To investigate the role of sex and the role of ammonia and amino acid metabolism, specifically the activity of glutamine synthetase, in survival and disease progression in amyotrophic lateral sclerosis.
We tested treatment with methionine sulfoximine (MSO) on the lifespan and neuromuscular ability of male and female SOD1 mice as measured by their ability to maintain their grip on an inverted wire grid. We also tested the effects of castration and ovariectomization on those measurements.
MSO treatment improves the survival of both male and female mice, but the effects are significantly greater on female mice. Saline-treated (control) female mice have delayed neuromuscular degeneration compared with saline-treated male mice, and MSO further delays disease progression in females, to a greater extent than in males. Ovariectomization or castration completely eliminates the effect of the drug on either survival or neuromuscular deterioration.
Sex is an important factor in disease progression and the response of SOD1 mice to a drug targeting a central enzyme in nitrogen metabolism, with female sex hormones playing a greater role than male sex hormones. Glutamine synthetase, or its reactants and products, therefore plays a role in this disease, and the sex specificity of treatments aimed at this or other metabolic targets may therefore be an important factor in the development of therapies to treat amyotrophic lateral sclerosis.
Metabolism interaction between corticosteroids and tacrolimus (Tac) exists and can be an important factor in providing rational pharmacotherapy in kidney transplantation patients. Both Tac and corticosteroids can induce adverse metabolic effects, such as hyperglycemia, post-transplantation diabetes mellitus, and dyslipidemia.
The main goal of this study was to detect corticosteroid dose influence on Tac level within the first 6 months of immunosuppressive therapy. The secondary goal of this research was to investigate sex differences on Tac−corticosteroid interaction. We also monitored biochemical-parameter changes, which are related to immunosuppressive treatment.
This retrospective pharmacokinetic study included 30 Serbian patients after kidney transplantation. Patients received a quaternary immunosuppressive regimen including Tac, mycophenolate, mofetil, basiliximab, and corticosteroids. To compare dose-normalized level and dose of Tac in different days after transplantation, we performed the Friedman test and Wilcoxon matched-pairs signed rank sum test. Mann-Whitney test was performed to compare differences in dose of Tac, level of Tac, and dose-normalized level of Tac between male and female patient groups. We used the Friedman test to compare biological and clinical data.
Obtained results show statistical significance between dose of Tac on day 180 post transplantation and dose on days 7, 14, 21, and 60 post transplantation. There was a statistical difference in dose-normalized level of Tac between days 7 and 21 post transplantation (P < 0.01), days 7 and 60 (P < 0.01), and between days 7 and 180 (P < 0.05). There is a statistical significance between male and female levels of Tac on day 21 after transplantation (P < 0.01). Significance also exists on day 60 after transplantation between male and female dose-normalized levels (P < 0.05). There is also a statistical difference in glucose, cholesterol, triglyceride, serum creatinine, and urea level and activity of alanine aminotransferase and alkaline phosphatase before and after operation.
Our study shows that dose of corticosteroid affects Tac level in kidney transplantation patients. Tac dose and level changes showed that corticosteroid−Tac interaction has more influence on male than female patients. According to biochemical monitoring, the immunosuppressive therapy used at present is quite well tolerated.
Biological sex and sociocultural gender influence stress-related diseases. Our goal was to explore whether sex and gender roles would predict both allostatic load and physical complaints.
This study investigated whether sex- and gender-based factors would correspond to objective and subjective health outcomes.
Thirty Montreal workers (mean [SE] age, 45.4 [2.1] years) participated. The 30-item Bem Sex Role Inventory was administered to assess scores for masculinity and femininity, which were then transformed into an androgyny index representing gender roles along a continuum. Fifteen biomarkers representing neuroendocrine, immune, metabolic, and cardiovascular systems were aggregated into an allostatic load index measuring physiological dysregulations. The 42-item Wahler Physical Symptoms Inventory was used to measure self-rated physical complaints.
Results using logistic and linear regressions controlling for age revealed that increased masculinity predicted inclusion in the high allostatic load group (P = 0.010; odds ratio = 0.715), and sex did not; increased masculinity and female sex together predicted increased physical complaints (P = 0.008; adjusted r2= 0.30); and high allostatic load group membership corresponded to increased physical complaints adjusted (P = 0.001; adjusted r2 = 0.301).
That higher masculinity was related to increased objective physiological dysregulations and subjective physical complaints suggests an increased vulnerability to hyperarousal pathologies, such as cardiovascular disease, among masculine-typed individuals.
Across the industrialized world, men experience an earlier onset of cardiovascular disease (CVD) and a life expectancy 5 to 10 years shorter than women. Low total testosterone (TT) concentrations in men have been suggested as a novel CVD risk factor, but its contribution to this gender gap is less well studied.
We used data of 4152 individuals (2113 women and 2039 men) aged 20 to 79 years from the longitudinal population-based cohort Study of Health in Pomerania, Germany. Multivariable Poisson and Cox proportional hazard regression models were used to investigate the risk of incident cardiovascular morbidity (5-year examination follow-up), as well as all-cause and CVD mortality (10-year follow-up) between men and women. Additionally, the added risk attributable to low TT in men (<10th percentile) was assessed.
Compared with women, men were uniformly at higher risk of incident cardiovascular morbidity, including overweight, hypertension, dyslipidemia, metabolic syndrome, and type 2 diabetes mellitus. Men were also at increased all-cause mortality (hazard ratio = 2.05; 95% CI, 1.61–2.60) and 10-year CVD risk compared with women. In subgroup analyses, men with low TT showed the highest 10-year CVD and mortality risk compared with both men with higher TT and women. TT was also negatively associated with cardiovascular risk as defined by the Framingham risk score (P < 0.001), after multivariable adjustment.
Analyzing a large population-based sample, we observed that men have a generally higher risk of incident cardiovascular morbidity and mortality. Furthermore, men with low TT concentrations were identified as high-risk individuals with regard to 10-year CVD and mortality risk.
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