Impact of inflammatory cytokine and adipokine gene variations in the development of HIV-associated lipodystrophy.

Cytokines affect lipid and glucose metabolism and also alter the body's habitus. They play a role in the development of lipodystrophy syndrome. Adipocytes secrete the pro-inflammatory cytokines IL-1, TNF-α and IL-6. The plasma cytokine concentration is associated with the percentage and distribution of fat tissue in the body. The metabolic disturbances are strongly associated with increased levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). Plasma levels of cytokines such as TNF-α, IL-6 and leptin were found to be increased while plasma resistin levels were found to be variable in patients suffering from obesity and type II diabetes mellitus. Until now, limited information has been available on the polymorphism of cytokine and adipokine genes in patients of HIV-associated lipodystrophy (HIVLD), which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. Hence, we studied the association of cytokine and adipokine gene polymorphisms in various diseases and their impact on HIVLD. We carry out an extensive search using several databases, including PubMed, EMBASE and Google Scholar. The distribution of cytokine and adipokine gene polymorphisms and their expression levels varied among various populations. We examined the variants of cytokine and adipokine genes, which can contribute to individual variations in susceptibility to metabolic diseases, especially to HIVLD. In the current review, we present a brief account of the risk factors of HIVLD, the pathogenesis of HIVLD and the polymorphism of cytokine and adipokine genes in various diseases with special reference to their impact on HIVLD.

Constructed wetland for improved wastewater management and increased water use efficiency in resource scarce SAT villages: a case study from Kothapally village, in India.

Evaluation a field-scale of constructed wetland (CW) for the treatment of rural wastewater (WW), in resource-scarce semi-arid tropic (SAT) villages, to provide improved wastewater management and increased water use efficiency, was the main objective of this study. A CW was commissioned in Kothapally village of Telangana to treat the wastewater generated from 100 households. The CW was vegetated with Typha latifolia and Canna indica. Average COD, sulfate and inorganic nitrogen removal efficiencies observed were 65%, 60% and 67% respectively, for the study period (one year). Removal efficiency for total coliform was consistently above 80%. The treated wastewater was stored in a farm pond and was utilized for irrigation in the nearby agricultural fields (0.6 ha). This perennial source of water, helped the nearby farmers to cultivate two additional crops, chickpea during rabi and sweetcorn during summer. The assured availability of water reduced their vulnerability to dry spells during the kharif by providing means for lifesaving irrigation. The biomass harvested from the constructed wetland was used as fodder for the livestock. A net additional income of Rs.70,000 (∼US$1,000) was realized by the farmers using the treated wastewater for cultivation. Similar constructed wetland-based wastewater management system can be scaled up across water scarce semi-arid tropics. Novelty statementField-scale performance evaluation of constructed wetland based wastewater treatment in a semi-arid tropic village is scarce in the literature. The work presented gives a feasibility assessment for this technology critical for its wide-scale application to augment rural wastewater management in resource poor villages.

Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity.

BACKGROUND: Micro RNAs act as a regulatory layer for pharmacogenomics-related gene ex-pression. It could play a role in the efficacy and toxicity of the drug. The SNPs in miRNA genes are linked with different functional consequences. METHODS: Hence, we examined the miR (146a G/C, 149C/T, and 196aC/T) polymorphisms in 34 pa-tients with hepatotoxicity, 123 patients without hepatotoxicity, and 155 healthy controls using a PCR-RFLP method. RESULTS: In patients with hepatotoxicity, miR196aCT genotype and combined genotype GCT showed a risk for hepatotoxicity severity with borderline significance (OR=2.08, P=0.07; OR=2.88, P=0.06). While comparing between patients with hepatotoxicity and healthy controls, the combined genotypes CCC and GCT have shown a susceptibility to hepatotoxicity severity (OR=2.89, P=0.05; OR=2.60, P=0.09). The miR196TT genotype was associated with the individuals of advanced HIV disease stage (OR=3.68, P=0.04). In HIV patients who consumed alcohol and did not have hepatotoxicity, the miR 196aCT genotype showed susceptibility to acquisition of hepatotoxicity with borderline significance (OR=2.36, P=0.06). DISCUSSION: The miR149TT and 196aTT genotypes showed a risk of acquisition of hepatotoxicity to nevirapine usage among HIV patients without hepatotoxicity (OR=4.19, P=0.07; OR=1.97, P=0.84). In HIV patients with and without hepatotoxicity, the miR 196aCT genotype showed a risk of acquisition of hepatotoxicity and its severity to the combined use of alcohol and nevirapine, respectively (OR=14.18, P=0.08; OR=2.29, P=0.08). In multivariate logistic regression, taking nevirapine, 196aCT genotype had an independent risk factor for hepatotoxicity severity (OR=5.98, P=0.005; OR=2.38, P=0.05).Conclusion: In conclusion, miR196aC/T polymorphism and combined genotypes GCT and CCC may facilitate the risk for acquisition of hepatotoxicity and its severity.

Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development of HAND and modulation of pathogenesis of HAND.

The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by host genetic susceptibility factors such as Matrix metalloproteinases (MMPs). Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene. Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A polymorphisms with development of HAND and the modulation of pathogenesis of HAND. We enrolled a total of 180 individuals, 50 HIVinfected individuals with HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3 were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607 1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR = 1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1- 16071G1G, MMP-3-16125A5A genotypes increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P = 0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607 1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P = 0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for pathogenesis of HAND.

Cardiac morbidity in an HIV-1 lipodystrophy patient cohort expressing the TNF-α-238 G/A single nucleotide gene polymorphism.

In the current study we investigated the prevalence of the TNF-α 238G/A single nucleotide polymorphism (SNP) of the TNF-α gene in the development of lipodystrophy among HIV-1 infected individuals who had been receiving antiretroviral therapy (ART) in the immunodeficiency clinics of the National AIDS Research Institute (NARI) at Pune, India. We assessed the association of this SNP with the development of lipoatrophy/dyslipidemia and insulin resistance in these patients and measured carotid intima thickening which is a surrogate marker for chronic cardiac morbidity. Our results show that the incidence of the TNF-α 238G/A SNP is ~ two fold higher in patients with lipodystrophy as compared to those without lipodystrophy. Patients with lipodystrophy demonstrated a higher likelihood of the development of metabolic syndrome as evident by increased insulin sensitivity and increased percentage (%) ß cell function. Further, a significant increase in left carotid intima thickness was observed in patients with lipodystrophy. Our study validates the association of the TNF-α 238G/A SNP allelic variant with the development of HIV- lipodystrophy via the modulation of TNF-α production, which contributes to dyslipidemia, increased lipolysis, increased insulin resistance, altered differentiation of adipocytes and increased carotid intima thickness. The contribution of genetic determinants such as the TNF-α 238G/A SNP to lipodystrophy, may provide insight into the mechanisms that underlie this disease condition and may be useful in the future for personalized therapy. Additionally, these findings will be useful in monitoring chronic cardiac morbidities among HIV infected individuals who express this SNP.

Recent Prescribing Trends of Anti- Microbial Agents and their Sensitivity Pattern in an Intensive Care Unit of a Tertiary Care Teaching Hospital

Background: Due to the injudicious and indiscriminate use of Anti-Microbial Agents (AMAs) among hospitalized patients especially in ICUs, it is extremely imperative to monitor and refine the prescribing pattern of antibiotics regularly. Hence an effective surveillance team consisting of a physician, a pharmacologist and a microbiologist should develop and implement an antimicrobial stewardship program based on the local antibiogam to increase the therapeutic benefits and curb the menace of Anti-Microbial Resistance (AMR). Aims:-To study the prescribing pattern of Anti-Microbial Agents and to evaluate the antimicrobial sensitivity pattern of common bacterial isolates in Medical ICU (MICU) of a tertiary care hospital. Methods: After taking approval from the Institutional ethical committee, this prospective observational study was conducted in the department of Pharmacology and Microbiology over a period of six months. Patient records were reviewed and analyzed to assess the prescribing pattern of antibiotics and Culture-sensitivity reports of various specimen from MICU were collected to determine the antibiotic sensitivity pattern. Results: Ceftriaxone (26%) was the most commonly prescribed drug followed by Metronidazole (16%). Fixed drug combinations such as Piperacillin+Tazobactam (14%), Amoxicillin + clavulanic acid (10%) and Cefoperazone + Sulbactam (8%) were also frequently used. The most predominant organism isolated was Klebseilla species (25%) followed by Acenitobacter species (19.4%). Colistin /Imipenem and Vancomycin/Linezolid depicted100% sensitivity for Gram-Negative (GNIs) and Gram-Positive Isolates (GPIs) respectively. Conclusions: The need of the hour is to preserve the power of the almost exhausted antimicrobial armamentarium against the rampantly emerging multidrug resistant organisms.