Genome-wide copy number variation analysis in idiopathic intellectual disability/multiple congenital anomalies.

New array technologies have facilitated the analysis of submicroscopic chromosomal imbalances and structural variants. Copy number variation (CNV) analysis can reveal genetic imbalances in up to 10% of cases involving intellectual disability (ID), with or without multiple congenital anomalies (MCA). Here we present 4 cases, diagnosed by CNV analysis using Affymetrix Genome Wide Human SNP 6.0 array, and their parents. CNVs ranging from 18 to 196 per subject, with a size range of 100kb- 6093kb, were detected in all cases. One case revealed inherited CNVs, whilst de novo ins/dels were found in the other three which may be causative factors in the development of clinical pictures. Microarray technology may help to reveal the etiology of ID and is a potentially useful diagnostic tool for patients with ID/MCA.

Serotonin transporter (5-HTTLPR) genotypes and trinucleotide repeats of androgen receptor exert a combinatorial effect on hormonal milieu in patients with lifelong premature ejaculation.

Premature ejaculation is one of the most common sexual disorders in men due to uncontrolled modulation of spinal reflexes controlled by cortico-limbic centers in the brain. In this study, we investigate the combinatorial effects of trinucleotide repeats of androgen receptor and allelic variants of the 5-HTTLPR gene on sex steroids, hypophyseal hormones, sexual performance, and premature ejaculation assessment parameters among evidence-based lifelong premature ejaculation subjects. A total of 271 outpatients (age 26.6 ± 1.9) consulting for evidence-based lifelong premature ejaculatory dysfunction were selected in this study. The control group consists of 155 men with normal IELT (>4 min). The study revealed that the subjects who have the highest (≥26) CAG stretches depicted a significantly higher serum oxytocin levels (102.1 pg/ml; n = 126, p < 0.001) compared with the control group (71.2 pg/ml; n = 75, p = <0.001) and patients which have medium (22-25) and short (≤21) CAG stretches (76.63 ng/ml; n = 64, p < 0.001 vs. 77.4 ng/ml; n = 81, p < 0.001). Almost 33 (26.1%) lifelong premature ejaculatory patients had AR variant of longer (≥26) CAG repeats was homozygous for S alleles (SS), 45 (35.7%) was homozygous for L allele (LL), and 48 (38%) had the L/S or S/L genotype of 5-HTTLPR gene. Homozygous (SS) alleles have a significant positive correlation (r = 0.44, p < 0.0001) with the high score of BDI-II (39.1, n = 126, p < 0.001). However, LL alleles have shown a significant positive correlation with PEDT (r = 0.46, p < 0.001) and negative correlation with self-estimated IELT and intercourse satisfaction (r = -0.35, p < 0.001). The innovative study design elaborates that androgen receptor trinucleotide repeats and 5-HTTLPR genotypes have combinatorial impact on hormonal milieu and sexual function regarding evidence-based lifelong premature ejaculatory dysfunction patients.

Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

OBJECTIVE: To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. MATERIALS AND METHODS: Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. RESULTS: NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). CONCLUSIONS: This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

Effects of N-acetylcysteine treatment on oxidative stress in acetic acid-induced experimental colitis in rats.

We assessed the possible protective effects of N-acetylcysteine (NAC) against toxic damage in the rat colon. Two doses of NAC (20 mg/kg and 100 mg/kg) given for 2 days and 7 days after acetic acid administration (to induce colitis) were tested. NAC was dissolved in saline and administered locally (intracolonic), systemically (intraperitoneal) or in a combination (intracolonic and intraperitoneal). Several parameters, including macroscopic and histopathological scores and myeloperoxidase, glutathione and nitric oxide concentrations were measured using standard assay procedures. Treatment with 100 mg/kg NAC for 7 days significantly decreased tissue myeloperoxidase, glutathione and nitric oxide concentrations. The 20 mg/kg dose had no protective effects. The data indicate that NAC substantially reduced the degree of colonic injury, probably by regulating free radical production and inhibiting inflammation. It may, therefore, have a role in the treatment of inflammatory bowel disease.

Lack of association between TNFalpha gene polymorphism at position -308 and risk of acute rheumatic fever in Turkish patients.

OBJECTIVE: Acute rheumatic fever (ARF) is a multisystem inflammatory disease process that follows nasopharyngeal infection caused by group A streptococcus (GAS) (Streptococcus pyogenes). Recent studies have demonstrated that allelic variations at the tumour necrosis factor alpha (TNFalpha) locus are involved in the nature of rheumatic diseases such as juvenile idiopathic arthritis and rheumatic heart disease. Thus, TNFalpha polymorphisms at -308 in ARF patients might be useful in contributing to identification of the primary factors associated with pathogenesis of ARF. METHODS: We performed a case-control association study between the common G/A promoter polymorphism at position -308 in the TNFalpha gene and ARF in Turkish patients, investigating whether this locus acts as a risk factor or has a modifying effect. RESULTS AND CONCLUSION: Previous studies have reported that TNFalpha plays a major role in the pathogenesis of a number of autoimmune and inflammatory diseases. Moreover, significantly elevated TNFalpha levels were reported in patients with ARF. However, in our sample of patients with ARF (n = 66), no such association was found. No interactive effect was found between the TNFalpha polymorphism at position -308 and no association was detected with disease progression. These findings suggest that the role of TNFalpha in ARF may be in linkage disequilibrium with some other severity genes not yet genetically determined.

Up-regulation of serine/threonine protein phosphatase type 2A regulatory subunits during methylprednisolone-induced differentiation of leukaemic HL-60 cells.

Serine/threonine protein phosphatase 2A (PP2A) may play a role in leukaemic cell differentiation of the HL-60 myeloid leukaemic cell-line after methylprednisolone induction. We have investigated the specific enzyme activity and expression of catalytic and regulatory subunits of PP2A. The resulting specific enzyme activity and immunoblots showed an increase in enzyme activity and the expression of regulatory subunits after methylprednisolone treatment. There was no change in the expression of PP2A catalytic subunits. It is suggested that the effect of methylprednisolone on leukaemic differentiation may be the result of PP2A upregulation.