This is the first study to investigate spermatozoal cell death-inducing DNA fragmentation factor-α-like effector A (CIDEA) gene expression and DNA fragmentations in the spermatozoa of men diagnosed with metabolic syndrome (MS) who have normal seminograms with unexplained infertility, and to correlate these parameters with seminal glucose concentration.This study included 120 participants: 75 male subjects with MS (38 fertile and 37 infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen analysis, and biochemical measurement of seminal plasma insulin and glucose levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions were performed by the RT-PCR method. The percentage of spermatozoal DNA fragmentation was also estimated.The spermatozoal insulin and CIDEA gene expression, as well as the DNA fragmentation, were significantly higher in the infertile MS group than in the fertile MS group, and significantly higher in both the MS groups than in the control group. Seminal glucose concentration showed significant positive correlations with seminal insulin level, spermatozoa insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a positive correlation between spermatozoa CIDEA gene expression and DNA fragmentation.It can be concluded that MS may affect male fertility at the molecular level, through its possible inducing effect of spermatozoa CIDEA and insulin gene expression, DNA fragmentation, and increased seminal glucose.
Cypermethrin, a type II synthetic pyrethroid pesticide, is widely used in pest control programmes in agriculture and public health. This study aimed to assess the potential effect of cypermethrin on human spermatozoa and the possible ameliorative effects of vitamins C and E. Semen samples of 20 healthy normozoospermic men were divided into six aliquots at room temperature. The first aliquot served as control not exposed to treatments, and the second was incubated with 20 mm vit. C and 2 mm vit. E where the third one was exposed to 10 μm cypermethrin for 6 h. The other three aliquots were incubated with vit. C, vit. E and both vitamins for 30 min before cypermethrin exposure. Semen aliquots were analysed for sperm motility, sperm viability, hypo-osmotic swelling test and modified alkaline comet assay. The results demonstrated a significant decrease in sperm motion, sperm function and increased sperm DNA damage in the cypermethrin group. Addition of vitamins C and E alone/combined led to significant improvement in sperm motion, sperm function and DNA damage, being maximal with both vitamins together. It is concluded that in vitro cypermethrin can alter sperm function and induce DNA damage in spermatozoa, which is improved after using vitamins C and E.
Journal of Pharmaceutical Research International (ISSN: 2456-9119) is dedicated to publish high quality papers in all areas of pharmaceutical Science including pharmaceutical drugs, community pharmacy, hospital pharmacy, clinical pharmacy, compounding pharmacy, consultant pharmacy, internet pharmacy, veterinary pharmacy, nuclear pharmacy, military pharmacy, pharmacy informatics, pharmaceutics, medicinal chemistry, pharmacognosy, pharmacotherapy, pharmacodynamics, pharmacokinetics, clinical pharmacology, neuropharmacology, psychopharmacology, pharmacogenetics, pharmacogenomics, pharmacoepidemiology, toxicology, theoretical pharmacology, posology, pharmacognosy, behavioral pharmacology, environmental pharmacology, medicine development and safety testing, drug legislation and safety, pharmaceutical microbiology, pharmaceutical molecular biology, pharmaceutical biotechnology. The journal also encourages the submission of useful reports of negative results. This is a quality controlled, OPEN peer reviewed, open access INTERNATIONAL journal.
The role of atrial natriuretic peptide (ANP) in edema formation in idiopathic nephrotic syndrome (INS) was studied before with conflicting results reported; however, the possible contribution of genes regulating ANP expression and receptors was never explored.One hundred children (60 with active INS and 40 in remission) were studied for plasma atrial natriuretic peptide (ANP), urinary sodium, ANP gene A2843G and ScaI polymorphisms, and natriuretic peptide receptor clearance C (-55) A polymorphism. For comparative purposes, 20 healthy controls were studied for ANP levels.ANP was higher in active compared to remission patients (p<0.001). ANP in the healthy control group was significantly lower than the ANP level of active INS (during edema) group (p=0.009) but did not show significant differences when compared to ANP levels of either active INS group after resolution of edema or remission group (p= 0.42 and 0.56, respectively). Urinary sodium levels in edematous patients were significantly lower while ANP levels were significantly higher during edema than after resolution (p< 0.001 for both). Genotypes' frequencies of studied polymorphisms did not differ between active and remission groups. Patients with the A1A1 genotype of ScaI polymorphism had higher ANP levels compared to other genotypes (p =0.01).During edema, ANP levels are elevated in INS children however this increment is not associated with natriuresis suggesting a blunted renal response to ANP. Polymorphisms of genes regulating ANP levels and receptors don't seem to be implicated in edema formation except for the A1A1 genotype of ScaI polymorphism however, its possible role needs further evaluation.
Hepatitis C virus (HCV) infection is a major health problem worldwide and its eradication is mandatory.Direct acting HCV polymerase inhibitors, such as Sofosbuvir (SOF), is an effective regimen.However, it has some side effects like mutagenesis, carcinogenesis, and the impairment of testicular function.It is important to evaluate the safety of SOF on the ovary, as there are no studies yet.Increasing the production of Reactive Oxygen Species (ROS), causes oxidative stress, which affects ovulation process, female reproduction, and fertility.Accumulation of SOF in the cells was demonstrated to promote ROS generation.Vitamin E (Vit E) is an antioxidant agent that has an essential role in the female reproductive system, its deficiency can cause infertility.We explored the effect of SOF treatment alone and co-treated with Vit E on ovarian ROS level and ovarian morphology experimentally using biochemical and immunohistochemical studies.Significant changes in oxidative stress markers; nitric oxide and malondialdehyde lipid peroxidation, antioxidant enzymes; catalase, super oxide dismutase, and reduced glutathione, proliferating markers; proliferation cell nuclear antigen and Ki-67 antigen and caspase 3 apoptotic marker were demonstrated.It was shown that where SOF induced oxidative stress, it also aggravated ovarian dysfunction.The essential role of Vit E as an antioxidant agent in protecting the ovarian tissue from the effect of oxidative stress markers and preserving its function was also displayed.This could be guidance to add Vit E supplements to SOF regimens to limit its injurious effect on ovarian function.
Background the present study aims to evaluate the possible anti-fibrotic effect of calcipotriol, cholecalciferol, aliskiren, eprosartan and ramipril on carbon tetrachloride (CCl4) induced liver fibrosis in rats.Methods: Fifty six Spague Dawely rats were randomly allocated into seven groups.All rats were exposed to induction of hepatic fibrosis by intraperitoneal (ip) injection of CCl4 twice/week for 8 successive weeks except control healthy group.The rats were treated with either calcipotriol (20 ug/Kg), Cholecalciferol (500 IU/kg), aliskiren (10mg/kg), eprosartan (60mg/kg) and ramipril (10mg/kg) simultaneously with CCl4 treatment.Results: all the tested drugs have significant improvement in liver function tests (liver enzymes, bilirubin and albumin), oxidative stress markers (reduced glutathione, malondialdehyde and nitric oxide), transforming growth factor-b1 (TGF-b1) and fibrotic score.Only calcipotriol and cholecalciferol are significantly decrease renin gene expression in liver and kidney tissues while cholecalciferol alone has significant increase in serum calcium and 25 hydroxy vitamin D [25(OH)D] levels.Conclusion: these results suggest that calcipotriol, cholecalciferol, aliskiren, eprosartan and ramipril have antifibrotic effect.Vitamin D receptor (VDR) agonists (Calcipotriol and cholecalciferol) inhibit renin gene expression and have better antifibrotic effect than renin angiotensin blockers (aliskiren, eprosartan and ramipril).Eprosartan has better antifibrotic effect than aliskiren and ramipri
This study aimed to assess the association of oestrogen receptor alpha (ER-α) gene polymorphisms and semen variables in infertile oligoasthenoteratozoospermic (OAT) men. In all, 141 men were grouped into fertile men (n = 60) and infertile OAT men (n = 81). They were subjected to assessment of semen analysis, acrosin activity, serum reproductive hormones and genotyping of ER-α gene. Frequencies of p and x alleles in ER-α gene PvuII and XbaI polymorphisms were more prevalent among fertile men compared with infertile OAT men. Presence of P and X alleles was associated with increased incidence of male infertility for genotypes PP, XX compared with genotypes pp and xx (OR = 2.8; 95% CI: 2.36–6.97; P = 0.001 and OR = 4.1, 95% CI: 1.49–11.39; P = 0.001, respectively). The mean of semen variables and sperm acrosin activity were significantly higher in cases associated with pp than PP and in xx than XX genotypes of ER-α gene. Mean levels of all serum reproductive hormones demonstrated nonsignificant differences in different ER-α genotypes except oestrogen that was elevated in PP and XX ER-α gene genotypes. It is concluded that as oestrogen is concerned in male gamete maturation, ER-α gene polymorphisms might play a role in the pathophysiology of male infertility.
Inflammation has been implicated as an etiological factor, in several human cancers. Allelic variants of the genes involved in
inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. Besides genetic factors,
environmental factors such as smoking are an important risk factor for prostate cancer. This study aimed to investigate whether
308 G/A single nucleotide polymorphism of tumor necrosis factor-α (TNF-α) gene promoter region was associated with
outcomes of prostate cancer and to analyze the gene environment interaction between 308 G/A TNF polymorphism and
cigarette smoking. A total of 282 patients with prostate cancer (143 smokers, 139 non smoker) and 212 patients with benign
prostatic hyperplasia (105 smokers, 107 non smokers) along with 115 healthy control were enrolled in the study. Urinary
Cotinine and serum TNF and PSA levels were measured using ELISA technique. TNF genotyping was performed using
PCR-RFLP technique. Prostate cancer was significantly associated with TNF G/G genotype and this is accompanied by
elevated plasma TNF, PSA and urinary Cotinine. Cancer smokers showed a high frequency of TNF-α 308 G allele compared
with other patient groups associated with increased TNF levels. Results of this study support the hypothesis that polymorphism
in proinflammatory genes may be important in prostate cancer development and the sequence variants in these inflammatory
genes may interact with environmental modifiers such as cigarette smoking to increase prostate cancer risk.