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Maternal major depressive disorder with peripartum onset presents health risks to the mother and the developing fetus. Using a rat model of chronic mild stress, we previously reported on the neurodevelopmental impact of maternal perinatal stress on their offspring. This study examined the cardiovascular impact of maternal perinatal stress on their offspring. The cardiovascular impact was assessed in terms of blood pressure and echocardiographic parameters. The results examined by a three-way ANOVA showed a significant association of cardiovascular parameters with maternal perinatal stress and offspring sex and age. Increased blood pressure was observed in adolescent female and adult male offspring of stress-exposed dams. Echocardiography showed an increase in left atrial dimension and a reduction in left ventricular systolic function in adolescent stress-exposed female offspring. Increased interventricular septum thickness at end-diastole and left ventricular diastolic dysfunction were observed in adult stress-exposed male offspring. The underlying mechanisms of cardiovascular impact were examined in stress-exposed adult offspring by assessing the levels of neurotransmitters and their metabolites in the medulla oblongata using high-performance liquid chromatography. A significant decrease in homovanillic acid, a dopamine metabolite and indicator of dopaminergic activity, was observed in adult stress-exposed female offspring. These results suggest a significant sex- and age-dependent impact of maternal stress during the peripartum period on the cardiovascular system in the offspring that extends to adulthood and suggests a multigenerational effect. The presented data urgently need follow-up to confirm their potential clinical and public health relevance. NEW & NOTEWORTHY: We demonstrate that maternal perinatal stress is associated with sex- and age-dependent impact on the cardiovascular system in their offspring. The effect was most significant in adolescent female and adult male offspring. Observed changes in hemodynamic parameters and dopaminergic activity of the medulla oblongata are novel results relevant to understanding the cardiovascular impact of maternal perinatal stress on the offspring. The cardiovascular changes observed in adult offspring suggest a potential long-term, multigenerational impact of maternal perinatal stress. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase 5 inhibitors (PDE5i), since their introduction in the late 1990s, have proven their efficacy in treating several conditions, predominantly pulmonary hypertension and erectile dysfunction where they remain the first-line therapeutic option. However, in the recent years, growing evidence from both animal and human studies has emerged to suggest the additional benefits of PDE5i in cardiovascular and metabolic disorders. This is of specific interest to the diabetes population where prevalent cardiovascular disease andmetabolic dysregulation significantly contribute to the increased morbidity and mortality. Objectives: To examine the available data on the non-standard, pleiotropic effects of PDE5i in patients with diabetes mellitus. Materials and methods: The review of the published background research, preclinical studies and clinical trials. Results: In human studies, PDE5 inhibition appeared to be associated with reduced cardiovascular mortality and overall improved clinical outcomes in those with established cardiovascular disease. PDE5i were also consistently found to reduce albuminuria in subjects with diabetic nephropathy. Furthermore, animal data suggest a plausible effect of this group of medication on sensory function and neuropathic symptoms in diabetic neuropathy as well as improved wound healing. A decrease in insulin resistance and augmentation of beta cell function seen in preclinical studies has not been consistently demonstrated in human trials. Discussion and conclusion: In animal models, PDE5 inhibition appears to decrease oxidative stress and reduce some of the micro- and macrovascular complications associated with diabetes. However, data from human trials are limited and largely inconsistent, highlighting the need for adequately powered, randomised-controlled trials in diabetic cohorts in order to fully assess the benefits of PDE5i in this group of patients. [ABSTRACT FROM AUTHOR]

Maternal depression during pregnancy affects 18–20% of women and is often associated with comorbidities and adverse health outcomes for the offspring. We have previously reported on neurodevelopmental delays in a rat model of maternal depression during pregnancy; current report presents echocardiographic (ECHO) data derived from the same experiment and focuses on cardiovascular response in the offspring to maternal perinatal depression. Rat dams were exposed to chronic mild stress (CMS) with repeated restraint before pregnancy. Cardiac functions were assessed in the 35-day-old offspring, derived from control (CO, n = 11) and stress-exposed dams (SO, n = 16), using echocardiography (ECHO). The expression of cardiac failure marker – B-type natriuretic peptide (BNP) was measured in the myocardium by RT-PCR. ECHO analysis revealed a significant increase in heart rate (HR) and impairment of left ventricular diastolic function parameters. Importantly, a significant increase in mitral valve flow E wave velocity (MVE) and a decrease of mitral valve deceleration time of E wave (MV DT) were observed in SO. The expression of BNP was significantly higher in SO. These results suggest that maternal depression during pregnancy impacts offspring cardiovascular function, and specifically the diastolic cardiac functions of the left ventricle. [ABSTRACT FROM AUTHOR]

Objective In ageing men, the incidence and clinical significance of testosterone (T) decline accompanied by elevated luteinizing hormone ( LH) are unclear. We describe the natural history, risk factors and clinical features associated with the development of biochemical primary hypogonadism ( PHG, T < 10·5 nmol/l and LH>9·4U/l) in ageing men. Design, Patients and Measurements A prospective observational cohort survey of 3,369 community-dwelling men aged 40-79 years, followed up for 4·3 years. Men were classified as incident (i) PHG (eugonadal [ EUG, T ≥ 10·5 nmol/l] at baseline, PHG at follow-up), persistent (p) PHG ( PHG at baseline and follow-up), pEUG ( EUG at baseline and follow-up) and reversed (r) PHG ( PHG at baseline, EUG at follow-up). Predictors and changes in clinical features associated with the development of PHG were analysed by regression models. Results Of 1,991 men comprising the analytical sample, 97·5% had pEUG, 1·1% iPHG, 1·1% pPHG and 0·3% rPHG. The incidence of PHG was 0·2%/year. Higher age (>70 years) [ OR 12·48 (1·27-122·13), P = 0·030] and chronic illnesses [ OR 4·24 (1·08-16·56); P = 0·038] predicted iPHG. Upon transition from EUG to PHG, erectile function, physical vigour and haemoglobin worsened significantly. Men with pPHG had decreased morning erections, sexual thoughts and haemoglobin with increased insulin resistance. Conclusions Primary testicular failure in men is uncommon and predicted by old age and chronic illness. Some clinical features attributable to androgen deficiency, but not others, accompanied the T decline in men who developed biochemical PHG. Whether androgen replacement can improve sexual and/or physical function in elderly men with PHG merits further study. [ABSTRACT FROM AUTHOR]

Maternal depression during pregnancy affects 18-20% of women and is often associated with comorbidities and adverse health outcomes for the offspring. We have previously reported on neurodevelopmental delays in a rat model of maternal depression during pregnancy; current report presents echocardiographic (ECHO) data derived from the same experiment and focuses on cardiovascular response in the offspring to maternal perinatal depression. Rat dams were exposed to chronic mild stress (CMS) with repeated restraint before pregnancy. Cardiac functions were assessed in the 35-day-old offspring, derived from control (CO, n  = 11) and stress-exposed dams (SO, n  = 16), using echocardiography (ECHO). The expression of cardiac failure marker - B-type natriuretic peptide (BNP) was measured in the myocardium by RT-PCR. ECHO analysis revealed a significant increase in heart rate (HR) and impairment of left ventricular diastolic function parameters. Importantly, a significant increase in mitral valve flow E wave velocity (MVE) and a decrease of mitral valve deceleration time of E wave (MV DT) were observed in SO. The expression of BNP was significantly higher in SO. These results suggest that maternal depression during pregnancy impacts offspring cardiovascular function, and specifically the diastolic cardiac functions of the left ventricle.