[Molecular mechanisms of male infertility: main directions of scientific research].

This review provides up-to-date information on the molecular basis of the pathogenesis of male infertility at the cellular and subcellular levels. The emphasis is on the importance of new next-generation sequencing technologies as a high-performance tool for studying the genome and epigenomic mechanisms, transcriptome, proteome and metabolome of ejaculate, and organs of the reproductive system. This methodology made it possible to identify differentially expressed metabolic and signaling pathways in fertile and infertile men that combine the genotype and phenotype of a particular individual into a single whole. The current ideas about the relationship between oxidative stress and imbalance of redox systems with DNA damage in spermatozoa as the leading mechanism for the development of idiopathic infertility are summarized. The role of miRNAs, methyloma aberrations, deficiency of phospholipase C zeta in spermatozoa in the pathology of fertility is given. Deciphering the molecular profile and molecular phenotypes of infertility as a result of the interaction of genetic and environmental factors is a necessary condition for screening the most informative biomarkers, assessing their stratification potential, and validating new molecules as potential targets for targeted therapy.

[Safety of tadalafil in patients with cardiovascular comorbidities].

Tadalafil is a drug from the phosphodiesterase-5 inhibitors (PDE-5) group, which is used to treat erectile dysfunction (ED), lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) and ED with LUTS in patients with BPH. The efficacy and safety of tadalafil were reviewed. The focus was on cardiovascular safety of tadalafil due to frequent cardiovascular comorbidities in patients with ED. We concluded that tadalafil is well tolerated and safe in patients with cardiovascular comorbidities and, in addition, has a beneficial effect on the cardiovascular system.

[Molecular aspects of the impact of the Speroton complex on the male fertility in idiopathic infertility].

AIM: To characterize the effect of the Speroton complex on the free radical homeostasis in the ejaculate of males of infertile couples and the likelihood of pregnancy in partners. MATERIALS AND METHODS: The study group comprised 30 men aged between 26 and 43 years (mean 33 +/- 4.8 years) with idiopathic infertility. All patients received Speroton one sachet once daily during meals for 3 months. The comparison group consisted of 29 men of fertile age having 1 to 3 healthy children. In infertile men, standard semen parameters including the ejaculate volume, sperm concentration, total count and proportion of abnormal forms were within the normal range. Markers of oxidative damage to ejaculate macromolecules were determined using standard diagnostic testing systems. RESULTS: The patients with idiopathic infertility were found to have statistically significant changes in the degree of chemical modification of ejaculate biopolymers. The level of lipid hydroperoxides in infertile men was significantly higher than in fertile participants. Taking Speroton resulted in the decrease of lipid hydroperoxides to the level that did not differ from that in the control group. Using Speroton was also accompanied by a decrease in the level of the oxidative damage DNA biomarker 8-oxodGu and a tendency toward normalization of the carbonyl modification of the ejaculate proteins. Five married couples in the treatment group reported achieving pregnancy. CONCLUSION: Taking Speroton was associated with the normalization of the balance of pro- and antioxidant processes in the ejaculate, as indicated by a decrease in the oxidative destruction of sperm biopolymers. The revealed molecular mechanism of the drug action is the basis for restoring the fertilizing ability and increasing the likelihood of pregnancy. The treatment effectiveness was 16.7%. Speroton is a promising drug that improves the functional sperm characteristics and contributes to achieving pregnancy in couples with a male infertility factor.

Interleukin-10 family cytokines pathway: genetic variants and psoriasis.

BACKGROUND: Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20 and IL-24 have been implicated in autoimmune diseases and we have previously reported that genetic variants in the IL10 gene cluster were associated with psoriasis. OBJECTIVES: To analyse the relationship between genetic polymorphisms in the IL10 gene cluster and psoriasis. This study also explores whether there are gene-gene interactions among these genetic polymorphisms. METHODS: A total of 377 patients with psoriasis and 403 matched healthy controls were enrolled to carry out a case-control study for 48 single-nucleotide polymorphisms (SNPs) of the IL10 gene cluster. Genotyping for the SNPs was conducted on the Applied Biosystems 3730 DNA Analyzer using SNPlex® technology. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to discover a likely gene-gene interaction model among the SNPs. RESULTS: The results showed that the allele distributions of IL10 gene cluster SNPs are significantly different between the case and control groups. Carriers of the IL10 T allele (rs1554286) and the IL20 T allele (rs1400986) conferred protection from psoriasis [odds ratio (OR) = 0·63, corrected P-value (Pc) = 0·007; OR = 0·62, Pc = 0·038, respectively]. GMDR analysis displayed a significant gene-gene interaction between IL10 (rs1554286) and IL20 (rs1518108) variants. The strongest protective effect was found with the block 1 haplotype ACATA in the IL10 gene (Pc = 0·004). CONCLUSIONS: This study presents a novel finding that the combination of the two SNPs, IL10 (rs1554286) and IL20 (rs1518108), is associated with a reduced risk of psoriasis. Our results indicate that genetic variants of the immunomodulatory IL10 and IL20 genes may offer a protective effect in Europeans from Russia. Independent studies are required to verify the results and find a possible functional explanation.

Dioxins in the semen of men with infertility.

The purpose of the present study was to assess ejaculate contamination by polychlorinated dibenzo-p-dioxins/furans in male infertility. The database of 168 infertile and 49 fertile men was included in the study. Dioxin content was determined using gas chromatography/high-resolution mass spectrometry (GC/HRMS). In the ejaculate of infertile men, the content of dioxins and furans was 2.2-2.3 times higher than in fertile donors. The maximum level of the most toxic dioxin congener was detected in pathospermia. Contamination of semen of infertile men by polychlorinated dibenzo-p-dioxins/furans supports the hypothesis about the relationship between environmental factors and reproductive health.

[Effects of L-carnitine on ejaculate parameters in males from infertile couples].

The aim of our investigation was detection of molecular mechanisms of an antioxidant action of L-carnitine (a transmembrane carrier of long-chain fatty acids) in idiopathic pathospermia. We treated 60 males from infertile couples with karniton (1 g/day). L-carnitine impact on ejaculate antioxidant status was assessed by registration of chemiluminescence and total antioxidant activity by colorimetric method according to changes in the color of ABTS chromogen. High dose-dependent antioxidant activity of the drug was found in testing on model systems in vitro. In vivo trials showed that patients given L-carnitine demonstrated a significant increase of the number of mobile spermatozoa of A category, positive changes in parameters of luminal-dependent and Fe2+ induced chemiluminescence of ejaculate in elevated antioxidant capacity of spermoplasma. After karniton treatment of the husbands 23% of their wives got pregnant. The treatment efficacy may be due to normalization of antioxidant status of ejaculate.

[The combined treatment of patients presenting with chronic pyelonephritis with the use of magnetolaserotherapy].

The present study included 70 patients (mean age 36.0 +- 1.5 years) presenting with chronic pyelonephritis. Thirty of them were given magnetolaserotherapy in addition to the conventional treatment. Their immune status as well as the levels of proinflammatory cytokines (interleukin-1 bets, interleukin-6, and tumour necrosis factor-alpha) were determined. It is shown that the combined treatment (basal therapy and magnetolaserotherapy) caused a significant decrease in the duration of the main clinical manifestations of the disease and normalization of the immune system and cytokine production.

[Differentiated physiotherapy of lumbar pain].

The results of the present study confirm the efficacy of combined differential treatment of pain sensation in the lower back with the use of the up-to-date physiotherapeutic methods. The choice of a concrete method depended on the mechanism of development of the vertebral syndrome (compression, disfixation, disgenia or aseptic inflammation). The treatment resulted in the improvement of major integral characteristics of the pathological process, marked reduction in the duration of therapy, and significant prolongation of the remission period.

[Molecular markers of ejaculate fertility in officers of Internal Affairs Ministry Special Forces, if under battle stress].

The article presents results of studies in males participated in anti-terrorist military operations in local conflict areas. Findings are intact general spermogram parameters with lower serum and/or ejaculate levels of glycodeline and inhibin B--that is a precondition for high risk reproductive disorders under battle stress.

[Spermicidal properties of major environmental pollutants assigned to polychlorbiphenyls class].

The authors considered accumulation of environmental pollutants assigned to polychlorbiphenyls class in fat tissue and reproductive organs of male rats, discovered major accumulation of the pollutants in epididymis, demonstrated significant changes in cellular contents and functional properties of sperm.

[Molecular genetic basis of predisposition to psoriasis].

Psoriasis is one of the most common chronic inflammatory dermatopathies, which is observed in 0.3-7% of the world population. Numerous twin-, familial- and population-based studies suggest the involvement of genetic factors in the disease development. The present review summarizes the present state of knowledge and analyzes of the most recent findings in the molecular genetics of psoriasis.

Gonadotoxic effect of polychlorobiphenyls.

The distribution of polychlorobiphenyls (environmental pollutants) in the reproductive organs and fatty tissues of rats was analyzed and selective accumulation of the toxicants in the epididymis, but not in the ovaries, was demonstrated. Reduction of the fertilizing activity of the ejaculate after chronic exposure to polychlorobiphenyls was detected. Mechanisms of spermatogenic dysfunction under conditions of high technogenic load are discussed.

[Spermatogenesis impairment by polychlorbiphenyls: endocrine and paracrine mechanisms of the damage]. / Narushenie spermatogeneza polokhlorbifenilami: éndokrinnye i parakrinnye mekhanizmy povrezhdeniia.

Possible role of changed contents of certain cytokines in the genesis of reproductive disorders was studied in an experiment with rats intoxicated chronically by polychlorbiphenyl (PCB) ecopollutants at the total doses of 0.3 g/kg of the body weight (0.05 LD50 and 3 g/kg of the body weight (0.5 LD50). The enzyme immunodetection was used to analyze blood serum, testicle tissues and sperm for interleukin-1beta, interleukin-6, interleukin-4, tumor necrosis factor alpha, and testosterone and estradiol. The experiment showed that chronic PCB intoxication significantly increases the production of pro-inflammatory cytokines and decreases the production of anti-inflammatory cytokines on a background of a sharp testosterone reduction and inversion of the androgen-estrogen profile. Implications of these shifts to steroido- and spermatogenesis are discussed along with cell and molecular mechanisms of cytokine-mediate PCB intoxication.