We have analyzed the following polymorphisms: C677T (rs 1801133) and A1298C (rs 1801131) in the methylenetetrahydrofolate reductase (MTHFR) gene in Bulgarian patients with non-obstructive azoospermia, attending reproductive clinics. We have compared the allele and genotype frequencies of both the MTHFR C677T and A1298C polymorphisms in our population to the European population and to a Bulgarian control group (n = 350). The results of our research have revealed a trend for a significantly higher frequency of the homozygote C/C genotype of MTHFR A1298C polymorphism in comparison to the European and Bulgarian controls (p < 0.08). The prevalence of the C/C homozygotes can be accepted as a risk factor for the development of non-obstructive azoospermia, especially in addition to other external and internal factors—diet, vitamin intake, other genetic polymorphisms or mutations in the genes involved in spermatogenesis.

Serotonin syndrome (SS) is a potentially life-threatening adverse drug effect that occurs after an overdose or combined administration of two or more drugs that increase the serotonin levels. In humans, SS is represented by a triad of symptoms including mental status changes, neuromuscular hyperactivity and autonomic dysfunction. The manifestations of the syndrome observed in rodents resemble the symptoms of SS in humans. Theoretically, SS can occur as a result of stimulation of any of the seven families of the serotonin receptors. However, most data support the involvement of 5-HT1A and 5-HT2A receptors. A number of studies indicate the effectiveness of 5-HT2 antagonists and GABA-ergic agents in the treatment of the hyperthermia and other symptoms of SS in rats. Therefore, animal models of SS may help to further elucidate the mechanism of its development and the possibilities for its treatment.

Background and aims: We investigated the effect of WAY-163909, a novel 5-hydroxytryptamine selective 2C receptor agonist on body weight, blood glucose levels, and insulin resistance in obese and diabetic Wistar rats. Materials and methods: We used twenty male Wistar rats with obesity and obesity-induced diabetes and twenty healthy Wistar rats as a control group. Each of these groups was separated into two subgroups: one with a daily intraperitoneal application of WAY-163909 (1 mg/kg) and one without. During the study, body weight, blood glucose levels, and immunoreactive insulin were tracked. Results: A reduction of 5.5% (p < 0.05) in body weight was registered in the rat group with diabetes and obesity and 2.56% in the control group with a daily application of WAY-163909 (1 mg/kg) at the end of the study. Decreases of 35.4% in blood glucose levels at week four in the diabetic and obese rat group with a daily application of WAY-163909 (1 mg/kg) were registered. A reduction of insulin levels of 4.1% (p < 0.05) in the diabetic and obese rats group using WAY-163909 was also observed. Conclusion: In our study, using WAY-163909 (1 mg/kg) led to a reduction of blood glucose levels, immunoreactive insulin, and body weight.

Unpredictable, dose-limiting toxicity remains a challenge in cancer treatment. We evaluated dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) plasma levels in the context of chemotherapy-induced toxicity and disease progression. Seventy gastrointestinal cancer patients (30 FOLFOX; 40 FOLFIRI) were enrolled. DPD and UGT1A1 plasma levels were determined using ELISA. Univariable and bivariable analyses and a general linear model (GLM) framework were used. Post-infusional reductions in white blood cell and granulocyte counts were observed. For FOLFOX, the granulocyte counts decreased by 17% (r = 0.54; p = 0.0030), while FOLFIRI caused a 41% reduction (r = 0.43; p = 0.0063). DPD levels were lower in FOLFOX than in FOLFIRI (2.543 vs. 3.579; p = 0.0363; Cohen’s d = 0.52). The multiple linear regression models associated DPD levels with cancer progression (b* = 0.258, p = 0.034). The bivariate analysis and multiple linear regression indicated some trends of association between UGT1A1 levels and reduction in white blood cell (b* = 0.359, p = 0.042) and granulocyte counts (b* = 0.383, p = 0.030) among FOLFIRI-treated patients. These preliminary observations suggest that DPD and UGT1A1 might contribute to evaluating response assessment.

Alcohol misuse can lead to alcohol-related brain damage (ARBD), a condition linked to long-term cognitive impairment and considerable disease burden. The pharmacological characteristics of alpha-lipoic acid (ALA) make it a promising candidate for the treatment of ARBD. In this study, adult male Wistar rats were divided into eight experimental groups. Four groups received a 20% (v/v) ethanol–tap water solution ad libitum for 15 weeks to induce early-stage ARBD, while the remaining received only tap water. After 14 weeks, all groups were administered daily injections for one week with either ALA, rivastigmine, or memantine. Behavioral testing included the step-through passive avoidance and rotarod performance tests. Whole-brain biochemical analyses assessed acetylcholinesterase activity, brain-derived neurotrophic factor, and oxidative stress biomarkers. Brain weight, relative brain weight, and brain histopathological changes were also evaluated. Results showed that, similar to memantine and rivastigmine, ALA improved STL at both 24 h and 8 days and reduced ethanol-induced Purkinje cell damage. It also decreased lipid peroxidation levels by 44%, unlike the reference drugs, and superoxide dismutase activity by 33%, similar to them. No other significant changes were detected. Albeit several limitations, this is the first study comparing ALA with rivastigmine and memantine in this experimental context.