Association of level of IL-6, IL-10, IL-18, tumour necrosis factor-?with rheumatic mitral stenosis and subsequent pulmonary hypertension

Background:Objective of the study was to provide insight on the immune response in patients of rheumatic heart disease, mitral stenosis and evaluation of various cytokines in pulmonary hypertension secondary to rheumatic heart disease.Methods:Total 163 subjects, more than 18 year of age, were enrolled in this study. 84 subjects with rheumatic mitral stenosis (group A) diagnosed on two-dimensional echocardiography (2D echo)and 79 normal healthy volunteers(group B). Patients with mitral stenosis were further divided into subgroups based on severity of mitral stenosis [mitral valve area (MVA >1 cm2 and MVA <1 cm2)(subgroup Aa and Ab)]and presence or absence of pulmonary hypertension [pulmonary arterial systolic pressure (PASP >36 mm Hg)(subgroup Ac and Ad)]. Interleukins IL-6, IL-10, IL-18, tumour necrosis factor alpha (TNF-?)andhigh-sensitivity C-reactive protein (hs-CRP)levels were assessed in both groups.Results:Mean IL-6, IL-10, IL-18, TNF-? and hs-CRP in group A and group B was 6.57�53 and 2.73�p?0.001), 8.185�8 and 3.51�86(p?0.001), 136.31�.0 and 47.96�76(p?0.001), 21.26�.59 and 5.36�57(p?0.001), 4.69�3 and 2.63�22(p?0.008) respectively. On subgroup analysis mean TNF-? in subgroup Aa was 20.71�.84, while in subgroup Ab was 7.56�93 (p?0.001). Mean IL-10 in subgroup Ac and Ad was 8.74�29 and 7.47�82, respectively. Differences in levels of other cytokines in these subgroups were not found statistically significant.Conclusions:This study finds increased IL-6, IL-10, IL-18, TNF-? and hs-CRP levels in subjects with rheumatic mitral stenosis. Subjects with severe mitral stenosis had increased TNF-? levels. Subjects of mitral stenosis having pulmonary hypertension had increased IL-10 levels.

Nucleated RBC Count as Predictor of Neurological Outcome in Perinatal Asphyxia.

The immediate and short term outcomes of term newborns with perinatal asphyxia were studied in relation to the nucleated red blood cell count at admission. The mean (SD) NRBC/100WBC (white blood cells) was significantly higher in sequelae group than normal [9.8 (98.9) vs. 2.9 (43); P = 0.001].

Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians.

Background: Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and PON1 L55M polymorphisms have been analyzed extensively, but data on association and role of these polymorphisms in the etiology of CAD are conflicting. In this study, we tested the genetic association between PON1 Q192R and PON1 L55M polymorphisms and CAD among north Indians. Materials and Methods: Two hundred eighty-five angiographically proven patients with coronary artery disease and 200 sex-matched and ethnically matched controls were genotyped for 2 PON1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in patients and controls using the chi-square test. Results: At PON1-192 locus, there were significant differences between patients and controls (P< 0.05), leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub-sample of smokers (2.84 and 1.45, respectively). Binary logistic regression analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences between patients and controls, but LL genotype and *L allele were significant risk factors in the nonsmoker group. RL haplotype was also significantly associated with CAD risk (OR= 1.44, CI: 1.08-1.93). Conclusions: PON1-192R allele and RR genotype are significantly associated with CAD patients from the north Indian population (Uttar Pradesh). This association was stronger in smokers, supporting the conclusion that an interaction between PON1 activity and smoking augments CAD risk. Further studies with larger sample size are warranted to confirm these associations in different Indian populations.

Does cytokine gene polymorphism affect steroid responses in idiopathic nephrotic syndrome?

Background: Immunological responses may be possibly involved in the pathogenesis of idiopathic nephrotic syndrome (INS). Cytokines act as a potent immunomodulator. Pathogenesis of INS is associated with Th1 and Th2 cytokines imbalance. Aims, Settings and Design: We have investigated the association of IL-4, IL-6, and TNF-alpha gene polymorphisms and analyzed the data to evaluate the effect of these polymorphisms on the pathogenesis and clinical course of INS. Materials and Methods: One hundred fifty children with INS were selected. Children were analyzed for IL-4, IL-6, and TNF-alpha gene polymorphisms by using polymerase chain reaction and restriction fragment length polymorphism. Statistical Analysis Used: Chi-square test was used for different comparisons. The synergistic effects of IL-4, IL-6, and TNF-alpha gene polymorphisms were evaluated by using logistic regression analysis. Results and Conclusions: We compared the steroid-resistant (SR) and steroid-responsive (SS) groups. Our results showed strong association of IL-6 -G174C, and IL-4 -C590T at genotypic level (P = 0.0121, OR = 14.71, 95% CI = 1.59-136.46; and P = 0.0386, OR = 7.29, 95% CI = 1.26-41.69). TNF-alpha revealed a strong association at genotypic level (P = 0.0121, OR = 14.71, 95% CI = 1.59-136.46), as well as at allelic level (P = 0.0433, OR = 2.251, 95% CI = 1.09-4.66), demonstrating that it may be considered one of the genetic risk factors affecting the steroid response in INS patients. The GG genotype of IL-6 -G174C, TT genotype of IL-4 -C590T, and AA genotype of TNF-alpha -G308A cytokine gene polymorphisms may be causative factors for nonresponsiveness towards steroid therapy among INS children.