Effect of methionine feeding on oxidative stress, intracellular calcium and contractility in cardiomyocytes isolated from male and female rats.

Homocysteine (Hcy) is a breakdown product of methionine metabolism. The risk of cardiovascular disease (CVD) correlates with an increase in plasma Hcy levels. The aim of this study was to investigate whether 1% methionine supplementation of adult rats altered intracellular reactive oxygen species (ROS) generation, intracellular Ca2+ content, and contractile activity in freshly isolated cardiomyocytes. This was measured under normal conditions and during oxidative stress in freshly isolated cardiomyocytes. Single rat cardiomyocytes from both sexes were isolated by enzymatic and mechanical dispersion techniques. Fluorescence microscopy was used to measure ROS production and intracellular Ca2+ concentration. Cell contraction was measured using a video camera. During exposure to 200 µM, H2O2 female cardiomyocytes produced significantly fewer ROS and had a higher intracellular Ca2+ concentration compared to male cardiomyocytes in control and methionine-fed conditions. The contractility of cardiomyocytes isolated from male rats was insignificantly decreased after methionine feeding compared to control, while the contractility of cardiomyocytes from female rats insignificantly reduced after methionine feeding and acute exposure to oxidative stress. These findings provide evidence that during exposure to 200 µM H2O2, cardiomyocytes from female rats produce less ROS and have higher intracellular Ca2+ levels. There were no significant effects on contractility in cardiomyocytes from either gender and under any of the different conditions.

A low protein maternal diet during gestation has negative effects on male fertility markers in rats - A Systematic Review and Meta-analysis.

Research indicates that some adult diseases including reproductive pathologies are programmed in utero during foetal development. In particular, maternal low dietary protein, during the most critical developmental periods of male foetal development, may have a detrimental impact on male fertility through direct and epigenetic mechanisms. The aim of our study was to evaluate the impact of a gestational low protein diet on fertility markers in male offspring in rats through a systematic review and meta-analysis. A systematic search using PubMed, and EMBASE databases was performed and two investigators independently screened the 1,703 prospective articles. Eleven articles met the eligibility criteria. Outcome measures were pooled using random-effects models and expressed as mean differences (MDs) at 95% CIs for each study. The results reveal significant reduction in testis weight (MD (mean difference) -0.08 g; -0.12, -0.42; p = .0001), epididymal sperm count (MD -35.34 × 106 cells; -52.15, -18.53; p = .0001), number of Sertoli cells (MD -7.27 × 106 (-13.92, -0.62; p = .03), testosterone (T) concentration (MD -0.29 ng/ml; -0.48, -0.09; p = .004) and luteinising hormone (LH) concentration (MD of -0.24 ng/ml; -0.45, 0.04; p = .02) in comparison with controls. In contrast, follicle-stimulating hormone (FSH) concentration (MD of 0.07 ng/ml; -0.16, 0.29; p = .56) was not significantly different from controls. We conclude that low gestational dietary protein maternal intake potentially negatively impacts fertility in male progeny later in life. The mechanisms of action responsible for these phenomena remain unclear.

The effect of dietary protein intake on factors associated with male infertility: A systematic literature review and meta-analysis of animal clinical trials in rats.

BACKGROUND: Studies have shown that the amount of protein in the diet affects the hypothalamic-pituitary-testis axis and sub-optimal quantity reduces male fertility potential in both animals and humans. However, individual research reports on the factors associated with male infertility are collectively uncharacterized. AIM: We systematically reviewed, and meta-analysed animal (rats) studies on the effect of low protein diet on factors associated with male infertility. METHODS: PubMed Central, EMBASE and Scopus databases were searched from inception to 30 March 2019 for the study concepts and related keywords in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data on the outcome measures were extracted and pooled across trials using random-effects model and expressed as mean differences (MD) at a 95% confidence interval (CI). RESULTS: Twelve trials identified from 3327 studies, met our inclusion criteria in the comparison of a low protein diet (2-10% protein) vs control protein diet (17-23% protein). The results showed that a low protein diet caused a significant reduction in the body weight (P = 0.0001) testis weight (P = 0.0001), seminal vesicle weight (P = 0.0003), epididymis weight P = 0.02), serum testosterone (P = 0.001) and follicle-stimulating hormone (FSH) concentrations (P = 0.04) compared with the control treatments. No effect on luteinizing hormone (LH) plasma concentration (P = 0.13) was observed. CONCLUSION: This study revealed that low protein diet caused significant reductions in body weight, testis, epididymis and seminal vesicle weights, serum testosterone and FSH concentration in rats. We infer that sub-optimal protein consumption reduces the gonadal and endocrine function, and consequently male infertility.

Effect of low- and high-protein maternal diets during gestation on reproductive outcomes in the rat: a systematic review and meta-analysis.

Studies with animal models have consistently demonstrated adverse health outcomes in offspring born following nutritional manipulation during gestation. However, the effects of gestational dietary protein modification on reproductive outcomes at birth are less clear. We, therefore, conducted a systematic review and meta-analysis of controlled trials to determine whether high- or low-protein diets are associated with altered reproductive outcomes in a commonly studied species, the rat. Included studies were identified through a systematic search using electronic databases and manual literature review to identify randomized studies published between June 1972 and March 2019. Thirty-two studies were identified and used to analyze the effects of low- and high-protein gestational diets on litter size, litter weight, gestational weight gain, and gestational feed intake. The results indicate that low-protein diets significantly reduced litter weight (P < 0.00001) and gestational weight gain (P < 0.0006), but did not influence litter size (P = 0.62) or gestational feed intake (P = 0.25). In contrast, high-protein diets were found to reduce gestational feed intake (P = 0.004) but did not influence litter size (P = 0.56), litter weight (P = 0.22), or gestational weight gain (P = 0.35). The results suggest that low but not high-protein gestational diets alter reproductive outcomes at birth in rats.

Blood pressure measurements in research: suitability of auscultatory, beat-to-beat, and ambulatory blood pressure measurements.

OBJECTIVE: The objective of this study was to validate the accuracy of beat-to-beat measurements with those taken with an aneroid sphygmomanometer by auscultatory method. A secondary aim was to explore differences between auscultatory and beat-to-beat blood pressure (BP) with daytime ambulatory BP measurements. PARTICIPANTS AND METHODS: A total of 46 participants, comprising 21 males, aged 47±13 years, height 171±8.5 cm and weight 82±16.8 kg attended the Exercise Physiology Laboratory at the University of New England (Armidale, New South Wales, Australia). During the visit, participants had their BP - systolic BP (SBP) and diastolic BP (DBP) - measured using auscultatory methods and a Finometer. An ambulatory BP monitor was fitted during the same visit and worn for a minimum of 12 h. RESULTS: Auscultatory measurements were slightly higher than beat-to-beat for both SBP and DBP. There was no difference between auscultatory and beat-to-beat SBP with a mean difference of 0.23 mmHg (P=0.87). There were disparities between auscultatory and beat-to-beat DBP, with a mean difference of 4.82 mmHg (P<0.01). Daytime ambulatory BP was higher than both auscultatory and beat-to-beat measurements for both SBP and DBP, with P less than 0.001 for all measures. CONCLUSION: There was a high level of reliability in the beat-to-beat SBP with that seen by auscultatory; however, there were disparities in DBP measurements using the same devices, which raise concerns over the accuracy of beat-to-beat DBP. Ambulatory systolic and diastolic measures were higher than beat-to-beat and auscultatory; however, they may be more suitable for monitoring diurnal changes in BP, depending upon the research model.

Hormonal changes, semen quality and variance in reproductive activity outcomes of post pubertal rabbits fed Moringa oleifera Lam. leaf powder.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. (Moringaceae) is an important plant based staple food, known for its nutritional and medicinal value and is usually prescribed by herbal practitioners in Nigeria and in other tropical countries for the treatment of male infertility problems and reproductive diseases in females. Although the aphrodisiac properties and fertility enhancement potential in males have been reported, the underlying mechanisms for the activity remain unclear. In this study, we investigated the influence of supplementing the diet with M. oleifera Lam. leaf powder on reproductive hormones and semen quality of New Zealand White (NZW) rabbits. MATERIALS AND METHODS: Thirty-two (32) NZW rabbits of 50:50 ratio bucks to does, were randomly distributed to four treatment groups (n = 4 bucks, n = 4 does per group). Graded levels (0, 5, 10 and 15 g/kg) of M. oleifera Lam. leaf powder was incorporated into rabbit growers pellet. The does and bucks were housed separately in hutches and sheltered under the same environmental conditions with free access to their respective treatment diets for a period of 12 weeks. RESULTS: In female rabbits, treatment revealed significant (P < 0.05) dose-dependent reduction in the concentration of serum FSH, LH and oestrogen. While in contrast the highest dose of leaf powder significantly (P < 0.05) increased progesterone and prolactin concentrations remained unaffected. On the other hand, the concentration of FSH and LH in bucks was significantly (P < 0.05) increased in treatment groups compared to the control group. Serum testosterone concentrations were significantly lower in the 5 and 10 g/kg treatment groups. Semen volume, sperm count and motility were significantly improved in a dose dependent manner with increasing amounts of M. oleifera Lam. leaf powder in the diet. CONCLUSIONS: We conclude that M. oleifera Lam. leaf powder supplementation to the diet was more beneficial to male rabbit fertility than the female, where it tended to have a negative impact through the hypothalamic-pituitary-gonadal axis. However, with the varying impact of M. oleifera Lam. leaf powder on the hypothalamic-pituitary-gonadal axis of male and female animals, further investigation is necessary to determine the mechanism through which it operates.

Can the sensitivity of the histopathological diagnosis of coeliac disease be increased and can treatment progression be monitored using mathematical modelling of histological sections? - A pilot study.

PURPOSE: The aim of this pilot study was to attempt to define a set of equations from histological observations of tissue affected with coeliac disease (CD) to predict Marsh score. MATERIAL/METHODS: Tissue from 15 patients with untreated CD, 6 patients with treated CD and 9 healthy control patients were stained using the standard H&E, Giemsa's staining for tissue sections and Alcian Blue protocols. A number of histological measures were then taken from each section and the data was used to ultimately design a set of linear predictive algorithms to calculate Marsh score. RESULTS: Using MANOVA and discriminant analysis, two linear functions were defined which could accurately predict the Marsh score of patients 62.5% (full Marsh score) to 79.2% (simplified Marsh score) of the time. CONCLUSIONS: This pilot study has shown that a set of objective histological measures can be used to define algorithms to predict Marsh score in CD patients and also monitor treatment compliance and progression.

Leptin pharmacokinetics in male mice.

Pharmacokinetics of leptin in mammals has not been studied in detail and only one study has examined more than one time point in non-mutant mice and this was in a female mice. This is the first study to describe leptin distribution over a detailed time course in normal male mice. A physiologic dose (12 ng) of radiolabelled leptin was injected into adult male mice via the lateral tail vein and tissues were dissected out and measured for radioactivity over a time course of up to two hours. Major targets were the digestive tract, kidneys, skin and lungs. The brain was not a major target, and 0.15% of the total dose was recovered from the brain 5 min after administration. Major differences appear to exist in the distribution of leptin between the male and female mice, indicating a high degree of sexual dimorphism. Although the half-lives were similar between male and female mice, almost twice the proportion of leptin was recovered from the digestive tract of male mice in comparison to that reported previously for females. This would seem to indicate a major difference in leptin distribution and possibly function between males and females.

The efficacy of isometric resistance training utilizing handgrip exercise for blood pressure management: A randomized trial.

INTRODUCTION: Hypertension is a major risk factor contributing to cardiovascular disease, which is the number one cause of deaths worldwide. Although antihypertensive medications are effective at controlling blood pressure, current first-line treatment for hypertension is nonpharmacological lifestyle modifications. Recent studies indicate that isometric resistance training (IRT) may also be effective for assisting with blood pressure management. The aim of this study was to determine the efficacy of IRT for blood pressure management and the suitability of a low-intensity working control group. METHODS: Forty hypertensive individuals, aged between 36 and 65 years, conducted IRT for 8 weeks. Participants were randomized into 2 groups, working at an intensity of either 5% or 30% of their maximum voluntary contraction. Participants performed 4 × 2 minute isometric handgrip exercises with their nondominant hand, each separated by a 3-minute rest period, 3 days a week. RESULTS: Blood pressure measurements were conducted at baseline and at the end of the protocol using a Finometer. Eight weeks of isometric resistance training resulted in a 7-mmHg reduction of resting systolic blood pressure (SBP) (136 ±â€Š12 to 129 ±â€Š15; P = 0.04) in the 30% group. Reductions of 4 mmHg were also seen in mean arterial pressure (MAP) (100 ±â€Š8 to 96 ±â€Š11; P = 0.04) in the 30% group. There were no statistically significant reductions in diastolic blood pressure for the 30% group, or any of the data for the 5% group. CONCLUSION: Isometric resistance training conducted using handgrip exercise at 30% of maximum voluntary contraction significantly reduced SBP and MAP. A lack of reduction in blood pressure in the 5% group indicates that a low-intensity group may be suitable as a working control for future studies.

The relationship between positive psychological characteristics and longer telomeres.

OBJECTIVE: Longer telomeres are associated with better health and longevity. This research investigated the relationship between positive psychological dispositional traits and telomere length. Positive traits examined were typical high positive affect, typical low negative affect, life satisfaction, trait mindfulness, trait emotional intelligence, general self-efficacy and optimism. DESIGN AND MEASURES: One hundred and twenty women and men, with a mean age of 40.92, completed measures of positive characteristics and provided samples for telomere length analysis. RESULTS: Together the positive dispositional characteristics explained significant variance in telomere length, R = .40. Among the individual characteristics, greater optimism and higher emotional intelligence were associated with longer telomeres after adjustment for age and gender and the association between optimism and telomere length remained significant after adjusting for age and gender as well as the other positive characteristics, with a partial correlation r of .30. CONCLUSION: These results in conjunction with previous research findings provide a platform for further exploration of biological pathways connecting positive characteristics such as optimism to telomere length and investigation of the impact of increasing a characteristic such as optimism on telomere functioning.

Isometric exercise training for blood pressure management: a systematic review and meta-analysis to optimize benefit.

The objective of our study was to examine the effects of isometric resistance training (IRT) on resting blood pressure in adults. We conducted a systematic review and meta-analysis of randomized-controlled trials lasting ⩾2 weeks, investigating the effects of isometric exercise on blood pressure in healthy adults (aged ⩾18 years), published in a peer-reviewed journal between 1 January 1966 to 31 January 2015. We included 11 randomized trials, totaling 302 participants. The following reductions were observed after isometric exercise training; systolic blood pressure (SBP) mean difference (MD) -5.20 mm Hg (95% confidence interval (CI) -6.08 to -4.33, P<0.00001); diastolic blood pressure (DBP) MD -3.91 mm Hg (95% CI -5.68 to -2.14, P<0.0001); and mean arterial blood pressure (MAP) MD -3.33 mm Hg (95% CI -4.01 to -2.66, P<0.00001). Sub-analyses showed males tended to reduce MAP MD -4.13 mm Hg (95% CI -5.08 to -3.18) more than females. Subjects aged ⩾45 years demonstrated larger reductions in MAP MD -5.51 mm Hg (95% CI -6.95 to -4.06) than those <45 years. Subjects undertaking ⩾8 weeks of IRT demonstrated a larger reduction in SBP MD -7.26 mm Hg (95% CI -8.47 to -6.04) and MAP MD -4.22 mm Hg (95% CI -5.08 to -3.37) than those undertaking<8 weeks. Hypertensive participants in IRT demonstrated a larger reduction in MAP MD -5.91 mm Hg (95% CI -7.94 to -3.87) than normotensive participants MD -3.01 mm Hg (95% CI -3.73 to -2.29). Our study indicated that IRT lowers SBP, DBP and MAP. The magnitude of effect may be larger in hypertensive males aged ⩾45 years, using unilateral arm IRT for >8 weeks.

Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep.

The aim of the present study was to determine the direct cause of the mutation-induced, increased ovulation rate in Booroola Merino (BB) sheep. Granulosa cells were removed from antral follicles before ovulation and post-ovulation from BB (n=5) and WT (n=12) Merino ewes. Direct immunofluorescence measurement of mature cell surface receptors using flow cytometry demonstrated a significant up-regulation of FSH receptor (FSHR), transforming growth factor beta type 1, bone morphogenetic protein receptor (BMPR1B), and LH receptor (LHR) in BB sheep. The increased density of FSHR and LHR provide novel evidence of a mechanism for increasing the number of follicles that are recruited during dominant follicle selection. The compounding increase in receptors with increasing follicle size maintained the multiple follicles and reduced the apoptosis, which contributed to a high ovulation rate in BB sheep. In addition, we report a mutation-independent mechanism of down-regulation to reduce receptor density of the leading dominant follicle in sheep. The suppression of receptor density coincides with the cessation of mitogenic growth and steroidogenic differentiation as part of the luteinization of the follicle. The BB mutation-induced attenuation of BMPR1B signaling led to an increased density of the FSHR and LHR and a concurrent reduction in apoptosis to increase the ovulation rate. The role of BMPs in receptor modulation is implicated in the development of multiple ovulations.

Biological determinants of depression following bereavement.

There is considerable variability among people in their response to bereavement. While most people adapt well to bereavement, some develop exaggerated and/or pathological responses and may meet criteria for a major depressive episode. Many studies have investigated the effect of psychosocial factors on bereavement outcome but biological factors have not received much attention, hence the focus of this paper. The biological factors studied to date in relation to bereavement outcomes include genetic polymorphisms, neuroendocrine factors, and immunologic/inflammatory markers. In addition, animal studies have shown the alterations of brain neurotransmitters as well as changes in the plasma levels of the neurotrophic growth factors under the influence of peer loss. Recent studies have also investigated the biological basis of stress resilience, and have found a few genetic polymorphisms and potential biomarkers as protective factors in the face of adversity. Longitudinal studies that include data collection prior to, and also after, bereavement and which chart both biological and psychological measures are needed to develop profiles for the prediction of response to bereavement and personalised interventions.

HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an Autistic Disorder.

Anxiety and Autistic Disorder (AD) are both neurological conditions and both disorders share some features that make it difficult to precisely allocate specific symptoms to each disorder. HPA and SAM axis activities have been conclusively associated with anxiety, and may provide a method of validating anxiety rating scale assessments given by parents and their children with AD about those children. Data from HPA axis (salivary cortisol) and SAM axis (salivary alpha amylase) responses were collected from a sample of 32 high-functioning boys (M age=11yr) with an Autistic Disorder (AD) and were compared with the boys' and their mothers' ratings of the boys' anxiety. There was a significant difference between the self-ratings given by the boys and ratings given about them by their mothers. Further, only the boys' self-ratings of their anxiety significantly predicted the HPA axis responses and neither were significantly related to SAM axis responses. Some boys showed cortisol responses which were similar to that previously reported in children who had suffered chronic and severe anxiety arising from stressful social interactions. As well as suggesting that some boys with an AD can provide valid self-assessments of their anxiety, these data also point to the presence of very high levels of chronic HPA-axis arousal and consequent chronic anxiety in these boys.

Exercise training program characteristics and magnitude of change in functional capacity of heart failure patients.

BACKGROUND: Intuitively higher exercise program volume may be the primary stimulus for physical adaptation. We sought to establish if aerobic exercise training program characteristics produced different effect sizes for change in cardiorespiratory fitness in heart failure patients. METHODS: We conducted a MEDLINE search (1966 to 2012), for exercise based rehabilitation trials in heart failure, using the search terms 'exercise training, left ventricular dysfunction, peak VO2, cardio-myopathy and systolic heart dysfunction'. Forty seven studies were included, producing 54 intervention groups; 3 (6%) were high-, 29 (54%) vigorous-, 20 (37%) moderate- and 2 (3%) low- intensity groups, providing a total of 2285 exercising subjects and 2098 control subjects, totaling 4383 participants. RESULTS: Peak VO2 increased by a mean difference of 3.3 ml kg(-1)min(-1) [95% CI 0.53 to 6.13, p=0.02] with high intensity training in exercise groups versus control, equating to a 23% improvement from baseline. The corresponding data for vigorous, moderate and low intensity were 8%, 13%; and 7% respectively. Weekly exercise energy expenditure >460 kcal was associated with a mean difference in peak VO2 of 2.6 ml kg(-1)min(-1) [95% CI 1.88 to 3.28, p<0.00001]. CONCLUSIONS: Our data suggest that high-intensity exercise, achieving at least 460 kcal weekly energy expenditure may elicit the greatest changes in cardiorespiratory fitness.

Application of testis germ cell transplantation in breeding systems of food producing species: a review.

A major benefit of advanced reproduction technologies (ART) in animal breeding is the ability to produce more progeny per individual parent. This is particularly useful with animals of high genetic merit. Testis germ cell transplantation (TGCT) is emerging as a novel reproductive technology with application in animal breeding systems, including the potential for use as an alternative to artificial insemination (AI), an alternative to transgenesis, part of an approach to reducing generation intervals, or an approach toward development of interspecies hybrids. There is one major difference in TGCT between rodents and some other species associated with immunotolerance in heterologous transplantation. In particular, livestock and aquatic species do not require an immunesuppression procedure to allow donor cell survival in recipient testis. Testicular stem cells from a genetically elite individual transplanted into others can develop and produce a surrogate male-an animal that produces the functional sperm of the original individual. Spermatozoa produced from testis stem cells are the only cells in the body of males that can transmit genetic information to the offspring. The isolation and genetic manipulation of testis stem cells prior to transplantation has been shown to create transgenic animals. However, the current success rate of the transplantation procedure in livestock and aquatic species is low, with a corresponding small proportion of donor spermatozoa in the recipient's semen. The propagation of donor cells in culture and preparation of recipient animals are the two main factors that limit the commercial application of this technique. The current paper reviews and compares recent progress and examines the difficulties of TGCT in both livestock and aquatic species, thereby providing new insights into the application of TGCT in food producing animals.

Clinical outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to establish whether aerobic exercise training intensity produces different effect sizes for fitness, adherence, event rates, mortality rates, and hospitalization rates in patients with heart failure. BACKGROUND: Intuitively, greater exercise intensity is considered to result in higher risk for serious events, but intensity may be the primary stimulus for physical adaptation. METHODS: A MEDLINE search (1985 to 2012) was conducted for exercise-based rehabilitation trials in heart failure, using the search terms "exercise training," "left ventricular dysfunction," "peak Vo2," "cardio-myopathy," and "systolic heart dysfunction." Seventy-four studies were included, producing 76 intervention groups; 9 (11.8%) were high-intensity, 38 (50%) vigorous-intensity, 24 (31.6%) moderate-intensity, and 5 (6.6%) low-intensity groups, providing a total of 3,265 exercising subjects and 2,612 control subjects. RESULTS: Peak oxygen consumption increased by a mean difference of 3.33 ml·kg(-1)·min(-1) (95% confidence interval [CI]: 0.53 to 6.13 ml·kg(-1)·min(-1); p = 0.02) with high-intensity training in exercise groups compared with control groups, equating to a 23% improvement from baseline. For vigorous intensity, the mean difference was 2.27 ml·kg(-1)·min(-1) (95% CI: 1.70 to 2.84 ml·kg(-1)·min(-1); p < 0.00001), with an 8% weighted mean; for moderate intensity, the mean difference was 2.17 ml·kg(-1)·min(-1) (95% CI: 1.34 to 2.99 ml·kg(-1)·min(-1); p < 0.00001), with a weighted mean of 13%; and for low intensity, the mean difference was 1.04 ml·kg(-1)·min(-1) (95% CI: -2.50 to 4.57 ml·kg(-1)·min(-1); p = 0.57), with a weighted mean of 7%. In 123,479 patient-hours of training, not a single death was directly attributable to exercise. CONCLUSIONS: As exercise training intensity rises, so may the magnitude of improvement in cardiorespiratory fitness, accompanied by lower study withdrawal in exercising patients. Total exercise time may be a confounder.

Effect of passive immunization against leptin on ovarian follicular development in prepubertal mice.

Leptin has been demonstrated to be essential for reproduction. However, all the relevant studies reported to date have investigated either the effect of a complete absence of leptin both centrally and peripherally, or excess leptin administration. The aim of this present study was to investigate the effect of reducing peripheral leptin concentrations on ovarian follicular development in prepubertal animals via administration of an anti-leptin antibody. Pre-pubertal female mice were administered anti-leptin antibody under the skin behind the head for four days, with or without gonadotropins, and ovaries were weighed and collected for follicle counting. Control animals were treated with non-immune serum. Passive immunization against leptin, with or without gonadotropins, resulted in a significant increase in ovarian weight compared with control ovaries. Furthermore, the ovaries from the anti-leptin group had significantly greater numbers of primary follicles per ovarian section than the control group, thus suggesting an increase in the transition of primordial to primary follicles after treatment. Interestingly, animals treated with anti-leptin plus gonadotropins had a significantly higher number of Graafian follicles in their ovaries compared with the other groups. Collectively, the results of the present study indicate that reduction of leptin in the circulation promotes ovarian follicle development in female mice, suggesting that peripheral leptin acts as an inhibitor of ovarian follicle development.

Insulinotrophic and insulin-like effects of a high molecular weight aqueous extract of Pterocarpus marsupium Roxb. hardwood.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterocarpus marsupium Roxb. (PM) is an Ayurvedic traditional medicine well known for its antidiabetic potential. AIM: To fractionate the antidiabetic constituent(s) of the aqueous of extract of PM hardwood (PME). MATERIALS AND METHODS: Bio-assay methods including, insulin secretion from mouse pancreas and glucose uptake by mouse skeletal muscle, were used to determine and fractionate the antidiabetic activity of PME. Results obtained from the in vitro experiments were then verified by examining the effect of PME on glucose clearance in normoglycemic, non-diabetic sheep in vivo. RESULTS: Exposure of mouse pancreatic and muscle tissues to PME stimulated the insulin secretion and glucose uptake, respectively, in a concentration-dependent manner. PME-mediated muscle glucose uptake was not potentiated in the presence of insulin indicating that PME acts via pathways which are utilized by insulin. Bio-assay-guided fractionation of PME yielded a high molecular weight fraction which had potent antidiabetic properties in vitro, and in in vivo. CONCLUSIONS: Our findings, we believe for the first time, provide novel insights for the antidiabetic constituents of PM and demonstrate that a high molecular weight constituent(s) of PM has potent insulinotrophic and insulin-like properties.

Stress-linked cortisol concentrations in hair: what we know and what we need to know.

Cortisol has major impacts upon a range of physiological homeostatic mechanisms and plays an important role in stress, anxiety and depression. Although traditionally described as being solely synthesised via the hypothalamic-pituitary-adrenal (HPA) axis, recent animal and human studies indicate that cortisol may also be synthesised via a functionally-equivalent 'peripheral' HPA-like process within the skin, principally within hair follicles, melanocytes, epidermal melanocytes and dermal fibroblasts. Current data indicate that basal levels of cortisol within hair vary across body regions, show diurnal variation effects, respond to the onset and cessation of environmental stressors, and may demonstrate some degree of localisation in those responses. There are conflicting data regarding the presence of variability in cortisol concentrations across the length of the hair shaft, thus challenging the suggestion that hair cortisol may be used as a historical biomarker of stress and questioning the primary origin of cortisol in hair. The need to comprehensively 'map' the hair cortisol response for age, gender, diurnal rhythm and responsivity to stressor type is discussed, plus the major issue of if, and how, the peripheral and central HPA systems communicate.