The IRF5 rs2004640 (G/T) polymorphism is not a genetic risk factor for systemic lupus erythematosus in population from south India

Background & objectives: Genetic aberrations disrupting toll-like receptor and interferon homeostasis enhance the risk of systemic lupus erythematosus (SLE). Raised serum interferon-alpha (IFN-?) levels in SLE patients have been ascribed to polymorphism (rs2004640 G/T) in interferon regulatory factor 5 (IRF5) gene, resulting in enhanced transcript splicing. A positive association between IRF5 polymorphism and SLE risk has been reported in many populations. This study was aimed to find out frequency of IRF5 rs2004640 G/T polymorphism in patients with SLE and healthy controls and to assess its influence on susceptibility, clinical and serological characteristics of SLE. Methods: IRF5 rs2004640 (G/T) polymorphism was analyzed in 300 SLE patients and 460 age and sex matched controls by real-time PCR. Results: The IRF5 rs2004640 (G/T) polymorphism did not confer risk of SLE or influence clinical or serological phenotype. However, the mutant allele conferred a borderline risk to develop thrombocytopenia (odds ratio: 2.05, 95% confidence interval: 0.97�3, P=0.06) in patients with SLE. Interpretation & conclusions: Our study revealed that the IRF5 rs2004640 polymorphism was not a risk factor for SLE in population from south India. It may, however, be a useful genetic marker for thrombocytopenia in SLE patients. Although we could not demonstrate susceptibility toward lupus in the presence of IRF5 rs2004640 (G/T) polymorphism, further exploration of the genetic variability of IRF5 may help uncover its pathogenic role in Indian SLE patients.

Multiple foreign bodies in a neonate.

We report a rare instance of nine foreign bodies in a neonate that included a coin, safety pin, screw, cotton piece, polythene piece, and four glass pieces. Of these, six foreign bodies were removed by esophagoscopy and endoscopy, two glass pieces were passed in feces and one could not be removed. The child died 5 days after admission.

Raised serum TNF-alpha, blood sugar and uric acid in preeclampsia in third trimester of pregnancy.

In preeclampsia, insulin resistance occurs but the exact cause is unknown. It is uncertain whether women destined to develop preeclampsia have preexisting insulin resistance or it is acquired with the development of the disease. Fasting blood samples were collected from 10 normal control pregnant women and from 30 cases of preeclampsia in the third trimester of pregnancy to measure circulating level of glucose, uric acid and tumor necrosis factor-alpha (TNF) concentrations. Preeclampsia was diagnosed as per standard guideline adapted from national high blood pressure education program working group. In control group (n=10) mean age was 25+/-3.71 years, mean sugar level was 86.73+/-13.06 mg/dl, uric acid level was 3.25+/-+/-.59 mg/dl and TNF-alpha level was 9.93+/-9.56 pg/dl. In preeclampsia group mean age was 25.56+/-3.96 years, mean sugar level was 93.46+/-18.6 mg/dl, uric acid was 6.00+/-1.64 mg/dl and TNF-alpha level was 67.66+/-61.83 pg/dl. Statistical analysis done using Kruskal Wallis's test showed significantly raised levels of TNF-alpha (p<0.001), uric acid (p<0.001) and blood sugar (p=0.201) in preeclampsia cases. In preeclampsia there was positive significant correlations of raised TNF-alpha with uric acid (p<0.005). Spearman's test for correlation showed positive correlation of TNF-alpha with blood sugar (p<0.043) in cases of preeclampsia. The findings suggest the involvement of cytokines (TNF-alpha) in preeclampsia and may have a role in gestational diabetes mellitus and insulin resistance. In the present study, there was positive association of raised level of TNF-alpha with blood sugar / and uric acid levels.

Peak expiratory flow rate of children working in lock factories.

Peak expiratory flow rate (PEFR) of 106 children working in different units of lock factory was measured and compared with age and sex matched control group of same socio-economic status children. All the children worked for about ten hours per day. It was observed that there was a significant decrease in PEFR of children working in the different units of lock factories i.e. Hand press, Polishing, Lock fitting, Lock packing units as compared to control group (P>0.001). The reduction percentage of PEFR was maximum in children working in polishing unit (25.48%).

Lipoprotein(a) as a marker of coronary artery disease and its association with dietary fat.

OBJECTIVE: The main objectives of the study were to evaluate the effect of dietary fat on plasma lipoprotein(a) [Lp(a)] levels and to study the potential of Lp(a) as a more reliable marker for CAD compared to other lipids and lipoproteins. METHODS: Twenty CAD patients and 20 healthy controls were recruited for the study. Their fasting plasma Lp(a) levels and complete lipid profile were assayed. The fat intake was calculated using 24 hours dietary recall method. The patients and controls were each divided into two subgroups: Group A consuming dietary fat > 30% and Group B consuming dietary fat < or = 30% of the total kilo-calories/day. RESULTS: Results indicated that plasma Lp(a), total serum cholesterol (TC), tryglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratio of CAD patients were significantly higher than the controls. High fat intake was found to be associated with higher plasma Lp(a) levels (p<0.05) in patients only. No significant correlation was found between Lp(a) levels and other conventional lipoproteins. CONCLUSION: The lack of correlation between Lp(a) and other lipoproteins indicates its potential as an independent risk factor for CAD. High fat intake led to higher plasma Lp(a) levels in patients; hence it would be worthwhile to evaluate the effect of quality and quantity of fat intake on plasma Lp(a) levels in a larger sample size.

Comparative bioavailability of two formulations of azithromycin.

AIM: To compare the bioequivalence of two brands of azithromycin capsules in healthy male volunteers for regulatory purpose. METHOD: A single oral dose of 500 mg of either test (Panacea Biotec Ltd.) or reference (Pfizer India Ltd.) preparation of azithromycin was administered to 12 volunteers in double blind randomised cross over fashion. Serum levels of azithromycin were analysed using microbiological assay. The pharmacokinetic parameters studied were Cmax, Tmax, AUC, t1/2, Ke, CL and MRT. In vitro dissolution tests were conducted for both the preparations and compared with in vivo absorption. RESULTS: The mean peak serum azithromycin concentration of 0.516 +/- 0.008 microgram/ml was observed at 2.33 +/- 0.22 h with test brand and was similar to that of reference brand with Cmax of 0.494 +/- 0.011 microgram/ml at 2.71 +/- 0.26 h. The statistical difference between all the other paharmacokinetic parameters were insignificant. CONCLUSION: Both the brands of azithromycin can be considered to be bioequivalent on the basis of results obtained.

Apolipoprotein(a) polymorphism and its association with plasma lipoprotein(a) levels: a north Indian study.

Elevated levels of lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of lipoprotein(a) is almost entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat isoforms were observed. Using SDS-agarose gel electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma lipoprotein(a) concentration with coronary artery disease. An inverse correlation was seen between lipoprotein concentration and isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.

Effect of endothelial cells on the lymphoproliferative response in Takayasu's arteritis.

Takayasu's arteritis, also known as 'non-specific aortoarteritis' is an inflammatory disease of the aorta and its major branches. It also involves the pulmonary artery. The aetiology of the disease is not known so far. Abnormalities of the endothelial cells in terms of their structure and function are seen in the pathology of a number of diseases affecting the blood vessel wall. However, involvement of the endothelial cells in non-specific aortoarteritis is not known. In an effort to identify the role of endothelial cells in the pathogenesis of Takayasu's arteritis, peripheral blood lymphocytes isolated from the blood of patients suffering from Takayasu's arteritis were cultured in the presence of endothelial cells alone and in the presence of mitogens concanavalin-A and phytohaemagglutinin-P. The peripheral blood lymphocytes of patients with Takayasu's arteritis showed a significantly decreased blastogenic response to the mitogen concanavalin-A when cultured in the presence of endothelial cells. Our result thus suggests that endothelial cells may probably induce an inhibitory effect on the lymphocytes in patients with Takayasu's arteritis.