Maternal serum interleukin-6 in the management of patients with preterm premature rupture of membranes

Aim: To evaluate the clinical usefulness of maternal serum interleukin-6 for the detection of subclinical chorioamnionitis and in the prediction of the latency period in patients with preterm premature rupture of membrane (PPROM).

Methods: The study group included 60 patients at 24–34 weeks of gestation complaining of PPROM. Laboratory investigations included serial measurements of IL-6, TLC and CRP. Conservative management was carried out till 36 weeks unless delivery was indicated beforehand. The main outcome measures were the latency period and the occurrence of subclinical chorioamnionitis.

Results: The mean gestational age at presentation was 30.9 weeks and 35.2 weeks at delivery. The mean IL-6 level at presentation was 4.7?pg/ml. There was no correlation between IL-6 at presentation and the latency period. In addition, those diagnosed as having subclinical chorioamnionitis by placental histopathology had significantly higher levels of IL-6 at delivery. Taking IL-6 level cutoff point of 8.5?pg/ml, histological chorioamnionitis, RDS and NICU admission were significantly higher above that level while neonatal birth weight, Apgar scores at one and five minutes were significantly lower.

Conclusion: Maternal serum IL-6 at the time of PPROM has no correlation to the latency period while IL-6 levels at the time of delivery have significant correlation to the subclinical chorioamnionitis and neonatal outcome measures.     

IL-6 promoter polymorphism (?174G/C) and systemic lupus erythematosus

We investigated the possible association between susceptibility to systemic lupus erythematosus (SLE) and single-nucleotide polymorphisms located in the promoter region of the interleukin-6 gene (?174 G/C) in a sample of the Egyptian population and the contribution of this polymorphism in the clinical or immunological manifestation of the disease. Forty-two Egyptian patients with SLE and 40 unrelated healthy control volunteers were genotyped by polymerase chain reaction followed by visualization on 4% agarose gel electrophoresis on ultraviolet transilluminator to detect the genotype distribution and allelic frequencies of the polymorphisms. The homozygous GG genotypes was significantly increased in SLE patients compared to control group (p value?=?0.04). On the other hand, the heterozygous G/C genotype was significantly elevated in the controls compared to SLE patients (p value?=?0.01). The odds ratio value for G/G was 2.6 with a 95% CI from 1.1 to 6.7. As regard the association of clinical manifestations to the genotype frequency, we found a statistical significant increase in the frequency of GG genotype with chest disease, nephritis, and arthritis. From this study, we suggest that G carrier is more susceptible to develop SLE and that SNP may have a role in the pathogenesis of the disease and may be associated with some of its clinical manifestations.     

Genome-wide association study identifies new prostate cancer susceptibility loci

Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade ≥ 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P= 4.3 × 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P= 8.6 × 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P= 0.72 and P= 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.     

Effect of piracetam,vincamine, vinpocetine,and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats

In this study, we investigated the effects of the memory-enhancing drugs piracetam, vincamine, and vinpocetine or the cholinesterase inhibitor donepezil on the development of oxidative stress, inflammation, and brain damage induced in rat brain by aluminum chloride (AlCl₃). Saline (control), piracetam (100 or 300 mg/kg), vincamine (10 or 20 mg/kg), vinpocetine (10 or 20 mg/kg), piracetam 100 mg/kg plus vincamine 10 mg/kg, piracetam 100 mg/kg plus vinpocetine 10 mg/kg, or donepezil 5 mg/kg were administered once daily intraperitoneally for 45 days along with AlCl₃ (10 mg/kg, intraperitoneally). Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, acetylcholinesterase (AChE), butrylcholinesterase (BChE), paraoxonase (PON1) activities, and prostaglandin E₂ (PGE₂) concentrations were measured in brain. Histopathology and caspase-3 immunohistochemistry (an apoptotic marker) were also performed. Results indicated that (1) compared to controls, injection of AlCl₃ significantly increased brain lipid peroxidation (MDA) and nitric oxide concentrations together with decreased GSH concentrations. PON1 activity in brain was significantly decreased, while AChE and BChE activities were significantly increased compared to control animals. Cortical atrophy, neuronal shrinkage, red neurons, surrounded by vacuolations with cytoplasmic neurofibrillary tangles, intense caspase-3 expression in degenerated neurons, and amyloid deposition were observed; (2) in AlCl₃-treated rats, (i) lipid peroxidation was significantly decreased by the lower doses of piracetam, vincamine, and vinpocetine as well as by piracetam plus either vincamine or vinpocetine; (ii) nitric oxide was significantly decreased by the lower doses of piracetam, and vinpocetine, by both doses of vincamine, and by piracetam plus either vincamine or vinpocetine; (iii) nitric oxide also showed significant decrease after treatment with donepezil; (iv) both GSH and PON1 activity showed significant increase following the administration of the test drugs; (v) PGE₂ significantly increased by the higher dose of piracetam, vincamine, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vi) AChE and BChE activities decreased after treatment with the lower dose of piracetam, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vii) AChE activity decreased following 20 mg/kg vincamine, and BChE activity decreased following 10 mg/kg vincamine; (viii) AChE but not BChE activity decreased after donepezil; (ix) on histopathology, the low dose of singly used drugs and donepezil had the best improvement in neuronal look, cortical thickness, and degree of vascular congestion. Rats treated with 10 mg/kg vinpocetine showed decreased capsase-3 immunoreactivity in brain and regenerating neurons. These results suggest that while the low therapeutic doses of the nootropic drugs piracetam, vincamine, and vinpocetine display anti-oxidant and neuroptotective effects, their high doses are likely to have prooxidant and proinflammatory properties.     

Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid

BACKGROUND: Oxidative stress mechanisms are involved in the pathophysiology of many reproductive disorders. The objective of this study was to characterize oxidative stress parameters in hydrosalpingeal fluid (HSF) and examine their possible role in early embryo development. METHODS AND RESULTS: HSF was aspirated at laparoscopic salpingectomy in 11 infertile women. Reactive oxygen species (ROS), total (non-enzymatic) antioxidant capacity (TAC) and lipid peroxidation (LPO) were assayed. Two-cell mouse embryos were incubated with 25, 50 or 75% HSF and the blastocyst development rate was observed. ROS was detected in five of 11 (45%) HSF samples with a mean of 4.2 x 10(4) c.p.m. LPO was detected in all samples at a mean (+/- SD) value of 5575.4 +/- 6091.9 micromol/l malonaldehyde. The mean blastocyst development rate at 25, 5+/- 0 and 75% HSF and in the control group was 88.9 +/- 9.4, 65.7 +/- 19.1, 45.7 +/- 5.7 and 96.7% respectively (P < 0.0001). The blastocyst development rate was positively correlated to ROS concentrations (P < 0.02) but was not significantly related to LPO. CONCLUSIONS: The blastocyst development rate decreased with increasing concentrations of HSF. For the first time, the presence of ROS, LPO and TAC activity in human HSF was characterized. A possible role of oxidative stress in the embryotoxicity of HSF is suggested.     

Association of C46T genetic polymorphism of coagulation factor XII with deep venous thrombosis: a cohort study on Egyptian patients

Deep vein thrombosis (DVT) is a common multi-factorial disease, with serious short- and long-term complications, and a potential fatal outcome. Many genes are involved in determining the interindividual variation in traits that define the onset and progression of disease, as well as the response to treatment. Several association studies have designed the relationship between factor XII C46T polymorphism and the risk of arterial and venous thrombosis. Some studies reported that FXII gene polymorphism is not associated with venous thrombosis, whereas other studies found an increased risk of venous thrombosis in carriers of a FXII-T variant. We constructed an age–gender–ethnic–matched case–control study including 52 DVT patients and 100 healthy volunteers. C46T polymorphism of the coagulation factor XII was carried out using allelic discrimination assay by real-time polymerase chain reaction for patients and controls, while plasma factor XII activity was detected by one-step clotting assay. FXII C46T genotyping in DVT patients revealed that 34.6% were heterozygous harboring the FXII-CT heterotype and 3.85% were homozygous; FXII-TT homotype, with no statistically significant difference in the distribution of the mutant genotypes between DVT patients and the control group. FXII activity was significantly reduced in DVT patients harboring the mutant genotypes. In the present study, FXII C46T gene polymorphism was not associated with increased risk of deep venous thrombosis.     

Comparison between testosterone oenanthate-induced azoospermia and oligozoospermia in a male contraceptive study. IV. Suppression of endogenous testicular and adrenal androgens

Administration of supraphysiological doses of testosterone to normal men causes inhibition of spermatogenesis, but while most become azoospermic, 30-55% maintain a low rate of spermatogenesis. We have investigated whether there are differences in endogenous androgen production, of testicular and adrenal origin, which may be related to the degree of suppression of spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m. injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic, while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a specific testicular product, was reduced to <10% of pretreatment values, with no differences between the groups. Similar results were obtained for other markers of testicular steroidogenesis. Urinary and plasma adrenal androgens were also reduced during TE treatment: a statistically significant decrease in both (P < 0.001 and P < 0.05 respectively) was seen in the azoospermic but not oligozoospermic responders. These results suggest that testicular steroidogenesis is decreased to <10% by the administration of supraphysiological doses of exogenous testosterone. Differences in the degree of ongoing steroidogenesis in the testis do not appear to account for incomplete suppression of spermatogenesis, thus differences in androgen metabolism may underlie this heterogeneous response. A small but significant reduction in secretion of adrenal androgens was also detectable, the relevance of which is unclear.