The effect of simvastatin in pancreas of diabetic rats

Growing evidences suggest that statins exert several cholesterol-independent pleiotropic effects in diabetes, but there is no consensus whether they are positive or negative. To shed more light on this issue, we examined the effect of simvastatin on β-cell regeneration in a diabetic state. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were additionally separated into two subgroups: treated with simvastatin (5 mg/kg/day, i.g., 12 days) and control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol/L). Our findings revealed that there is no increase in the area of insulin-immunopositive cells neither normalization of serum insulin level after simvastatin treatment of diabetic animals, although simvastatin increased nuclear immunopositivity for pancreas duodenum homeobox-1 (PDX-1) and proliferating cell nuclear antigen (PCNA). The data from this study suggest that 12-day treatment with simvastatin did not improve diabetes- induced disturbances in β-cell mass/function

Impact of nutrition on human fertility

Infertility is one of the most serious medical issues that is dramatically rising worldwide. Extensive research dedicated to this problem clearly shows that infertility is a disease of modern society and that a nutrition has a great infl uence on the development of sterility. Thus, the impact of specifi c nutritional factors, i.e. diet pattern on both male and female fertility is included in this review. It is encouraging that modifi cation of nutritional habits can help couples to conceive spontaneously, or increase their chances of conception with in vitro fertilization (IVF) treatment

Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling

Background: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. Materials and methods: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. Results: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. Conclusions: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology

Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut

Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43. Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population

Valdecoxib stability properties under forced degradation conditions

The present work describes forced degradation study of valdecoxib, under different ICH recommended stress conditions - photolytic degradation, oxidation, hydrolysis in alkaline and acidic conditions as well as its thermal degradation. Stress studies were performed at valdecoxib drug substance and the final dosage form. Chromatographic separations of drug and the degradation products formed under various experimental conditions was successfully achieved on RP-18e Chromolith® performance monolithic column (100 mm × 4.6 mm, macropore size 2 μm, mesopore size 13 nm) with an eluent containing the mixture of methanol and water solution of TEA (1%, pH 7.4) in the ratio 40:60 (v/v) while the column temperature was adjusted to 30°C. Detection was performed using photodiode array detector on several wavelengths in order to ensure the proper insight into drug degradation pathway in case the formed products differ in absorption characteristics

Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology.

Infertility is a significant global health problem that currently affects one of six couples in reproductive age. The quality of male reproductive cells dramatically decreased over the last years and almost every aspect of modern life additionally worsen sperm functional parameters that consequently markedly increase male infertility. This clearly points out the importance of finding a new approach to treat male infertility. Redox signaling mediated by reactive oxygen, nitrogen and sulfur species (ROS, RNS, and RSS respectively), has appeared important for sperm reproductive function. Present review summarizes the current knowledge of ROS, RNS, and RSS in male reproductive biology and identifies potential targets for development of novel pharmacological and therapeutic approaches for male infertility by targeted therapeutic modulation of redox signaling

Level of NO/nitrite and 3-nitrotyrosine in seminal plasma of infertile men: Correlation with sperm number, motility and morphology.

Nitric oxide (NO) is a signaling molecule responsible for initiation of molecular events that influence sperm functionality in a concentration-dependent manner. It is still not fully understood how seminal plasma NO contributes to sperm pathologies. The aim of this study was to elucidate whether and how NO is implicated in etiology of different sperm abnormalities. To this end we determine NO, nitrite and 3-nitrotyrosine (3-NT) content in seminal plasma of infertile men with specific pathologies (terato-, oligoterato- and oligoasthenoteratospermia) and relate it to infertile normospermic samples. To gain further understanding of NO metabolism in seminal plasma we determine protein expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). Here we show that NO, nitrite and 3-NT levels in seminal plasma of men with suboptimal semen parameters are significantly lower compared to normospermic men. An increase in protein expression of eNOS and no change in protein expression of iNOS is observed in men with sperm pathologies. Association of seminal plasma 3-NT level with functional sperm parameters is observed - positive correlation with sperm count, motility and morphology in normospermia, teratospermia and oligoteratospermia, as well as negative correlation with sperm morphology and motility in oligoasthenoteratospermia. Present study revealed that suboptimal seminal plasma NO content is found in all examined sperm pathologies. This result unequivocally shows the importance of NO for sperm function and involvement of suboptimal NO level in etiology of sperm abnormalities. Lower seminal plasma 3-NT level and its significant association with sperm parameters, found in pathologies, strongly indicates that protein nitration is important for spermatozoa function and that failure to establish this post-translational protein modification might be involved in etiology of sperm abnormalities. According to our results, NO measurement can discriminate infertile men with sperm pathologies from infertile normospermic men but is not indicative of a specific type of sperm pathology

The role of nitric oxide in diabetic skin (patho)physiology

The role of nitric oxide (NO) in cutaneous physiology/pathology became a growing research field since the discovery that almost all types of skin cells can synthetize this redox signaling molecule about 20 years ago. Now, it is evident that NO is an important player in skin physiological processes and in responses of cutaneous cells to external insults, while the impaired NO signaling has an important consequence in skin pathology. Skin disorders are common complications in diabetic conditions. Various metabolic/biochemical and immunological dysregulations in diabetic skin are tightly coupled with the disturbances in the redox state, primarily the ratio between NO and superoxide (O(cyrillic) 2 - ). This review describes possible therapeutic significance of different redox state modulators in the treatment of diabetic skin disorders. The focus is on those modulators that tightly control NO/O(cyrillic) 2 - ratio through the complex mechanisms affecting endogenous NO and O(cyrillic) 2 - producing and removing systems. The fact that classic antioxidants failed to show significant benefits in diabetes, emphasizes the importance of such redox mechanism-based and targeted approaches

Physiological regulation and metabolic role of browning in white adipose tissue

Great progress has been made in our understanding of the browning process in white adipose tissue (WAT) in rodents. The recognition that i) adult humans have physiologically inducible brown adipose tissue (BAT) that may facilitate resistance to obesity and ii) that adult human BAT molecularly and functionally resembles beige adipose tissue in rodents, reignited optimism that obesity and obesity-related diabetes type 2 can be battled by controlling the browning of WAT. In this review the main cellular mechanisms and molecular mediators of browning of WAT in different physiological states are summarized. The relevance of browning of WAT in metabolic health is considered primarily through a modulation of biological role of fat tissue in overall metabolic homeostasis.Hormone Molecular Biology and Clinical Investigation (2017), 31(1): 2017003