the existence of oxidative stress by studying the influence of the free radical scavenger superoxide dismutase (SOD) on the vasodilator responses to both ACh and NO.In both isolated aortic segments and mesenteric microvessels, the endothelium-mediated concentration-dependent relaxant responses elicited by ACh were significantly decreased when the vessels were obtained from diabetic animals but only with HbA1c values higher than 7.5%. There was a high correlation between HbA1c levels and the impairment of ACh-induced relaxations, measured by pD2 values.The concentration-dependent vasorelaxant responses to NO in endothelium-denuded aortic segments were significantly reduced only in vessels from diabetic animals with HbA1c values higher than 7.5%. Again, a very high correlation was found between the HbA1c values and pD2 for NO-evoked responses.In the presence of SOD, the responses to ACh or NO were only increased in the segments from diabetic rats with HbA1c levels higher than 7.5%, but not in those from non-diabetic or diabetic rats with a good metabolic control (HbA1c levels <7.5%).These results suggest the existence of: (1) a close relation between the degree of endothelial dysfunction and the metabolic control of diabetes, estimated by the levels of HbA1c; and (2) an increased production of superoxide anions in the vascular wall of the diabetic rats, which is also related to the metabolic control of the disease. PMID:9605553

P27/Kip1 is responsible for magnolol-induced U373 apoptosis in vitro and in vivo.

PubMed

Chen, Li-Ching; Lee, Wen-Sen

2013-03-20

Previously, we demonstrated that magnolol, a hydroxylated biphenyl compound isolated from the bark of Magnolia officinalis, at low concentrations (3-10 μM) exerted an antiproliferation effect in colon cancer, hepatoma, and glioblastoma (U373) cell lines through upregulation of the p21/Cip1 protein. Magnolol at a higher concentration of 100 μM, however, induced apoptosis and upregulated p27/Kip1 expression in U373. In the present study, we further studied whether the increased p27/Kip1 expression contributes to the magnolol-induced apoptosis in U373. Our data show that knock-down of p27/Kip1 expression significantly suppressed the magnolol-induced apoptosis, suggesting that p27/Kip1 might play an important role in the regulation of magnolol-induced apoptosis. This notion was further supported by demonstrating that magnolol induced an increase of the caspase activity in U373 in vitro and in vivo, and these effects were abolished by pretransfection of the cell with p27/Kip1 siRNA. To delineate the possible signaling pathways involved in the magnolol-induced increases of p27/Kip1 expression and apoptosis, we found that magnolol (100 μM) increased the levels of phosphorylated cSrc (p-cSrc), p-ERK, p-p38 MAP kinase (p-p38 MAPK), and p-AKT but not p-JNK in U373. Moreover, pretreatment of U373 with a cSrc inhibitor (PP2), a PI3K inhibitor (LY294002), an ERK inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) but not a JNK inhibitor (SP600125) significantly reduced the magnolol-induced increases of p27/Kip1 protein levels and apoptosis. Taken together, our data suggest that magnolol at a higher concentration of 100 μM induced apopotosis in U373 cells through cSrc-mediated upregulation of p27/Kip1.

A genetically-based latitudinal cline in the emission of herbivore-induced plant volatile organic compounds.

PubMed

Wason, Elizabeth L; Agrawal, Anurag A; Hunter, Mark D

2013-08-01

The existence of predictable latitudinal variation in plant defense against herbivores remains controversial. A prevailing view holds that higher levels of plant defense evolve at low latitudes compared to high latitudes as an adaptive plant response to higher herbivore pressure on low-latitude plants. To date, this prediction has not been examined with respect to volatile organic compounds (VOCs) that many plants emit, often thus attracting the natural enemies of herbivores. Here, we compared genetically-based constitutive and herbivore-induced aboveground vegetative VOC emissions from plants originating across a gradient of more than 10° of latitude (>1,500 km). We collected headspace VOCs from Asclepias syriaca (common milkweed) originating from 20 populations across its natural range and grown in a common garden near the range center. Feeding by specialist Danaus plexippus (monarch) larvae induced VOCs, and field environmental conditions (temperature, light, and humidity) also influenced emissions. Monarch damage increased plant VOC concentrations and altered VOC blends. We found that genetically-based induced VOC emissions varied with the latitude of plant population origin, although the pattern followed the reverse of that predicted-induced VOC concentration increased with increasing latitude. This pattern appeared to be driven by a greater induction of sesquiterpenoids at higher latitudes. In contrast, constitutive VOC emission did not vary systematically with latitude, and the induction of green leafy volatiles declined with latitude. Our results do not support the prevailing view that plant defense is greater at lower than at higher latitudes. That the pattern holds only for herbivore-induced VOC emission, and not constitutive emission, suggests that latitudinal variation in VOCs is not a simple adaptive response to climatic factors.

Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

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

Huda, Nazmul; Department of Medicine, Rajshahi Medical College, Rajshahi 6000; Hossain, Shakhawoat

Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measuredmore » by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with PUA. • Arsenic-endemic hypertensive study subjects had elevated levels of PUA. • Increased PUA levels may be implicated in arsenic-induced CVDs.« less

Passive stretch reduces calpain activity through nitric oxide pathway in unloaded soleus muscles.

PubMed

Xu, Peng-Tao; Li, Quan; Sheng, Juan-Juan; Chang, Hui; Song, Zhen; Yu, Zhi-Bin

2012-08-01

Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles.

Putting prey back together again: integrating predator-induced behavior, morphology, and life history.

PubMed

Hoverman, Jason T; Auld, Josh R; Relyea, Rick A

2005-07-01

The last decade has seen an explosion in the number of studies exploring predator-induced plasticity. Recently, there has been a call for more comprehensive approaches that can identify functional relationships between traits, constraints on phenotypic responses, and the cost and benefits of alternative phenotypes. In this study, we exposed Helisoma trivolvis, a freshwater snail, to a factorial combination of three resource levels and five predator environments (no predator, one or two water bugs, and one or two crayfish) and examined ten traits including behavior, morphology, and life history. Each predator induced a unique suite of behavioral and morphological responses. Snails increased near-surface habitat use with crayfish but not with water bugs. Further, crayfish induced narrow and high shells whereas water bugs induced wide shells and wide apertures. In terms of life history, both predators induced delayed reproduction and greater mass at reproduction. However, crayfish induced a greater delay in reproduction that resulted in reduced fecundity whereas water bugs did not induce differences in fecundity. Resource levels impacted the morphology of H. trivolvis; snails reared with greater resource levels produced higher shells, narrower shells, and wider apertures. Resource levels also impacted snail life history; lower resources caused longer times to reproduction and reduced fecundity. Based on an analysis of phenotypic correlations, the morphological responses to each predator most likely represent phenotypic trade-offs. Snails could either produce invasion-resistant shells for defense against water bugs or crush-resistant shells for defense against crayfish, but not both. Our use of a comprehensive approach to examine the responses of H. trivolvis has provided important information regarding the complexity of phenotypic responses to different environments, the patterns of phenotypic integration across environments, and the potential costs and benefits associated with plastic traits.

The role of BDNF, leptin, and catecholamines in reward learning in bulimia nervosa.

PubMed

Homan, Philipp; Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

2014-12-07

A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. AMPT-induced differences in plasma BDNF levels were positively correlated with the AMPT-induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; P<.0001). The plasma leptin levels were higher under catecholamine depletion compared with placebo in the whole sample (treatment effect; P=.0004). This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with remitted bulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Regional differences in vitamin D levels and incidence of food-induced anaphylaxis in South Korea.

PubMed

Kim, Si-Heon; Ban, Ga-Young; Park, Hae-Sim; Kim, Su-chin; Ye, Young-Min

2016-03-01

Previous studies have suggested low vitamin D as a potential risk factor for food allergy/anaphylaxis. However, few studies have investigated the association between vitamin D and food-induced anaphylaxis (FIA) in South Korea. To examine regional differences in serum vitamin D levels and FIA incidence. We used nationwide data collected from 2011 to 2013. Data on vitamin D were obtained from the Korea National Health and Nutrition Examination Survey; data on FIA were obtained from the Health Insurance and Assessment Service. Districts were grouped into region 1 (lower solar radiation) and region 2 (higher solar radiation). We examined differences in FIA incidence and vitamin D levels between the regions, adjusting for age. The study included 2,814 patients with FIA and 15,367 people with available serum vitamin D measurements. Age-adjusted FIA incidence was 2.2 per 100,000 person-years in region 1 and 1.8 per 100,000 person-years in region 2 (relative risk, 1.23; 95% confidence interval, 1.09-1.39). Age-adjusted serum vitamin D levels were 16.5 ng/mL in region 1 and 17.8 ng/mL in region 2 (mean difference, 1.3 ng/mL; 95% confidence interval, 0.9-1.9). After stratification by age, sex, and area of residence, region 1 still had higher FIA incidence and lower vitamin D levels than region 2. The present study found a higher incidence of FIA in regions with lower vitamin D levels in the population. Further investigation is necessary to identify any direct associations between vitamin D and food allergy/anaphylaxis. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Immune mediators associated to male infertility in a mouse model of DNA immunization with the sperm protease proacrosin.

PubMed

Russi, Romina; García, María Inés; Vignatti, Paulina; Veiga, María Florencia; Vazquez-Levin, Mónica Hebe; Veaute, Carolina

2016-11-01

The immune response has relevant physiological functions both in the male and female reproductive system, and must be tightly controlled to achieve a successful pregnancy. Several immune factors have been related to infertility, among them humoral and cellular immune responses triggered by sperm antigens. The present study was aimed at evaluating the immune profile induced by DNA immunization against the sperm protease proacrosin in CF1 male mice and its effect upon fertility. Immunized animals exhibited higher anti-proacrosin antibodies levels than controls (indirect ELISA), both in serum (p<0.01) and in seminal vesicle fluid (SVF; p<0.05). IgG2a levels were higher than IgG1 in serum (p<0.01) and similar in SVF. IL-10 and TGF-β1 mRNA levels were lower in testis (p<0.05), whereas TNF-α and IFN-γ transcript levels were increased in SV tissue (p<0.05). Immunized mice showed a trend toward higher IFN-γ concentration in serum and SVF than controls. Male fertility rate was diminished in immunized mice (p<0.01) and inversely correlated with serum and SVF anti-proacrosin IgG levels (p<0.001). Immunized animals also had fewer pups born than controls (p<0.01). To our knowledge, this is the first report on DNA immunization done in CF1 mice. Injection of proacrosin DNA induces an immune response in the male reproductive tract characterized by high levels of specific antibodies and cytokine changes. These factors may alter the crucial balance of the genital tract microenvironment required for adequate fertilization and pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hypoxia inducible factor 1 links fast-patterned muscle activity and fast muscle phenotype in rats.

PubMed

Lunde, Ida G; Anton, Siobhan L; Bruusgaard, Jo C; Rana, Zaheer A; Ellefsen, Stian; Gundersen, Kristian

2011-03-15

Exercise influences muscle phenotype by the specific pattern of action potentials delivered to the muscle, triggering intracellular signalling pathways. PO2 can be reduced by an order of magnitude in working muscle. In humans, carriers of a hyperactive polymorphism of the transcription factor hypoxia inducible factor 1α (HIF-1α) have 50% more fast fibres, and this polymorphism is prevalent among strength athletes. We have investigated the putative role of HIF-1α in mediating activity changes in muscle.When rat muscles were stimulated with short high frequency bursts of action potentials known to induce a fast muscle phenotype, HIF-1α increased by about 80%. In contrast, a pattern consisting of long low frequency trains known to make fast muscles slow reduced the HIF-1α level of the fast extensor digitorum longus (EDL) muscle by 44%. Nuclear protein extracts from normal EDL contained 2.3-fold more HIF-1α and 4-fold more HIF-1β than the slow soleus muscle, while von-Hippel-Lindau protein was 4.8-fold higher in slow muscles. mRNA displayed a reciprocal pattern; thus FIH-1 mRNA was almost 2-fold higher in fast muscle, while the HIF-1α level was half, and consequently protein/mRNA ratio for HIF-1α was more than 4-fold higher in the fast muscle, suggesting that HIF-1α is strongly suppressed post-transcriptionally in slow muscles.When HIF-1α was overexpressed for 14 days after somatic gene transfer in adult rats, a slow-to-fast transformation was observed, encompassing an increase in fibre cross sectional area, oxidative enzyme activity and myosin heavy chain. The latter was shown to be regulated at the mRNA level in C2C12 myotubes.

Male mice are susceptible to high fat diet-induced hyperglycaemia and display increased circulatory retinol binding protein 4 (RBP4) levels and its expression in visceral adipose depots.

PubMed

Asha, G V; Raja Gopal Reddy, M; Mahesh, M; Vajreswari, A; Jeyakumar, S M

2016-01-01

Vitamin A and its metabolites are known to modulate adipose tissue development and its associated complications. Here, we assessed the vitamin A status and its metabolic pathway gene expression in relation to sexual dimorphism by employing 35 days old C57BL/6J male and female mice, which were fed either stock or high fat (HF) diet for 26 weeks. HF diet feeding increased body weight/weight gain and white adipose tissue (WAT) of visceral and subcutaneous regions, however, increase in vitamin A levels observed only in subcutaneous WAT. Further, the expression of most of the vitamin A metabolic pathway genes showed no sexual dimorphism. The observed HF diet-induced hyperglycaemia in male corroborates with increased retinol binding protein 4 (RBP4) levels in plasma and its expression in visceral adipose depots. In conclusion, the male mice are susceptible to high fat diet-induced hyperglycaemia and display higher plasma RBP4 levels, possibly due to its over-expression in visceral adipose depots.

Infusion of oxytocin induces successful delivery in prostanoid FP-receptor-deficient mice.

PubMed

Kawamata, Masaki; Yoshida, Masahide; Sugimoto, Yukihiko; Kimura, Tadashi; Tonomura, Yutaka; Takayanagi, Yuki; Yanagisawa, Teruyuki; Nishimori, Katsuhiko

2008-02-13

The dramatic increase of oxytocin (OT) receptor (OTR) in the myometrium as well as circulating progesterone withdrawal has been thought to be the most important factor in the induction and accomplishment of parturition since delivery fails in prostaglandin F2alpha receptor (FP) knockout (FP KO) mice. The expression levels of OTR mRNA/protein were not dramatically increased in the near-term uteri of FP KO mice. However, OT-induced myometrial contractions and the concentration-response curves in FP KO in vitro were almost similar to those in wild-type (WT) mice. OT-infusion (0.3 U/day) enabled FP KO mice to experience successful delivery, and furthermore the duration until the onset was hastened by a higher dose of OT (3 U/day). The plasma progesterone levels of FP KO females were maintained at high levels, but decreased during labor by OT-infusion (3 U/day). These results suggest that OT has potentials to induce strong myometrial contractions in uterus with low expression levels of OTR and luteolysis in ovary, which enabled FP KO females to undergo successful delivery.

Involvement of the Endocannabinoid System in the Development and Treatment of Breast Cancer

DTIC Science & Technology

2014-04-01

tetrahydrocannabinol ( THC ) treatment-induced autophagy in U87-MG glioblastoma cells based on GFP-LC3 puncta formation and electron microscopic autophagosome imaging...Shrivastava et al. (2011) and Salazar et al. (2009) showed that CBD and THC , respectively, induced autophagic effects that were linked to the induction of...animals treated with THC and the synthetic cannabinoid JWH-133 express higher levels of cleaved caspase-3 when compared to vehicle (Caffarel et al

Enhanced protection against Clonorchis sinensis induced by co-infection with Trichinella spiralis in rats.

PubMed

Chu, K-B; Kim, S-S; Lee, S-H; Lee, H-S; Joo, K-H; Lee, J-H; Lee, Y-S; Zheng, S; Quan, F-S

2014-10-01

Although co-infection with multiple parasites is a frequent occurrence, changes in the humoral immune response against a pre-existing parasite induced as a result of a subsequent parasitic infection remain undetermined. Here, we utilized enzyme-linked immunosorbent assay (ELISA) to investigate antibody responses, cytokine production and enhanced resistance in Clonorchis sinensis-infected rats (Sprague-Dawley) upon Trichinella spiralis infection. Higher levels of C. sinensis-specific IgG and IgA were elicited upon T. spiralis infection, and these levels remained higher than in rats infected with C. sinensis alone. Upon subsequent infection with T. spiralis, IgG antibodies against C. sinensis appeared to be rapidly boosted at day 3, and IgA antibodies were boosted at day 7. Challenge infection of C. sinensis-infected rats with T. spiralis induced substantial mucosal IgG and IgA responses in the liver and intestine and increases in antibody-secreting plasma cells in the spleen and bone marrow. Subsequent infection also appeared to confer effective control of liver C. sinensis loads, resulting in enhanced resistance. Memory B cells generated in response to C. sinensis infection were rapidly amplified into antibody-secreting cells upon T. spiralis infection. These results indicate that enhanced C. sinensis clearance induced by co-infection is associated with systemic and mucosal IgG and IgA responses. © 2014 John Wiley & Sons Ltd.

Differential Expression Analysis of a Subset of Drought-Responsive GmNAC Genes in Two Soybean Cultivars Differing in Drought Tolerance

PubMed Central

Thao, Nguyen Phuong; Thu, Nguyen Binh Anh; Hoang, Xuan Lan Thi; Van Ha, Chien; Tran, Lam-Son Phan

2013-01-01

The plant-specific NAC transcription factors play important roles in plant response to drought stress. Here, we have compared the expression levels of a subset of GmNAC genes in drought-tolerant DT51 and drought-sensitive MTD720 under both normal and drought stress conditions aimed at identifying correlation between GmNAC expression levels and drought tolerance degree, as well as potential GmNAC candidates for genetic engineering. The expression of 23 selected dehydration-responsive GmNACs was assessed in both stressed and unstressed root tissues of DT51 and MTD720 using real-time quantitative PCR. The results indicated that expression of GmNACs was genotype-dependent. Seven and 13 of 23 tested GmNACs showed higher expression levels in roots of DT51 in comparison with MTD720 under normal and drought stress conditions, respectively, whereas none of them displayed lower transcript levels under any conditions. This finding suggests that the higher drought tolerance of DT51 might be positively correlated with the higher induction of the GmNAC genes during water deficit. The drought-inducible GmNAC011 needs to be mentioned as its transcript accumulation was more than 76-fold higher in drought-stressed DT51 roots relative to MTD720 roots. Additionally, among the GmNAC genes examined, GmNAC085, 092, 095, 101 and 109 were not only drought-inducible but also more highly up-regulated in DT51 roots than in that of MTD720 under both treatment conditions. These data together suggest that GmNAC011, 085, 092, 095, 101 and 109 might be promising candidates for improvement of drought tolerance in soybean by biotechnological approaches. PMID:24322442

Plastic protein microarray to investigate the molecular pathways of magnetic nanoparticle-induced nanotoxicity

NASA Astrophysics Data System (ADS)

Liu, Yingshuai; Li, Xuelian; Bao, Shujuan; Lu, Zhisong; Li, Qing; Li, Chang Ming

2013-05-01

Superparamagnetic iron oxide nanoparticles (SPIONs) (about 15 nm) were synthesized via a hydrothermal method and characterized by field emission scanning electron microscopy, transmission electron microscopy, dynamic light scattering, x-ray diffraction, and vibrating sample magnetometer. The molecular pathways of SPIONs-induced nanotoxicity was further investigated by protein microarrays on a plastic substrate from evaluation of cell viability, reactive oxygen species (ROS) generation and cell apoptosis. The experimental results reveal that 50 μg ml-1 or higher levels of SPIONs cause significant loss of cell viability, considerable generation of ROS and cell apoptosis. It is proposed that high level SPIONs could induce cell apoptosis via a mitochondria-mediated intrinsic pathway by activation of caspase 9 and caspase 3, an increase of the Bax/Bcl-2 ratio, and down-regulation of HSP70 and HSP90 survivor factors.

Neutrophil autophagy and extracellular DNA traps contribute to airway inflammation in severe asthma.

PubMed

Pham, D L; Ban, G-Y; Kim, S-H; Shin, Y S; Ye, Y-M; Chwae, Y-J; Park, H-S

2017-01-01

Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated. We compared autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non-severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs). Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light chain 3-II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN). Untreated and IL-8-treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production levels negatively were correlated with FEV1/FVC (r = -0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin-1, and IL-8 production from AECs. Higher levels of NET-induced ECP and EDN were released from PBEs in SA compared with NSA groups. Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA. © 2016 John Wiley & Sons Ltd.

Stress Exacerbates Infectivity and Pathogenicity of Blastocystis hominis: In Vitro and In Vivo Evidences

PubMed Central

Chandramathi, Samudi; Suresh, Kumar; Sivanandam, Sinnadurai; Kuppusamy, Umah Rani

2014-01-01

Background Stress alters the oxidant-antioxidant state and immune cell responses which disrupts its function to combat infection. Blastocystis hominis, a common intestinal protozoan has been reported to be opportunistic in immunocompromised patients namely cancer. B. hominis infectivity in other altered immune system conditions especially stress is unknown. We aimed to demonstrate the stress effects towards the susceptibility and pathogenicity of B. hominis infection. Methods/Findings Three-week-old Wistar rats were divided into four groups: (a)control; (b)stress-induced; (c)B. hominis infected; (d)stress-induced with B. hominis infection; (n = 20 respectively). Stress was induced for an hour daily (30 days) using a Belly Dancer Shaker. Weight gain was monitored, stool samples were collected for B. hominis screening and blood for the determination of differential count, levels of immunoglobulin, oxidative damage, and peripheral blood mononuclear cell (PBMC) proliferation upon induction with solubilized antigen of B. hominis (Blasto-Ag). Group (b) exhibited the highest level of weight gain. Group (d) had higher levels of parasite cyst count in stools, serum IgE, oxidized protein and lipid compared to the group (c). Levels of monocyte and antioxidant in group (d) were decreased and their PBMCs showed highest inhibition of proliferation level when exposed to Blasto-Ag. Monocyte level in Group (b) showed insignificant difference compared to group (a) but was significantly lower compared to group (c). Antioxidant levels in group (c) were generally lower compared to group (a) and (b). Inhibition level exhibited by Blasto-Ag treated PBMCs of group (c) was higher compared to group (a) and (b). Conclusion The pathogenicity and augmentation of B. hominis infection is enhanced when stress is present. Lifestyles today are becoming increasingly stressed and the present findings suggest that the parasite which has been reported to be one of the most common organisms seen in stool surveys, namely in developing countries, may tend to be more pathogenic in stressful situations. PMID:24788756

Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent

PubMed Central

Song, Anren; Zhang, Yujin; Han, Leng; Yegutkin, Gennady G.; Liu, Hong; Sun, Kaiqi; D'Alessandro, Angelo; Li, Jessica; Karmouty-Quintana, Harry; Iriyama, Takayuki; Weng, Tingting; Zhao, Shushan; Wang, Wei; Wu, Hongyu; Nemkov, Travis; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Hansen, Kirk C.; Zhang, Hong; Bogdanov, Mikhail; Dowhan, William; Jin, Jianping; Kellems, Rodney E.; Eltzschig, Holger K.; Blackburn, Michael; Roach, Robert C.; Xia, Yang

2017-01-01

Faster acclimatization to high altitude upon re-ascent is seen in humans; however, the molecular basis for this enhanced adaptive response is unknown. We report that in healthy lowlanders, plasma adenosine levels are rapidly induced by initial ascent to high altitude and achieved even higher levels upon re-ascent, a feature that is positively associated with quicker acclimatization. Erythrocyte equilibrative nucleoside transporter 1 (eENT1) levels are reduced in humans at high altitude and in mice under hypoxia. eENT1 deletion allows rapid accumulation of plasma adenosine to counteract hypoxic tissue damage in mice. Adenosine signalling via erythrocyte ADORA2B induces PKA phosphorylation, ubiquitination and proteasomal degradation of eENT1. Reduced eENT1 resulting from initial hypoxia is maintained upon re-ascent in humans or re-exposure to hypoxia in mice and accounts for erythrocyte hypoxic memory and faster acclimatization. Our findings suggest that targeting identified purinergic-signalling network would enhance the hypoxia adenosine response to counteract hypoxia-induced maladaptation. PMID:28169986

New steroid derivative with hypoglycemic activity

PubMed Central

Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Lenin, Hau-Heredia; Elodia, García-Cervera; Eduardo, Pool-Gómez; Marcela, Rosas-Nexticapa; Bety, Sarabia-Alcocer

2014-01-01

Data indicates that some steroid derivatives may induce changes on glucose levels; nevertheless, data are very confusing. Therefore, more pharmacological data are needed to characterize the activity induced by the steroid derivatives on glucose levels. The aim of this study was to synthesize a new steroid derivative for evaluate its hypoglycemic activity. The effects of steroid derivative on glucose concentration were evaluated in a diabetic animal model using glibenclamide and metformin as controls. In addition, the pregnenolone-dihydrotestosterone conjugate was bound to Tc-99m using radioimmunoassay methods, to evaluate the pharmacokinetics of the steroid derivative over time. The results showed that the pregnenolone-dihydrotestosterone conjugate induces changes on the glucose levels in similar form than glibenclamide. Other data showed that the biodistribution of Tc-99m-steroid derivativein brain was higher in comparison with spleen, stomach, intestine liver and kidney. In conclusion, the pregnenolone-dihydrotestosterone conjugate exerts hypoglycemic activity and this phenomenon could depend of its physicochemical properties which could be related to the degree of lipophilicity of the steroidderivative. PMID:25550906

Prenatal chronic mild stress induces depression-like behavior and sex-specific changes in regional glutamate receptor expression patterns in adult rats.

PubMed

Wang, Y; Ma, Y; Hu, J; Cheng, W; Jiang, H; Zhang, X; Li, M; Ren, J; Li, X

2015-08-20

Chronic stress during critical periods of human fetal brain development is associated with cognitive, behavioral, and mood disorders in later life. Altered glutamate receptor (GluR) expression has been implicated in the pathogenesis of stress-dependent disorders. To test whether prenatal chronic mild stress (PCMS) enhances offspring's vulnerability to stress-induced behavioral and neurobiological abnormalities and if this enhanced vulnerability is sex-dependent, we measured depression-like behavior in the forced swimming test (FST) and regional changes in GluR subunit expression in PCMS-exposed adult male and female rats. Both male and female PCMS-exposed rats exhibited stronger depression-like behavior than controls. Males and females exhibited unique regional changes in GluR expression in response to PCMS alone, FST alone (CON-FST), and PCMS with FST (PCMS-FST). In females, PCMS alone did not alter N-methyl-d-aspartate receptor (NMDAR) or metabotropic glutamate receptor (mGluR) expression, while in PCMS males, higher mGluR2/3, mGluR5, and NR1 expression levels were observed in the prefrontal cortex. In addition, PCMS altered the change in GluR expression induced by acute stress (the FST test), and this too was sex-specific. Male PCMS-FST rats expressed significantly lower mGluR5 levels in the hippocampus, lower mGluR5, NR1, postsynaptic density protein (PSD)95, and higher mGluR2/3 in the prefrontal cortex, and higher mGluR5 and PSD95 in the amygdala than male CON-FST rats. Female PCMS-FST rats expressed lower NR1 in the hippocampus, lower NR2B and PSD95 in the prefrontal cortex, lower mGluR2/3 in the amygdala, and higher PSD95 in the amygdala than female CON-FST rats. PCMS may increase the offspring's vulnerability to depression by altering sex-specific stress-induced changes in glutamatergic signaling. Copyright © 2015. Published by Elsevier Ltd.

IgG2 Antibodies against a Clinical Grade Plasmodium falciparum CSP Vaccine Antigen Associate with Protection against Transgenic Sporozoite Challenge in Mice

PubMed Central

Schwenk, Robert; Nikki, Jennifer; Rein, Lisa; Spaccapelo, Roberta; Crisanti, Andrea; Wightman, Paul D.; Ockenhouse, Christian F.; Dutta, Sheetij

2014-01-01

The availability of a highly purified and well characterized circumsporozoite protein (CSP) is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D) was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP). A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE) of CS/D in combination with the Toll-Like Receptor 4 (TLR4) agonist Glucopyranosyl Lipid A (GLA/SE), or one of two TLR7/8 agonists: R848 (un-conjugated) or 3M-051 (covalently conjugated). Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive TH1/TH2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants further evaluation for protective responses in humans. PMID:25343487

Influence of caffeine on allyl alcohol-induced hepatotoxicity in rats. I. In vivo study.

PubMed

Karas, M; Chakrabarti, S K

2001-01-01

Cotreatment of rats with a low hepatotoxic dose (30.7 mg/kg, i.p.) of allyl alcohol (AA) and a higher, but nontoxic, dose (150 mg/kg, oral) of caffeine (CF) potentiated the hepatotoxicity of AA. This was verified by significantly higher levels of plasma alanine aminotransferase (ALT) activity and histopathologically greater severity of lesions in the periportal hepatocytes than those due to AA alone. Treatment of rats with 4-methylpyrazole (4-MP) (0.5 mmol/kg, i.p.) (an inhibitor liver alcohol dehydrogenase) for 30 minutes, followed by similar cotreatment with AA and CF, completely prevented the elevation of plasma levels of ALT and histological damage induced by cotreatment with CF and AA 24 hours following their administration. Severe liver damage induced by cotreatment with CF and AA was further, markedly enhanced by phenobarbital pretreatment (80 mg/kg, i.p., 3 days). Thus, extensive necrosis of periportal hepatocytes was noted, as well as edema and accumulation of inflammatory cells in the necrotic foci caused by such pretreatment. The depression of hepatic nonprotein sulfhydryls resulting from CF plus AA was much more severe than that caused by AA or CF alone and appeared as early as 30 minutes after administration. However, much less marked depletion of protein thiols was observed following similar treatments. Significant increase in lipid peroxidation (as measured by melondialdehyde [MDA] formation) was also observed in rat liver but only 24 hours after administration. The production ofMDA in the rat liver was significantly higher after administration of AA plus CF than after administration of AA alone. Pretreatment of rats with phenobarbital further significantly enhanced the formation of 2,4-dinitrophenylhydrazine (DNP)-reactive metabolite(s) (measured as DNP-acrolein adduct equivalents) in rat liver induced by AA (30.7 mg/kg) plus CF (150 mg/kg) within 1 hour following such treatment. Cotreatment with AA and a higher dose of CF resulted in significantly higher excretion of urinary thioethers or mercapturic acids than in rats treated with AA alone. Thus, these data suggest that an increased bioactivation pathway of acrolein involving a P450 mixed-function oxidase system caused by CF may be involved in such potentiating effects of CF on AA-induced hepatotoxicity in rats.

Comparative Assessment of Induced Immune Responses Following Intramuscular Immunization with Fusion and Cocktail of LeIF, LACK and TSA Genes Against Cutaneous Leishmaniasis in BALB/c Mice.

PubMed

Maspi, Nahid; Ghaffarifar, Fatemeh; Sharifi, Zohreh; Dalimi, Abdolhossein; Dayer, Mohammad Saaid

2018-02-01

In the present study, we evaluated induced immune responses following DNA vaccine containing cocktail or fusion of LeIF, LACK and TSA genes or each gene alone. Mice were injected with 100 µg of each plasmid containing the gene of insert, plasmid DNA alone as the first control group or phosphate buffer saline as the second control group. Then, cellular and humoral responses, lesion size were measured for all groups. All vaccinated mice induced Th1 immune responses against Leishmania characterized by higher IFN-γ and IgG2a levels compared with control groups (p < 0.05). In addition, IFN-γ levels increased in groups immunized with fusion and cocktail vaccines in comparison with LACK (p < 0.001) and LeIF (p < 0.01) groups after challenge. In addition, fusion and cocktail groups produced higher IgG2a values than groups vaccinated with a gene alone (p < 0.05). Lesion progression delayed for all immunized groups compared with control groups from 5th week post-infection (p < 0.05). Mean lesion size decreased in immunized mice with fusion DNA than three groups vaccinated with one gene alone (p < 0.05). While, lesion size decreased significantly in cocktail recipient group than LeIF recipient group (p < 0.05). There was no difference in lesion size between fusion and cocktail groups. Overall, immunized mice with cocktail and fusion vaccines showed stronger Th1 response by production of higher IFN-γ and IgG2a and showed smaller mean lesion size. Therefore, use of multiple antigens can improve induced immune responses by DNA vaccination.

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.

PubMed

Silva, F M C; Oliveira, E E; Gouveia, A C C; Brugiolo, A S S; Alves, C C; Correa, J O A; Gameiro, J; Mattes, J; Teixeira, H C; Ferreira, A P

2017-07-01

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity. © 2017 British Society for Immunology.

Solar power plant and still

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

Taylor, W.P.

This patent describes a solar energy system. It comprises: a water pond which is heated by solar energy; a cover above the pond which transmits solar energy; an air space between the pond and the cover through which warm air and vaporized water move; a chimney which induces the rapid flow of warm humid air into its lower end and delivers such air at its upper end; a fresh water heat sink which receives condensed vapor from the chimney-induced flow; a heat energy driven engine, the power output of which is a function of the temperature difference between higher andmore » lower temperature levels; a first heat exchanger in the engine connected to the top of the chimney, and arranged to convert the vapor condensation energy into the higher temperature level of th engine; a second heat exchanger in the engine arranged to provide the lower temperature of the engine by connection to the heat sink; and power transfer means driven by the temperature differential energy of the engine.« less

Polyamines induce adaptive responses in water deficit stressed cucumber roots.

PubMed

Kubiś, Jan; Floryszak-Wieczorek, Jolanta; Arasimowicz-Jelonek, Magdalena

2014-01-01

The aim of this study was to investigate the effect of exogenous polyamines (PAs) on the membrane status and proline level in roots of water stressed cucumber (Cucumis sativus cv. Dar) seedlings. It was found that water shortage resulted in an increase of membrane injury, lipoxygenase (LOX) activity, lipid peroxidation and proline concentration in cucumber roots during progressive dehydration. PA pretreatment resulted in a distinct reduction of the injury index, and this effect was reflected by a lower stress-evoked LOX activity increase and lipid peroxide levels at the end of the stress period. In contrast, PA-supplied stressed roots displayed a higher proline accumulation. The presented results suggest that exogenous PAs are able to alleviate water deficit-induced membrane permeability and diminish LOX activity. Observed changes were accompanied by an accumulation of proline, suggesting that the accumulation of this osmolyte might be another possible mode of action for PAs to attain higher membrane stability, and in this way mitigate water deficit effects in roots of cucumber seedlings.

Development of chitosan-pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies.

PubMed

Cevher, Erdal; Salomon, Stefan K; Somavarapu, Satyanarayana; Brocchini, Steve; Alpar, H Oya

2015-01-01

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239-405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC-pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

[The effect of aluminum adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine].

PubMed

Wang, Fang; Zhang, Ming; Xie, Bing-Feng; Cao, Han; Tong, Shao-Yong; Wang, Jun-Rong; Yu, Xiao-Ping; Tang, Yang; Yang, Jing-Ran; Sun, Ming-Bo

2013-04-01

To study the effect of aluminume adjuvant and immunization schedule on immunogenicity of Sabin inactivated poliovirus vaccine. Four batches of Sabin IPV were produced by different concentrations of type 1, 2, and 3 poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4 months on rats. Serum samples were collected one month after each dose and neutralizing antibody titers against three types poliovirus were determined by micro-neutralization assay. The GMTs of neutralizing antibodies against three types poliovirus increased significantly and the seropositivity rates were 100% in all groups after 3 doses. There was no significant difference between two immunization schedules, and the 0, 2, 4 month schedule could induce higher level neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with aluminum adjuvant could induce higher level neutralizing antibody compared to the groups without adjuvant. Aluminum djuvant and immunization schedule could improve the immunogenicity of Sabin IPV.

Simultaneous measurement of noise-activated middle-ear muscle reflex and stimulus frequency otoacoustic emissions.

PubMed

Goodman, Shawn S; Keefe, Douglas H

2006-06-01

Otoacoustic emissions serve as a noninvasive probe of the medial olivocochlear (MOC) reflex. Stimulus frequency otoacoustic emissions (SFOAEs) elicited by a low-level probe tone may be the optimal type of emission for studying MOC effects because at low levels, the probe itself does not elicit the MOC reflex [Guinan et al. (2003) J. Assoc. Res. Otolaryngol. 4:521]. Based on anatomical considerations, the MOC reflex activated by ipsilateral acoustic stimulation (mediated by the crossed olivocochlear bundle) is predicted to be stronger than the reflex to contralateral stimulation. Broadband noise is an effective activator of the MOC reflex; however, it is also an effective activator of the middle-ear muscle (MEM) reflex, which can make results difficult to interpret. The MEM reflex may be activated at lower levels than measured clinically, and most previous human studies have not explicitly included measurements to rule out MEM reflex contamination. The current study addressed these issues using a higher-frequency SFOAE probe tone to test for cochlear changes mediated by the MOC reflex, while simultaneously monitoring the MEM reflex using a low-frequency probe tone. Broadband notched noise was presented ipsilaterally at various levels to elicit probe-tone shifts. Measurements are reported for 15 normal-hearing subjects. With the higher-frequency probe near 1.5 kHz, only 20% of subjects showed shifts consistent with an MOC reflex in the absence of an MEM-induced shift. With the higher-frequency probe near 3.5 kHz, up to 40% of subjects showed shifts in the absence of an MEM-induced shift. However, these responses had longer time courses than expected for MOC-induced shifts, and may have been dominated by other cochlear processes, rather than MOC reflex. These results suggest caution in the interpretation of effects observed using ipsilaterally presented acoustic activators intended to excite the MOC reflex.

Antibody response in sheep following immunization with Streptococcus bovis in different adjuvants.

PubMed

Shu, Q; Bir, S H; Gill, H S; Duan, E; Xu, Y; Hiliard; Rowe, J B

2001-01-01

Recent studies have shown that immunization with Streptococcus bovis using Freund's complete adjuvant (FCA) may confer protection against lactic acidosis in sheep. The major objective of this study was to compare the antibody responses to S. bovis in a practically acceptable adjuvant (Freund's incomplete adjuvant (FIA); QuilA; dextran sulphate (Dex); Imject Alum; or Gerbu) and in FCA. Thirty-five sheep were randomly allocated to 7 treatment groups. Six groups were immunized with S. bovis in an adjuvant; the other group served as the non-immunization control. The primary immunization was administered intramuscularly on day 0. followed by a booster injection on day 28. Immunization with FCA induced the highest saliva and serum antibody responses. The saliva antibody concentrations in the FIA and QuilA groups were significantly higher than those in the Alum, Dex and Gerbu groups (p < 0.01). The serum antibody concentration in the FIA group was significantly higher than those in the QuilA, Alum. Dex and Gerbu groups (p < 0.01). Immunization enhanced the antibody level in faeces (p < 0.05), but there was no significant difference between the different adjuvant groups (p > 0.05). Seven and 14 days following booster immunization, the saliva antibody levels induced by QuilA and/or FIA were comparable with the level stimulated by FCA (p > 0.05). There was a strongly positive correlation (R2 = 0.770, p < 0.01) between the antibody concentrations in salival and serum. Compared with the controls, a higher faecal dry matter content was observed in the animals immunized with either FCA or QuilA. The change in faecal dry matter content was positively associated with the faecal antibody concentration (R2 = 0.441, p < 0.05). These results indicate that FIA and QuilA were effective at inducing high levels of antibody responses to S. bovis, and suggest that either Freund's incomplete adjuvant or QuilA may be useful for preparing a practically acceptable vaccine against lactic acidosis.

Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

PubMed

de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

2018-04-01

Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

Irreversible airway obstruction assessed by high-resolution computed tomography (HRCT), exhaled nitric oxide (FENO), and biological markers in induced sputum in patients with asthma.

PubMed

Zhang, Lanlan; Gang, Jin; Zhigang, Cao; Yali, Cui; Baozhong, Shen; Fangbiao, Zhang; Liu, Chuntao

2014-09-01

The objective of this study was to explore the significance of assessing irreversible airway obstruction (IAO) in asthma patients by high-resolution computed tomography (HRCT), biological markers in induced sputum, and exhaled nitric oxide (FENO). The study was conducted in 34 patients with IAO, 46 patients with reversible airway obstruction (RAO), 40 patients who did not have airway obstruction (NAO), and 40 healthy subjects serving as controls. These patients received a step therapy for at least 3 months based on the guidelines for the prevention and treatment of asthma. After achieving complete or partial control of asthma, HRCT, lung function, FENO, and chemokine levels in induced sputum were measured. The airway wall area (WA; %) correlated with forced expiratory volume-1 (FEV-1(L); r = -0.67, p < 0.0001), and significant differences in bronchial wall thickening (BWT) of the LEVEL E generation airways were observed between the asthma and control groups (p < 0.01). FENO levels correlated with FEV-1 (%) in the IAO group (r = 0.49, p = 0.01). The levels of matrix metalloproteases-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in asthma patients with IAO, RAO, and NAO were significantly higher than those in the controls (p < 0.05). The level of neutrophilia in the sputum from the IAO group was higher than that from the RAO, NAO and control groups. Asthma patients with IAO have an increased BWT. Airway measurements with HRCT scans appear to be valuable in the evaluation of airway remodeling in asthma patients with IAO.

Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats.

PubMed

Ozgun, E; Ozgun, G S; Gokmen, S S; Eskıocak, S; Sut, N; Akıncı, M; Goncu, E; Cakır, E

2016-02-05

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities. © Georg Thieme Verlag KG Stuttgart · New York.

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney

PubMed Central

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Objective: Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger (Zingiber officinale) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Results: Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. Conclusion: In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron. PMID:29299437

The protective effect of hydroalcoholic extract of Ginger (Zingiber officinale Rosc.) against iron-induced functional and histological damages in rat liver and kidney.

PubMed

Gholampour, Firouzeh; Behzadi Ghiasabadi, Fatemeh; Owji, Seyed Mohammad; Vatanparast, Jaafar

2017-01-01

Iron overload in the body is related with toxic effects and threatens the health. The aim of this study was to evaluate the protective role of hydroalcoholic extract of ginger ( Zingiber officinale ) against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. The rats were divided into four groups (n=7): Sham, Sham + G.E (ginger extract, 400 mg/kg/day for 14 days), FS (ferrous sulfate, 30 mg/kg/day for 14 days), FS+G.E (ferrous sulfate, 30 mg/kg/day for 14 days; ginger extract, 400 mg/kg/day for 11 days from the fourth day of ferrous sulfate injection). After 24 hr, blood, urine and tissue samples were collected. Compared with Sham and Sham + G.E groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium (p<0.001). This was accompanied by increased malondialdehyde levels and histological damages (p<0.001). In the FS + G.E, ginger extract significantly (p<0.01) reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides and cholesterol and decreased bilirubin concentration in the blood. All these changes were corroborated by histological observations of liver and kidney. In conclusion, ginger extract appears to exert protective effects against ferrous sulfate-induced hepatic and renal toxicity by reducing lipid peroxidation and chelating iron.

Higher platelet reactivity and platelet-monocyte complex formation in Gram-positive sepsis compared to Gram-negative sepsis.

PubMed

Tunjungputri, Rahajeng N; van de Heijden, Wouter; Urbanus, Rolf T; de Groot, Philip G; van der Ven, Andre; de Mast, Quirijn

2017-09-01

Platelets may play a role in the high risk for vascular complications in Gram-positive sepsis. We compared the platelet reactivity of 15 patients with Gram-positive sepsis, 17 with Gram-negative sepsis and 20 healthy controls using a whole blood flow cytometry-based assay. Patients with Gram-positive sepsis had the highest median fluorescence intensity (MFI) of the platelet membrane expression of P-selectin upon stimulation with high dose adenosine diphosphate (ADP; P = 0.002 vs. Gram-negative and P = 0.005 vs. control groups) and cross-linked collagen-related peptide (CRP-XL; P = 0.02 vs. Gram-negative and P = 0.0001 vs. control groups). The Gram-positive group also demonstrated significantly higher ADP-induced fibrinogen binding (P = 0.001), as wll as platelet-monocyte complex formation (P = 0.02), compared to the Gram-negative group and had the highest plasma levels of platelet factor 4, β-thromboglobulin and soluble P-selectin. In contrast, thrombin-antithrombin complex and C-reactive protein levels were comparable in both patient groups. In conclusion, common Gram-positive pathogens induce platelet hyperreactivity, which may contribute to a higher risk for vascular complications.

Effects of high fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects

PubMed Central

Le, MyPhuong T.; Frye, Reginald F.; Rivard, Christopher J.; Cheng, Jing; McFann, Kim K.; Segal, Mark S.; Johnson, Richard J.; Johnson, Julie A.

2011-01-01

Objective It is unclear whether high fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared to sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- versus sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Materials/Methods Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hr. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Results Fructose area under the curve and maximum concentration, dose normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared to sucrose-sweetened beverages. Conclusions Compared to sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects. PMID:22152650

Effects of high-fructose corn syrup and sucrose on the pharmacokinetics of fructose and acute metabolic and hemodynamic responses in healthy subjects.

PubMed

Le, Myphuong T; Frye, Reginald F; Rivard, Christopher J; Cheng, Jing; McFann, Kim K; Segal, Mark S; Johnson, Richard J; Johnson, Julie A

2012-05-01

It is unclear whether high-fructose corn syrup (HFCS), which contains a higher amount of fructose and provides an immediate source of free fructose, induces greater systemic concentrations of fructose as compared with sucrose. It is also unclear whether exposure to higher levels of fructose leads to increased fructose-induced adverse effects. The objective was to prospectively compare the effects of HFCS- vs sucrose-sweetened soft drinks on acute metabolic and hemodynamic effects. Forty men and women consumed 24 oz of HFCS- or sucrose-sweetened beverages in a randomized crossover design study. Blood and urine samples were collected over 6 hours. Blood pressure, heart rate, fructose, and a variety of other metabolic biomarkers were measured. Fructose area under the curve and maximum concentration, dose-normalized glucose area under the curve and maximum concentration, relative bioavailability of glucose, changes in postprandial concentrations of serum uric acid, and systolic blood pressure maximum levels were higher when HFCS-sweetened beverages were consumed as compared with sucrose-sweetened beverages. Compared with sucrose, HFCS leads to greater fructose systemic exposure and significantly different acute metabolic effects. Copyright © 2012 Elsevier Inc. All rights reserved.

The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells.

PubMed

Wangpaichitr, Medhi; Sullivan, Elizabeth J; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G; Lampidis, Theodore J; Kuo, Macus T; Savaraj, Niramol

2012-03-01

Elimination of cisplatin-resistant lung cancer cells remains a major obstacle. We have shown that cisplatin-resistant tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here, we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1 and contributed to higher ROS in cisplatin-resistant tumors in vivo and in vitro. By reconstituting TRX1 protein in cisplatin-resistant cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. Cisplatin-resistant cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase mRNA, which contributed to oxidative metabolism (OXMET) when compared with parental cells. Restoring intracellular TRX1 protein in cisplatin-resistant cells resulted in lowering ASS and fumarase mRNAs, which in turn sensitized them to arginine deprivation. Interestingly, cisplatin-resistant cells also had significantly higher basal levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Overexpressing TRX1 lowered ACC and FAS proteins expressions in cisplatin-resistant cells. Chemical inhibition and short interfering RNA of ACC resulted in significant cell death in cisplatin-resistant compared with parental cells. Conversely, TRX1 overexpressed cisplatin-resistant cells resisted 5-(tetradecyloxy)-2-furoic acid (TOFA)-induced death. Collectively, lowering TRX1 expression through increased secretion leads cisplatin-resistant cells to higher ROS production and increased dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin-resistant lung cancer.

The Relationship of Thioredoxin-1 and Cisplatin Resistance: Its Impact on ROS and Oxidative Metabolism in Lung Cancer Cells

PubMed Central

Wangpaichitr, Medhi; Theodoropoulos, George; Wu, Chunjing; You, Min; Feun, Lynn G.; Kuo, Macus T.; Savaraj, Niramol

2012-01-01

Elimination of cisplatin resistant (CR) lung cancer cells remains a major obstacle. We have shown that CR tumors have higher reactive oxygen species (ROS) levels and can be exploited for targeted therapy. Here we show that increased secretion of the antioxidant thioredoxin-1 (TRX1) resulted in lowered intracellular TRX1, and contributed to higher ROS in CR tumors in vivo and in vitro. By reconstitutingTRX1 protein in CR cells, we increased sensitivity to cisplatin but decreased sensitivity to elesclomol (ROS inducer). Conversely, decreased TRX1 protein in parental cells reduced the sensitivity to cisplatin but increased sensitivity to elesclomol. CR cells had increased endogenous oxygen consumption and mitochondrial activity but decreased lactic acid production. They also exhibited higher levels of argininosuccinate synthetase (ASS) and fumarase (FH) mRNA which contributed to oxidative metabolism (OXMET) when compared to parental cells. Restoring intracellular TRX1 protein in CR cells resulted in lowering ASS and FH mRNAs which in turn sensitized them to arginine deprivation. Interestingly, CR cells also possessed significantly higher basal levels of acetyl-CoA-carboxylase (ACC) and fatty acid synthase (FAS). Over-expressing TRX1 lowered ACC and FAS proteins expressions in CR cells. Chemical inhibition and siRNA of ACC resulted in significant cell death in CR compared to parental cells. Conversely, TRX1 over-expressed CR cells resisted to TOFA-induced death. Collectively, lowering TRX1 expression through increased secretion leads CR cells to higher ROS production and increase in dependency on OXMET. These changes raise an intriguing therapeutic potential for future therapy in cisplatin resistant lung cancer. PMID:22248473

Renal mitochondrial impairment is attenuated by AT1 blockade in experimental Type I diabetes.

PubMed

de Cavanagh, Elena M V; Ferder, León; Toblli, Jorge E; Piotrkowski, Bárbara; Stella, Inés; Fraga, Cesar G; Inserra, Felipe

2008-01-01

To investigate whether ANG II type 1 (AT(1)) receptor blockade could protect kidney mitochondria in streptozotocin-induced Type 1 diabetes, we treated 8-wk-old male Sprague-Dawley rats with a single streptozotocin injection (65 mg/kg ip; STZ group), streptozotocin and drinking water containing either losartan (30 mg.kg(-1).day(-1); STZ+Los group) or amlodipine (3 mg.kg(-1).day(-1); STZ+Amlo group), or saline (intraperitoneally) and pure water (control group). Four-month-long losartan or amlodipine treatments started 30 days before streptozotocin injection to improve the antioxidant defenses. The number of renal lesions, plasma glucose and lipid levels, and proteinuria were higher and creatinine clearance was lower in STZ and STZ+Amlo compared with STZ+Los and control groups. Glycemia was higher in STZ+Los compared with control. Blood pressure, basal mitochondrial membrane potential and mitochondrial pyruvate content, and renal oxidized glutathione levels were higher and NADH/cytochrome c oxidoreductase activity was lower in STZ compared with the other groups. In STZ and STZ+Amlo groups, mitochondrial H(2)O(2) production rate was higher and uncoupling protein-2 content, cytochrome c oxidase activity, and renal glutathione level were lower than in STZ+Los and control groups. Mitochondrial nitric oxide synthase activity was higher in STZ+Amlo compared with the other groups. Mitochondrial pyruvate content and H(2)O(2) production rate negatively contributed to electron transfer capacity and positively contributed to renal lesions. Uncoupling protein-2 content negatively contributed to mitochondrial H(2)O(2) production rate and renal lesions. Renal glutathione reduction potential positively contributed to mitochondria electron transfer capacity. In conclusion, AT(1) blockade protects kidney mitochondria and kidney structure in streptozotocin-induced diabetes independently of blood pressure and glycemia.

Variation in plant defense against invasive herbivores: evidence for a hypersensitive response in eastern hemlocks (Tsuga canadensis).

PubMed

Radville, Laura; Chaves, Arielle; Preisser, Evan L

2011-06-01

Herbivores can trigger a wide array of morphological and chemical changes in their host plants. Feeding by some insects induces a defensive hypersensitive response, a defense mechanism consisting of elevated H(2)O(2) levels and tissue death at the site of herbivore feeding. The invasive hemlock woolly adelgid Adelges tsugae ('HWA') and elongate hemlock scale Fiorinia externa ('EHS') feed on eastern hemlocks; although both are sessile sap feeders, HWA causes more damage than EHS. The rapid rate of tree death following HWA infestation has led to the suggestion that feeding induces a hypersensitive response in hemlock trees. We assessed the potential for an herbivore-induced hypersensitive response in eastern hemlocks by measuring H(2)O(2) levels in foliage from HWA-infested, EHS-infested, and uninfested trees. Needles with settled HWA or EHS had higher H(2)O(2) levels than control needles, suggesting a localized hypersensitive plant response. Needles with no direct contact to settled HWA also had high H(2)O(2) levels, suggesting that HWA infestation may induce a systemic defense response in eastern hemlocks. There was no similar systemic defensive response in the EHS treatment. Our results showed that two herbivores in the same feeding guild had dramatically different outcomes on the health of their shared host.

Concorde noise-induced building vibrations John F. Kennedy International Airport

NASA Technical Reports Server (NTRS)

Mayes, W. H.; Deloach, R.; Stephens, D. G.; Cawthorn, J. M.; Holmes, H. K.; Lewis, R. B.; Holliday, B. G.; Ward, D. W.

1978-01-01

The outdoor and indoor noise levels resulting from aircraft flyovers and certain nonaircraft events were recorded at six home sites along with the associated vibration levels in the walls, windows, and floors of these test homes. Limited subjective tests conducted to examine the human detection and annoyance thresholds for building vibration and rattle caused by aircraft noise showed that both vibration and rattle were detected subjectively in several houses for some operations of both the Concorde and subsonic aircraft. Preliminary results indicate that the relationship between window vibration and aircraft noise is: (1) linear, with vibration levels being accurately predicted from OASPL levels measured near the window; (2) consistent from flyover to flyover for a given aircraft type under approach conditions; (3) no different for Concorde than for other conventional jet transports (in the case of window vibrations induced under approach power conditions); and (4) relatively high levels of window vibration measured during Concorde operations are due more to higher OASPL levels than to unique Concorde source characteristics.

Maltreatment increases spontaneous false memories but decreases suggestion-induced false memories in children.

PubMed

Otgaar, Henry; Howe, Mark L; Muris, Peter

2017-09-01

We examined the creation of spontaneous and suggestion-induced false memories in maltreated and non-maltreated children. Maltreated and non-maltreated children were involved in a Deese-Roediger-McDermott false memory paradigm where they studied and remembered negative and neutral word lists. Suggestion-induced false memories were created using a misinformation procedure during which both maltreated and non-maltreated children viewed a negative video (i.e., bank robbery) and later received suggestive misinformation concerning the event. Our results showed that maltreated children had higher levels of spontaneous negative false memories but lower levels of suggestion-induced false memories as compared to non-maltreated children. Collectively, our study demonstrates that maltreatment both increases and decreases susceptibility to memory illusions depending on the type of false memory being induced. Statement of contribution What is already known on this subject? Trauma affects memory. It is unclear how trauma affects false memory. What does this study add? This study focuses on two types of false memories. © 2017 The Authors. British Journal of Developmental Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Fresh frozen plasma resuscitation attenuates platelet dysfunction compared with normal saline in a large animal model of multisystem trauma.

PubMed

Sillesen, Martin; Johansson, Pär I; Rasmussen, Lars S; Jin, Guang; Jepsen, Cecilie H; Imam, Ayesha; Hwabejire, John O; Deperalta, Danielle; Duggan, Michael; DeMoya, Marc; Velmahos, George C; Alam, Hasan B

2014-04-01

Platelet dysfunction following trauma has been identified as an independent predictor of mortality. We hypothesized that fresh frozen plasma (FFP) resuscitation would attenuate platelet dysfunction compared with 0.9% normal saline (NS). Twelve swine were subjected to multisystem trauma (traumatic brain injury, liver injury, rib fracture, and soft tissue injury) with hemorrhagic shock (40% of estimated blood volume). Animals were left in shock (mean arterial pressure, 30-35 mm Hg) for 2 hours followed by resuscitation with three times shed volume NS (n = 6) or one times volume FFP (n = 6) and monitored for 6 hours. Platelet function was assessed by adenosine diphosphate (ADP)-induced platelet aggregation at baseline, after 2 hours of shock following resuscitation, and 6 hours after resuscitation. Fibrinogen levels and markers of platelet activation (transforming growth factor β [TGF-β], sP-Selectin, and CD40L) as well as endothelial injury (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) were also assayed. Thromboelastography was used to measure clotting activity. ADP-induced platelet aggregation was significantly higher in the FFP group (46.3 U vs. 25.5 U, p < 0.01) following resuscitation. This was associated with higher fibrinogen levels (202 mg/dL vs. 80 mg/dL, p < 0.01) but lower endothelial activation (VCAM-1, 1.25 ng/mL vs. 3.87 ng/mL, p = 0.05). Other markers did not differ.After 6 hours of observation, ADP-induced platelet aggregation remained higher in the FFP group (53.8 U vs. 37.0 U, p = 0.03) as was fibrinogen levels (229 mg/dL vs. 153 mg/dL, p < 0.01). Endothelial activation was lower (ICAM-1, 21.0 ng/mL vs. 24.4 ng/mL, p = 0.05), whereas TGF-β levels were higher (2,138 pg/mL vs. 1,802 pg/mL, p = 0.03) in the FFP group. Other markers did not differ. Thromboelastography revealed increased clot strength in the FFP group at both postresuscitation time points. Resuscitation with FFP resulted in an immediate and sustained improvement in platelet function and clot strength compared with high-volume NS resuscitation. This was associated with an increase in fibrinogen levels and an attenuation of endothelial activation.

Toxicogenomic analysis identifies the apoptotic pathway as the main cause of hepatotoxicity induced by tributyltin.

PubMed

Zhou, Mi; Feng, Mei; Fu, Ling-Ling; Ji, Lin-Dan; Zhao, Jin-Shun; Xu, Jin

2016-11-01

Tributyltin (TBT) is one of the most widely used organotin biocides, which has severe endocrine-disrupting effects on marine species and mammals. Given that TBT accumulates at higher levels in the liver than in any other organ, and it acts mainly as a hepatotoxic agent, it is important to clearly delineate the hepatotoxicity of TBT. However, most of the available studies on TBT have focused on observations at the cellular level, while studies at the level of genes and proteins are limited; therefore, the molecular mechanisms of TBT-induced hepatotoxicity remains largely unclear. In the present study, we applied a toxicogenomic approach to investigate the effects of TBT on gene expression in the human normal liver cell line HL7702. Gene expression profiling identified the apoptotic pathway as the major cause of hepatotoxicity induced by TBT. Flow cytometry assays confirmed that medium- and high-dose TBT treatments significantly increased the number of apoptotic cells, and more cells underwent late apoptosis in the high-dose TBT group. The genes encoding heat shock proteins (HSPs), kinases and tumor necrosis factor receptors mediated TBT-induced apoptosis. These findings revealed novel molecular mechanisms of TBT-induced hepatotoxicity, and the current microarray data may also provide clues for future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

PubMed

Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

2008-01-01

To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (p<0.01), higher serum albumin level, and reduced increase in narcotic-induced sleeping time. Thus, setarud showed protective activity against CCl4-induced hepatotoxicity in rats. Further studies of its efficacy in liver disease are warranted.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes.

PubMed

Mohamed, Jamaludin; Shing, Saw Wuan; Idris, Muhd Hanis Md; Budin, Siti Balkis; Zainalabidin, Satirah

2013-10-01

The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

Immune alterations in male and female mice after 2-deoxy-D-glucose administration

NASA Technical Reports Server (NTRS)

Dreau, D.; Morton, D. S.; Foster, M.; Swiggett, J. P.; Sonnenfeld, G.

1997-01-01

Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

Behavioral and hormonal changes associated with the infective dose in experimental taeniasis in golden hamsters (Mesocricetus auratus).

PubMed

Domínguez-Roldan, Rosa; Hallal-Calleros, Claudia; Sciutto, Edda; Hernández, Marisela; Aguirre-Flores, Virginio; García-Jiménez, Sara; Báez-Saldaña, Armida; Flores-Pérez, Fernando Iván

2016-07-01

It has been reported that behavioral changes relate to infection in different parasitoses. However, the relation between the extent of the behavioral changes and the magnitude of the infection has been scarcely studied. The aim of this study was to evaluate the relationship between different doses of infection and the behavioral changes induced in the experimental Taenia pisiformis taeniasis in golden hamsters. Groups of nine hamsters were infected with three or six T. pisiformis metacestodes. The locomotor activity was quantified daily in an open field test during the 21 days after infection; anxiety test was performed in an elevated plus-maze with a dark/light area at 7, 14 and 21 days post-infection, and serum cortisol levels were determined by radioimmunoassay before infection and at day 22 after infection. The challenge itself induced modifications on behavior and cortisol levels in hamsters, with or without successful infection (taenia development). Animals challenged with three metacestodes induced a decrease in locomotor activity and an increase in anxiety in infected animals. A higher and earlier decrease in locomotor activity and increased anxiety levels were observed in hamsters challenged with six cysticerci, which were accompanied by higher levels of sera cortisol at the end of the experiment. At necropsy, 44-55% of hamster became infected with an efficiency of implantation of 22-26%, challenged with three or six cysticerci respectively. The challenge of hamsters with metacestodes, promote behavioral changes in an extent dependent on the magnitude of the challenge, disregarding the effectiveness of the infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Preventive Effect of Geraniol on Diethylnitrosamine-Induced Hepatocarcinogenesis in Rats.

PubMed

Sawada, Shintaro; Okano, Jun-Ichi; Imamoto, Ryu; Yasunaka, Yuki; Abe, Ryo; Koda, Masahiko; Murawaki, Yoshikazu; Isomoto, Hajime

2016-03-01

Geraniol is a plant-derived phytochemical possessing anti-cancer action. The anti-carcinogenic effect of geraniol was investigated in the diethylnitrosamine (DEN)-induced hepatocarcinogenic rat model. Male Wistar rats were intraperitoneally injected with 300 μL of phosphate-buffered saline (PBS) (G1; n = 4) or DEN (100 mg/kg body weight) dissolved in PBS (G2; n = 8) every 2 weeks on experimental weeks 2, 4 and 6. The rats were treated with a low concentration (0.07%) of geraniol (G3; n = 9) and high concentration (0.35%) of geraniol (G4; n = 7) for 12 weeks. To evaluate the effects of geraniol on the DEN-induced hepatocarcinogenesis, we compared the relative liver weight, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and expression levels of proliferating cell nuclear antigen (PCNA) and glutathione S transferase-P (GST-P) by immunohistochemical analyses among each group. Relative liver weight was significantly higher in G2 than in G1 (P < 0.01). Both serum AST and ALT levels were significantly higher in G2 than in G3 and in G4 (P < 0.05). Serum ALP levels did not show a significant difference among each group. Percentages of both PCNA- and GST-P- positive area were significantly decreased in G3 and in G4 compared to in G2 (P < 0.001, respectively), suggesting anti-hepatocarcinogenic effects of geraniol. Geraniol is a promising compound useful for suppression of hepatocellular carcinoma. The mechanisms of action are required to be clarified in the future intensive study.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

PubMed Central

Mohamed, Jamaludin; Shing, Saw Wuan; Md Idris, Muhd Hanis; Budin, Siti Balkis; Zainalabidin, Satirah

2013-01-01

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients. PMID:24212844

Soybean NADP-Malic Enzyme Functions in Malate and Citrate Metabolism and Contributes to Their Efflux under Al Stress.

PubMed

Zhou, Ying; Yang, Zhenming; Xu, Yuezi; Sun, Haoran; Sun, Zhitao; Lin, Bao; Sun, Wenjing; You, Jiangfeng

2017-01-01

Malate accumulation has been suggested to balance Al-induced citrate synthesis and efflux in soybean roots. To test this hypothesis, characteristics of Al-induced accumulation and efflux of citrate and malate were compared between two soybean genotypes combining a functional analysis of GmME1 putatively encode a cytosolic NADP-malic enzyme. Similar amounts of citrate were released, and root elongation was equally inhibited before 8 h of Al treatment of Jiyu 70 and Jiyu 62 cultivars. Jiyu 70 began to secrete more citrate and exhibited higher Al resistance than did Jiyu 62 at 12 h. A sustained increase in internal malate and citrate concentrations was observed in Jiyu 70 at 24 h of Al treatment. However, Jiyu 62 decreased its malate concentration at 12 h and its citrate concentration at 24 h of Al treatment. GmME1 localized to the cytoplast and clustered closely with cytosolic malic enzymes AtME2 and SgME1 and was constitutively expressed in the roots. Al treatment induced higher NADP-malic enzyme activities and GmME1 expression levels in Jiyu 70 than in Jiyu 62 within 24 h. Compared with wild-type hairy roots, over-expressing GmME1 in hairy roots ( GmME1 -OE) produced higher expression levels of GmME1 but did not change the expression patterns of either of the putative citrate transporter genes GmAACT1 and GmFRDL or the malate transporter gene GmALMT1 , with or without Al treatment. GmME1 -OE showed a higher internal concentration and external efflux of both citrate and malate at 4 h of Al stress. Lighter hematoxylin staining and lower Al contents in root apices of GmME1 -OE hairy roots indicated greater Al resistance. Comprehensive experimental results suggest that sustaining Al-induced citrate efflux depends on the malate pool in soybean root apices. GmME1 encodes a cytosolic malic enzyme that contributes to increased internal malate and citrate concentrations and their external efflux to confer higher Al resistance.

Abdominal adipose tissue: early metabolic dysfunction associated to insulin resistance and oxidative stress induced by an unbalanced diet.

PubMed

Rebolledo, O R; Marra, C A; Raschia, A; Rodriguez, S; Gagliardino, J J

2008-11-01

The possible contribution of early changes in lipid composition, function, and antioxidant status of abdominal adipose tissue (AAT) induced by a fructose-rich diet (FRD) to the development of insulin resistance (IR) and oxidative stress (OS) was studied. Wistar rats were fed with a commercial diet with (FRD) or without 10% fructose in the drinking water for 3 weeks. The glucose (G), triglyceride (TG), and insulin (I) plasma levels, and the activity of antioxidant enzymes, lyposoluble antioxidants, total glutathione (GSH), lipid peroxidation as TBARS, fatty acid (FA) composition of AAT-TG as well as their release by incubated pieces of AAT were measured. Rats fed with a FRD have significantly higher plasma levels of G, TG, and I. Their AAT showed a marked increase in content and ratios of saturated to monounsaturated and polyunsaturated FAs, TBARS, and catalase, GSH-transferase and GSH-reductase, together with a decrease in superoxide dismutase and GSH-peroxidase activity, and total GSH, alpha-tocopherol, beta-carotene and lycopene content. Incubated AAT from FRD released in vitro higher amount of free fatty acids (FFAs) with higher ratios of saturated to monounsaturated and polyunsaturated FAs. Our data suggest that FRD induced an early prooxidative state and metabolic dysfunction in AAT that would favor the overall development of IR and OS and further development of pancreatic beta-cell failure; therefore, its early control would represent an appropriate strategy to prevent alterations such as the development of type 2 diabetes.

Electron backscatter and X-ray diffraction studies on the deformation and annealing textures of austenitic stainless steel 310S

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

Nezakat, Majid, E-mail: majid.nezakat@usask.ca

We studied the texture evolution of thermo-mechanically processed austenitic stainless steel 310S. This alloy was cold rolled up to 90% reduction in thickness and subsequently annealed at 1050 °C. At the early stages of deformation, strain-induced martensite was formed from deformed austenite. By increasing the deformation level, slip mechanism was found to be insufficient to accommodate higher deformation strains. Our results demonstrated that twinning is the dominant deformation mechanism at higher deformation levels. Results also showed that cold rolling in unidirectional and cross rolling modes results in Goss/Brass and Brass dominant textures in deformed samples, respectively. Similar texture components aremore » observed after annealing. Thus, the annealing texture was greatly affected by texture of the deformed parent phase and martensite did not contribute as it showed an athermal reversion during annealing. Results also showed that when the fraction of martensite exceeds a critical point, its grain boundaries impeded the movement of austenite grain boundaries during annealing. As a result, recrystallization incubation time would increase. This caused an incomplete recrystallization of highly deformed samples, which led to a rational drop in the intensity of the texture components. - Highlights: •Thermo-mechanical processing through different cold rolling modes can induce different textures. •Martensite reversion is athermal during annealing. •Higher fraction of deformation-induced martensite can increase the annealing time required for complete recrystallization. •Annealing texture is mainly influenced by the deformation texture of austenite.« less

Monoacylglycerol-enriched oil increases EPA/DHA delivery to circulatory system in humans with induced lipid malabsorption conditions.

PubMed

Cruz-Hernandez, Cristina; Destaillats, Frédéric; Thakkar, Sagar K; Goulet, Laurence; Wynn, Emma; Grathwohl, Dominik; Roessle, Claudia; de Giorgi, Sara; Tappy, Luc; Giuffrida, Francesca; Giusti, Vittorio

2016-12-01

It was hypothesized that under induced lipid malabsorption/maldigestion conditions, an enriched sn-1(3)-monoacylglycerol (MAG) oil may be a better carrier for n-3 long-chain PUFAs (LC-PUFAs) compared with triacylglycerol (TAG) from fish oil. This monocentric double blinded clinical trial examined the accretion of EPA (500 mg/day) and DHA (300 mg/day) when consumed as TAG or MAG, into the erythrocytes, plasma, and chylomicrons of 45 obese (BMI ≥30 kg/m 2 and ≤40 kg/m 2 ) volunteers who were and were not administered Orlistat, an inhibitor of pancreatic lipases. Intake of MAG-enriched oil resulted in higher accretion of LC-PUFAs than with TAG, the concentrations of EPA and DHA in erythrocytes being, respectively, 72 and 24% higher at 21 days (P < 0.001). In addition, MAG increased the plasma concentration of EPA by 56% (P < 0.001) as compared with TAG. In chylomicrons, MAG intake yielded higher levels of EPA with the area under the curve (0-10 h) of EPA being 55% greater (P = 0.012). In conclusion, in obese human subjects with Orlistat-induced lipid maldigestion/malabsorption conditions, LC-PUFA MAG oil increased LC-PUFA levels in erythrocytes, plasma, and chylomicrons to a greater extent than TAG. These results indicate that MAG oil might require minimal enzymatic digestion prior to intestinal uptake and transfer across the epithelial barrier. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Monoacylglycerol-enriched oil increases EPA/DHA delivery to circulatory system in humans with induced lipid malabsorption conditions1

PubMed Central

Cruz-Hernandez, Cristina; Destaillats, Frédéric; Thakkar, Sagar K.; Goulet, Laurence; Wynn, Emma; Grathwohl, Dominik; Roessle, Claudia; de Giorgi, Sara; Tappy, Luc; Giuffrida, Francesca; Giusti, Vittorio

2016-01-01

It was hypothesized that under induced lipid malabsorption/maldigestion conditions, an enriched sn-1(3)-monoacylglycerol (MAG) oil may be a better carrier for n-3 long-chain PUFAs (LC-PUFAs) compared with triacylglycerol (TAG) from fish oil. This monocentric double blinded clinical trial examined the accretion of EPA (500 mg/day) and DHA (300 mg/day) when consumed as TAG or MAG, into the erythrocytes, plasma, and chylomicrons of 45 obese (BMI ≥30 kg/m2 and ≤40 kg/m2) volunteers who were and were not administered Orlistat, an inhibitor of pancreatic lipases. Intake of MAG-enriched oil resulted in higher accretion of LC-PUFAs than with TAG, the concentrations of EPA and DHA in erythrocytes being, respectively, 72 and 24% higher at 21 days (P < 0.001). In addition, MAG increased the plasma concentration of EPA by 56% (P < 0.001) as compared with TAG. In chylomicrons, MAG intake yielded higher levels of EPA with the area under the curve (0–10 h) of EPA being 55% greater (P = 0.012). In conclusion, in obese human subjects with Orlistat-induced lipid maldigestion/malabsorption conditions, LC-PUFA MAG oil increased LC-PUFA levels in erythrocytes, plasma, and chylomicrons to a greater extent than TAG. These results indicate that MAG oil might require minimal enzymatic digestion prior to intestinal uptake and transfer across the epithelial barrier. PMID:27707818

Maternal administration of melatonin prevents spatial learning and memory deficits induced by developmental ethanol and lead co-exposure.

PubMed

Soleimani, Elham; Goudarzi, Iran; Abrari, Kataneh; Lashkarbolouki, Taghi

2017-05-01

Melatonin is a radical scavenger with the ability to remove reactive oxidant species. There is report that co-exposure to lead and ethanol during developmental stages induces learning and memory deficits and oxidative stress. Here, we studied the effect of melatonin, with strong antioxidant properties, on memory deficits induced by lead and ethanol co-exposure and oxidative stress in hippocampus. Pregnant rats in lead and ethanol co-exposure group received lead acetate of 0.2% in distilled drinking water and ethanol (4g/kg) by oral gavages once daily from the 5th day of gestation until weaning. Rats received 10mg/kg melatonin by oral gavages. On postnatal days (PD) 30, rats trained with six trials per day for 6 consecutive days in the water maze. On day 37, a probe test was done and oxidative stress markers in the hippocampus were evaluated. Results demonstrated lead and ethanol co-exposed rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency in probe trial test and had significantly higher malondialdehyde (MDA) levels, significantly lower superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities in the hippocampus. Melatonin treatment could improve memory deficits, antioxidants activity and reduced MDA levels in the hippocampus. We conclude, co-exposure to lead and ethanol impair memory and melatonin can prevent from it by oxidative stress modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

PubMed

Kanazawa, H; Fujiwara, H; Hirata, K; Yoshikawa, J

1998-12-01

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

Virus detection and cytokine profile in relation to age among acute exacerbations of childhood asthma.

PubMed

Kato, Masahiko; Suzuki, Kazuo; Yamada, Yoshiyuki; Maruyama, Kenichi; Hayashi, Yasuhide; Mochizuki, Hiroyuki

2015-09-01

Little information is available regarding eosinophil activation and cytokine profiles in relation to age in virus-induced bronchial asthma. We therefore explored the association between age, respiratory viruses, serum eosinophil cationic protein (ECP), and cytokines/chemokines in acute exacerbations of childhood asthma. We investigated viruses in nasal secretions from 88 patients with acute exacerbation of childhood asthma by using antigen detection kits and/or RT-PCR, followed by direct DNA sequencing analysis. We also measured peripheral eosinophil counts, and the serum levels of ECP and 27 types of cytokines/chemokines in 71 virus-induced acute asthma cases and 13 controls. Viruses were detected in 71(80.7%) of the 88 samples. The three major viruses detected were rhinoviruses, RS viruses, and enteroviruses; enteroviruses were found to be dominant in patients aged ≥3 years. There was no change in the levels of rhinoviruses and RS viruses between the two age groups, defined as children aged <3 years and children aged ≥3 years. Serum concentrations of ECP, IL-5, and IP-10 were significantly elevated in virus-induced acute asthma cases compared with controls. Serum ECP values were significantly higher in patients with virus-induced asthma at age ≥3 years compared with those aged <3 years. Among the 27 cytokines/chemokines, serum IP-10 was significantly higher in virus-induced asthma in patients <3 years than in those ≥3 years. Serum ECP and IL-5 production correlated significantly with age, whereas serum IP-10 showed an inverse correlation with age. Age-related differences in cytokine profiles and eosinophil activation may be related to virus-induced acute exacerbations of childhood asthma. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

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

Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent

Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD{sub 10} dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen ledmore » to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-{alpha}, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 {+-} 14.0 nmol/min/g heart in ND versus 400.2 {+-} 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-{alpha}2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3 pathway.« less

Reduction of Slit Diaphragm-associated Molecules by Sirolimus: Is it Enough to Induce Proteinuria?

PubMed

Kim, B S; Lee, J G; Cho, Y; Song, S H; Huh, K H; Kim, M S; Kim, Y S

2017-06-01

Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer. The mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the SRL-treated mice, but serum creatinine levels were found to increase dose-dependently and were significantly higher in the animals treated with 30 mg/kg of SRL than in untreated controls. Glomerular mRNA expression profiling showed down-regulations of podocyte-related genes (Wilms tumor 1, synaptopodin, nephrin, CD2-associated protein, and podocin) and of transforming growth factor-beta (a marker of fibrosis) in sirolimus-treated mice. In addition, expressions of the antiapoptotic genes Bcl-2 and Bcl-xL were also down-regulated. Furthermore, the protein levels of these genes in mice kidney were also decreased by sirolimus. Although sirolimus treatment reduced the expressions of slit diaphragm-associated molecules and increased serum creatinine levels, it failed to induce proteinuria. Our findings indicate that proteinuria is not induced by isolated SRL treatment. Further studies are required to identify conditions in which sirolimus induces proteinuria. Copyright © 2017 Elsevier Inc. All rights reserved.

Pivotal response treatment prompts a functional rewiring of the brain among individuals with autism spectrum disorder.

PubMed

Venkataraman, Archana; Yang, Daniel Y-J; Dvornek, Nicha; Staib, Lawrence H; Duncan, James S; Pelphrey, Kevin A; Ventola, Pamela

2016-09-28

Behavioral interventions for autism have gained prominence in recent years; however, the neural-systems-level targets of these interventions remain poorly understood. We use a novel Bayesian framework to extract network-based differences before and after a 16-week pivotal response treatment (PRT) regimen. Our results suggest that the functional changes induced by PRT localize to the posterior cingulate and are marked by a shift in connectivity from the orbitofrontal cortex to the occipital-temporal cortex. Our results illuminate a potential PRT-induced learning mechanism, whereby the neural circuits involved during social perception shift from sensory and attentional systems to higher-level object and face processing areas.

Pivotal Response Treatment Prompts a Functional Rewiring of the Brain amongst Individuals with Autism Spectrum Disorder

PubMed Central

Venkataraman, Archana; Yang, Daniel Y.-J.; Dvornek, Nicha; Staib, Lawrence H.; Duncan, James S.; Pelphrey, Kevin A.; Ventola, Pamela

2016-01-01

Behavioral interventions for autism have gained prominence in recent years; however, the neural-systems-level targets of these interventions remain poorly understood. We use a novel Bayesian framework to extract network-based differences before and after a 16-week Pivotal Response Treatment (PRT) regimen. Our results suggest that functional changes induced by PRT localize to the posterior cingulate and are marked by a shift in connectivity from the orbitofrontal cortex to the occipital temporal cortex. Our results illuminate a potential PRT-induced learning mechanism, whereby the neural circuits involved during social perception shift from sensory and attentional systems to higher-level object and face processing areas. PMID:27532879

Inflammation-induced effects on iron-related proteins in splenic macrophages and the liver in mice.

PubMed

Sukumaran, Abitha; Venkatraman, Aparna; Jacob, Molly

2012-06-15

Anemia of inflammation is characterized by disturbances in systemic iron homeostasis. In order to better understand the events involved, we carried out a time-course study on the effects of acute and chronic inflammation on iron-related proteins in mouse splenic macrophages and the liver. Mice were sacrificed at various time points ranging from 0 h up to 4 weeks after induction of inflammation with turpentine oil. Expression levels of iron-related proteins in the splenic macrophages and liver were determined. Iron levels in the serum, spleen and liver were also measured. Hepatic hepcidin was found to be induced in response to inflammation. In the macrophages, expression levels of ferroportin and TfR1 were decreased at some of the time points. The expression of hepatic TfR1 and ferritin was significantly higher at the early time points. Ferritin levels in the liver decreased progressively thereafter; this was associated with significantly higher ferroportin expression in the liver, despite high levels of hepcidin, suggesting that hepcidin may not regulate ferroportin levels in the liver, unlike in the macrophages. The effects of hepcidin, thus, appeared to be tissue-specific. Serum iron levels were decreased initially; these then rose and were associated with decreasing iron levels in the liver and spleen. Thus, inflammation affected the expression levels of many proteins involved in iron homeostasis in splenic macrophages and the liver, with differences seen in the effects at these 2 sites. These effects are likely to contribute to the development of anemia of inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

Portable music player users: cultural differences and potential dangers.

PubMed

Levey, Sandra; Fligor, Brian J; Cutler, Cecelia; Harushimana, Immaculee

2013-01-01

Many studies have examined the use of portable music players portable listening devices (PLDs) from various ethnic groups. Some findings suggest that there may be differences among ethnic groups that lead to louder or longer listening when using PLD devices. For example, some studies found that Hispanic PLD users listen at higher volume levels while other studies found that African American PLD users listen at higher volume levels. No investigator has explained the reasons for differences among ethnic groups in listening intensity. This paper will address the possible reasons for these differences and offer guidelines for the prevention of noise-induced hearing loss.

Influence of atomic densities on propagation property for ultrashort pulses in a two-level medium

NASA Astrophysics Data System (ADS)

Liu, Bingxin; Gong, Shangqing; Song, Xiaohong; Jin, Shiqi

2005-05-01

The influence of atomic densities on the propagation property for ultrashort pulses in a two-level atom (TLA) medium is investigated. With higher atomic densities, the self-induced transparency (SIT) cannot be recovered even for 2? ultrashort pulses. New features such as pulse splitting, red-shift and blue-shift of the corresponding spectra arise, and the component of central frequency gradually disappears.

Determination of antibody to Streptococcus mutans from radiation-induced xerostomia patients. Agglutination activity against cariogenic microorganisms, active immunoglobulin classes, and post-irradiation caries activity in cancer patients. Final report 15 jul 77-14 apr 79

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

Brown, L.R.; O'Neill, P.A.; Dreizen, S.

1979-07-01

The relationship between specific agglutination (Ag) and caries activity during 30 month post radiation was assessed in 36 head and neck cancer patients. Ag titers in 444 saliva and 481 serum samples from these patients and 16 noncancer controls were determined against formalinized cellular antigens of Streptococcus mutans (Sm), Streptococcus sanguis (Ss), Streptococcus mitis, Lactobacillus fermenti (Lf), and Lactobacillus casei. Saliva IgA and IgG levels and Ag titers were significantly higher in cancer patients than in noncancer controls. Post radiation-induced xerostomic changes in saliva IgA reflected changes in specific Ag against oral microbes, particularly Sm serotype c. Patients with highmore » saliva IgA levels had significantly higher saliva Ag titers to Sm, Ss and Lf, lower plaque Sm counts and lower caries activity than patients with low saliva IgA levels. Serum Ag titers, however, showed no significant relationship with either serum Ig levels, microbial counts or caries activity. Chromatographic separation of Ig classes showed that Ag activity in saliva stemmed mainly from secretory IgA. Most serum Ag activity was found in regions corresponding to IgG and 7S IgA.« less

Stabilization of Fermi level via electronic excitation in Sn doped CdO thin films

NASA Astrophysics Data System (ADS)

Das, Arkaprava; Singh, Fouran

2018-04-01

Pure and Sn doped CdO sol-gel derived thin films were deposited on corning glass substrate and further irradiated by swift heavy ion (SHI) (Ag and O) with fluence upto 3×1013 ions/cm2. The observed tensile stress from X-ray diffraction pattern at higher fluence for Ag ions can be corroborated to the imbrications of cylindrical tracks due to multiple impacts. The anomalous band gap enhancement after irradiation may be attributed to the consolidated effect of Burstein-Moss shift (BMS) and impurity induced virtual gap states (ViGs). At higher excitation density as Fermi stabilization level (EFS) tends to coincide with charge neutrality level (CNL), band gap enhancement saturates as further creation of additional defects inside the lattice becomes unsustainable. Raman spectroscopy divulges an intensity enhancement of 478 cm-1 LO phonon mode with Sn doping and irradiation induces further asymmetric peak broadening due to damage and disordering inside the lattice. However for 3% Sn doped thin film irradiated with Ag ions having 3×1013 fluence shows a drastic change in structural properties and reduction in band gap which might be attributed to the generation of localized energy levels between conduction and valance band due to high density of defects.

Gastric myoelectrical and autonomic cardiac reactivity to laboratory stressors

PubMed Central

GIANAROS, PETER J.; QUIGLEY, KAREN S.; MORDKOFF, J. TOBY; STERN, ROBERT M.

2010-01-01

We evaluated the effects of two laboratory stressors (speech preparation and isometric handgrip) on gastric myoelectrical and autonomic cardiac activity, and the extent to which autonomic responses to these stressors and somatization predict reports of motion sickness during exposure to a rotating optokinetic drum. Both stressors prompted a decrease in preejection period (PEP) and respiratory sinus arrhythmia (RSA), and an increase in a dysrhythmic pattern of gastric myoelectrical activity, termed gastric tachyarrhythmia. Stressor-induced decreases in RSA and higher somatization scores predicted increased reports of motion sickness during drum rotation. These results demonstrate that laboratory stressors concurrently affect gastric myoelectrical activity and autonomic control of the heart, and that stressor-induced decreases in RSA and higher levels of somatization predict motion sickness susceptibility. PMID:11446577

Correlation of TLR4 and KLF7 in Inflammation Induced by Obesity.

PubMed

Wang, Cuizhe; Ha, Xiaodan; Li, Wei; Xu, Peng; Gu, Yajuan; Wang, Tingting; Wang, Yan; Xie, Jianxin; Zhang, Jun

2017-02-01

Objective Recent studies have revealed a link between toll-like receptors (TLRs), Kruppel-like factors (KLFs), and the adipose tissue inflammation associated with obesity. TLR4 is associated with chronic inflammation in obesity. KLF7 is known to play an important role in the differentiation of adipocytes, but its role in visceral adipose tissue inflammation has not yet been investigated. Thus, the objective of this study was to determine the correlation of TLR4 and KLF7 in inflammation induced by obesity. Methods A total of 32 Wistar male rat subjects were fed in the center for experimental animals of Shihezi University. The rats were divided into normal control (NC) and high-fat diet (HFD) group. Surgical instruments were used to collect rats' visceral adipose tissue samples in the 10th week after HFD feeding. Ninety-five Uygur subjects between 20 and 90 years old were enrolled in the present study. The subjects were divided into two groups: the normal control group (NC, 18.0 kg/m 2  ≤ BMI ≤ 23.9 kg/m 2 , n = 50) and the obesity group (OB, BMI ≥ 28 kg/m 2 , n = 45), and visceral adipose tissue was collected from the subjects. Anthropometric and clinical parameters were measured using standard procedures; biochemical indices were detected using the glucose oxidase-peroxidase method and a standardized automatic biochemistry analyzer; the plasma levels of inflammatory factors and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA); the mRNA and protein expression levels of key genes involved in the inflammatory signaling pathway were measured by real-time PCR and Western blot. Results In rats, compared with the NC group, the weight, Lee's index, waist circumference, visceral fat mass, and the plasma level of Glu, TG, FFA, and TNF-α were higher in the HFD group, while the plasma levels of LPT and APN were significantly lower in the HFD group in the 10th week. Furthermore, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were higher in the HFD group, and KLF7 was significantly positively correlated with LDL, TLR4, SRC, and IL-6 (P < 0.05). Meanwhile, in the Uygur population, the plasma levels of TG, LDL, and TNF-α in the OB group were significantly higher than those in the NC group (P < 0.05). Moreover, compared with the NC group, visceral adipose tissue's mRNA expression levels of TLR4, KLF7, and SRC were significantly higher in the OB group (P < 0.05), and KLF7 was significantly positively correlated with TC, TLR4, MYD88, SRC, and IL-6 (P < 0.05); the protein expression levels of TLR4 and KLF7 were significantly higher than those in the NC group (P < 0.05). Conclusion Higher expression of TLR4 and KLF7 may play a vital role in the process of inflammation induced by obesity in visceral adipose tissue.

Intrathecal oxotremorine affects formalin-induced behavior and spinal nitric oxide synthase immunoreactivity in rats.

PubMed

Przewlocka, B; Mika, J; Capone, F; Machelska, H; Pavone, F

1999-03-01

The present research was undertaken to investigate, by behavioral and immunohistochemical methods, the effects of intrathecal (i.th.) injection of the muscarinic agonist oxotremorine on the response to the long-lasting nociceptive stimulus induced by injection of formalin into the rat hind paw. Formalin injection induced a biphasic, pain-induced behavioral response (paw jerks), as well as an increase in the number of nitric oxide (NO) synthase-labeled neurons in laminae I-III, IV, and X, but not in laminae V-VI. Oxotremorine (0.1-10 ng, i.th.) inhibited paw-jerk frequency in both phases of formalin-induced behavior. The immunohistochemical results showed that i.th.-injected oxotremorine differently affected the level of NO synthase in lumbar part of the spinal cord: no change or increase after the dose of 1 ng, and a significant reduction of nitric oxide synthase neurons after the higher dose (10 ng). These results evidenced a role of cholinergic system in the modulation of tonic pain and in nitric oxide synthase expression at the spinal cord level, which further suggests that these two systems could be involved in phenomena induced by long-lasting nociceptive stimulation.

Shock wave induced phase transition in α -FePO 4

NASA Astrophysics Data System (ADS)

Joshi, K. D.; Suresh, N.; Jyoti, G.; Kulshreshtha, S. K.; Gupta, S. C.; Sikka, S. K.

Shock wave induced response of the berlinite form of FePO 4 has been investigated up to 8.5 GPa. The X-ray diffraction measurements on the shock recovered samples reveal transition to the mixture of an amorphous phase and an orthorhombic phase around 5 GPa. The proportion of the amorphous material in the recovered sample is found to decrease at higher pressure. The results are interpreted in terms of a three-level free energy diagram for the crystal to amorphous transitions.

Effect of red maca (Lepidium meyenii) on prostate zinc levels in rats with testosterone-induced prostatic hyperplasia.

PubMed

Gonzales, C; Leiva-Revilla, J; Rubio, J; Gasco, M; Gonzales, G F

2012-05-01

Lepidium meyenii (maca) is a plant that grows exclusively above 4000 m in the Peruvian central Andes. Red maca (RM) extract significantly reduced prostate size in rats with benign prostatic hyperplasia (BPH) induced by testosterone enanthate (TE). Zinc is an important regulator of prostate function. This study aimed to determine the effect of RM on prostate zinc levels in rats with BPH induced by TE. Also, the study attempted to determine the best marker for the effect of RM on sex accessory glands. Rats treated with RM extract from day 1 to day 14 reversed the effect of TE administration on prostate weight and zinc levels. However, RM administered from day 7 to day 14 did not reduce the effect of TE on all studied variables. Finasteride (FN) reduced prostate, seminal vesicle and preputial gland weights in rats treated with TE. Although RM and FN reduced prostate zinc levels, the greatest effect was observed in TE-treated rats with RM from day 1 to day 14. In addition, prostate weight and zinc levels showed the higher diagnosis values than preputial and seminal vesicle weights. In conclusion, RM administered from day 1 to day 14 reduced prostate size and zinc levels in rats where prostatic hyperplasia was induced with TE. Also, this experimental model could be used as accurately assay to determine the effect of maca obtained under different conditions and/or the effect of different products based on maca. © 2011 Blackwell Verlag GmbH.

Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation

PubMed Central

Jhun, Joo-Yeon; Yoon, Bo-Young; Park, Mi-Kyung; Oh, Hye-Joa; Byun, Jae-Kyeong; Lee, Seon-Young; Min, Jun-Ki; Park, Sung-Hwan; Kim, Ho-Youn

2012-01-01

White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-α. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA. PMID:22513335

Combined administration of synthetic RNA and a conventional vaccine improves immune responses and protection against foot-and-mouth disease virus in swine.

PubMed

Borrego, Belén; Blanco, Esther; Rodríguez Pulido, Miguel; Mateos, Francisco; Lorenzo, Gema; Cardillo, Sabrina; Smitsaart, Eliana; Sobrino, Francisco; Sáiz, Margarita

2017-06-01

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity.

PubMed

O'Brien, William G; Berka, Vladimir; Tsai, Ah-Lim; Zhao, Zhaoyang; Lee, Cheng Chi

2015-08-07

Erythrocytes are the key target in 5'-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3(-/-) mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages

PubMed Central

Cudejko, Céline; Wouters, Kristiaan; Fuentes, Lucía; Hannou, Sarah Anissa; Paquet, Charlotte; Bantubungi, Kadiombo; Bouchaert, Emmanuel; Vanhoutte, Jonathan; Fleury, Sébastien; Remy, Patrick; Tailleux, Anne; Chinetti, Giulia; Dombrowicz, David; Staels, Bart; Paumelle, Réjane

2011-01-01

The CDKN2A locus, which contains the tumor suppressor gene p16INK4a, is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize towards classically (CAMφ) or alternatively (AAMφ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16INK4a-deficiency (p16−/−) modulates the macrophage phenotype. Transcriptome analysis revealed that p16−/− bone marrow-derived macrophages (BMDM) exhibit a phenotype resembling interleukin (IL)-4-induced macrophage polarization. In line with this observation, p16−/− BMDM displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16−/− bone marrow displayed higher hepatic AAMφ marker expression levels upon Schistosoma mansoni infection, an in vivo model of AAMφ phenotype-skewing. Surprisingly, p16−/− BMDM did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and LPS-induced IKKα,β phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. These findings identify p16INK4a as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases. PMID:21636855

Relationship between high on aspirin platelet reactivity and oxidative stress in coronary artery by-pass grafted patients.

PubMed

Kuliczkowski, Wiktor; Golanski, Ryszard; Bijak, Michal; Boryczka, Katarzyna; Kaczmarski, Jacek; Watala, Cezary; Golanski, Jacek

2016-03-01

The aim of the study was to assess the responsiveness of blood platelets to acetylsalicylic acid (ASA) in patients following coronary artery bypass grafting (CABG) surgery with relation to oxidative and antioxidative plasma status. The study included 37 patients treated with the CABG procedure. During the first 24 h after CABG patients were given 300 mg of ASA with the following dose of 150 mg daily. The blood was collected before the procedure and 10 days after. Whole blood platelet aggregation induced with arachidonic acid, collagen and adenosine diphosphate (ADP) was performed together with whole blood generation of thromboxane B2 (TxB2). Oxidative stress was measured before and 10 days after CABG with total oxidative plasma status (TOS) and total antioxidative status of the plasma (TAS). TOS/TAS index was calculated. We observed a significant increase in the TOS and TOS/TAS index and ADP-induced aggregation 10 days after CABG in comparison with its level before operation. There was a significant decrease in the arachidonic acid-induced aggregation and serum TxB2 level. Patients with ADP-induced and collagen-induced aggregation in the upper quartile had significantly higher TOS and TOS/TAS index before (ADP) and after the operation (ADP and collagen). There were 19 patients (51%) with high on aspirin platelet reactivity after CABG who had also higher TOS and TOS/TAS index and lower TAS value in comparison with aspirin responders. Despite ASA use, increased oxidative stress after CABG can overcome its antiplatelet effect and increase platelet activation through other pathways.

[Immunological characteristics of Mycobacterium tuberculosis antigen Rv2628].

PubMed

Yin, Yuelan; Gao, Yunfei; Zhao, Dan; Lian, Kai; Chen, Xiang; Xu, Zhengzhong; Pan, Zhiming; Jiao, Xin'an

2014-02-01

Antigen Rv2628 of Mycobacterium tuberculosis is associated with latent tuberculosis infection. In this study, Rv2628 was prokaryotic expressed and purified, its immunological characteristics was evaluated with macrophage cell line RAW264.7 and BALB/c mice. The results show that Rv2628 was mainly expressed in form of inclusion body confirmed by SDS-PAGE, and could react with rabbit anti-H37Rv polyclonal antibody detected by Western blotting assay, indicating that the protein had an effective immunoreactivity. The interactions between Rv2628 and macrophage cell line RAW264.7 confirmed that it could effectively induce cells to produce pro-inflammatory cytokines, the relative expression level of IL-6 mRNA was higher than the control group in 1-12 h. BALB/c mice were subcutaneously immunized with Rv2628 protein, the production of IFN-gamma and IL-4 in the spleen cells was determined by Sandwich ELISA, in the Rv2628 immunized group, the level of IFN-gamma was significantly higher than that of IL-4 (P < 0.000 1). It indicated the protein induced Th1-tendency immune responses. At the same time, Rv2628(11-30) peptide used as coating antigen, the murine serum antibody titer detected by indirect-ELISA was 1:1 600, which demonstrated that Rv2628 could also induce humoral immune responses. In summary, Rv2628 could induce specific pro-inflammatory cytokines, affectively induce strongly Th1-tendency immune response and humoral response, it could be a potential target for developing subunit vaccine against TB. In addition, it laid foundation for probing the cross-talk between M. tb and host.

Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.

PubMed

Wang, Zhen-Yu; Liu, Wen-Ge; Muharram, Akram; Wu, Zhao-Yan; Lin, Jian-Hua

2014-01-01

To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture. SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale. The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis. The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI. © 2014 S. Karger AG, Basel

Pheromonal communication in nereids and the likely intervention by petroleum derived pollutants.

PubMed

Müller, Carsten T; Priesnitz, Frank M; Beckmann, Manfred

2005-01-01

Nereis succinea and Platynereis dumerilii (Annelida, Polychaeta) are broadcast spawners and reproduce semelparously. The final events in reproduction, swarming and spawning are co-ordinated by sex pheromones.A water-soluble fraction of crude oil, the volatile fraction (C9-C16) of EKO FISK crude oil was found to induce release of gametes in male nereids at levels <0.3 ppm.Using vacuum distillation, column chromatography, preparative GC and GC-MS analysis we showed that C(5)-alkylated benzenes were most potent in inducing sperm release, of those n-butyl-4-methylbenzene and 1,4-diethyl-2-methylbenzene were found to induce release of gametes at concentrations ≥4 nM. This threshold is lower than those reported for natural pheromones (nereithione: 60 nM, uric acid: 600 nM) but higher than background levels of aromatic compounds of 0.05 nM and below.Other oil fractions showed additional effects, blocking pheromone reception or narcotising and intoxicating animals. Part of these effects could be assigned to naphthalenes at levels down to approx. 320 nM. In the original mixtures, their action was modified or compensated by the presence of gamete release inducing alkylated benzenes. Other highly paralysing substances remained elusive.

Assessment of amiodarone-induced phospholipidosis in chimeric mice with a humanized liver.

PubMed

Sanoh, Seigo; Yamachika, Yuto; Tamura, Yuka; Kotake, Yaichiro; Yoshizane, Yasumi; Ishida, Yuji; Tateno, Chise; Ohta, Shigeru

2017-01-01

It is important to consider susceptibility to drug-induced toxicity between animals and humans. Chimeric mice with a humanized liver are expected to predict hepatotoxicity in humans. Drug-induced phospholipidosis (DIPL), in which phospholipids accumulate, is a known entity. In this study, we examined whether chimeric mice can reveal species differences in DIPL. Changes in various phosphatidylcholine (PhC) molecules were investigated in the liver of chimeric mice after administering amiodarone, which induces phospholipidosis. Liquid chromatography-tandem mass spectrometry revealed that levels of PhCs tended to increase in the liver after administration of amiodarone. The liver of chimeric mice consists of human hepatocytes and residual mouse hepatocytes. We used imaging mass spectrometry (IMS) to evaluate the increase of PhCs in human and mouse hepatocytes after administration of amiodarone. IMS visualizes localization of endogenous and exogenous molecules in tissues. The IMS analysis suggested that the localized levels of several PhCs tended to be higher in the human hepatocytes than those in mouse hepatocytes, and PhC levels changed in response to amiodarone. Chimeric mice with a humanized liver will be useful to evaluate species differences in DIPL between mice and humans.

Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

PubMed

Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

2012-03-01

Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Safety and antibody response, including antibody persistence for 5 years, after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older adults.

PubMed

Musher, Daniel M; Manof, Susan B; Liss, Charlie; McFetridge, Richard D; Marchese, Rocio D; Bushnell, Bonnie; Alvarez, Frances; Painter, Carla; Blum, Michael D; Silber, Jeffrey L

2010-02-15

This study assessed antibody levels for 5 years after primary vaccination or revaccination with 23-valent pneumococcal polysaccharide vaccine (PN23). Subjects were enrolled into 4 study groups by age (50-64 or > or = 65 years) and prior vaccination status (no prior vaccination or 1 vaccination 3-5 years previously). Blood was obtained on day 0 (before primary vaccination or revaccination), day 30, day 60, and annually during years 2-5. Levels of immunoglobulin G (IgG) to 8 vaccine serotypes were measured by enzyme-linked immunosorbent assay. Of 1008 enrolled subjects, 551 completed year 5. For each serotype and age group, baseline geometric mean concentrations (GMCs) of IgG were higher in revaccination than primary vaccination subjects. Primary vaccination or revaccination with PN23 induced significant increases in levels of antibody to all serotypes tested. Although day 30 and 60 antibody levels tended to be modestly lower after revaccination, study groups had similar GMCs at later time points. For serotypes 4, 6B, 8, 9V, 12F, 14, and 23F, GMCs during years 2-5 after primary vaccination or revaccination remained higher than in vaccine-naive persons. Levels of antibody to serotype 3 returned to baseline by year 2. Both primary vaccination and revaccination with PN23 induce antibody responses that persist during 5 years of observation.

Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids.

PubMed

Le Foll, Christelle; Dunn-Meynell, Ambrose A; Miziorko, Henri M; Levin, Barry E

2014-04-01

Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes.

Regulation of Hypothalamic Neuronal Sensing and Food Intake by Ketone Bodies and Fatty Acids

PubMed Central

Le Foll, Christelle; Dunn-Meynell, Ambrose A.; Miziorko, Henri M.; Levin, Barry E.

2014-01-01

Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes. PMID:24379353

Character and temporal evolution of apoptosis in acetaminophen-induced acute liver failure*.

PubMed

Possamai, Lucia A; McPhail, Mark J W; Quaglia, Alberto; Zingarelli, Valentina; Abeles, R Daniel; Tidswell, Robert; Puthucheary, Zudin; Rawal, Jakirty; Karvellas, Constantine J; Leslie, Elaine M; Hughes, Robin D; Ma, Yun; Jassem, Wayel; Shawcross, Debbie L; Bernal, William; Dharwan, Anil; Heaton, Nigel D; Thursz, Mark; Wendon, Julia A; Mitry, Ragai R; Antoniades, Charalambos G

2013-11-01

To evaluate the role of hepatocellular and extrahepatic apoptosis during the evolution of acetaminophen-induced acute liver failure. A prospective observational study in two tertiary liver transplant units. Eighty-eight patients with acetaminophen-induced acute liver failure were recruited. Control groups included patients with nonacetaminophen-induced acute liver failure (n = 13), nonhepatic multiple organ failure (n = 28), chronic liver disease (n = 19), and healthy controls (n = 11). Total and caspase-cleaved cytokeratin-18 (M65 and M30) measured at admission and sequentially on days 3, 7, and 10 following admission. Levels were also determined from hepatic vein, portal vein, and systemic arterial blood in seven patients undergoing transplantation. Protein arrays of liver homogenates from patients with acetaminophen-induced acute liver failure were assessed for apoptosis-associated proteins, and histological assessment of liver tissue was performed. Admission M30 levels were significantly elevated in acetaminophen-induced acute liver failure and non-acetaminophen induced acute liver failure patients compared with multiple organ failure, chronic liver disease, and healthy controls. Admission M30 levels correlated with outcome with area under receiver operating characteristic of 0.755 (0.639-0.885, p < 0.001). Peak levels in patients with acute liver failure were seen at admission then fell significantly but did not normalize over 10 days. A negative gradient of M30 from the portal to hepatic vein was demonstrated in patients with acetaminophen-induced acute liver failure (p = 0.042) at the time of liver transplant. Analysis of protein array data demonstrated lower apoptosis-associated protein and higher catalase concentrations in acetaminophen-induced acute liver failure compared with controls (p < 0.05). Explant histological analysis revealed evidence of cellular proliferation with an absence of histological evidence of apoptosis. Hepatocellular apoptosis occurs in the early phases of human acetaminophen-induced acute liver failure, peaking on day 1 of hospital admission, and correlates strongly with poor outcome. Hepatic regenerative/tissue repair responses prevail during the later stages of acute liver failure where elevated levels of M30 are likely to reflect epithelial cell death in extrahepatic organs.

Function of the Golgi-located phosphate transporter PHT4;6 is critical for senescence-associated processes in Arabidopsis

PubMed Central

Hassler, Sebastian; Jung, Benjamin; Lemke, Lilia; Novák, Ondřej; Strnad, Miroslav; Martinoia, Enrico; Neuhaus, H. Ekkehard

2016-01-01

The phosphate transporter PHT4;6 locates to the trans-Golgi compartment, and its impaired activity causes altered intracellular phosphate compartmentation, leading to low cytosolic Pi levels, a blockage of Golgi-related processes such as protein glycosylation and hemicellulose biosynthesis, and a dwarf phenotype. However, it was unclear whether altered Pi homeostasis in pht4;6 mutants causes further cellular problems, typically associated with limited phosphate availability. Here we report that pht4;6 mutants exhibit a markedly increased disposition to induce dark-induced senescence. In control experiments, in which pht4;6 mutants and wild-type plants developed similarly, we confirmed that accelerated dark-induced senescence in mutants is not a ‘pleiotropic’ process associated with the dwarf phenotype. In fact, accelerated dark-induced senescence in pht4;6 mutants correlates strongly with increased levels of toxic NH4 + and higher sensitivity to ammonium, which probably contribute to the inability of pht4;6 mutants to recover from dark treatment. Experiments with modified levels of either salicylic acid (SA) or trans-zeatin (tZ) demonstrate that altered concentrations of these compounds in pht4;6 plants act as major cellular mediators for dark-induced senescence. This conclusion gained further support from the notion that the expression of the pht4;6 gene is, in contrast to genes coding for major phosphate importers, substantially induced by tZ. Taken together, our findings point to a critical function of PHT4;6 to control cellular phosphate levels, in particular the cytosolic Pi availability, required to energize plant primary metabolism for proper plant development. Phosphate and its allocation mediated by PHT4;6 is critical to prevent onset of dark-induced senescence. PMID:27325894

Cough hypersensitivity in patients with obstructive sleep apnea hypopnea syndrome.

PubMed

Shi, Cuiqin; Liang, Siwei; Xu, Xianghuai; Chen, Qiang; Wang, Lan; Yu, Li; Lv, Hanjing; Qiu, Zhongmin

2018-02-16

The purpose of this study was to investigate cough hypersensitivity and its potential mechanisms in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Fifteen OSAHS patients, 12 simple snoring patients, and 15 healthy volunteers received cough sensitivity test and induced sputum cytology. Cough thresholds C2 and C5 (the minimum of capsaicin inducing ≥ 2 and ≥ 5 coughs, respectively), total cell count, cell differentials and the levels of bradykinin, histamine, prostaglandin E 2 , substance P, calcitonin gene-related peptide, pepsin, and interleukin-2 in the induced sputum detected by enzyme-linked immunosorbent assay were compared. The linear correlation between lgC2 and lgC5 and apnea hypopnea index, cell differentials, and inflammatory mediators in the induced sputum was calculated in OSAHS patients. OSAHS patients presented with a significant lower C2 and C5 (P < 0.01), increased lymphocyte but decreased macrophage and neutrophil proportions in the induced sputum (P < 0.01), and higher contents of substance P, calcitonin gene-related peptide and interleukin-2 (P < 0.01) but similar levels of bradykinin, pepsin, prostaglandin E 2 , and histamine (P > 0.05) in the supernatant of induced sputum, when compared with simple snoring patients and healthy volunteers. However, theses variable were comparable between simple snoring patients and healthy volunteers (P > 0.05). Finally, lgC2 or lgC5 was negatively related to apnea hypopnea index, lymphocyte percentage, and the levels of substance P, calcitonin gene-related peptide or interleukin-2 in the sputum (P < 0.01). There was a positive linear correlation between lymphocyte percentage and interleukin-2 level in the induced sputum (r = 0.63, P = 0.00). OSAHS patients have a predisposition of cough hypersensitivity associated with airway inflammation.

Sort-Seq Approach to Engineering a Formaldehyde-Inducible Promoter for Dynamically Regulated Escherichia coli Growth on Methanol

PubMed Central

2017-01-01

Tight and tunable control of gene expression is a highly desirable goal in synthetic biology for constructing predictable gene circuits and achieving preferred phenotypes. Elucidating the sequence–function relationship of promoters is crucial for manipulating gene expression at the transcriptional level, particularly for inducible systems dependent on transcriptional regulators. Sort-seq methods employing fluorescence-activated cell sorting (FACS) and high-throughput sequencing allow for the quantitative analysis of sequence–function relationships in a robust and rapid way. Here we utilized a massively parallel sort-seq approach to analyze the formaldehyde-inducible Escherichia coli promoter (Pfrm) with single-nucleotide resolution. A library of mutated formaldehyde-inducible promoters was cloned upstream of gfp on a plasmid. The library was partitioned into bins via FACS on the basis of green fluorescent protein (GFP) expression level, and mutated promoters falling into each expression bin were identified with high-throughput sequencing. The resulting analysis identified two 19 base pair repressor binding sites, one upstream of the −35 RNA polymerase (RNAP) binding site and one overlapping with the −10 site, and assessed the relative importance of each position and base therein. Key mutations were identified for tuning expression levels and were used to engineer formaldehyde-inducible promoters with predictable activities. Engineered variants demonstrated up to 14-fold lower basal expression, 13-fold higher induced expression, and a 3.6-fold stronger response as indicated by relative dynamic range. Finally, an engineered formaldehyde-inducible promoter was employed to drive the expression of heterologous methanol assimilation genes and achieved increased biomass levels on methanol, a non-native substrate of E. coli. PMID:28463494

A prospective cohort study on radiation-induced hypothyroidism: development of an NTCP model.

PubMed

Boomsma, Marjolein J; Bijl, Hendrik P; Christianen, Miranda E M C; Beetz, Ivo; Chouvalova, Olga; Steenbakkers, Roel J H M; van der Laan, Bernard F A M; Wolffenbuttel, Bruce H R; Oosting, Sjoukje F; Schilstra, Cornelis; Langendijk, Johannes A

2012-11-01

To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism. The thyroid-stimulating hormone (TSH) level of 105 patients treated with (chemo-) radiation therapy for head-and-neck cancer was prospectively measured during a median follow-up of 2.5 years. Hypothyroidism was defined as elevated serum TSH with decreased or normal free thyroxin (T4). A multivariate logistic regression model with bootstrapping was used to determine the most important prognostic variables for radiation-induced hypothyroidism. Thirty-five patients (33%) developed primary hypothyroidism within 2 years after radiation therapy. An NTCP model based on 2 variables, including the mean thyroid gland dose and the thyroid gland volume, was most predictive for radiation-induced hypothyroidism. NTCP values increased with higher mean thyroid gland dose (odds ratio [OR]: 1.064/Gy) and decreased with higher thyroid gland volume (OR: 0.826/cm(3)). Model performance was good with an area under the curve (AUC) of 0.85. This is the first prospective study resulting in an NTCP model for radiation-induced hypothyroidism. The probability of hypothyroidism rises with increasing dose to the thyroid gland, whereas it reduces with increasing thyroid gland volume. Copyright © 2012 Elsevier Inc. All rights reserved.

Continuing Exposure to Low-Dose Nonylphenol Aggravates Adenine-Induced Chronic Renal Dysfunction and Role of Rosuvastatin Therapy

PubMed Central

2012-01-01

Background Nonylphenol (NP), an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS) synthesis. Chronic exposure to low-dose adenine (AD) has been reported to induce chronic kidney disease (CKD). Methods In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control), group 2 (AD in fodder at a concentration of 0.25%), group 3 (NP: 2 mg/kg/day), group 4 (combined AD & NP), and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day). Treatment was continued for 24 weeks for all animals before being sacrificed. Results By the end of 24 weeks, serum blood urea nitrogen (BUN) and creatinine levels were increased in group 4 than in groups 1–3, but significantly reduced in group 5 as compared with group 4 (all p < 0.05). Histopathology scorings of renal-parenchymal and tubular damages were significantly higher in group 4 than in groups 1–3, but remarkably lower in group 5 compared with group 4 (all p < 0.01). Both gene and protein levels of inflammation, oxidative stress, ROS, and cellular apoptosis were remarkably higher in group 4 compared with groups 1–3, but lowered in group 5 than in group 4 (all p < 0.001). Conversely, both gene and protein levels of anti-oxidants, anti-inflammation and anti-apoptosis were markedly increased in group 5 compared with group 4 (all p < 0.001). Conclusion NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy. PMID:22812704

Reduction of aflatoxin level in aflatoxin-induced rats by the activity of probiotic Lactobacillus casei strain Shirota.

PubMed

Nikbakht Nasrabadi, E; Jamaluddin, R; Abdul Mutalib, M S; Khaza'ai, H; Khalesi, S; Mohd Redzwan, S

2013-05-01

Aflatoxin B1 (AFB1 ) is considered as the most toxic food contaminant, and microorganisms, especially bacteria, have been studied for their potential to reduce the bioavailability of mycotoxins including aflatoxins. Therefore, this research investigated the efficacy of oral administration of Lactobacillus casei Shirota (LcS) in aflatoxin-induced rats. Sprague Dawley rats were divided into three groups of untreated control, the group induced with AFB1 only, and the group given probiotic in addition to AFB1. In the group induced with AFB1 only, food intake and body weight were reduced significantly. The liver and kidney enzymes were significantly enhanced in both groups induced with AFB1 , but they were lower in the group given LcS. AFB1 was detected from all serum samples except for untreated control group's samples. Blood serum level of AFB1 in the group induced with AFB1 only was significantly higher than the group which received probiotic as a treatment (P < 0·05), and there was no significant difference between the control group and the group treated with probiotic. LcS supplementation could improve the adverse effect of AFB1 induction on rats' body weight, plasma biochemical parameters and also could reduce the level of AFB1 in blood serum. This study's outcomes contribute to better understanding of the potential of probiotic to reduce the bioavailability ofAFB1 . Moreover, it can open an opportunity for future investigations to study the efficacy of oral supplementation of probiotic LcS in reducing aflatoxin level in human. © 2013 The Society for Applied Microbiology.

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

PubMed Central

Shafran, Yana; Zurgil, Naomi; Ravid-Hermesh, Orit; Sobolev, Maria; Afrimzon, Elena; Hakuk, Yaron; Shainberg, Asher; Deutsch, Mordechai

2017-01-01

Estrogen-induced apoptosis has become a successful treatment for postmenopausal metastatic, estrogen receptor-positive breast cancer. Nitric oxide involvement in the response to this endocrine treatment and its influence upon estrogen receptor-positive breast cancer progression is still unclear. Nitric oxide impact on the MCF7 breast cancer line, before and after estrogen-induced apoptosis, was investigated in 3D culture systems using unique live-cell imaging methodologies. Spheroids were established from MCF7 cells vulnerable to estrogen-induced apoptosis, before and after exposure to estrogen. Spheroids derived from estrogen-treated cells exhibited extensive apoptosis levels with downregulation of estrogen receptor expression, low proliferation rate and reduced metabolic activity, unlike spheroids derived from non-treated cells. In addition to basic phenotypic differences, these two cell cluster types are diverse in their reactions to exogenous nitric oxide. A dual effect of nitric oxide was observed in the breast cancer phenotype sensitive to estrogen-induced apoptosis. Nitric oxide, at the nanomolar level, induced cell proliferation, high metabolic activity, downregulation of estrogen receptor and enhanced collective invasion, contributing to a more aggressive phenotype. Following hormone supplementation, breast cancer 3D clusters were rescued from estrogen-induced apoptosis by these low nitric oxide-donor concentrations, since nitric oxide attenuates cell death levels, upregulates survivin expression and increases metabolic activity. Higher nitric oxide concentrations (100nM) inhibited cell growth, metabolism and promoted apoptosis. These results suggest that nitric oxide, in nanomolar concentrations, may inhibit estrogen-induced apoptosis, playing a major role in hormonal therapy. Inhibiting nitric oxide activity may benefit breast cancer patients and ultimately reduce tumor recurrence. PMID:29312577

[HIF-2α/Notch3 pathway mediates CoCl2-induced migration and invasion in human breast cancer MCF-7 cells].

PubMed

Wang, Jian-Guo; Yuan, Lei

2016-12-25

The aim of this study is to investigate the effects of hypoxia inducible factor-2α (HIF-2α) and Notch3 on CoCl 2 -induced migration and invasion of human breast cancer cell line MCF-7. MCF-7 cells were exposed to normoxia (21% O 2 ) or chemical hypoxia (21% O 2 plus CoCl 2 ). Short hairpin RNA (shRNA) was used to knock down HIF-2α and Notch3 in MCF-7 cells. The mRNA expression levels of HIF-2α, Notch3 and Hey1 were measured by RT-PCR. Western blot was performed to determine the protein expression levels of HIF-2α, Notch3, Hey1, Snail and E-cadherin. CoCl 2 treatment resulted in higher protein expression levels of HIF-2α, Notch3, Hey1, Snail (P < 0.05) and lower levels of E-cadherin (P < 0.05), and promoted migration and invasion of MCF-7 cells (P < 0.05). shRNA-HIF-2α suppressed CoCl 2 -induced mRNA expression of Notch3 and Hey1. Notch3 knockdown down-regulated Snail and up-regulated E-cadherin at protein level under simulated hypoxia (P < 0.05), and inhibited CoCl 2 -induced migration and invasion of MCF-7 cells (P < 0.05). In conclusion, our data provide evidence that HIF-2α may promote the migration and invasion of MCF-7 cells under chemical hypoxic conditions by potentiating Notch3 pathway.

Phenotypical, physiological and biochemical analyses provide insight into selenium-induced phytotoxicity in rice plants.

PubMed

Mostofa, Mohammad Golam; Hossain, Mohammad Anwar; Siddiqui, Md Nurealam; Fujita, Masayuki; Tran, Lam-Son

2017-07-01

The present study investigated the phenotypical, physiological and biochemical changes of rice plants exposed to high selenium (Se) concentrations to gain an insight into Se-induced phytotoxicity. Results showed that exposure of rice plants to excessive Se resulted in growth retardation and biomass reduction in connection with the decreased levels of chlorophyll, carotenoids and soluble proteins. The reduced water status and an associated increase in sugar and proline levels indicated Se-induced osmotic stress in rice plants. Measurements of Se contents in roots, leaf sheaths and leaves revealed that Se was highly accumulated in leaves followed by leaf sheaths and roots. Se also potentiated its toxicity by impairing oxidative metabolism, as evidenced by enhanced accumulation of hydrogen peroxide, superoxide and lipid peroxidation product. Se toxicity also displayed a desynchronized antioxidant system by elevating the level of glutathione and the activities of superoxide dismutase, glutathione-S-transferase and glutathione peroxidase, whereas decreasing the level of ascorbic acid and the activities of catalase, glutathione reductase and dehydroascorbate reductase. Furthermore, Se triggered methylglyoxal toxicity by inhibiting the activities of glyoxalases I and II, particularly at higher concentrations of Se. Collectively, our results suggest that excessive Se caused phytotoxic effects on rice plants by inducing chlorosis, reducing sugar, protein and antioxidant contents, and exacerbating oxidative stress and methylglyoxal toxicity. Accumulation levels of Se, proline and glutathione could be considered as efficient biomarkers to indicate degrees of Se-induced phytotoxicity in rice, and perhaps in other crops. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemotherapy-Induced Fatigue Correlates With Higher Fatigue Scores Before Treatment.

PubMed

Araújo, José Klerton Luz; Giglio, Adriana Del; Munhoz, Bruna Antenusse; Fonseca, Fernando Luiz Affonso; Cruz, Felipe Melo; Giglio, Auro Del

2017-06-01

Cancer chemotherapy can induce fatigue in about 20% to 30% of patients. So far, there is very little information as to the predictors of chemotherapy-induced fatigue (CIF). We evaluated potential predictors of CIF in a sample of patients with cancer with several types of solid tumors scheduled to receive chemotherapy according to institutional protocols. Before their first and second chemotherapy cycles, patients answered to the Brief Fatigue Inventory (BFI), Chalder, Mini Nutritional Assessment (MNA), Stress thermometer, and HADS questionnaires as well as provided blood samples for inflammatory markers. We evaluated 52 patients, 37 (71%) were female and mean age was 53 years. The most common tumors were breast cancer 21 (40%) and gastrointestinal tumors 12 (23%). Although 14 (25.2%) patients had an increase in their fatigue BFI scores equal or above 3 points from baseline, we observed no significant overall differences between BFI scores before and after chemotherapy. The only 2 factors associated with an increase of 3 points in the BFI scores after chemotherapy were race and higher baseline BFI levels. By multivariate analysis, overall BFI and Chalder scores after chemotherapy also correlated significantly with their respective baseline scores before treatment. HADS scores before treatment correlated with overall BFI scores postchemotherapy, whereas MNA scores before chemotherapy and female sex correlated with higher Chalder scores after treatment. We conclude that fatigue induced by chemotherapy is common and consistently associated with higher fatigue scores before treatment. Screening for fatigue before chemotherapy may help to identify patients who are prone to develop CIF.

Salinity induced effects on the growth rates and mycelia composition of basidiomycete and zygomycete fungi.

PubMed

Venâncio, C; Pereira, R; Freitas, A C; Rocha-Santos, T A P; da Costa, J P; Duarte, A C; Lopes, I

2017-12-01

Soil salinization, as the combination of primary and secondary events, can adversely affect organisms inhabiting this compartment. In the present study, the effects of increased salinity were assessed in four species of terrestrial fungi: Lentinus sajor caju, Phanerochaete chrysosporium, Rhizopus oryzae and Trametes versicolor. The mycelial growth and biochemical composition of the four fungi were determined under three exposure scenarios: 1) exposure to serial dilutions of natural seawater (SW), 2) exposure to serial concentrations of NaCl (potential surrogate of SW); and 3) exposure to serial concentrations of NaCl after a period of pre-exposure to low levels of NaCl. The toxicity of NaCl was slightly higher than that of SW, for all fungi species: the conductivities causing 50% of growth inhibition (EC 50 ) were within 14.9 and 22.0 mScm -1 for NaCl and within 20.2 and 34.1 mScm -1 for SW. Phanerochaete chrysosporium showed to be the less sensitive species, both for NaCl and SW. Exposure to NaCl caused changes in the biochemical composition of fungi, mainly increasing the production of polysaccharides. When fungi were exposed to SW this pattern of biochemical response was not observed. Fungi pre-exposed to low levels of salinity presented higher EC 50 than fungi non-pre-exposed, though 95% confidence limits overlapped, with the exception of P. chrysosporium. Pre-exposure to low levels of NaCl also induced changes in the biochemical composition of the mycelia of L. sajor caju and R. oryzae, relatively to the respective control. These results suggest that some terrestrial fungi may acquire an increased tolerance to NaCl after being pre-exposed to low levels of this salt, thus, suggesting their capacity to persist in environments that will undergo salinization. Furthermore, NaCl could be used as a protective surrogate of SW to derive safe salinity levels for soils, since it induced toxicity similar or higher than that of SW. Copyright © 2017 Elsevier Ltd. All rights reserved.

Understanding EUV mask blank surface roughness induced LWR and associated roughness requirement

NASA Astrophysics Data System (ADS)

Yan, Pei-Yang; Zhang, Guojing; Gullikson, Eric M.; Goldberg, Ken A.; Benk, Markus P.

2015-03-01

Extreme ultraviolet lithography (EUVL) mask multi-layer (ML) blank surface roughness specification historically comes from blank defect inspection tool requirement. Later, new concerns on ML surface roughness induced wafer pattern line width roughness (LWR) arise. In this paper, we have studied wafer level pattern LWR as a function of EUVL mask surface roughness via High-NA Actinic Reticle Review Tool. We found that the blank surface roughness induced LWR at current blank roughness level is in the order of 0.5nm 3σ for NA=0.42 at the best focus. At defocus of ±40nm, the corresponding LWR will be 0.2nm higher. Further reducing EUVL mask blank surface roughness will increase the blank cost with limited benefit in improving the pattern LWR, provided that the intrinsic resist LWR is in the order of 1nm and above.

Is moral elevation an approach-oriented emotion?

PubMed Central

Van de Vyver, Julie; Abrams, Dominic

2017-01-01

Abstract Two studies were designed to test whether moral elevation should be conceptualized as an approach-oriented emotion. The studies examined the relationship between moral elevation and the behavioral activation and inhibition systems. Study 1 (N = 80) showed that individual differences in moral elevation were associated with individual differences in behavioral activation but not inhibition. Study 2 (N = 78) showed that an elevation-inducing video promoted equally high levels of approach orientation as an anger-inducing video and significantly higher levels of approach orientation than a control video. Furthermore, the elevation-inducing stimulus (vs. the control condition) significantly promoted prosocial motivation and this effect was sequentially mediated by feelings of moral elevation followed by an approach-oriented state. Overall the results show unambiguous support for the proposal that moral elevation is an approach-oriented emotion. Applied and theoretical implications are discussed. PMID:28191027

Quantification of the effects of audible rattle and source type on the human response to environmental vibration.

PubMed

Woodcock, J; Sica, G; Peris, E; Sharp, C; Moorhouse, A T; Waddington, D C

2016-03-01

The present research quantifies the influence of source type and the presence of audible vibration-induced rattle on annoyance caused by vibration in residential environments. The sources of vibration considered are railway and the construction of a light rail system. Data were measured in the United Kingdom using a socio-vibration survey (N = 1281). These data are analyzed using ordinal logit models to produce exposure-response relationships describing community annoyance as a function of vibration exposure. The influence of source type and the presence of audible vibration-induced rattle on annoyance are investigated using dummy variable analysis, and quantified using odds-ratios and community tolerance levels. It is concluded that the sample population is more likely to express higher levels of annoyance if the vibration source is construction compared to railway, and if vibration-induced rattle is audible.

Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice.

PubMed

Kim, Juyoung; Kim, Juhae; Kwon, Young Hye

2016-08-01

Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including LXRα, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

Improved antitumor activity and reduced cardiotoxicity of epirubicin using hepatocyte-targeted nanoparticles combined with tocotrienols against hepatocellular carcinoma in mice.

PubMed

Nasr, Magda; Nafee, Noha; Saad, Hoda; Kazem, Amani

2014-09-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Epirubicin (EPI), an anthracycline derivative, is one of the main line treatments for HCC. However, serious side effects including cardiomyopathy and congestive heart failure limit its long term administration. Our main goal is to develop a delivery strategy that ensures improved efficacy of the chemotherapeutic agent together with reduced cardiotoxicity. In this context, EPI was loaded in chitosan-PLGA nanoparticles linked with asialofetuin (EPI-NPs) selectively targeting hepatocytes. In an attempt to reduce cardiotoxicity, targeted EPI-NPs were coadministered with tocotrienols. EPI-NPs significantly enhanced the antiproliferative effect compared to free EPI as studied on Hep G2 cell line. Nanoencapsulated EPI injected in HCC mouse model revealed higher p53-mediated apoptosis and reduced angiogenesis in the tumor. Combined therapy of EPI-NPs with tocotrienols further enhanced apoptosis and reduced VEGF level in a dose dependent manner. Assessment of cardiotoxicity indicated that EPI-NPs diminished the high level of proinflammatory cytokine tumor necrosis factor-α (TNF-α) as well as oxidative stress-induced cardiotoxicity as manifested by reduced level of lipid peroxidation products (TBARS) and nitric oxide (NO). EPI-NPs additionally restored the diminished level of superoxide dismutase (SOD) and reduced glutathione (GSH) in the heart. Interestingly, tocotrienols provided both antitumor activity and higher protection against oxidative stress and inflammation induced by EPI in the heart. This hepatocyte-targeted biodegradable nanoparticle/tocotrienol combined therapy represents intriguing therapeutic strategy for EPI providing not only superior efficacy but also higher safety levels. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2012-01-01

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

Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.

PubMed

Bhatt, Parloop; Makwana, Dharmesh; Santani, Devdas; Goyal, Ramesh

2007-05-01

The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.

The role of soluble tumor necrosis factor like weak inducer of apoptosis and interleukin-17A in the etiopathogenesis of celiac disease

PubMed Central

Yuksel, Mahmut; Kaplan, Mustafa; Ates, Ihsan; Kilic, Zeki Mesut Yalın; Kilic, Hasan; Suna, Nuretdin; Ates, Hale; Kayacetin, Ertugrul

2016-01-01

Abstract Our aim in this study was to determine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) and interleukin-17A (IL-17A) levels in celiac disease, and their association with the gluten diet and autoantibodies. Eighty patients with celiac diagnosis and 80 healthy control individuals with similar age, gender and body mass index to the patient group were included in the study. Serum sTWEAK and IL-17A levels were measured by the serum enzyme-linked immunosorbent assay kit. The median IL-17A (117.5 pg/mL vs. 56.7 pg/mL; P = 0.001) level in celiac patients was higher than in the control group, while the median sTWEAK (543 pg/mL vs. 643 pg/mL; P = 0.016) level in patients was determined to be lower. In the patient group, patients who complied with the gluten diet had a lower level of median IL-17A (98.1 pg/mL vs. 197.5 pg/mL; P = 0.034) and a higher level of sTWEAK (606 pg/mL vs. 522.8 pg/mL; P = 0.031) than those who did not adhere. Furthermore, the IL-17A level was higher and the sTWEAK level was lower in celiac patients with positive antibody than those with negative antibody. A positive correlation was determined among anti-gliadin antibody IgA, anti-gliadin antibody IgG, anti-tissue transglutaminase IgG levels and the IL-17A level, and a negative correlation was determined with the sTWEAK level. In celiac disease, the sTWEAK and IL-17A levels differ between patients who cannot adapt to the gluten diet and who are autoantibody positive, and patients who adapt to the diet and are autoantibody negative. We believe that sTWEAK and IL-17A are associated with the inflammation in celiac pathogenesis. PMID:27367991

5,7-Dimethoxycoumarin prevents chronic mild stress induced depression in rats through increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

PubMed

Yang, Wei; Wang, Huanlin

2018-02-01

The current study was aimed to investigate the role of 5,7-dimethoxycoumarin in the prevention of chronic mild stress induced depression in rats. The chronic mild stress rat model was prepared using the known protocols. The results from open-field test showed that rats in the chronic mild stress group scored very low in terms of crossings and rearings than those of the normal rats. However, pre-treatment of the rats with 10 mg/kg doses of 5,7-dimethoxycoumarin prevented decline in the locomotor activity by chronic mild stress. The level of monoamine oxidase-A in the chronic mild stress rat hippocampus was markedly higher. Chronic mild stress induced increase in the monoamine oxidase-A level was inhibited by pre-treatment with 10 mg/kg doses of 5,7-dimethoxycoumarin in the rats. Chronic mild stress caused a marked increase in the level of caspase-3 mRNA and proteins in rat hippocampus tissues. The increased level of caspase-3 mRNA and protein level was inhibited by treatment of rats with 5,7-dimethoxycoumarin (10 mg/kg). 5,7-Dimethoxycoumarin administration into the rats caused a marked increase in the levels of heat shock protein-70 mRNA and protein. The levels of heat shock protein-70 were markedly lower both in normal and chronic mild stress groups of rats compared to the 5,7-dimethoxycoumarin treated groups. Thus 5,7-dimethoxycoumarin prevented the chronic mild stress induced depression in rats through an increase in the expression of heat shock protein-70 and inhibition of monoamine oxidase-A levels.

An elevated level of copper zinc superoxide dismutase fails to prevent oxygen induced retinopathy in mice.

PubMed

Klaeger, C; de Sa, L; Klaeger, A J; Carlson, E J; Good, W V; Epstein, C J

1996-05-01

To determine whether a higher level of copper zinc superoxide dismutase (CuZnSOD) can reduce the severity of oxygen induced retinopathy (OIR) in a mouse model. CuZnSOD transgenic mice with a threefold increase in CuZnSOD activity and control non-transgenic mice were exposed to 90% oxygen for 12 hours a day during the first 5 days of life. After oxygen treatment, all mice were reared in room air for 10 days. Another group of transgenic and non-transgenic mice were kept in room air for 15 days and served as control groups for the oxygen effect. At day 15, all mice were killed and perfused with India ink. The retinas were flat mounted on slides and examined with a light microscope. There was a statistically significant increase in the incidence of OIR in mice exposed to high levels of oxygen, whether or not they were transgenic. However, there was no statistically significant difference in the severity of OIR between oxygen treated transgenic and non-transgenic mice. A threefold higher CuZnSOD activity does not protect against OIR in mice. This is an unexpected finding, since oxygen radicals are considered a major factor causing OIR, and increased CuZnSOD activity has reduced oxygen radical induced damage in several neuronal and non-neuronal systems. The possibility of a damaging role for other radicals not affected by CuZnSOD cannot be excluded.

ω-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone Marrow Stimulation in Mice.

PubMed

Murakami, Kohei; Miyata, Hiroshi; Miyazaki, Yasuhiro; Makino, Tomoki; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-07-01

ω-3 Fatty acids exert several benefits during chemotherapy, such as preventing intestinal mucosal damage and improving response to chemotherapy. However, little is known about the effect of ω-3 fatty acids on chemotherapy-induced hematological toxicities. Mice that had consumed either an ω-3-rich or an ω-3-poor diet for 2 weeks were intraperitoneally administered cisplatin. The resultant changes in blood cell count, bone marrow cell count, and cytokine levels in bone marrow supernatant were analyzed. The effect of ω-3 fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to cisplatin was also examined. Although peripheral blood cell counts decreased after cisplatin treatment in both groups of mice, the decrease in white blood cell count was significantly lower in mice that consumed the ω-3-rich diet. The decrease in bone marrow cells after cisplatin treatment was also reduced in mice that consumed the ω-3-rich diet. Levels of stem cell factor (SCF) and fibroblast growth factor 1 (FGF-1) were significantly higher in bone marrow supernatants from mice that consumed the ω-3-rich diet. The rate of apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing ω-3 fatty acids was significantly lower than in PBMCs cultured in control medium. ω-3-Rich diets reduced chemotherapy-induced leukopenia in mice. This may be the result of increased numbers of bone marrow cells due to higher levels of SCF and FGF-1 in the bone marrow.

Latent Herpes Simplex Virus 1 Infection Does Not Induce Apoptosis in Human Trigeminal Ganglia

PubMed Central

Lindemann, Anja; Sinicina, Inga; Strupp, Michael; Brandt, Thomas; Hüfner, Katharina

2015-01-01

Herpes simplex virus 1 (HSV-1) can establish lifelong latency in human trigeminal ganglia. Latently infected ganglia contain CD8+ T cells, which secrete granzyme B and are thus capable of inducing neuronal apoptosis. Using immunohistochemistry and single-cell reverse transcription-quantitative PCR (RT-qPCR), higher frequency and transcript levels of caspase-3 were found in HSV-1-negative compared to HSV-1-positive ganglia and neurons, respectively. No terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay-positive neurons were detected. The infiltrating T cells do not induce apoptosis in latently infected neurons. PMID:25762734

An exploratory study of linguistic-colour associations across languages in multilingual synaesthetes.

PubMed

Barnett, Kylie J; Feeney, Joanne; Gormley, Michael; Newell, Fiona N

2009-07-01

In one of the most common forms of synaesthesia, linguistic-colour synaesthesia, colour is induced by stimuli such as numbers, letters, days of the week, and months of the year. It is not clear, however, whether linguistic-colour synaesthesia is determined more by higher level semantic information--that is, word meaning--or by lower level grapheme or phoneme structure. To explore this issue, we tested whether colour is consistently induced by grapheme or phoneme form or word meaning in bilingual and trilingual linguistic-colour synaesthetes. We reasoned that if the induced colour was related to word meaning, rather than to the acoustic or visual properties of the words, then the induced colours would remain consistent across languages. We found that colours were not consistently related to word meaning across languages. Instead, induced colours were more related to form properties of the word across languages, particularly visual structure. However, the type of inducing stimulus influenced specific colour associations. For example, colours to months of the year were more consistent across languages than were colours to numbers or days of the week. Furthermore, the effect of inducing stimuli was also associated with the age of acquisition of additional languages. Our findings are discussed with reference to a critical period in language acquisition on synaesthesia.

Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant.

PubMed

Tjiurutue, Muvari Connie; Sandler, Hilary A; Kersch-Becker, Monica F; Theis, Nina; Adler, Lynn A

2016-02-01

Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics.

Large splenic volume may be a useful predictor for partial splenic embolization-induced liver functional improvement in cirrhotic patients.

PubMed

Hayashi, Hiromitsu; Beppu, Toru; Masuda, Toshiro; Okabe, Hirohisa; Imai, Katsunori; Hashimoto, Daisuke; Ikuta, Yoshiaki; Chikamoto, Akira; Watanabe, Masayuki; Baba, Hideo

2014-01-01

Partial splenic embolization (PSE) for cirrhotic patients has been reported not only to achieve an improvement in thrombocytopenia and portal hypertension, but also to induce PSE-associated fringe benefit such as individual liver functional improvement. The purpose of this study was to clarify the predictive marker of liver functional improvement due from PSE in cirrhotic patients. From April 1999 to January 2009, 83 cirrhotic patients with hypersplenism-induced thrombocytopenia (platelet count <10 × 10(4)/μl) underwent PSE. Of them, 71 patients with follow-up for more than one year after PSE were retrospectively investigated. In liver tissues after PSE, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were remarkably increased, speculating that PSE induced liver regenerative response. Indeed, serum albumin and cholinesterase levels increased to 104 ± 14% and 130 ± 65% each of the pretreatment level at one year after PSE. In a multiple linear regression analysis, preoperative splenic volume was extracted as the predictive factor for the improvement in cholinesterase level after PSE. Cirrhotic patients with preoperative splenic volume >600 ml obtained significantly higher serum albumin and cholinesterase levels at one year after PSE compared to those with less than 600 ml (P-values were 0.029 in both). A large preoperative splenic volume was the useful predictive marker for an effective PSE-induced liver functional improvement. © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Pulmonary serotonin and histamine in experimental asbestosis

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

Keith, I.M.; Day, R.; Lemaire, S.

1986-03-01

Adult male Wistar rats were treated once with tracheal instillation of 5 mg Crysotile B asbestos fibers in 0.5 ml saline under ketamine/xylaxine anesthesia. Control rats (n = 37) received 0.5 ml saline. Test and control rats were killed at 7 and 14 d., and 1, 3 and 6 mo. post instillation. Serotonin (5-HT) was quantitated in lung tissue homogenate from all rats using HPLC and electrochemical detection. Among rats killed at 1, 3 and 6 mo., lung tissue histamine-o-phthaldialdehyde complex was quantitated using reverse phase HPLC coupled to a fluorometric detector. Furthermore, 5-HT was quantitated in the cytoplasm ofmore » grouped (NEB) and individual (NEC) neuroendocrine cells and in mast cells using formaldehyde-vapor-induced fluorescence and microspectrofluorometry, and mast cell numbers were determined. Test rats had higher pulmonary 5-HT and histamine levels than controls at 1, 3 and 6 mo. Test rats also had higher cellular 5-HT compared to controls in NEB's at 1 mo., but not in NECs, and tended to have higher 5-HT-levels in mast cells at 6 mo. Mast cell numbers were higher among tests at 1 and 3 mo. The authors results suggest that NEBs may contribute to the early asbestos induced rise in 5-HT, and that the major source of 5-HT and histamine is from the increased numbers of mast cells.« less

Mental stress induces sustained elevation of blood pressure and lipid peroxidation in postmenopausal women.

PubMed

Morimoto, Keiko; Morikawa, Mayuko; Kimura, Hiroko; Ishii, Nobuko; Takamata, Akira; Hara, Yasuko; Uji, Masami; Yoshida, Ken-Ichi

2008-01-02

Mental stress is thought to underlie cardiovascular events, but there is information on oxidative stress induced by mental stress in association with cardiovascular responses in women. Using a sensitive assay for plasma 4-hydroxy-2-nonenal (HNE), as a marker for oxidative stress, we addressed the relation between pressor responses and oxidative stress induced by mental or physical stress in premenopausal and postmenopausal women. Healthy subjects (7 postmenopausal and 8 premenopausal women, in early and late follicular phases) were subjected to mental and physical stress evoked by a Color Word Test (CWT) and isometric handgrip, respectively. The CWT induced a rapid elevation of diastolic blood pressure (DBP), at a higher level in the postmenopausal than in the premenopausal women (p<0.01), and this higher DBP was sustained during the CWT and recovery (p<0.01). The CWT induced a significant elevation in plasma noradrenaline in premenopausal women in the early follicular phase and in postmenopausal women (p<0.05). Plasma nitric oxide metabolites were higher in postmenopausal than in the premenopausal women in the late follicular phase (p<0.05), but did not change during exposure to the two types of stress in either group. Plasma HNE was increased during recovery from the CWT, but not the handgrip, in postmenopausal women (2.4 times, p<0.05). There was a significant difference in the time course of the CWT-induced HNE response between the postmenopausal and premenopausal women (p<0.05). These findings suggest that mental, but not physical, stress causes sustained diastolic blood pressure elevation in postmenopausal women, accompanied by heightened oxidative stress.

Interaction between Cucumber mosaic virus 2b protein and plant catalase induces a specific necrosis in association with proteasome activity.

PubMed

Murota, Katsunori; Shimura, Hanako; Takeshita, Minoru; Masuta, Chikara

2017-01-01

Cucumber mosaic virus (CMV) can induce a specific necrosis on Arabidopsis through the interaction between the CMV 2b protein and host catalase, in which the ubiquitin-proteasome pathway may be involved. We previously reported that the CMV 2b protein, the viral RNA silencing suppressor, interacted with the H 2 O 2 scavenger catalase (CAT3), leading to necrosis on CMV-inoculated Arabidopsis leaves. We here confirmed that CMV could more abundantly accumulate in the CAT3-knockout mutant (cat3), and that CAT3 makes host plants a little more tolerant to CMV. We also found that the necrosis severity is not simply explained by a high level of H 2 O 2 given by the lack of CAT3, because the recombinant CMV, CMV-N, induced much milder necrosis in cat3 than in the wild type, suggesting some specific mechanism for the necrosis induction. To further characterize the 2b-inducing necrosis in relation to its binding to CAT3, we conducted the agroinfiltration experiments to overexpress CAT3 and 2b in N. benthamiana leaves. The accumulation levels of CAT3 were higher when co-expressed with the CMV-N 2b (N2b) than with CMV-Y 2b (Y2b). We infer that N2b made a more stable complex with CAT3 than Y2b did, and the longevity of the 2b-CAT3 complex seemed to be important to induce necrosis. By immunoprecipitation (IP) with an anti-ubiquitin antibody followed by the detection with anti-CAT3 antibodies, we detected a higher molecular-weight smear and several breakdown products of CAT3 among the IP-proteins. In addition, the proteasome inhibitor MG132 treatment could actually increase the accumulation levels of CAT3. This study suggests that the host proteasome pathway is, at least partially, responsible for the degradation of CAT3, which is manifested in CMV-infected tissues.

[Analysis on content of serum monoamine neurotransmitters in macaques with anger-in-induced premenstrual syndrome and liver-qi depression syndrome].

PubMed

Wei, Sheng; Hou, Jin-Liang; Chao, Yu-Bin; Du, Xi-Yang; Zong, Shao-Bo

2012-08-01

To observe the changes in content of monoamine neurotransmitters in the serum of rhesus macaques, and explore the role of serum monoamine neurotransmitters in premenstrual syndrome (PMS) and liver-qi depression induced by anger-in emotion. Social level pressure was applied on 24 female macaques to induce the angry emotional reaction, and then nine of the low-status macaques with anger-in emotional reaction were screened out and were divided into anger-in emotion group, PMS and liver-qi depression group (model group) and Jingqianshu Granule group. Macaques in the last two groups were suffered extruding in a pack cage for inducing PMS liver-qi depression. After 5 d of extruding, experimental animals were evaluated according to the emotional evaluation scale, meanwhile, macaque serum of follicular phase and middle-late luteal phase was collected to analyze the content of serum norepinephrine, dopamine, and 5-hydroxytryptamine. Compared with the normal control group, the scores of depression of the model group and the anger-in emotion group evaluated with emotional evaluation scale were significantly increased (P<0.01, P<0.05); while the score of the model group was significantly higher than that of the anger-in emotion group (P<0.05), and it returned to normal after Jingqianshu Granule treatment. As compared to the normal control group, serum monoamine neurotransmitter levels of the model group and the anger-in emotion group were increased (P<0.05, P<0.01), and the serum monoamine neurotransmitter levels of the model group were significantly higher than those of the anger-in emotion group (P<0.05), while there was no significant difference when compared with the normal control group after the treatment. Anger-in emotion can induce liver-qi depression syndrome which is related to the changes in monoamine neurotransmitters.

Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

PubMed

Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

2017-01-01

Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of platelet-expressed FVIII than are required for therapeutic efficacy in hemophilia A are not associated with a thrombotic predilection. © 2016 International Society on Thrombosis and Haemostasis.

Proteomic identification of OsCYP2, a rice cyclophilin that confers salt tolerance in rice (Oryza sativa L.) seedlings when overexpressed

PubMed Central

2011-01-01

Background High Salinity is a major environmental stress influencing growth and development of rice. Comparative proteomic analysis of hybrid rice shoot proteins from Shanyou 10 seedlings, a salt-tolerant hybrid variety, and Liangyoupeijiu seedlings, a salt-sensitive hybrid variety, was performed to identify new components involved in salt-stress signaling. Results Phenotypic analysis of one protein that was upregulated during salt-induced stress, cyclophilin 2 (OsCYP2), indicated that OsCYP2 transgenic rice seedlings had better tolerance to salt stress than did wild-type seedlings. Interestingly, wild-type seedlings exhibited a marked reduction in maximal photochemical efficiency under salt stress, whereas no such change was observed for OsCYP2-transgenic seedlings. OsCYP2-transgenic seedlings had lower levels of lipid peroxidation products and higher activities of antioxidant enzymes than wild-type seedlings. Spatiotemporal expression analysis of OsCYP2 showed that it could be induced by salt stress in both Shanyou 10 and Liangyoupeijiu seedlings, but Shanyou 10 seedlings showed higher OsCYP2 expression levels. Moreover, circadian rhythm expression of OsCYP2 in Shanyou 10 seedlings occurred earlier than in Liangyoupeijiu seedlings. Treatment with PEG, heat, or ABA induced OsCYP2 expression in Shanyou 10 seedlings but inhibited its expression in Liangyoupeijiu seedlings. Cold stress inhibited OsCYP2 expression in Shanyou 10 and Liangyoupeijiu seedlings. In addition, OsCYP2 was strongly expressed in shoots but rarely in roots in two rice hybrid varieties. Conclusions Together, these data suggest that OsCYP2 may act as a key regulator that controls ROS level by modulating activities of antioxidant enzymes at translation level. OsCYP2 expression is not only induced by salt stress, but also regulated by circadian rhythm. Moreover, OsCYP2 is also likely to act as a key component that is involved in signal pathways of other types of stresses-PEG, heat, cold, or ABA. PMID:21324151

High atmospheric carbon dioxide-dependent alleviation of salt stress is linked to RESPIRATORY BURST OXIDASE 1 (RBOH1)-dependent H2O2 production in tomato (Solanum lycopersicum).

PubMed

Yi, Changyu; Yao, Kaiqian; Cai, Shuyu; Li, Huizi; Zhou, Jie; Xia, Xiaojian; Shi, Kai; Yu, Jingquan; Foyer, Christine Helen; Zhou, Yanhong

2015-12-01

Plants acclimate rapidly to stressful environmental conditions. Increasing atmospheric CO2 levels are predicted to influence tolerance to stresses such as soil salinity but the mechanisms are poorly understood. To resolve this issue, tomato (Solanum lycopersicum) plants were grown under ambient (380 μmol mol(-1)) or high (760 μmol mol(-1)) CO2 in the absence or presence of sodium chloride (100mM). The higher atmospheric CO2 level induced the expression of RESPIRATORY BURST OXIDASE 1 (SlRBOH1) and enhanced H2O2 accumulation in the vascular cells of roots, stems, leaf petioles, and the leaf apoplast. Plants grown with higher CO2 levels showed improved salt tolerance, together with decreased leaf transpiration rates and lower sodium concentrations in the xylem sap, vascular tissues, and leaves. Silencing SlRBOH1 abolished high CO2 -induced salt tolerance and increased leaf transpiration rates, as well as enhancing Na(+) accumulation in the plants. The higher atmospheric CO2 level increased the abundance of a subset of transcripts involved in Na(+) homeostasis in the controls but not in the SlRBOH1-silenced plants. It is concluded that high atmospheric CO2 concentrations increase salt stress tolerance in an apoplastic H2O2 dependent manner, by suppressing transpiration and hence Na(+) delivery from the roots to the shoots, leading to decreased leaf Na(+) accumulation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Processing of whey modulates proliferative and immune functions in intestinal epithelial cells.

PubMed

Nguyen, Duc Ninh; Sangild, Per T; Li, Yanqi; Bering, Stine B; Chatterton, Dereck E W

2016-02-01

Whey protein concentrate (WPC) is often subjected to heat treatment during industrial processing, resulting in protein denaturation and loss of protein bioactivity. We hypothesized that WPC samples subjected to different degrees of thermal processing are associated with different levels of bioactive proteins and effects on proliferation and immune response in intestinal epithelial cells (IEC). The results showed that low-heat-treated WPC had elevated levels of lactoferrin and transforming growth factor-β2 compared with that of standard WPC. The level of aggregates depended on the source of whey, with the lowest level being found in WPC derived from acid whey. Following acid activation, WPC from acid whey enhanced IEC proliferation compared with WPC from sweet whey or nonactivated WPC. Low-heat-treated WPC from acid whey induced greater secretion of IL-8 in IEC than either standard WPC from acid whey or low-heat-treated WPC from sweet whey. Following acid activation (to activate growth factors), low-heat-treated WPC from sweet whey induced higher IL-8 levels in IEC compared with standard WPC from sweet whey. In conclusion, higher levels of bioactive proteins in low-heat-treated WPC, especially from acid whey, may enhance proliferation and cytokine responses of IEC. These considerations could be important to maintain optimal bioactivity of infant formulas, including their maturational and immunological effects on the developing intestine. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Incorporating "omics" in the study of reproduction and development: Virtual Tissue Models in Developmental Toxicity Research

EPA Science Inventory

In recent years, ground breaking research in genomic applications in the area of reproductive and developmental toxicology have been successful in linking changes in the expression of specific genes and their higher-level biological processes to effects induced by drugs or chemic...

Cellular defense against UVB-induced phototoxicity by cytosolic NADP(+)-dependent isocitrate dehydrogenase.

PubMed

Jo, Seung-Hee; Lee, So-Hyun; Chun, Hang Suk; Lee, Su Min; Koh, Ho-Jin; Lee, Sung-Eun; Chun, Jang-Soo; Park, Jeen-Woo; Huh, Tae-Lin

2002-03-29

Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP(+)-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study we investigated the role of cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc) against UV radiation-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to UVB (312 nm), the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly overexpressed IDPc exhibited enhanced resistance against UV radiation, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against UV radiation-induced oxidative injury. (c)2002 Elsevier Science (USA).

Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

PubMed

Kim, Sun Yee; Park, Jeen-Woo

2003-03-01

Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients

PubMed Central

Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J.; Kiferle, Lorenzo; Turkheimer, Federico E.; Bain, Peter; Molloy, Sophie; Piccini, Paola

2014-01-01

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7.

PubMed

Ruocco, Nadia; Varrella, Stefano; Romano, Giovanna; Ianora, Adrianna; Bentley, Matt G; Somma, Domenico; Leonardi, Antonio; Mellone, Stefano; Zuppa, Antonio; Costantini, Maria

2016-07-01

Diatoms are an important class of unicellular algae that produce bioactive secondary metabolites with cytotoxic activity collectively termed oxylipins, including polyunsaturated aldehydes (PUAs), hydroxyacids (HEPEs), oxo-acids and epoxyalcohols. Previous results showed that at higher concentrations, the PUA decadienal induced apoptosis on copepods and sea urchin embryos via caspase-3 activation; at lower concentrations decadienal affected the expression levels of the caspase-8 gene in embryos of the sea urchin Paracentrotus lividus. In the present work, we studied the effects of other common oxylipins produced by diatoms: two PUAs (heptadienal and octadienal) and four hydroxyacids (5-, 9- 11- and 15-HEPE) on P. lividus cell death and caspase activities. Our results showed that (i) at higher concentrations PUAs and HEPEs induced apoptosis in sea urchin embryos, detected by microscopic observation and through the activation of caspase-3/7 and caspase-8 measured by luminescent assays; (ii) at low concentrations, PUAs and HEPEs affected the expression levels of caspase-8 and caspase-3/7 (isolated for the first time here in P. lividus) genes, detected by Real Time qPCR. These findings have interesting implications from the ecological point of view, given the importance of diatom blooms in nutrient-rich aquatic environments. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic effects of tributyltin on multiple biomarkers responses in juvenile common carp, Cyprinus carpio.

PubMed

Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

2016-08-01

In this study, the chronic toxic effects of tributyltin (TBT), an antifouling paints commonly present in surface and ground water, on morphological indices, reactive oxygen species (ROS) generation, and ATPase activity and heat shock protein (Hsp) 70 protein in tissues (liver, gill, and white muscle) of common carp were investigated. Fish were exposed at sublethal concentrations of TBT (75 ng/L, 0.75 μg/L, and 7.5 μg/L) for 60 days. When compared with the control, there was significant lower condition factor in fish exposed at the higher concentration of TBT. ROS levels in three tissues increased significantly at higher TBT concentrations (0.75 and 7.5 μg/L). The hepatic antioxidant enzymes (total antioxidative capacity and superoxide dismutase) activities were induced at higher concentrations (0.75 μg/L) of TBT. When compared with the hepatic antioxidant enzymes activities in fish exposed to 0.75 μg/L of TBT, there was a decreasing trend in those exposed to TBT with a concentration of 7.5 μg/L. However, all the antioxidant enzymes activities were significantly inhibited in gill and muscle of fish exposed to higher TBT concentrations (0.75 and 7.5 μg/L). Moreover, there was significant lower Na-K-ATPase in three tissues after long-term exposure to higher concentration of TBT, but a significant higher Hsp70 protein levels was observed. In short, environmental concentrations of TBT could not induce obvious impacts on fish, but long-term exposure to higher concentrations of TBT could affect seriously the health status of fish. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 937-944, 2016. © 2015 Wiley Periodicals, Inc.

Predictive value of the complement system for sepsis-induced disseminated intravascular coagulation in septic patients in emergency department.

PubMed

Zhao, Xin; Chen, Yun-Xia; Li, Chun-Sheng

2015-04-01

To investigate changes in circulating complement component C3, membrane attack complex (MAC), and mannose-binding lectin (MBL) in patients with sepsis-induced disseminated intravascular coagulation (DIC). Adult septic patients admitted to the emergency department (ED) of Beijing Chao-Yang Hospital were enrolled. A DIC score of 5 or higher was considered sepsis-induced DIC. Circulating C3, MAC, and MBL levels were detected on ED arrival and compared between patients with and without DIC. The predictive value of C3, MAC, and MBL for sepsis-induced DIC at ED arrival and development of DIC after admission were assessed by receiver operating characteristic curve and logistic regression. We enrolled 267 septic patients between February and December 2013. Complement 3, MAC, and MBL were higher in the DIC group (P < .01). Membrane attack complex was the independent predictor of sepsis-induced DIC. The area under the curve of MAC in predicting sepsis-induced DIC was 0.793. During hospitalization, 25 patients without DIC at enrollment developed DIC. Membrane attack complex and Sequential Organ Failure Assessment independently predicted progress to DIC. The area under the curve of MAC was 0.741. Complement 3, MAC, and MBL were significantly increased in septic patients with DIC. Membrane attack complex independently predicted sepsis-induced DIC and development of DIC after ED admission. Copyright © 2014 Elsevier Inc. All rights reserved.

Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

PubMed

Mesa-Gresa, Patricia; Ramos-Campos, Marta; Redolat, Rosa

2016-05-01

Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant: animals allocated in EE during Phase I of the study showed higher corticosterone levels, lower body weight and higher fluid intake than SE mice. "Initial Stress" had significant long-term actions on food intake and exploratory behavior: animals initially reared under stress conditions displayed higher food intake and lower exploration levels on the hole-board test than non-stressed mice. In the elevated plus-maze, there were significant interactions between factors "Initial Housing" and "Initial Stress". These factors did not reach statistical significance for motor activity or learning task. We can conclude that both short- and long-term effects of housing conditions are evident for corticosterone levels, body weight and fluid intake. Social stress induced short-term effects on body weight, food and fluid intake and exploratory behavior whereas long-acting effects were reflected on food intake and exploratory behavior. Further studies are needed in order to explore more in depth behavioral and physiological consequences of social stress and environmental enrichment. Copyright © 2016. Published by Elsevier Inc.

Myocardial blood flow and its transit time, oxygen utilization, and efficiency of highly endurance-trained human heart.

PubMed

Heinonen, Ilkka; Kudomi, Nobuyuki; Kemppainen, Jukka; Kiviniemi, Antti; Noponen, Tommi; Luotolahti, Matti; Luoto, Pauliina; Oikonen, Vesa; Sipilä, Hannu T; Kopra, Jaakko; Mononen, Ilkka; Duncker, Dirk J; Knuuti, Juhani; Kalliokoski, Kari K

2014-07-01

Highly endurance-trained athlete's heart represents the most extreme form of cardiac adaptation to physical stress, but its circulatory alterations remain obscure. In the present study, myocardial blood flow (MBF), blood mean transit time (MTT), oxygen extraction fraction (OEF) and consumption (MVO2), and efficiency of cardiac work were quantified in highly trained male endurance athletes and control subjects at rest and during supine cycling exercise using [(15)O]-labeled radiotracers and positron emission tomography. Heart rate and MBF were lower in athletes both at rest and during exercise. OEF increased in response to exercise in both groups, but was higher in athletes (70 ± 21 vs. 63 ± 11 % at rest and 86 ± 13 vs. 73 ± 10 % during exercise). MTT was longer and vascular resistance higher in athletes both at rest and during exercise, but arterial content of 2,3-diphosphoglycerate (oxygen affinity) was unchanged. MVO2 per gram of myocardium trended (p = 0.08) lower in athletes both at rest and during exercise, while myocardial efficiency of work and MVO2 per beat were not different between groups. Arterial levels of free fatty acids were ~twofold higher in athletes likely leading to higher myocardial fatty acid oxidation and hence oxygen cost, which may have blunted the bradycardia-induced decrease in MVO2. Finally, the observed group differences in MBF, OEF, MTT and vascular resistance remained significant also after they were controlled for differences in MVO2. In conclusion, in highly endurance-trained human heart, increased myocardial blood transition time enables higher oxygen extraction levels with a lower myocardial blood flow and higher vascular resistance. These physiological adaptations to exercise training occur independently of the level of oxygen consumption and together with training-induced bradycardia may serve as mechanisms to increase functional reserve of the human heart.

Type-1 polarised dendritic cells are a potent immunogen against Mycobacterium tuberculosis.

PubMed

Satake, Y; Nakamura, Y; Kono, M; Hozumi, H; Nagata, T; Tsujimura, K; Enomoto, N; Fujisawa, T; Inui, N; Fujiyama, T; Tokura, Y; Matsui, T; Yokomura, K; Shirai, M; Hayakawa, H; Suda, T

2017-05-01

Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6). Although DC1s from TB patients expressed the same levels of multiple co-stimulatory molecules (CD83, CD86, CD80 and CD40) as the standard DCs (sDCs), DC1s secreted substantially higher levels of IL-12p70. Furthermore, when DCs pulsed with or without ESAT-6 were cultured with lymphocytes from the same patients, DC1s induced much higher numbers of ESAT-6-specific IFN-γ-producing T-cells than sDCs, as manifested by their superior induction of natural killer cell activation and antigen-independent suppression of regulatory T-cells. TB antigen-loaded DC1s are potent inducers of antigen-specific T-cells, which could be used to develop improved immunotherapies of TB.

Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway.

PubMed

Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

2014-02-18

Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU.

Loss of Smad4 in colorectal cancer induces resistance to 5-fluorouracil through activating Akt pathway

PubMed Central

Zhang, B; Zhang, B; Chen, X; Bae, S; Singh, K; Washington, M K; Datta, P K

2014-01-01

Background: Higher frequency of Smad4 inactivation or loss of expression is observed in metastasis of colorectal cancer (CRC) leading to unfavourable survival and contributes to chemoresistance. However, the molecular mechanism of how Smad4 regulates chemosensitivity of CRC is unknown. Methods: We evaluated how the loss of Smad4 in CRC enhanced chemoresistance to 5-fluorouracil (5-FU) using two CRC cell lines in vitro and in vivo. Immunoblotting with cell and tumour lysates and immunohistochemical analyses with tissue microarray were performed. Results: Knockdown or loss of Smad4 induced tumorigenicity, migration, invasion, angiogenesis, metastasis, and 5-FU resistance. Smad4 expression in mouse tumours regulated cell-cycle regulatory proteins leading to Rb phosphorylation. Loss of Smad4 activated Akt pathway that resulted in upregulation of anti-apoptotic proteins, Bcl-2 and Bcl-w, and Survivin. Suppression of phosphatidylinositol-3-kinase (PI3K)/Akt pathway by LY294002 restored chemosensitivity of Smad4-deficient cells to 5-FU. Vascular endothelial growth factor-induced angiogenesis in Smad4-deficient cells might also lead to chemoresistance. Low levels of Smad4 expression in CRC tissues correlated with higher levels of Bcl-2 and Bcl-w and with poor overall survival as observed in immunohistochemical staining of tissue microarrays. Conclusion: Loss of Smad4 in CRC patients induces resistance to 5-FU-based therapy through activation of Akt pathway and inhibitors of this pathway may sensitise these patients to 5-FU. PMID:24384683

EGR-1 and DUSP-1 are important negative regulators of pro-allergic responses in airway epithelium.

PubMed

Golebski, Korneliusz; van Egmond, Danielle; de Groot, Esther J; Roschmann, Kristina I L; Fokkens, Wytske J; van Drunen, Cornelis M

2015-05-01

Primary nasal epithelium of house dust mite allergic individuals is in a permanently activated inflammatory transcriptional state. To investigate whether a deregulated expression of EGR-1 and/or DUSP-1, two potential negative regulators of pro-inflammatory responses, could contribute to the activation of the inflammatory state. We silenced the expression of EGR-1 or DUSP-1 in the airway epithelial cell line NCI-H292. The cell lines were stimulated in a 24-h time course with the house dust mite allergen or poly(I:C). RNA expression profiles of cytokines were established using q-PCR and protein levels were determined in supernatants with ELISA. The shRNA-mediated gene silencing reduced expression levels of EGR-1 by 92% (p<0.0001) and of DUSP-1 by 76% (p<0.0001). Both mutant cells lines showed an increased and prolonged response to the HDM allergen. The mRNA induction of IL-6 was 4.6 fold (p=0.02) and 2.4 fold higher (p=0.01) in the EGR-1 and DUSP-1 knock-down, respectively when compared to the induced levels in the control cell line. For IL-8, the induction levels were 4.6 fold (p=0.01) and 13.0 (p=0.001) fold higher. The outcome was largely similar, yet not identical at the secreted protein levels. Furthermore, steroids were able to suppress the poly(I:C) induced cytokine levels by 70-95%. Deregulation of EGR-1 and/or DUSP-1 in nasal epithelium could be responsible for the prolonged activated transcriptional state observed in vivo in allergic disease. This could have clinical consequences as cytokine levels after the steroid treatment in EGR-1 or DUSP-1 knock-down remained higher than in the control cell line. Copyright © 2015 Elsevier Ltd. All rights reserved.

Utility of temporally distinct baculovirus promoters for constitutive and baculovirus-inducible transgene expression in transformed insect cells.

PubMed

Lin, Chi-Hung; Jarvis, Donald L

2013-05-10

Genetically transformed lepidopteran insect cell lines have biotechnological applications as constitutive recombinant protein production platforms and improved hosts for baculovirus-mediated recombinant protein production. Insect cell transformation is often accomplished with a DNA construct(s) encoding a foreign protein(s) under the transcriptional control of a baculovirus immediate early promoter, such as the ie1 promoter. However, the potential utility of increasingly stronger promoters from later baculovirus gene classes, such as delayed early (39K), late (p6.9), and very late (polh), has not been systematically assessed. Hence, we produced DNA constructs encoding secreted alkaline phosphatase (SEAP) under the transcriptional control of each of the four temporally distinct classes of baculovirus promoters, used them to transform insect cells, and compared the levels of SEAP RNA and protein production obtained before and after baculovirus infection. The ie1 construct was the only one that supported SEAP protein production by transformed insect cells prior to baculovirus infection, confirming that only immediate early promoters can be used to isolate transformed insect cells for constitutive recombinant protein production. However, baculovirus infection activated transgene expression by all four classes of baculovirus promoters. After infection, cells transformed with the very late (polh) and late (p6.9) promoter constructs produced the highest levels of SEAP RNA, but only low levels of SEAP protein. Conversely, cells transformed with the immediate early (ie1) and delayed early (39K) promoter constructs produced lower levels of RNA, but equal or higher levels of SEAP protein. Unexpectedly, the 39K promoter construct provided tightly regulated, baculovirus-inducible protein production at higher levels than the later promoter constructs. Thus, this study demonstrated the utility of the 39K promoter for insect cell engineering, particularly when one requires higher levels of effector protein production than obtained with ie1 and/or when constitutive transgene expression adversely impacts host cell fitness and/or genetic stability. Copyright © 2013 Elsevier B.V. All rights reserved.

Vitamin C supplementation does not influence plasma and blood mononuclear cell IL-6 and IL-10 levels after exercise.

PubMed

Aguiló, Antoni; Monjo, Marta; Moreno, Carlos; Martinez, Pau; Martínez, Sonia; Tauler, Pedro

2014-01-01

The aim of this study was to determine whether the highest vitamin C supplementation associated with complete bioavailability influences the plasma and blood mononuclear cell IL-6 and IL-10 response to exercise. A double-blinded study of supplementation with vitamin C was performed. After 15 days of supplementation with vitamin C (500 mg · day(-1), n = 16) or a placebo (n = 15), participants in the study completed a 15-km run competition. Blood samples were taken before and after competition. Oxidative stress markers, antioxidants, cortisol, IL-6 and IL-10 were determined in plasma or serum. IL-6 and IL-10 protein and mRNA levels were measured in blood mononuclear cells. Although higher plasma and blood mononuclear cell vitamin C levels were observed in the supplemented group when compared with the placebo one, the two groups showed identical exercise-induced changes in all the measured parameters. Exercise induced increased IL-6 and IL-10 levels in plasma and blood mononuclear cells. IL-6 and IL-10 mRNA levels in blood mononuclear cells increased after the competition. After recovery, IL-6 mRNA returned to basal levels and IL-10 mRNA levels remained elevated. In conclusion, exercise induced increased IL-6 and IL-10 production in blood mononuclear cells. However, vitamin C supplementation did not influence IL-6 and IL-10 response to exercise.

Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells dose-dependently attenuates hyperoxia-induced lung injury in neonatal rats.

PubMed

Chang, Yun Sil; Choi, Soo Jin; Sung, Dong Kyung; Kim, Soo Yoon; Oh, Wonil; Yang, Yoon Sun; Park, Won Soon

2011-01-01

Intratracheal transplantation of human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuates the hyperoxia-induced neonatal lung injury. The aim of this preclinical translation study was to optimize the dose of human UCB-derived MSCs in attenuating hyperoxia-induced lung injury in newborn rats. Newborn Sprague-Dawley rats were randomly exposed to hyperoxia (95% oxygen) or normoxia after birth for 14 days. Three different doses of human UCB-derived MSCs, 5 × 10(3) (HT1), 5 × 10(4) (HT2), and 5 × 10(5) (HT3), were delivered intratracheally at postnatal day (P) 5. At P14, lungs were harvested for analyses including morphometry for alveolarization, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining, myeoloperoxidase activity, mRNA level of tumor necross factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β), human glyceradehyde-3-phosphate dehydrogenase (GAPDH), and p47(phox), and collagen levels. Increases in TUNEL-positive cells were attenuated in all transplantation groups. However, hyperoxia-induced lung injuries, such as reduced alveolarization, as evidenced by increased mean linear intercept and mean alveolar volume, and increased collagen levels were significantly attenuated in both HT2 and HT3, but not in HT1, with better attenuation in HT3 than in HT2. Dose-dependent human GAPDH expression, indicative of the presence of human RNA in lung tissue, was observed only in the transplantation groups, with higher expression in HT3 than in HT2, and higher expression in HT2 than in HT1. Hyperoxia-induced inflammatory responses such as increased myeloperoxidase acitivity, mRNA levels of TNF-α, IL-1β, IL-6, and TGF-β of the lung tissue, and upregulation of both cytosolic and membrane p47(phox), indicative of oxidative stress, were significantly attenuated in both HT2 and HT3 but not in HT1. These results demonstrate that intratracheal transplantation of human UCB-derived MSCs with appropriate doses may attenuate hyperoxia-induced lung injury through active involvement of these cells in modulating host inflammatory responses and oxidative stress in neonatal rats.

Comparisons of Serum Total IgE, IgG, and IgG1 Levels in Patients with and without Echinococcosis-Induced Anaphylactic Shock

PubMed Central

Li, Yimei; Zheng, Hong; Gu, Meilin; Cao, Xinghua; Wen, Hao; Liu, Zaoling; Liu, Tao

2012-01-01

We investigated serum total immunoglobulin E (IgE), IgG, and IgG1 levels in patients with and without echinococcosis-induced anaphylactic shock. This was a case-control study of 11 patients with echinococcosis-induced anaphylactic shock and 22 echinococcosis patients with cyst rupture but without anaphylactic shock. Blood was collected before surgery (T0), at the time of cyst rupture (T1), and shock (Tx), 1 h (T2), 1 day (T3), and 1 week (T4) after cyst rupture. Serum IgE, IgG, and IgG1 were determined by enzyme-linked immunosorbent assay. Serum IgE, IgG, and IgG1 levels were significantly higher in patients who developed anaphylactic shock at all time points. Increased pre-surgical IgG and IgG1 levels were identified to be a significant risk factors for developing anaphylactic shock. The results showed that a serum IgG concentration of 312.25 μg/mL could be used as a cut-off point to predict whether an echinococcosis patient would develop anaphylactic shock. PMID:22764299

Effect of sample initial magnetic field on the metal magnetic memory NDT result

NASA Astrophysics Data System (ADS)

Moonesan, Mahdi; Kashefi, Mehrdad

2018-08-01

One of the major concerns regarding the use of Metal Magnetic Memory (MMM) technique is the complexity of residual magnetization effect on output signals. The present study investigates the influence of residual magnetic field on stress induced magnetization. To this end, various initial magnetic fields were induced on a low carbon steel sample, and for each level of residual magnetic field, the sample was subjected to a set of 4-point bending tests and, their corresponding MMM signals were collected from the surface of the bended sample using a tailored metal magnetic memory scanning device. Results showed a strong correlation between sample residual magnetic field and its corresponding level of stress induced magnetic field. It was observed that the sample magnetic field increases with applying the bending stress as long as the initial residual magnet field is low (i.e. <117 mG), but starts decreasing with higher levels of initial residual magnetic fields. Besides, effect of bending stress on the MMM output of a notched sample was investigated. The result, again, showed that MMM signals exhibit a drop at stress concentration zone when sample has high level of initial residual magnetic field.

Leptin does not induce an inflammatory response in the murine placenta.

PubMed

Appel, S; Turnwald, E-M; Alejandre-Alcazar, M A; Ankerne, J; Rother, E; Janoschek, R; Wohlfarth, M; Vohlen, C; Schnare, M; Meißner, U; Dötsch, J

2014-06-01

Leptin is described as a pro-inflammatory signal in fat tissue, which is released from adipocytes and in turn activates immune cells. Also, leptin levels are known to be increased in pregnancies complicated with enhanced inflammatory processes in the placenta. Hence, we assumed that increased leptin amounts might contribute to inducing an inflammatory response in the placenta. To test this hypothesis, pregnant mice were continuously infused with recombinant murine leptin s. c. from day g13 to g16, resulting in a 3-fold increase of maternal circulating serum leptin levels. Dissected placentas were examined for the expression of pro-inflammatory cytokines IL-6 and TNF-alpha and the anti-inflammatory cytokine IL-10 using qPCR analysis. No changes were found except for TNF-alpha, which was slightly elevated upon leptin stimulation. However, TNF-alpha protein levels were not significantly higher in placentas from leptin treated mice. Also, leukocyte infiltration in the labyrinth section of placentas was not increased. In summary, our data demonstrate for the first time that elevated leptin levels alone do not induce an inflammatory response in the placenta. © Georg Thieme Verlag KG Stuttgart · New York.

Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes.

PubMed

Tsuzuki, Takamasa; Kobayashi, Hiroyuki; Yoshihara, Toshinori; Kakigi, Ryo; Ichinoseki-Sekine, Noriko; Naito, Hisashi

2017-03-01

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.

Social Isolation-Induced Territorial Aggression in Male Offspring Is Enhanced by Exposure to Diesel Exhaust during Pregnancy

PubMed Central

Yokota, Satoshi; Oshio, Shigeru; Moriya, Nozomu; Takeda, Ken

2016-01-01

Diesel exhaust particles are a major component of ambient particulate matter, and concern about the health effects of exposure to ambient particulate matter is growing. Previously, we found that in utero exposure to diesel exhaust affected locomotor activity and motor coordination, but there are also indications that such exposure may contribute to increased aggression in offspring. Therefore, the aim of the present study was to test the effects of prenatal diesel exhaust exposure on social isolation-induced territorial aggression. Pregnant mice were exposed to low concentrations of diesel exhaust (DE; mass concentration of 90 μg/m3: DE group: n = 15) or clean air (control group: n = 15) for 8 h/day during gestation. Basal locomotion of male offspring was measured at 10 weeks of age. Thereafter, male offspring were individually housed for 2 weeks and subsequently assessed for aggression using the resident−intruder test at 12 weeks of age, and blood and brain tissue were collected from the male offspring on the following day for measuring serum testosterone levels and neurochemical analysis. There were no significant differences in locomotion between control and DE-exposed mice. However, DE-exposed mice showed significantly greater social isolation-induced territorial aggressive behavior than control mice. Additionally, socially-isolated DE-exposed mice expressed significantly higher concentrations of serum testosterone levels than control mice. Neurochemical analysis revealed that dopamine levels in the prefrontal cortex and nucleus accumbens were higher in socially isolated DE-exposed mice. Serotonin levels in the nucleus accumbens, amygdala, and hypothalamus were also lower in the socially isolated DE-exposed mice than in control mice. Thus, even at low doses, prenatal exposure to DE increased aggression and serum testosterone levels, and caused neurochemical changes in male socially isolated mice. These results may have serious implications for pregnant women living in regions with high levels of traffic-related air pollution. PMID:26919122

Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study.

PubMed

Li, Jingxia; Mu, Shuangfeng; Mu, Lixiang; Zhang, Xiaohui; Pang, Ranran; Gao, Shegan

2015-01-01

To examine the relationship between cytokine levels of transforming growth factor-beta-1 (TGF-β1), interleukin-1 beta (IL-1β), and angiotensin-converting enzyme (ACE) in the plasma of esophageal carcinoma patients and radiation-induced pneumonitis (RP). Sixty-three patients with esophageal carcinoma were treated with three-dimensional conformal radiotherapy (RT) using the Elekta Precise treatment planning system with a prescribed dose of 50-70 Gy. Dose-volume histograms were collected from three-dimensional conformal RT to determine the volume percentage of the lung received V5, V10, V20, and the normal tissue complication probability. RP was diagnosed based on computed tomography imaging, respiratory symptoms, and signs. The severity of radiation-induced lung toxicity was determined using the Lent-Soma scale defined by the Radiation Therapy Oncology Group. Plasma samples obtained before RT, during RT (at 40 Gy), and at 1 day, 1 month, and 3 months after RT were assayed for TGF-β1, IL-1β, and ACE levels by enzyme-linked immunosorbent assay. From the 63 patients, 17 (27%) developed RP, and 13 (21%) had RP of grade I and four (6%) had grade II or higher. We found plasma TGF-β1 levels were elevated in the patients that had RP when compared with the other 46 patients who did not have RP. The plasma IL-1β levels were not changed. The ACE levels were significantly lower in the 17 patients with RP compared to the 46 patients without RP throughout the RT. As expected, RP is associated with a higher dose of irradiation (>60 Gy); no other factors, including dose-volume histogram, age, sex, smoking status, location of tumor, and methods of treatment, are associated with RP. Elevated plasma TGF-β1 levels can be used as a marker for RP.

Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

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

Sharma, Som D.; Katiyar, Santosh K., E-mail: skatiyar@uab.ed; Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm{sup 2}) on alternate days for 1 month. The mice were thenmore » euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E{sub 2} production, proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-kappaB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.« less

Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.

PubMed

Sinha, Rajita; Fox, Helen C; Hong, Kwang-Ik Adam; Hansen, Julie; Tuit, Keri; Kreek, Mary Jeanne

2011-09-01

Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Inpatient treatment in a community mental health center and hospital-based research unit. Treatment-engaged alcohol-dependent individuals and healthy controls. Time to alcohol relapse and to heavy drinking relapse. Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

Effect of Phlebodium Decumanum on the Immune Response Induced by Training in Sedentary University Students

PubMed Central

Gonzalez-Jurado, Jose A.; Pradas, Francisco; Molina, Edgardo S.; de Teresa, Carlos

2011-01-01

Exercise training is considered a good model to provoke different degrees of immune dysfunction affecting physical performance and some physiological responses related to oxidative stress and low grade inflammation. Phlebodium decumanum is a polypodiaceae may induce shown immunomodulating effects, specifically directed to the release of proinflammatory cytokines by macrophages in response to various stimuli, as reported different in vitro studies. The aim of this study was to evaluate the modulating effect of phlebodium decumanum, on the immune response induced by physical exercise. Thirty-one subjects (males only) were randomly divided into two groups: Group PD (n = 18); age: 22.1 ± 1.81, weight 74.21 ± 8.74 kg) that was treated with phlebodium decumanum; Group P (n = 13); age: 22.5 ± 1.63, weight 78 ± 12.5 kg) that was treated with a placebo. Before and after one month training program performed by both groups (three times a week), the following performance parameters and immune response variables were measured: Dynamic Maximum Force; Interval-Training; Tennis test; pro-inflammatory (TNF , IL6) and anti-inflammatory (TNFα-IIrs, IL1-ra) cytokines levels. Data were statistically analyzed with Mann- Whitney U test and Wilcoxon paired test (p < 0.05). Statistically significant differences were recorded within groups before and after the training program. PD group showed a significant improvement in the performance parameters (Strength Muscle Test: dorsal: p < 0.002; deltoids: p < 0.03; and pectorals: p < 0.07; Interval Training: p < 0.06; Tennis Test: p < 0.02). Cytokine levels resulted in a more positive profile in the PD group rather than in the P group, in which higher levels of IL-6 (p < 0.02) and a reduction of TNF-IIrs (p < 0.003) and IL1-ra (p < 0.03) were recorded. In this study the use of phlebodium decumanum demonstrated beneficial effects in the modulation of the immune response during physical performance. Key points Practicing sport or physical activity of medium-high intensity three times a week during 4 weeks induces changes in immune response indicators levels; The assumption of phlebodium decumanum induced a reduction in pro-inflammatory cytokines levels and a higher concentration of anti-inflammatory cytokines. Anti-inflammatory cytokines have a protective and modulating effect on the immune response. PMID:24149877

Modulatory Role of Omentin-1 in Inflammation: Cytokines and Dietary Intake.

PubMed

Zabetian-Targhi, Fateme; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Obesity is known as a chronic inflammatory state whereby anti-inflammatory adipokines, such as omentin-1 levels, are decreased. The present study aims to determine omentin-1 levels in relation to dietary intake, inflammation, and immune response in healthy obese individuals. A total of 170 obese participants (body mass index [BMI] ≥ 30) were recruited in this cross-sectional study. Body composition was evaluated by a body composition analyzer, and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin (IL)-4, IL-6, IL-1β, IL-17, IL-10, IL-13, and tumor necrosis factor-alpha [TNF-α]) were measured by enzyme-linked immunosorbent assay (ELISA) kits. We observed associations between higher serum levels of omentin-1 and lower levels of fasting insulin, glucose, total cholesterol, IL-6, and TNF-α concentrations; higher levels of IL-13, IL-4, and IL-1β were associated with higher serum levels of omentin-1 (all p < 0.05). Omentin-1 levels were not associated with IL-10, hs-CRP, and IL-17 concentrations. We also observed associations between higher intake of saturated fatty acid (SFA) and omentin-1 levels, even after adjustment for total energy intake (p = 0.04). Women with low intake of SFA had higher levels of omentin-1 (p = 0.03); a similar relation was not observed in men. Omentin-1 has an anti-inflammatory role in obesity and exerts its effects probably by inducing an increase in Th-2 cytokines comprising IL-13 and IL-4. Omentin-1 is not related to IL-17, a regulatory T cell cytokine, which modulates T helper balance. Levels of inflammatory cytokines are decreased in higher concentrations of omentin-1, except IL-1β. Lower intake of SFA may modify omentin-1 levels in women. Our study demonstrated the probable protective role of omentin-1 in obesity-related inflammation and insulin resistance.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats.

PubMed

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats*

PubMed Central

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; de Almeida, Francine Maria; da Silva, Bárbara Soares; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation. PMID:25210965

Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle

PubMed Central

2013-01-01

Background In the present study, we tested the hypothesis that carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II. Methods 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control, obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for 4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. Results The plasma level of carnitine were lower in the obese control group compared to the lean control group and higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiber-specific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine uptake, fatty acid transport, β-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in M. rectus femoris compared to the other groups (P < 0.05). Conclusion The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. PMID:23842456

Early Mitochondrial Adaptations in Skeletal Muscle to Obesity and Obesity Resistance Differentially Regulated by High-Fat Diet.

PubMed

Sun, Jingyu; Huang, Tao; Qi, Zhengtang; You, Songhui; Dong, Jingmei; Zhang, Chen; Qin, Lili; Zhou, Yunhe; Ding, Shuzhe

2017-09-01

The mechanism for different susceptibilities to obesity after short-term high-fat diet (HFD) feeding is largely unknown. Given the close association between obesity occurrence and mitochondrial dysfunction, the early events in skeletal muscle mitochondrial adaptations between HFD-induced obesity (DIO) and HFD-induced obesity resistant (DIO-R) lean phenotype under excess nutritional environment were explored.ICR/JCL male mice were randomly divided into 2 groups, as follows: low-fat diet (LFD) and HFD groups. After 6 weeks on HFD, HFD-fed mice were classified as DIO or DIO-R according to their body weight gain. Serum parameters, oxidative stress biomarkers, the activation of AMPK/ACC axis, and the expression profiles of mitochondrial biogenesis were measured by using corresponding methods among the LFD control, DIO, and DIO-R groups. Serum glucose, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels were significantly increased in DIO and DIO-R mice compared with LFD controls. However, DIO-R mice had significantly higher MDA levels and exhibited a significantly higher level of AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase (ACC) inactivation than DIO mice. Furthermore, the transcript and protein levels of transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) and estrogen-related receptor-α (ERRα) in DIO-R mice were significantly up-regulated compared with the DIO mice. Although the body weight gain differed, the DIO and DIO-R mice had similar metabolic disturbance of glucose and lipids after short-term HFD consumption. The diverse alterations on fatty acid oxidation and mitochondrial biogenesis pathway induced by AMPK activation might be involved in different susceptibilities to obesity when consuming HFD. © Georg Thieme Verlag KG Stuttgart · New York.

Expression of hypoxia-inducible factor 1α mRNA in hearts and lungs of broiler chickens with ascites syndrome induced by excess salt in drinking water.

PubMed

Zhang, Jianjun; Feng, Xuejian; Zhao, Lihong; Wang, Wei; Gao, Mingyu; Wu, Boning; Qiao, Jian

2013-08-01

Hypoxia-inducible factor 1 (HIF-1) is a ubiquitously expressed heterodimeric transcription factor that mediates adaptive responses to hypoxia in all nucleated cells of metazoan organisms. Hypoxia-inducible factor 1α is involved in the pathogenesis of pulmonary hypertension in humans and animals, but whether HIF-1α is associated with the development of pulmonary hypertension syndrome (also known as ascites syndrome, AS) in broiler chickens has not been determined. In the present paper we addressed this issue by measuring the expression of HIF-1α mRNA in hearts and lungs of broiler chickens with AS induced by excess salt in drinking water. We conducted 2 experiments. The first experiment was used to observe the effects of excess salt on AS incidence. The results indicated that total incidence (20%) of AS in excess salt group (receiving 0.3% NaCl in drinking water) was much higher compared with the control group (receiving tap water) over a 43-d time course (P < 0.05). In the second experiment, we determined mean pulmonary arterial pressure (mPAP), ascites heart index (AHI), and expression of HIF-1α mRNA in lungs and hearts of broiler chickens after the excess salt treatment. Our results showed that excess salt induced pulmonary hypertension (indicated by higher mPAP) and right ventricular hypertrophy (greater ascites heart index) in broiler chickens. Meanwhile, the expression levels of HIF-1α mRNA in lungs and hearts were significantly increased at different time points in the excess salt group compared with the control group. Linear correlation analysis showed that the expression of HIF-1α mRNA in lungs was significantly positively correlated with mPAP (correlation coefficient = 0.79, P < 0.001), demonstrating that expression of HIF-1α mRNA was gradually increased in the excess salt group with the increase of pulmonary arterial pressure. In addition, the ascitic chickens showed significantly higher transcriptional levels of HIF-1α in hearts and lungs, compared with the age-matched healthy chickens, respectively. Our findings hinted that HIF-1α might be associated with the development of AS induced by excess salt in drinking water in broiler chickens.

Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats.

PubMed

Yuan, Yi-Ming; Luo, Li; Guo, Zhen; Yang, Ming; Ye, Ren-Song; Luo, Chuan

2015-06-01

To explore the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (P<0.05), and ACE2 expression levels significantly increased. Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH. © The Author(s) 2015.

Lipopolysaccharide-induced murine embryonic resorption involves changes in endocannabinoid profiling and alters progesterone secretion and inflammatory response by a CB1-mediated fashion.

PubMed

Wolfson, Manuel L; Correa, Fernando; Leishman, Emma; Vercelli, Claudia; Cymeryng, Cora; Blanco, Julieta; Bradshaw, Heather B; Franchi, Ana María

2015-08-15

Genital tract infections are a common complication of human pregnancy that can result in miscarriage. We have previously shown that a lipopolysaccharide (LPS) induces embryonic resorption in a murine model of inflammatory miscarriage. This is accompanied by a dramatic decrease in systemic progesterone levels associated with a robust pro-inflammatory response that results in embryo resorption. Here, we tested the hypothesis that the endogenous cannabinoid system (eCS), through cannabinoid receptor 1 (CB1), plays a role in regulating progesterone levels and, therefore, the pro-inflammatory response. We show that LPS treatment in pregnant mice causes significant changes in the eCS ligands, which are reversed by progesterone treatment. We further show the CB1-KO mice maintain higher plasma progesterone levels after LPS treatment, which is associated with a feebler uterine inflammatory response and a significant drop in embryo resorption. These data suggest that manipulation of CB1 receptors and/or ligands is a potential therapeutic avenue to decrease infection-induced miscarriage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.

PubMed

Spignoli, G; Pepeu, G

1987-07-01

The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.

Superluminescence from an optically pumped molecular tunneling junction by injection of plasmon induced hot electrons

PubMed Central

Braun, Kai; Wang, Xiao; Kern, Andreas M; Adler, Hilmar; Peisert, Heiko; Chassé, Thomas; Zhang, Dai

2015-01-01

Summary Here, we demonstrate a bias-driven superluminescent point light-source based on an optically pumped molecular junction (gold substrate/self-assembled molecular monolayer/gold tip) of a scanning tunneling microscope, operating at ambient conditions and providing almost three orders of magnitude higher electron-to-photon conversion efficiency than electroluminescence induced by inelastic tunneling without optical pumping. A positive, steadily increasing bias voltage induces a step-like rise of the Stokes shifted optical signal emitted from the junction. This emission is strongly attenuated by reversing the applied bias voltage. At high bias voltage, the emission intensity depends non-linearly on the optical pump power. The enhanced emission can be modelled by rate equations taking into account hole injection from the tip (anode) into the highest occupied orbital of the closest substrate-bound molecule (lower level) and radiative recombination with an electron from above the Fermi level (upper level), hence feeding photons back by stimulated emission resonant with the gap mode. The system reflects many essential features of a superluminescent light emitting diode. PMID:26171286

Synergistic anti-inflammatory effects of Nobiletin and Sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells

PubMed Central

Guo, Shanshan; Qiu, Peiju; Xu, Guang; Wu, Xian; Dong, Ping; Yang, Guanpin; Zheng, Jinkai; McClements, David Julian; Xiao, Hang

2012-01-01

Inflammation plays important roles in initiation and progress of many diseases including cancers in multiple organ sites. Herein, we investigated the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN) in combination. Non-cytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that combined NBN and SFN treatments produced much stronger inhibitory effects on the production of nitric oxide (NO) than NBN or SFN alone at higher concentrations. These enhanced inhibitory effects were synergistic based on the isobologram analysis. Western blot analysis showed that combined NBN and SFN treatments synergistically decreased iNOS and COX-2 protein expression levels and induced heme oxygenase-1 (HO-1) protein expression. Real-time PCR analysis indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels, and synergistically increased HO-1 mRNA levels. Overall our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells. PMID:22335189

Social and economic inequalities in induced abortion in Spain as a function of individual and contextual factors.

PubMed

Pérez, Gloria; Ruiz-Muñoz, Dolores; Gotsens, Merce; Cases, Mariona Casals; Rodríguez-Sanz, Maica

2014-02-01

The socioeconomic position of women who have an induced abortion has been explored extensively, but without taking contextual factors into account. The objective was to describe socioeconomic inequalities in the rate of induced abortion in Spain in 2001, jointly evaluating the effects of both regional and individual socioeconomic characteristics. A cross-sectional study using a multilevel approach was carried out among women who were resident in Spain in 2001, considering the hierarchical structure of relevant factors. Analyses were carried out at the individual and regional level. We fit Poisson regression models to calculate adjusted relative risks (aRR) of induced abortion and 95% confidence intervals (CIs). The estimated abortion rate was 6.26 per 1000 women aged 20-49 years. Induced abortion was more frequent among younger women (aRR = 1.55 for women aged 20-24 years, compared with those aged 25-34 years) and those with less than primary education (aRR = 2.25 compared with women with university studies). Women residing in regions with lower public spending on non-university education (aRR = 0.83, 95% CI: 0.70-0.98) and a higher percentage of non-European Union immigrants (aRR = 1.06, 95% CI: 1.02-1.10) were also more likely to have had an induced abortion. Socioeconomic inequalities in the practice of induced abortion in Spain exist not only at the individual level but also at the regional level. The prevention of unintended pregnancy should be approached using a global political strategy aimed at changing contextual and individual factors that contribute to unintended pregnancy.

Brazilian Morus nigra Attenuated Hyperglycemia, Dyslipidemia, and Prooxidant Status in Alloxan-Induced Diabetic Rats

PubMed Central

Júnior, Ivanildo I. da S.; Barbosa, Humberto de Moura; Carvalho, Débora C. R.; Barros, Ruideglan de Alencar; Albuquerque, Flávia Peixoto; da Silva, Dionísio Henrique Amaral; Souza, Grasielly R.; Souza, Nathália A. C.; Silva, Flaviane M. M.; Duarte, Glória I. B. P.; de Oliveira Júnior, Flávio Monteiro; Gomes, Dayane A.

2017-01-01

Morus nigra has been used popularly for several proposes, including diabetic. In an attempt to support medicinal value, the acute hypoglycemic, hypolipidemic, and antioxidant effects of the ethanolic extract of Morus nigra (EEMn 200 or 400 mg/kg b.w.) were evaluated in normal and alloxan-induced diabetic treated for 14 days. Serum biochemical and antioxidant analysis were performed at the end of experiment. Oral glucose tolerance test was performed at 10th and 15th days. Chromatographic analysis by HPLC-DAD of EEMn was performed. Insulin was used as positive control to glycemic metabolism as well as fenofibrate to lipid metabolism. EEMn (400 mg/kg/day) reduced fasting and postprandial glycaemia, improved oral glucose tolerance, and reduced lipolysis and proteolysis in diabetic rats. EEMn decreased the blood levels of total cholesterol and increased HDL level when compared to the diabetic control rats. At higher levels, EEMn reduced triglycerides and VLDL levels in diabetic rats. Also, EEMn reduced malondialdehyde and increased the reduced glutathione levels in liver of diabetic rats. Chromatographic analysis identified the presence of the flavonoids rutin, isoquercetin, and kaempferitrin. Acute EEMn treatment reduced hyperglycemia, improved oral glucose tolerance, and minimized dyslipidemia and oxidative stress leading to a reduction in atherogenic index in alloxan-induced diabetic rats. PMID:28567440

Shifts in information processing level: the speed theory of intelligence revisited.

PubMed

Sircar, S S

2000-06-01

A hypothesis is proposed here to reconcile the inconsistencies observed in the IQ-P3 latency relation. The hypothesis stems from the observation that task-induced increase in P3 latency correlates positively with IQ scores. It is hypothesised that: (a) there are several parallel information processing pathways of varying complexity which are associated with the generation of P3 waves of varying latencies; (b) with increasing workload, there is a shift in the 'information processing level' through progressive recruitment of more complex polysynaptic pathways with greater processing power and inhibition of the oligosynaptic pathways; (c) high-IQ subjects have a greater reserve of higher level processing pathways; (d) a given 'task-load' imposes a greater 'mental workload' in subjects with lower IQ than in those with higher IQ. According to this hypothesis, a meaningful comparison of the P3 correlates of IQ is possible only when the information processing level is pushed to its limits.

Thyrotropin Receptor Antibody (TRAb)-IgM Levels Are Markedly Higher Than TRAb-IgG Levels in Graves' Disease Patients and Controls, and TRAb-IgM Production Is Related to Epstein-Barr Virus Reactivation.

PubMed

Kumata, Keisuke; Nagata, Keiko; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Fukata, Shuji; Hayashi, Kazuhiko

2016-10-01

Graves' disease is an autoimmune thyroid disorder that mainly presents as hyperthyroidism and is caused by thyrotropin receptor antibodies (TRAbs) that stimulate thyroid-stimulating hormone receptors. We previously reported that Graves' disease patients and healthy controls both had Epstein-Barr virus (EBV)-infected TRAb-positive B cells and the EBV-reactivated induction of these B cells in cultures may induce the production of TRAbs. In the present study, we quantified serum TRAb-IgG and TRAb-IgM levels in 34 Graves' disease patients and 15 controls using ELISA to elucidate the mechanisms underlying EBV-related antibody production. As expected, TRAb-IgG and TRAb-IgM levels were higher in Graves' disease patients than in controls; however, TRAb-IgM levels were significantly higher than those of TRAb-IgG levels, whereas total IgM levels were lower than total IgG levels. On the other hand, the enhanced production of TRAb-IgM was frequently observed in patients with EBV reactivation. These results are consistent with the fact that the percentage of autoreactive IgM B cells are higher than that of autoreactive IgG B cells, and support the EBV-related polyclonal B cell activation. It is necessary to clarify the biological characteristics of TRAb-IgM and the relationship between TRAb isotypes and the biology of Graves' disease.

HIF-inducible miR-191 promotes migration in breast cancer through complex regulation of TGFβ-signaling in hypoxic microenvironment.

PubMed

Nagpal, Neha; Ahmad, Hafiz M; Chameettachal, Shibu; Sundar, Durai; Ghosh, Sourabh; Kulshreshtha, Ritu

2015-04-13

The molecular mechanisms of hypoxia induced breast cell migration remain incompletely understood. Our results show that hypoxia through hypoxia-inducible factor (HIF) brings about a time-dependent increase in the level of an oncogenic microRNA, miR-191 in various breast cancer cell lines. miR-191 enhances breast cancer aggressiveness by promoting cell proliferation, migration and survival under hypoxia. We further established that miR-191 is a critical regulator of transforming growth factor beta (TGFβ)-signaling and promotes cell migration by inducing TGFβ2 expression under hypoxia through direct binding and indirectly by regulating levels of a RNA binding protein, human antigen R (HuR). The levels of several TGFβ pathway genes (like VEGFA, SMAD3, CTGF and BMP4) were found to be higher in miR-191 overexpressing cells. Lastly, anti-miR-191 treatment given to breast tumor spheroids led to drastic reduction in spheroid tumor volume. This stands as a first report of identification of a microRNA mediator that links hypoxia and the TGFβ signaling pathways, both of which are involved in regulation of breast cancer metastasis. Together, our results show a critical role of miR-191 in hypoxia-induced cancer progression and suggest that miR-191 inhibition may offer a novel therapy for hypoxic breast tumors.

Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes.

PubMed

Wang, Yue; Gao, Hong; Na, Xiao-Lin; Dong, Shu-Ying; Dong, Hong-Wei; Yu, Jia; Jia, Li; Wu, Yong-Hui

2016-11-30

The toxicity and carcinogenicity of aniline in humans and animals have been well documented. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear. In our research, primary cultured hepatocytes were exposed to aniline (0, 1.25, 2.50, 5.0 and 10.0 μg/mL) for 24 h in the presence or absence of N -acetyl-l-cysteine (NAC). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), mitochondrial membrane potential, DNA damage, cell viability, and apoptosis were detected. Levels of ROS and MDA were significantly increased and levels of GSH and CAT, activity of SOD, and mitochondrial membrane potential in hepatocytes were significantly decreased by aniline compared with the negative control group. The tail moment and DNA content of the tail in exposed groups were significantly higher than those in the negative control group. Cell viability was reduced and apoptotic death was induced by aniline in a concentration-dependent manner. The phenomena of ROS generation, oxidative damage, loss of mitochondrial membrane potential, DNA damage and apoptosis could be prevented if ROS inhibitor NAC was added. ROS generation is involved in the loss of mitochondrial membrane potential and DNA injury, which may play a role in aniline-induced apoptosis in hepatocytes. Our study provides insight into the mechanism of aniline-induced toxicity and apoptosis of hepatocytes.

Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes

PubMed Central

Wang, Yue; Gao, Hong; Na, Xiao-Lin; Dong, Shu-Ying; Dong, Hong-Wei; Yu, Jia; Jia, Li; Wu, Yong-Hui

2016-01-01

The toxicity and carcinogenicity of aniline in humans and animals have been well documented. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear. In our research, primary cultured hepatocytes were exposed to aniline (0, 1.25, 2.50, 5.0 and 10.0 μg/mL) for 24 h in the presence or absence of N-acetyl-l-cysteine (NAC). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), mitochondrial membrane potential, DNA damage, cell viability, and apoptosis were detected. Levels of ROS and MDA were significantly increased and levels of GSH and CAT, activity of SOD, and mitochondrial membrane potential in hepatocytes were significantly decreased by aniline compared with the negative control group. The tail moment and DNA content of the tail in exposed groups were significantly higher than those in the negative control group. Cell viability was reduced and apoptotic death was induced by aniline in a concentration-dependent manner. The phenomena of ROS generation, oxidative damage, loss of mitochondrial membrane potential, DNA damage and apoptosis could be prevented if ROS inhibitor NAC was added. ROS generation is involved in the loss of mitochondrial membrane potential and DNA injury, which may play a role in aniline-induced apoptosis in hepatocytes. Our study provides insight into the mechanism of aniline-induced toxicity and apoptosis of hepatocytes. PMID:27916916

Effects of low-molecular-weight-chitosan on the adenine-induced chronic renal failure rats in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhi, Xuan; Han, Baoqin; Sui, Xianxian; Hu, Rui; Liu, Wanshun

2015-02-01

The effects of low-molecular-weight-chitosan (LMWC) on chronic renal failure (CRF) rats induced by adenine were investigated in vivo and in vitro. Chitosan were hydrolyzed using chitosanase at pH 6-7 and 37° for 24 h to obtain LMWC. In vitro, the effect of LMWC on the proliferation of renal tubular epithelial cells (RTEC) showed that it had no cytotoxic effect and could promote cell growth. For the in vivo experiment, chronic renal failure rats induced by adenine were randomly divided into control group, Niaoduqing group, and high-, medium- and low-dose LMWC groups. For each group, we detected serum creatinine (SCR), blood urea nitrogen (BUN), and total superoxide dismutase (T-SOD), glutathione oxidase (GSH-Px) activities of renal tissue, and obtained the ratio of kidney weight/body weight, pathological changes of kidney. The levels of serum SCR, BUN were higher in the adenine-induced rats than those in the control group, indicating that the rat chronic renal failure model worked successfully. The results after treatment showed that LMWC could reduce the SCR and BUN levels and enhance the activities/levels of T-SOD and GSH-PX in kidney compared to control group. Histopathological examination revealed that adenine-induced renal alterations were restored by LMWC at three tested dosages, especially at the low dosage of 100 mg kg-1 d-1.

A description of phases with induced hybridisation at finite temperatures

NASA Astrophysics Data System (ADS)

Golosov, D. I.

2018-05-01

In an extended Falicov-Kimball model, an excitonic insulator phase can be stabilised at zero temperature. With increasing temperature, the excitonic order parameter (interaction-induced hybridisation on-site, characterised by the absolute value and phase) eventually becomes disordered, which involves fluctuations of both its phase and (at higher T) its absolute value. In order to build an adequate mean field description, it is important to clarify the nature of degrees of freedom associated with the phase and absolute value of the induced hybridisation, and the corresponding phase space volume. We show that a possible description is provided by the SU(4) parametrisation on-site. In principle, this allows to describe both the lower-temperature regime where phase fluctuations destroy the long-range order, and the higher temperature crossover corresponding to a decrease of absolute value of the hybridisation relative to the fluctuations level. This picture is also expected to be relevant in other contexts, including the Kondo lattice model.

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

Tan, Lizhen; Kim, B. K.; Yang, Ying

Ferritic-martensitic steels such as T91 and NF616 are candidate materials for several nuclear applications. Here, this study evaluates radiation resistance of T91 and NF616 by examining their microstructural evolutions and hardening after the samples were irradiated in the Advanced Test Reactor to ~4.3 displacements per atom (dpa) at an as-run temperature of 469 °C. In general, this irradiation did not result in significant difference in the radiation-induced microstructures between the two steels. Compared to NF616, T91 had a higher number density of dislocation loops and a lower level of radiation-induced segregation, together with a slightly higher radiation-hardening. Unlike dislocation loopsmore » developed in both steels, radiation-induced cavities were only observed in T91 but remained small with sub-10 nm sizes. Lastly, other than the relatively stable M 23C 6, a new phase (likely Sigma phase) was observed in T91 and radiation-enhanced MX → Z phase transformation was identified in NF616. Laves phase was not observed in the samples.« less

Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism.

PubMed

Francini, Flavio; Castro, María C; Gagliardino, Juan J; Massa, María L

2009-09-01

We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 +/- 0.35 vs. 11.27 +/- 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.

Arbuscular mycorrhizal growth responses are fungal specific but do not differ between soybean genotypes with different phosphate efficiency

PubMed Central

Wang, Xiurong; Zhao, Shaopeng; Bücking, Heike

2016-01-01

Background and Aims Arbuscular mycorrhizal (AM) fungi play a key role in the phosphate (P) uptake of many important crop species, but the mechanisms that control their efficiency and their contribution to the P nutrition of the host plant are only poorly understood. Methods The P uptake and growth potential of two soybean genotypes that differ in their root architectural traits and P acquisition efficiency were studied after colonization with different AM fungi and the transcript levels of plant P transporters involved in the plant or mycorrhizal P uptake pathway were examined. Key Results The mycorrhizal growth responses of both soybean genotypes ranged from highly beneficial to detrimental, and were dependent on the P supply conditions, and the fungal species involved. Only the colonization with Rhizophagus irregularis increased the growth and P uptake of both soybean genotypes. The expression of GmPT4 was downregulated, while the mycorrhiza-inducible P transporter GmPT10 was upregulated by colonization with R. irregularis. Colonization with both fungi also led to higher transcript levels of the mycorrhiza-inducible P transporter GmPT9, but only in plants colonized with R. irregularis were the higher transcript levels correlated to a better P supply. Conclusions The results suggest that AM fungi can also significantly contribute to the P uptake and growth potential of genotypes with a higher P acquisition efficiency, but that mycorrhizal P benefits depend strongly on the P supply conditions and the fungal species involved. PMID:27208734

Effects of peritoneal fluid from endometriosis patients on the release of vascular endothelial growth factor by neutrophils and monocytes.

PubMed

Na, Yong-Jin; Yang, Seung-Hong; Baek, Dae-Won; Lee, Dong-Hyung; Kim, Ki-Hyung; Choi, Young-Min; Oh, Sung-Tack; Hong, Young-Seoub; Kwak, Jong-Young; Lee, Kyu-Sup

2006-07-01

An increase in the level of the vascular endothelial growth factor (VEGF) production has been reported in the peritoneal fluid (PF) of endometriosis patients. This suggests that changes in the vascular permeability and angiogenesis play an important role in the pathophysiology of this disease. This study examined the effects of the PF obtained from endometriosis patients on the release of VEGF by neutrophils and monocytes. Neutrophils and monocytes were obtained from young healthy volunteers and cultured with the PF obtained from either endometriosis patients (EPF) (n=18) or a control group (CPF) (n=4). A human monocyte/macrophage cell line, THP-1, was cultured with either 10% EPF or 10% CPF. The PF and culture supernatants were assayed for VEGF using ELISA. Real-time PCR and Western blotting were used to measure the VEGF mRNA and protein expression level, respectively. The VEGF levels were higher in the EPF than in the CPF (591+/-75 versus 185+/-31 pg/ml, P<0.05). However, the level of VEGF released by THP-1 cells in CPF and EPF was similar. The EPF induced the release of VEGF by neutrophils, but no VEGF was released by monocytes. The VEGF mRNA expression levels in the neutrophils were higher in the EPF, which was abrogated by cycloheximide, suggesting that the EPF induces the production of VEGF in neutrophils. Neutralizing antibodies against IL-8 and TNF-alpha did not completely prevent the EPF-induced release of VEGF by the neutrophils, even though these growth factors stimulated the release of VEGF by neutrophils. There was a positive correlation between the VEGF and IL-10 concentrations in the EPF (correlation coefficient=0.549, P=0.012, n=18), but the neutralizing antibody of IL-10 did not affect the release of VEGF by the EPF-treated neutrophils. The EPF induced the production and release of VEGF by neutrophils, suggesting that neutrophils may be a source of peritoneal VEGF. In addition, neutrophil-derived VEGF might be a marker for diagnosing endometriosis.

Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

PubMed

Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

2016-12-01

Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prolonged intervals during Mycobacterium tuberculosis subunit vaccine boosting contributes to eliciting immunity mediated by central memory-like T cells.

PubMed

Bai, Chunxiang; He, Juanjuan; Niu, Hongxia; Hu, Lina; Luo, Yanping; Liu, Xun; Peng, Liang; Zhu, Bingdong

2018-05-01

It is believed that central memory T cells (T CM ) provide long-term protection against tuberculosis (TB). However, the effects of TB subunit vaccine immunization schedule, especially the vaccination intervals, on T cell immune memory is still unclear. In this study, mice were immunized with fusion protein ESAT6-Ag85B-MPT64 (190-198)-Mtb8.4-Rv2626c (LT70) based subunit vaccine three times according to the following schedules: ① 0, 3rd and 6th week respectively (0-3-6w), ② 0, 4th and 12th week (0-4-12w), and ③ 0, 4th and 24th week (0-4-24w). We found that both schedules of 0-4-12w and 0-4-24w induced higher level of antigen specific IL-2, IFN-γ and TNF-α than 0-3-6w immunization. Among them, 0-4-12w induced the highest level of IL-2, which is a key cytokine mainly produced by T CM . Moreover, by cultured IFN-γ ELISPOT and cell proliferation assay etc., we found that the vaccination schedule of 0-4-12w elicited higher numbers of T CM like cells, stronger T CM - mediated immune responses and higher protective efficacy against M. bovis BCG challenge than 0-3-6w did. It suggests that prolonging the vaccination interval of TB subunit vaccine to some extent contributes to inducing more abundant T CM like cells and providing stronger immune protection against mycobacteria infection. Copyright © 2018. Published by Elsevier Ltd.

Diet-induced obesity, energy metabolism and gut microbiota in C57BL/6J mice fed Western diets based on lean seafood or lean meat mixtures.

PubMed

Holm, Jacob Bak; Rønnevik, Alexander; Tastesen, Hanne Sørup; Fjære, Even; Fauske, Kristin Røen; Liisberg, Ulrike; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

2016-05-01

High protein diets may protect against diet-induced obesity, but little is known regarding the effects of different protein sources consumed at standard levels. We investigated how a mixture of lean seafood or lean meat in a Western background diet modulated diet-induced obesity, energy metabolism and gut microbiota. Male C57BL/6J mice fed a Western diet (WD) containing a mixture of lean seafood (seafood WD) for 12weeks accumulated less fat mass than mice fed a WD containing a mixture of lean meat (meat WD). Meat WD-fed mice exhibited increased fasting blood glucose, impaired glucose clearance, elevated fasting plasma insulin and increased plasma and liver lipid levels. We observed no first choice preference for either of the WDs, but over time, mice fed the seafood WD consumed less energy than mice fed the meat WD. Mice fed the seafood WD exhibited higher spontaneous locomotor activity and a lower respiratory exchange ratio (RER) than mice fed the meat WD. Thus, higher activity together with the decreased energy intake contributed to the different phenotypes observed in mice fed the seafood WD compared to mice fed the meat WD. Comparison of the gut microbiomes of mice fed the two WDs revealed significant differences in the relative abundance of operational taxonomic units (OTUs) belonging to the orders Bacteroidales and Clostridiales, with genes involved in metabolism of aromatic amino acids exhibiting higher relative abundance in the microbiomes of mice fed the seafood WD. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of 1,25-dihydroxycholecalciferol and 1,25-dihydroxycholecalciferol glycoside on 2,3-diphosphoglycerate levels of the rat erythrocyte.

PubMed

Skliar, M I; Fernandez, M C; Faienza, H; Orsatti, M B; Puche, R C; Boland, R L; Skliar, M I

1980-12-01

The erythrocytes of rats treated with 1, 25-dihydroxycholecalciferol or 1, 25-dihydroxycholecalciferol glycoside showed decreased levels of 2, 3-diphosphoglycerate. The same result has been obtained in vitro, indicating a direct effect of the sterol on the red cell. The glycoside is less active than the free sterol in vivo and more active in vitro. The decreased levels of diphosphoglycerate induced tissue hypoxia as shown by a higher plasma lactate/pyruvate ratio and a three fold increase in plasma erythropoietin concentration.

Serum Vancomycin Levels Resulting from Continuous or Intermittent Infusion in Critically Ill Burn Patients With or Without Continuous Renal Replacement Therapy

DTIC Science & Technology

2012-12-01

associated with higher vancomycin levels in gen- eral and fewer levels of ᝺ μg/mL, significant nephrotoxicity or neutropenia was not observed. Fifty...therapeutic course. An absolute neutrophil count (ANC) of ≤500 cells/μL was used to define neutropenia .11 As a standardized definition for drug-induced...150,000 plate- lets/μL (Table 3, data not shown). The lowest ANC at the end of therapy was 1800 cells/μL. No patients had neutropenia (defined as 

The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity.

PubMed

Doseyici, S; Mehmetoglu, I; Toker, A; Yerlikaya, F H; Erbay, E

2014-07-01

Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.

Branched-chain amino acids supplementation protects streptozotocin-induced insulin secretion and the correlated mechanism.

PubMed

Lu, Ming; Zhang, Xiujuan; Zheng, Dongmei; Jiang, Xiuyun; Chen, Qing

2015-01-01

Significant evidence demonstrates that oxidative stress can impair insulin secretion and contribute to the development of type 2 diabetes. Branched-chain amino acids (BCAAs) are reported to be positively related to insulin secretion. This study aimed to determine how oxidative stress affects the function of islets and whether BCAAs can ameliorate the oxidative stress, and accompanying c-jun N-terminal kinase (JNK), protein kinase D1 (PKD1), and pancreatic/duodenal homeobox-1 (PDX-1) changes induced by streptozotocin (STZ). Plasma glucose, plasma insulin, and JNK, PKD1 and PDX-1 mRNA and protein expression were measured in rats treated with STZ and BCAAs. The glucose level in STZ-induced diabetic rats was much higher than that in control animals, and the elevated plasma glucose level in diabetic rats could be significantly inhibited by BCAAs treatment. Consistent with the change in glucose levels, the levels of insulin were also affected by BCAAs treatment. The mRNA and protein expression of JNK, PDX-1, and PKD1 were significantly altered in diabetic rats compared with the control group (P<0.01) and treatment with a low dose of BCAA reversed these changes in those above markers significantly (P<0.01). The present study demonstrated that STZ-induced oxidative stress could reduce serum insulin levels and alter the JNK, PDX-1, and PKD1 expression. BCAAs restored the levels of serum insulin reversed changes in JNK, PDX-1, and PKD1 expression. © 2014 International Union of Biochemistry and Molecular Biology.

Oxidative stress and kidney injury in trans-radial catheterization.

PubMed

Tsarouhas, Konstantinos; Tsitsimpikou, Christina; Papantoni, Xrisoula; Lazaridou, Dimitra; Koutouzis, Michael; Mazzaris, Savvas; Rezaee, Ramin; Mamoulakis, Charalambos; Georgoulias, Panagiotis; Nepka, Charitini; Rentoukas, Elias; Kyriakides, Zenon; Tsatsakis, Aristidis; Spandidos, Demetrios A; Kouretas, Demetrios

2018-05-01

Oxidative stress is linked to coronary artery disease and is a major mechanism in contrast-induced nephropathy. Trans-radial approach in coronary angiography (CA) with minimized peri-procedural bleeding is expected to reduce acute kidney injury incidence. In the present study, oxidative stress patterns observed in radial CA and their associations with early manifestations of kidney injury are described. A total of 20 stable coronary disease patients submitted to CA and 17 sex-matched patients undergoing computed tomography for myoskeletal reasons were enrolled. Reduced glutathione, catalase, thiobarbituric acid reactive species (TBARS) levels and total anti-oxidant status were measured at various time points postangiography. In ischemic patients baseline TBARS levels were 2-fold lower compared to controls, while carbonyls levels were 35% higher. Glutathione was almost 4-fold lower than the control group. Glutathione and lipid peroxidation in ischemic patients gradually increased after contrast medium administration and reached 180% (P<0.001) and 20% (P=0.021) after 4-6 h, respectively. Four patients presented early evidence of contrast-induced nephropathy postangiography, while no control patient developed acute kidney injury. In the multiple logistic regression analysis, only the creatinine levels at baseline influenced the frequency of early contrast-induced nephropathy development (β =0.36, 95% CI: 0.285-0.438, P=0.01). Glutathione low levels were dominant in the baseline values of ischemic patients who developed contrast-induced nephropathy. Glutathione levels rapidly increased while protein oxidation decreased at the expense of lipid peroxidation. In conclusion, early oxidative stress changes occur in trans-radial CA patients with a mild profile, sufficient to mobilize patient antioxidant defenses.

Analysis of natural variation in bermudagrass (Cynodon dactylon) reveals physiological responses underlying drought tolerance.

PubMed

Shi, Haitao; Wang, Yanping; Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

2012-01-01

Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H₂O₂ content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system.

Acoustic response variability in automotive vehicles

NASA Astrophysics Data System (ADS)

Hills, E.; Mace, B. R.; Ferguson, N. S.

2009-03-01

A statistical analysis of a series of measurements of the audio-frequency response of a large set of automotive vehicles is presented: a small hatchback model with both a three-door (411 vehicles) and five-door (403 vehicles) derivative and a mid-sized family five-door car (316 vehicles). The sets included vehicles of various specifications, engines, gearboxes, interior trim, wheels and tyres. The tests were performed in a hemianechoic chamber with the temperature and humidity recorded. Two tests were performed on each vehicle and the interior cabin noise measured. In the first, the excitation was acoustically induced by sets of external loudspeakers. In the second test, predominantly structure-borne noise was induced by running the vehicle at a steady speed on a rough roller. For both types of excitation, it is seen that the effects of temperature are small, indicating that manufacturing variability is larger than that due to temperature for the tests conducted. It is also observed that there are no significant outlying vehicles, i.e. there are at most only a few vehicles that consistently have the lowest or highest noise levels over the whole spectrum. For the acoustically excited tests, measured 1/3-octave noise reduction levels typically have a spread of 5 dB or so and the normalised standard deviation of the linear data is typically 0.1 or higher. Regarding the statistical distribution of the linear data, a lognormal distribution is a somewhat better fit than a Gaussian distribution for lower 1/3-octave bands, while the reverse is true at higher frequencies. For the distribution of the overall linear levels, a Gaussian distribution is generally the most representative. As a simple description of the response variability, it is sufficient for this series of measurements to assume that the acoustically induced airborne cabin noise is best described by a Gaussian distribution with a normalised standard deviation between 0.09 and 0.145. There is generally considerable variability in the roller-induced noise, with individual 1/3-octave levels varying by typically 15 dB or so and with the normalised standard deviation being in the range 0.2-0.35 or more. These levels are strongly affected by wheel rim and tyre constructions. For vehicles with nominally identical wheel rims and tyres, the normalised standard deviation for 1/3-octave levels in the frequency range 40-600 Hz is 0.2 or so. The distribution of the linear roller-induced noise level in each 1/3-octave frequency band is well described by a lognormal distribution as is the overall level. As a simple description of the response variability, it is sufficient for this series of measurements to assume that the roller-induced road noise is best described by a lognormal distribution with a normalised standard deviation of 0.2 or so, but that this can be significantly affected by the tyre and rim type, especially at lower frequencies.

Two genes with similarity to bacterial response regulators are rapidly and specifically induced by cytokinin in Arabidopsis

NASA Technical Reports Server (NTRS)

Brandstatter, I.; Kieber, J. J.; Evans, M. L. (Principal Investigator)

1998-01-01

Cytokinins are central regulators of plant growth and development, but little is known about their mode of action. By using differential display, we identified a gene, IBC6 (for induced by cytokinin), from etiolated Arabidopsis seedlings, that is induced rapidly by cytokinin. The steady state level of IBC6 mRNA was elevated within 10 min by the exogenous application of cytokinin, and this induction did not require de novo protein synthesis. IBC6 was not induced by other plant hormones or by light. A second Arabidopsis gene with a sequence highly similar to IBC6 was identified. This IBC7 gene also was induced by cytokinin, although with somewhat slower kinetics and to a lesser extent. The pattern of expression of the two genes was similar, with higher expression in leaves, rachises, and flowers and lower transcript levels in roots and siliques. Sequence analysis revealed that IBC6 and IBC7 are similar to the receiver domain of bacterial two-component response regulators. This homology, coupled with previously published work on the CKI1 histidine kinase homolog, suggests that these proteins may play a role in early cytokinin signaling.

Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes

PubMed Central

Mallet, Justin D.; Bastien, Nathalie; Gendron, Sébastien P.; Rochette, Patrick J.

2016-01-01

Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced. PMID:27611318

Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: vulnerability to relapse to heroin-seeking in rats

PubMed Central

Zhou, Yan; Leri, Francesco; Cummins, Erin; Jeanne Kreek, Mary

2014-01-01

Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided to high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking. PMID:25446223

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

PubMed

Havelund, Jesper F; Andersen, Andreas D; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Faergeman, Nils J; Gramsbergen, Jan Bert

2017-09-01

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia. © 2017 International Society for Neurochemistry.

Hyperparasitoids Use Herbivore-Induced Plant Volatiles to Locate Their Parasitoid Host

PubMed Central

Poelman, Erik H.; Bruinsma, Maaike; Zhu, Feng; Weldegergis, Berhane T.; Boursault, Aline E.; Jongema, Yde; van Loon, Joop J. A.; Vet, Louise E. M.; Harvey, Jeffrey A.; Dicke, Marcel

2012-01-01

Plants respond to herbivory with the emission of induced plant volatiles. These volatiles may attract parasitic wasps (parasitoids) that attack the herbivores. Although in this sense the emission of volatiles has been hypothesized to be beneficial to the plant, it is still debated whether this is also the case under natural conditions because other organisms such as herbivores also respond to the emitted volatiles. One important group of organisms, the enemies of parasitoids, hyperparasitoids, has not been included in this debate because little is known about their foraging behaviour. Here, we address whether hyperparasitoids use herbivore-induced plant volatiles to locate their host. We show that hyperparasitoids find their victims through herbivore-induced plant volatiles emitted in response to attack by caterpillars that in turn had been parasitized by primary parasitoids. Moreover, only one of two species of parasitoids affected herbivore-induced plant volatiles resulting in the attraction of more hyperparasitoids than volatiles from plants damaged by healthy caterpillars. This resulted in higher levels of hyperparasitism of the parasitoid that indirectly gave away its presence through its effect on plant odours induced by its caterpillar host. Here, we provide evidence for a role of compounds in the oral secretion of parasitized caterpillars that induce these changes in plant volatile emission. Our results demonstrate that the effects of herbivore-induced plant volatiles should be placed in a community-wide perspective that includes species in the fourth trophic level to improve our understanding of the ecological functions of volatile release by plants. Furthermore, these findings suggest that the impact of species in the fourth trophic level should also be considered when developing Integrated Pest Management strategies aimed at optimizing the control of insect pests using parasitoids. PMID:23209379

Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon carcinogenesis.

PubMed

Kanna, P Suresh; Saralaya, M G; Samanta, K; Chatterjee, M

2005-01-01

The trace mineral vanadium inhibits cancer development in a variety of experimental animal models. The present study was to gain insight into a putative anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo study was intended to clarify the effect of vanadium on DNA-protein cross-links (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon carcinogenesis. The comet assay showed statistically higher mean base values of DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the carcinogen-induced group after treatment with proteinase K. Treatment with vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking water for the entire experimental period caused a significant (p<0.02) reduction (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation status of vanadium was ascertained measuring the drug metabolising enzymes, glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly, there was an increase in glutathione S-transferase and cytochrome P-450 levels (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared to their carcinogen controls. As an endpoint marker, we also evaluated the effect of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with vanadium showed a marked improvement in colonic architecture with less number of aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone, thereby exhibiting its anti-carcinogenicity by modulating the markers studied herein.

Fructose diet alleviates acetaminophen-induced hepatotoxicity in mice.

PubMed

Cho, Sungjoon; Tripathi, Ashutosh; Chlipala, George; Green, Stefan; Lee, Hyunwoo; Chang, Eugene B; Jeong, Hyunyoung

2017-01-01

Acetaminophen (APAP) is a commonly used analgesic and antipyretic that can cause hepatotoxicity due to production of toxic metabolites via cytochrome P450 (Cyp) 1a2 and Cyp2e1. Previous studies have shown conflicting effects of fructose (the major component in Western diet) on the susceptibility to APAP-induced hepatotoxicity. To evaluate the role of fructose-supplemented diet in modulating the extent of APAP-induced liver injury, male C57BL/6J mice were given 30% (w/v) fructose in water (or regular water) for 8 weeks, followed by oral administration of APAP. APAP-induced liver injury (determined by serum levels of liver enzymes) was decreased by two-fold in mice pretreated with fructose. Fructose-treated mice exhibited (~1.5 fold) higher basal glutathione levels and (~2 fold) lower basal (mRNA and activity) levels of Cyp1a2 and Cyp2e1, suggesting decreased bioactivation of APAP and increased detoxification of toxic metabolite in fructose-fed mice. Hepatic mRNA expression of heat shock protein 70 was also found increased in fructose-fed mice. Analysis of bacterial 16S rRNA gene amplicons from the cecal samples of vehicle groups showed that the fructose diet altered gut bacterial community, leading to increased α-diversity. The abundance of several bacterial taxa including the genus Anaerostipes was found to be significantly correlated with the levels of hepatic Cyp2e1, Cyp1a2 mRNA, and glutathione. Together, these results suggest that the fructose-supplemented diet decreases APAP-induced liver injury in mice, in part by reducing metabolic activation of APAP and inducing detoxification of toxic metabolites, potentially through altered composition of gut microbiota.

Linking sex differences in corticosterone with individual reproductive behaviour and hatch success in two species of uniparental shorebirds.

PubMed

Edwards, Darryl B; Chin, Eunice H; Burness, Gary; Gilchrist, H Grant; Schulte-Hostedde, Albrecht I

2013-09-01

In birds, corticosterone (CORT) appears to facilitate reproductive activity because baseline and stress-induced CORT levels are elevated in breeding individuals compared with other times of the year. In particular, CORT is lower in the sex providing most of the parental care (i.e., incubation), which could be an important adaptation to tolerate stressors that result in abandoning reproduction. Therefore, one explanation for sex differences in CORT is that lower levels are favoured during the incubation/parental phase of reproduction. Using two species of uniparental shorebird - polyandrous red phalaropes (Phalaropus fulicarius) and polygynous white-rumped sandpipers (Calidris fuscicollis) - we predicted that the incubating sex would have lower baseline and stress-induced CORT, and incubating individuals with lower CORT would more effectively defend nests against a simulated intrusion, would return more quickly afterwards, and would ultimately have higher hatch success. We found that phalaropes followed the predicted pattern: incubating individuals (males) had lower baseline and stress-induced CORT than females but for baseline CORT these differences existed prior to males commencing incubation. Incubating male phalaropes with lower baseline and stress-induced CORT returned to incubate more quickly after a disturbance and there was non-significant tendency for baseline CORT to be lower in successful nests. In sandpipers, we observed no sex differences and no significant relationships between individual CORT levels and nest defence behaviours or hatch success. Our results demonstrate that in phalaropes at least, selection favours lower baseline and stress-induced CORT during the nesting period. These results can explain sex differences in stress-induced levels of CORT, however sex differences in baseline CORT were present prior to incubation. Copyright © 2013 Elsevier Inc. All rights reserved.

Association between increased serum d-serine and cognitive gains induced by intensive cognitive training in schizophrenia.

PubMed

Panizzutti, Rogerio; Fisher, Melissa; Garrett, Coleman; Man, Wai Hong; Sena, Walter; Madeira, Caroline; Vinogradov, Sophia

2018-04-23

Neuroscience-guided cognitive training induces significant improvement in cognition in schizophrenia subjects, but the biological mechanisms associated with these changes are unknown. In animals, intensive cognitive activity induces increased brain levels of the NMDA-receptor co-agonist d-serine, a molecular system that plays a role in learning-induced neuroplasticity and that may be hypoactive in schizophrenia. Here, we investigated whether training-induced gains in cognition were associated with increases in serum d-serine in outpatients with schizophrenia. Ninety patients with schizophrenia and 53 healthy controls were assessed on baseline serum d-serine, l-serine, and glycine. Schizophrenia subjects performed neurocognitive tests and were assigned to 50 h of either cognitive training of auditory processing systems (N = 47) or a computer games control condition (N = 43), followed by reassessment of cognition and serum amino acids. At study entry, the mean serum d-serine level was significantly lower in schizophrenia subjects vs. healthy subjects, while the glycine levels were significantly higher. There were no significant changes in these measures at a group level after the intervention. However, in the active training group, increased d-serine was significantly and positively correlated with improvements in global cognition and in Verbal Learning. No such associations were observed in the computer games control subjects, and no such associations were found for glycine. d-Serine may be involved in the neurophysiologic changes induced by cognitive training in schizophrenia. Pharmacologic strategies that target d-serine co-agonism of NMDA-receptor functioning may provide a mechanism for enhancing the behavioral effects of intensive cognitive training. Copyright © 2017 Elsevier B.V. All rights reserved.

Soy protein supports cardiovascular health by downregulating hydroxymethylglutaryl-coenzyme A reductase and sterol regulatory element-binding protein-2 and increasing antioxidant enzyme activity in rats with dextran sodium sulfate-induced mild systemic inflammation.

PubMed

Marsh, Tanya G; Straub, Rachel K; Villalobos, Fatima; Hong, Mee Young

2011-12-01

Animal and human studies have indicated that the presence of soy in the diet improves cardiovascular health. Inflammation plays a pivotal role in the progression of cardiovascular disease (CVD). However, little is known about how dextran sodium sulfate (DSS)-induced systemic inflammation impacts overall heart health and, correspondingly, how soy protein modulates risk of CVD development in DSS-induced systemic inflammation. We hypothesized that soy protein-fed rats would have a lower risk of CVD by beneficial alteration of gene expression involving lipid metabolism and antioxidant capacity in DSS-induced systemic inflammation. Forty Sprague-Dawley rats were divided into 4 groups: casein, casein + DSS, soy protein, and soy protein + DSS. After 26 days, inflammation was induced in one group from each diet by incorporating 3% DSS in drinking water for 48 hours. Soy protein-fed rats had lower final body weights (P = .010), epididymal fat weights (P = .049), total cholesterol (P < .001), and low-density lipoprotein cholesterol (P < .001). In regard to gene expression, soy protein-fed rats had lower sterol regulatory element-binding protein-2 (P = .032) and hydroxymethylglutaryl-coenzyme A reductase (P = .028) levels and higher low-density lipoprotein receptor levels (P = .036). Antioxidant enzyme activity of superoxide dismutase and catalase was higher among the soy protein groups (P = .037 and P = .002, respectively). These results suggest that soy protein positively influences cardiovascular health by regulating serum lipids through modified expression of sterol regulatory element-binding protein-2 and its downstream genes (ie, hydroxymethylglutaryl-coenzyme A reductase and low-density lipoprotein receptor) and by promoting the antioxidant enzyme activity of superoxide dismutase and catalase. Copyright © 2011 Elsevier Inc. All rights reserved.

Cadherin-11 Regulation of Fibrosis through Modulation of Epithelial-to-Mesenchymal Transition: Implications for Pulmonary Fibrosis in Scleroderma

DTIC Science & Technology

2013-10-01

4A, TGFbeta decreased E- cadherin expression and increase Col1a1 expression in MLE12 cells. Soluble Cad11 Fc fusion protein inhibited EMT induced by...TGFbeta as noted my higher E-cadherin levels and a significant reduction in Col1a1 mRNA. In contrast, when Cad11 Fc fusion protein was immobilized...Fc fusion protein alone was able to induce Col1a1 expression at the 50 ug/ml concentration, although E-cadherin expression was also increased. In

Functional convergence of oxylipin and abscisic acid pathways controls stomatal closure in response to drought.

PubMed

Savchenko, Tatyana; Kolla, Venkat A; Wang, Chang-Quan; Nasafi, Zainab; Hicks, Derrick R; Phadungchob, Bpantamars; Chehab, Wassim E; Brandizzi, Federica; Froehlich, John; Dehesh, Katayoon

2014-03-01

Membranes are primary sites of perception of environmental stimuli. Polyunsaturated fatty acids are major structural constituents of membranes that also function as modulators of a multitude of signal transduction pathways evoked by environmental stimuli. Different stresses induce production of a distinct blend of oxygenated polyunsaturated fatty acids, "oxylipins." We employed three Arabidopsis (Arabidopsis thaliana) ecotypes to examine the oxylipin signature in response to specific stresses and determined that wounding and drought differentially alter oxylipin profiles, particularly the allene oxide synthase branch of the oxylipin pathway, responsible for production of jasmonic acid (JA) and its precursor 12-oxo-phytodienoic acid (12-OPDA). Specifically, wounding induced both 12-OPDA and JA levels, whereas drought induced only the precursor 12-OPDA. Levels of the classical stress phytohormone abscisic acid (ABA) were also mainly enhanced by drought and little by wounding. To explore the role of 12-OPDA in plant drought responses, we generated a range of transgenic lines and exploited the existing mutant plants that differ in their levels of stress-inducible 12-OPDA but display similar ABA levels. The plants producing higher 12-OPDA levels exhibited enhanced drought tolerance and reduced stomatal aperture. Furthermore, exogenously applied ABA and 12-OPDA, individually or combined, promote stomatal closure of ABA and allene oxide synthase biosynthetic mutants, albeit most effectively when combined. Using tomato (Solanum lycopersicum) and Brassica napus verified the potency of this combination in inducing stomatal closure in plants other than Arabidopsis. These data have identified drought as a stress signal that uncouples the conversion of 12-OPDA to JA and have revealed 12-OPDA as a drought-responsive regulator of stomatal closure functioning most effectively together with ABA.

The protective effect of royal jelly on chronic lambda-cyhalothrin toxicity: serum biochemical parameters, lipid peroxidation, and genotoxic and histopathological alterations in swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The present study was undertaken to investigate the protective effect of royal jelly (RJ) against toxicity induced by a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), in Swiss albino mice. Animals were randomly divided into six groups of six animals each. The control group received distilled water alone, whereas mice in the treatment groups received RJ alone (100 or 250 mg/kg of body weight), LCT alone (668 ppm), or RJ+LCT for 21 days. All mice (100%) survived until the end of experiment and were sacrificed at the end of 24 hours. Blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and reduced glutathione (GSH) levels and micronucleus (MN) frequency, chromosomal aberrations (CAs), and pathological damages. Serum AST, ALT, BUN, and creatinine levels were elevated in mice treated with LCT alone compared with the other tested groups (P<.05). LCT-induced oxidative damage caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. LCT alone-treated mice presented higher frequencies (P<.05) of MNs, CAs, and abnormal metaphases compared with the controls; moreover, the mitotic index was lower than in controls (P<.05). Oral treatment with RJ significantly ameliorated the indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity induced by LCT. Both doses of RJ tested provided significant protection against LCT-induced toxicity, and its strongest effect was observed at the dose level of 250 mg/kg of body weight. In vivo results suggest that RJ is a potent antioxidant against LCT-induced toxicity, and its protective effect is dose dependent.

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

PubMed

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

2013-11-01

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

Powdery mildew suppresses herbivore-induced plant volatiles and interferes with parasitoid attraction in Brassica rapa

USDA-ARS?s Scientific Manuscript database

The co-occurrence of different antagonists on a plant can greatly affect infochemicals with ecological consequences for higher trophic levels. Here we investigated how the presence of a plant pathogen, the powdery mildew Erysiphe cruciferarum, on Brassica rapa affects 1) plant volatiles emitted in r...