EFFECT OF STRESS ON HISTOPATHOLOGY OF MALE REPRODUCTIVE SYSTEM IN RATS

Background: Although relatively little is known about factors affecting fertility. Latest literature suggests that environmental and lifestyle factors play an important role. Recently, oxidative stress has become the focus of interest as potential cause of male infertility. Oxidative stress may play a role in a number of conditions known to be detrimental to male fertility Method: Adult male albino rats weighing 200 - 220 g and aged 12-15 weeks male rats were selected for the study. The rats were randomly analyzed into 3 groups Group 1: Control rat, Group 2: Swimming stress without treatment, Group 3: Treated with vitamin C 30mg/kg/day doses. All rats were subjected to swimming stress daily between 9.00 AM to 10.00 AM until 50 days. Drugs were administered orally for 50 days half an hour before subjecting to stress. At end of the study the reproductive organs testes, seminal vesicles, Vas deferens and prostate were dissected and the samples were used for the histo-pathological evaluation. Result: In stress group section of testis shows seminiferous tubules showed focial poor spermatogenesis with reduction in number of sperm containing seminiferous tubules and absence of spermatozoa was clearly recognized in some seminiferous tubules. Treatment with antioxidant showed recovery but still some of the seminiferous tubules showed decreased spermatozoa. Stress changes in seminal vesicle: the hyperplasia of epithelial lining, histological features of mucosa severely affected and reduced number of gland. Stress induced changes in vas deferens: produced desquamated ling epithelium with atrophic changes and mild exploited epithelium, degenerated basement membrane of vas deferens. Stress induced changes in prostate: Prostatic acini with many papillary folds, desquamated epithelial cells, epithelial proliferation was seen. Conclusion: Oxidative stress produced deleterious effects on male reproductive system and supplementation of antioxidants such as vitamin C have been shown to be protecting effect against the histological changes produced by the oxidative stress on male reproductive system in rats.KEYWORDS:  Stress; Male reproductive organs; Histopathology; Rat

EFFECT OF STRESS ON HISTOPATHOLOGY OF MALE REPRODUCTIVE SYSTEM IN RATS

Background: Although relatively little is known about factors affecting fertility. Latest literature suggests that environmental and lifestyle factors play an important role. Recently, oxidative stress has become the focus of interest as potential cause of male infertility. Oxidative stress may play a role in a number of conditions known to be detrimental to male fertility Method: Adult male albino rats weighing 200 - 220 g and aged 12-15 weeks male rats were selected for the study. The rats were randomly analyzed into 3 groups Group 1: Control rat, Group 2: Swimming stress without treatment, Group 3: Treated with vitamin C 30mg/kg/day doses. All rats were subjected to swimming stress daily between 9.00 AM to 10.00 AM until 50 days. Drugs were administered orally for 50 days half an hour before subjecting to stress. At end of the study the reproductive organs testes, seminal vesicles, Vas deferens and prostate were dissected and the samples were used for the histo-pathological evaluation. Result: In stress group section of testis shows seminiferous tubules showed focial poor spermatogenesis with reduction in number of sperm containing seminiferous tubules and absence of spermatozoa was clearly recognized in some seminiferous tubules. Treatment with antioxidant showed recovery but still some of the seminiferous tubules showed decreased spermatozoa. Stress changes in seminal vesicle: the hyperplasia of epithelial lining, histological features of mucosa severely affected and reduced number of gland. Stress induced changes in vas deferens: produced desquamated ling epithelium with atrophic changes and mild exploited epithelium, degenerated basement membrane of vas deferens. Stress induced changes in prostate: Prostatic acini with many papillary folds, desquamated epithelial cells, epithelial proliferation was seen. Conclusion: Oxidative stress produced deleterious effects on male reproductive system and supplementation of antioxidants such as vitamin C have been shown to be protecting effect against the histological changes produced by the oxidative stress on male reproductive system in rats.KEYWORDS:  Stress; Male reproductive organs; Histopathology; Rat

Role of Antioxidants in Male Reproduction: Review

To counter oxidative stress, cells constitutively express enzymes that detoxify the reactive oxygen species and repair the damage. An antioxidant is any substance that when present at low concentrations compared to those of an oxidizable substrate significantly delays or prevents oxidation of that substrate. The antioxidant enzymes are major cell defense against acute oxygen toxicity. The functions of these antioxidant enzymes are to protect the membrane and cytosolic components against damage caused by free radicals. Glutathione peroxidase, Superoxide dismutase, glutathione-s-transferase, catalase, xanthine oxidase. Amongst a variety of antioxidants; vitamin E antioxidant use is essential because it travels through the body in molecules called lipoproteins and protect them from oxidation. For Many years, vitamin E considered as an anti-sterility factor. In the male reproductive system, vitamin C is known to protect spermatogenesis, and it plays a major role in semen integrity and fertility in men. It increases testosterone levels and prevents sperm agglutination. It is an important chain-breaking antioxidant, contributing up to 65 % of the total antioxidant capacity of seminal plasma found intracellularly and extracellularly. N-Acetyl cysteine reacts with highly oxidizing radicals such as ˙OH, ˙NO2, CO3˙‑, and also bind redox-active metal ions. Thiosl can also afford radioprotection through the donation of reducing equivalents. Keywords: Antioxidants; Male fertility; Sperm quality

Role of Antioxidants in Male Reproduction: Review

To counter oxidative stress, cells constitutively express enzymes that detoxify the reactive oxygen species and repair the damage. An antioxidant is any substance that when present at low concentrations compared to those of an oxidizable substrate significantly delays or prevents oxidation of that substrate. The antioxidant enzymes are major cell defense against acute oxygen toxicity. The functions of these antioxidant enzymes are to protect the membrane and cytosolic components against damage caused by free radicals. Glutathione peroxidase, Superoxide dismutase, glutathione-s-transferase, catalase, xanthine oxidase. Amongst a variety of antioxidants; vitamin E antioxidant use is essential because it travels through the body in molecules called lipoproteins and protect them from oxidation. For Many years, vitamin E considered as an anti-sterility factor. In the male reproductive system, vitamin C is known to protect spermatogenesis, and it plays a major role in semen integrity and fertility in men. It increases testosterone levels and prevents sperm agglutination. It is an important chain-breaking antioxidant, contributing up to 65 % of the total antioxidant capacity of seminal plasma found intracellularly and extracellularly. N-Acetyl cysteine reacts with highly oxidizing radicals such as ˙OH, ˙NO2, CO3˙‑, and also bind redox-active metal ions. Thiosl can also afford radioprotection through the donation of reducing equivalents. Keywords: Antioxidants; Male fertility; Sperm quality

Hyperphosphaturic Mesenchymal Tumor induced Osteomalacia– A Case Report

Hyperphosphaturic Mesenchymal Tumor (HMT) is a very rare benign tumor of the soft tissue or bone which produces tumorinduced osteomalacia, also called as oncogenic osteomalacia. This activity can only be stopped by the surgical removal of thetumor. We present a 23 years old man who presented with long standing bony pains without any relief by a variety ofmedications. The clue to the diagnosis was taken from pelvis skiagram, Magnetic Resonance Imaging (MRI) of the body, PETscan and the blood chemistry

Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B

Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-α and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines

Cardiorespiratory fitness, fatness and the acute blood pressure response to exercise in adolescence

Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) areindependent contributors to cardiovascular risk, but their interrelated associationswith exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort ofadolescents.Methods: 2292 adolescents from the Avon Longitudinal Study of Parents andChildren (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercisestep test that allowed fitness (VO2 max) to be determined from workload and heart rateusing a validated equation. Exercise BP was measured immediately on test cessationand fatness calculated as the ratio of total fat mass to total body mass measured byDXA.Results: Post-exercise systolic BP decreased stepwise with tertile of fitness (146(18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142(16); 149 (18) mmHg). In separate models, fitness and fatness were associated withpost-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomicstatus (standardized β: −1.80, 95%CI: −2.64, −0.95 mmHg/SD and 4.31, 95%CI:3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in thesame model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69,5.61 mmHg/SD).Conclusion: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness mayonly be realized with more favorable body composition

Mutations in the latent TGF-beta binding protein 3 (LTBP3) gene cause brachyolmia with amelogenesis imperfecta

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Structural Modeling and DNA Binding Autoinhibition Analysis of Ergp55, a Critical Transcription Factor in Prostate Cancer

BACKGROUND: The Ergp55 protein belongs to Ets family of transcription factor. The Ets proteins are highly conserved in their DNA binding domain and involved in various development processes and regulation of cancer metabolism. To study the structure and DNA binding autoinhibition mechanism of Ergp55 protein, we have produced full length and smaller polypeptides of Ergp55 protein in E. coli and characterized using various biophysical techniques. RESULTS: The Ergp55 polypeptides contain large amount of α-helix and random coil structures as measured by circular dichorism spectroscopy. The full length Ergp55 forms a flexible and elongated molecule as revealed by molecular modeling, dynamics simulation and structural prediction algorithms. The binding analyses of Ergp55 polypeptides with target DNA sequences of E74 and cfos promoters indicate that longer fragments of Ergp55 (beyond the Ets domain) showed the evidence of auto-inhibition. This study also revealed the parts of Ergp55 protein that mediate auto-inhibition. SIGNIFICANCE: The current study will aid in designing the compounds that stabilize the inhibited form of Ergp55 and inhibit its binding to promoter DNA. It will contribute in the development of drugs targeting Ergp55 for the prostate cancer treatment