Interleukin-1 receptor antagonist gene polymorphism and obesity: A pilot study from north India.

The main adverse consequences of excess bodyweight are cardiovascular disease, type II diabetes, and several cancers, IL-1Ra serum concentration has been reported earlier to increase in human obesity and it is therefore assumed that the polymorphism of IL-1Ra may influence cytokine production. We designed this study to investigate whether the IL-1Ra polymorphism was associated with obesity. A total number of 103 individuals; 19 lean (BMI<25 Kg/m(2)), 51 overweight (BMI 25-29.9 Kg/m(2)) and 33 obese (BMI≥30.0 Kg/m(2)) were enrolled in this study. Genotyping was performed using a polymerase chain reaction PCR amplification of the intron-2 fragment harboring a variable number of tandem repeat (VNTR) nucleotide sequences 86 pb of tandem repeat. The PCR products were separated on 2% agarose gel. Statistical analysis was performed using SPSS software (version 11.5). We found no significant difference in genotype and allele frequencies between the three groups; lean vs. overweight and lean vs. obese (p=0.323; 0.202; 0.123 and 0.068 resp). However, an increased risk for obesity had a propensity to be higher in those having genotype II/II. This genotype has been reported to be a 'high producer' of IL-1Ra. Although no statistically significant relationship between IL-1Ra polymorphism and BMI was observed, however, a trend towards an increase of allele(*)II in overweight and obese group was observed. This may suggest that IL-1Ra appears to be induced by inflammatory stimuli as well as obesity-associated factors. This is relatively a pilot study: but nevertheless, may assist in identifying the pathophysiological cause for obesity.

Use of intra- and extra-amniotic prostaglandins for the termination of pregnancies--report of multicentric trial in India.

The Indian Council of Medical Research initiated a multicentric trial with prostaglandins in 1976 to assess the safety and efficacy of their use in midtrimester abortions. PGF2 alpha and 15-Me-PGF2 alpha were compared using the intra-amniotic (I.A.) route. 15-Me-PGF2 alpha was also evaluated by extra-amniotic (E.A.) route. With intra-amniotic instillation, success rate was 88.1 per cent with PGF2 alpha and 93.0 per cent with 15-Me-PGF2 alpha within 48 hours and by the extra-amniotic route it was 78.1 per cent within 36 hours. The mean induction-abortion interval was 19 hours with I.A. and 14.8 hours with E.A. Abortions were complete in 48.8 per cent of the women following I.A. PGF2 alpha, 56.0 per cent following I.A. 15-Me-PGF2 alpha and only 23.0 per cent following E.A. administration. Vomiting and diarrhoea were the most commonly reported side effects. Cervical injuries were 4.7 per cent with I.A. PGF2 alpha, 1.4 per cent with I.A. 15-Me-PGF2 alpha and only 0.6 per cent with E.A. route.

Indian experience with a single long-acting vaginal suppository for the termination of pregnancies.

The Indian Council of Medical Research conducted a multicentric trial with a single vaginal suppository containing 3 mg 15-Me-PGF2 alpha for terminating pregnancies. Success rate in the 290 women investigated was 79.2 per cent at 30 hours observation. The mean induction-abortion interval was 14.7 hours and the incidence of complete abortions was 58.3 per cent. Vomiting and diarrhoea were the most common side-effects noted. Vomiting was experienced by 72.3 per cent women and diarrhoea by 76.8 per cent. Although the vaginal route for administering 15-Me-PGF2 alpha is simple and the induction-abortion interval short, it is suggested that the combination of a vaginal suppository and prostaglandins intra-muscularly may lead to higher percentage of complete abortions.

Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors.

Schwannomas are peripheral nerve sheath tumors that often occur in the setting of an inherited tumor predisposition syndrome, including neurofibromatosis types 1 (NF1) and 2 (NF2), familial schwannomatosis and Carney complex. Loss of the NF2 tumor suppressor (encoding NF2, or Merlin) is associated with upregulation of the Rac1 small GTPase, which is thought to have a key role in mediating tumor formation. In prior studies, we generated a mouse model of schwannomas by performing tissue-specific knockout (KO) of the Carney complex gene Prkar1a, which encodes the type 1A regulatory subunit of protein kinase A. These tumors exhibited down-regulation of Nf2 protein and an increase in activated Rac1. To assess the requirement for Rac1 in schwannoma formation, we generated a double KO (DKO) of Prkar1a and Rac1 in Schwann cells and monitored tumor formation. Loss of Rac1 reduced tumor formation by reducing proliferation and enhancing apoptosis. Surprisingly, the reduction of tumor formation was accompanied by re-expression of the Nf2 protein. Furthermore, activated Rac1 was able to downregulate Nf2 in vitro in a Pak-dependent manner. These in vivo data indicate that activation of Rac1 is responsible for suppression of Nf2 protein production; deficiency of Nf2 in Schwann cells leads to loss of cellular growth control and tumor formation. Further, PKA activation through mutation in Prkar1a is sufficient to initiate Rac1 signaling, with subsequent reduction of Nf2 and schwannomagenesis. Although in vitro evidence has shown that loss of Nf2 activates Rac1, our data indicate that signaling between Nf2 and Rac1 occurs in a bidirectional fashion, and these interactions are modulated by PKA.

E-nephrology.

Diagnosis of renal diseases is often delayed owing to the scarcity of trained physicians, lack of facilities, and shortage of funds limits effective management, particularly when it comes to the red zone of renal replacement therapy. The Internetis expected to open up a myriad resource of knowledge and applications for academicians, researchers and clinicians alike in all health care professions across the globe. Also, the Internet has grown rapidly over the years and will inevitably expand even more. Evolving technologies offer modern applications for information management, communications with multimedia and virtual reality. Now, these innovative technologies have opened up newer possibilities for nephrologists. As Internet is serving as a backbone for these modern technologies, it is an utmost necessity to use and refine Internet applications for future nephrologists. Increasingly easy access to Internet has dramatically reduced barriers in sharing of information among basic and clinical nephrologists. Considering the growing scope for nephrologists in the use of Internet, it is necessary to understand Internet as a source of information and backbone of modern application. This review illustrates expanding roles of the Internet for the nephrologists and provides ready to use compilation of useful academic, research, clinical resources and is expected to introduce, stimulate and guide nephrologists into the realm of the world wide web. It also investigates how Internet is supporting in growth and development of the field of nephrology and present and future scopes of Internet as a tool for professionals involved in this area as well as information about biological sciences, and it also gives information about societies in various continents working in field of nephrology and the links useful for clinicians and research scientists.

Interleukin-1beta and receptor antagonist (IL-1Ra) gene polymorphisms and the prediction of the risk of end-stage renal disease.

Cytokines play an important role in the pathogenesis of kidney disease and its progression to end-stage renal disease (ESRD). Inflammation is regulated by the genes of the interleukin 1 (IL-1) gene cluster. Therefore, it was hypothesized that a polymorphism in this gene cluster may be associated with the risk of ESRD. Polymorphisms in the IL-1 gene cluster were examined in a cohort of 222 ESRD patients and 206 controls of similar ethnicity. These individuals were genotyped for IL-1 beta (promoter -511 and exon-5 +3953) genes and a variable number of tandem repeats (VNTR) in the IL-1 receptor antagonist gene (IL-1Ra). There was significant difference in genotype frequencies between ESRD patients and control group for IL-1beta (promoter region and exon-5) and IL-1Ra gene polymorphism (p < 0.001, 0.006 and < 0.001, respectively). A significant difference was observed in IL-1Ra for 1/1 (410/410) and 1/2 (410/240) genotypes, and the risk for ESRD was higher in those carrying the 1/1 genotype (p = 0.014, OR = 1.692, and p < 0.001, OR = 0.163). Also identified was a novel, rare allele of a single copy of 86 bp in ESRD patients as compared with the controls. The haplotype 'T-E2-1' frequency distribution between patients and controls revealed greater than threefold risk (p = 0.001, OR = 3.572, 95% CI = 1.589-8.032). Genetic linkage between the IL-1beta promoter region and exon-5 and between the IL-1beta promoter and IL-1Ra of IL-1 gene demonstrated a strong association among the variants in controls (D' = 0.42, p < 0.001, and D' = 0.39, p=0.001). Thus, the three polymorphisms within the IL-1 cluster are associated with ESRD. This finding is perhaps one of the strongest associations between genotype and ESRD reported, and it suggests that the IL-1 gene cluster affects the risk of development of ESRD.