Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice?

Glutathione S-transferases (GSTs) are a major group of phase II detoxification enzymes involved in the metabolism of both endogenous and xenobiotic compounds. In addition to their catalytic function in detoxification, GSTs participate in binding to nonsubstrate ligands such as bilirubin. Ligandin, which is one of the principal hepatic-binding proteins, is also a member of the GST family. The aim of the present study was to investigate the possible relationship between neonatal jaundice and the GST gene polymorphisms. The study cohort consisted of a patient group of 116 newborns (plasma bilirubin levels > or = 15 mg/dl) and a control group of 54 newborns (plasma bilirubin levels <13 mg/dl). In the patient group, the null genotype frequencies in GSTM1 and GSTT1 were 52.6 and 19%, respectively; in the control group, these were 63 and 27.8%, respectively. The frequencies of GSTM1 and GSTT1 were similar in the patient and control groups (p > 0.05). Total bilirubin levels were found to be significantly higher in patients with the GSTM1 null genotype than in patients with the GSTM1 wild genotype (p = 0.042). There was no statistically significant difference in total bilirubin levels between patients with the null GSTT1 genotype and those with the wild GSTT1 genotype. It is conceivable that there is a relation between GSTM1 gene polymorphism and total bilirubin levels in neonatal jaundice. We suggest that GSTM1 gene polymorphisms may affect ligandin functions in hepatocytes, which are important in bilirubin transportation. Consequently, patients with the GSTM1 null genotype may have higher total levels of bilirubin.

Serum nitrite/nitrate and arginase levels in patients with allergic rhinitis.

Nitric oxide (NO) plays an important role in the regulation of upper respiratory function. Patients with untreated allergic rhinitis (AR) have an increased level of NO in the nasal cavity compared to normal individuals. We aimed to investigate serum levels of arginase and NO metabolites nitrite/nitrate in patients with AR during the symptomatic period. The patient and control groups consisted of 14 males and 12 females (mean age: 29, range: 20-40 years), and 10 males and 10 females (mean age: 27, range: 22-38 years), respectively. Nitrite/nitrate levels were 0.98 +/- 0.33 ng/ml in the patients with AR, and 0.78 +/- 0.26 ng/ml in the control group (p = 0.03). Arginase levels were 28.8 +/- 14.1 ng/ml in the patients with AR, and 20.8 +/- 13.5 ng/ml in the control group. The difference between the groups was statistically insignificant (p = 0.24). Our results support the view that NO plays an important role in the pathogenesis of AR, and NO metabolites may be used as a marker for monitoring the disease activity and therapy.

N-acetyltransferase 2 gene polymorphism and presbycusis.

OBJECTIVES/HYPOTHESIS: The enzyme of N-acetyltransferase (NAT) is involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species (ROS). The excessive amount of ROS generation occurs in the ageing inner ear. The exact etiopathogenesis of presbycusis is not known, but it is generally accepted that it is the result of series of insults, such as physiologic age-related degeneration, noise exposure, medical disorders and their treatment, as well as hereditary susceptibility. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of NAT2 genotypes may be associated with the risk of presbycusis. STUDY DESIGN: Hospital-based, case-control study. METHODS: We examined 68 adults with presbycusis and 98 healthy controls. DNA was extracted from whole blood, and the polymorphisms of NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. RESULTS: Gene polymorphisms at NAT2*5A, NAT2*7A/B, and NAT2*14A in subjects with presbycusis were not significantly different from in the controls (P > .05). However, in NAT2*6A, the risk of presbycusis was 15.2-fold more in individuals with mutant allele than subjects with wild genotype (P = .013). Individuals with NAT2*6A heterozygote allele had a 0.34-fold less risk in the development of presbycusis than subjects with mutant allele (P = .032) CONCLUSION: We demonstrated a significant association between the NAT2*6A polymorphism and age-related hearing loss in this population. However, the sample size was relatively small, and further studies need to investigate the exact role of NAT2 gene polymorphism in the etiopathogenesis of the presbycusis.

The potential inflammatory role of arginase and iNOS in children with chronic adenotonsillar hypertrophy.

OBJECTIVE: Nitric oxide (NO) induced tissue damage has been implicated in the pathogenesis of several diseases. Although recurrent/chronic tonsillitis and hypertrophy are still the most frequent surgical procedures carried out on children in order to cure these pathologies, etiopathogenetic mechanisms underlying these entities are still unknown. We aimed to investigate the potential inflammatory role of NO regulatory enzymes, arginase and inducible nitric oxide synthase (iNOS), in children with adenotonsillar hypertrophy. MATERIALS AND METHODS: The study consisted of 22 children with chronic adenotonsillar hypertrophy and 30 control subjects with similar age and sex. All the patients and/or their parents had complaints of snoring, mouth breathing and pausing of breathe during sleep at least 6 months. All patients underwent an adenotonsillectomy operation under general anesthesia with curettage and cold dissection methods. Venous blood samples were taken pre-operatively and 4 weeks post-operatively. iNOS activity was based on the diazotization of sulfanilic acid by nitric oxide at acid pH and subsequent coupling to N-(1-naphthtyl)-ethylenediamine. Arginase activity was measured by the spectrophotometric method. RESULTS: The mean pre-operative and post-operative arginase activities in patient group were 4283.7 +/- 1823.7 and 2754.5 +/- 889.3 IU/L, respectively. In the control group, mean arginase activity was 2254.7 +/- 903 IU/L. When pre-, post-operative and control arginase values were compared with each other, the mean activity in pre-operative activity was significantly different from the post-operative and control values (p < 0.001). In the patient group, the mean levels of pre- and post-operative iNOS were 2.84 +/- 1.16 and 1.99 +/- 0.78 IU/ml, respectively. The difference was statistically significant (p = 0.007). Similarly, post-operative and control values were not significantly different (p > 0.05). CONCLUSION: The results of the present study supports that L-arginine:NO pathway may be key the participant in the pathogenesis of chronic adenotonsillar disease; arginase and iNOS activities are altered in children with adenotonsillar hypertrophy and this alteration improves after tonsillectomy.

Malondialdehyde and antioxidant enzymes in children with obstructive adenotonsillar hypertrophy.

OBJECTIVE: Free radical induced tissue damage has been implicated in the pathogenesis of several diseases. We aimed to investigate the role of free radicals and scavenging enzymes in children with obstructive adenotonsillar hypertrophy. MATERIALS AND METHODS: The study consisted of 29 children with obstructive adenotonsillar hypertrophy and 51 control subjects with similar age and sex. All the patients and/or their parents had complaints of snoring, mouth breathing, and pausing of breath during sleep for at least 6 months. All patients underwent an adenotonsillectomy operation under general anesthesia with curettage and cold dissection methods. Venous blood was taken preoperatively and 4 weeks postoperatively. After collection of blood samples into citrate (3.5 mg/ml blood) containing glass tubes, erythrocyte sediments were prepared for the analyses. Then malondialdehyde (MDA) level, and superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (CAT) activities were measured. RESULTS: The levels of MDA and activities of SOD and GSHPx were significantly higher in the pre-tonsillectomy period than in the post-tonsillectomy period. However, CAT activity was not different in pre- and postoperative period. CONCLUSION: Our study supports the notion that oxidant and antioxidant defense mechanisms are altered in children with obstructive adenotonsillar hypertrophy, and this alteration improves after tonsillectomy.