Nalini Ganesan

Activation of intrinsic apoptotic signaling pathway in cancer cells by Cymbopogon citratus polysaccharide fractions.

Essential oils of Cymbopogon citratus were already reported to have wide ranging medical and industrial applications. However, information on polysaccharides from the plant and their anticancer activities are limited. In the present study, polysaccharides from C. citratus were extracted and fractionated by anion exchange and gel filtration chromatography. Two different polysaccharide fractions such as F1 and F2 were obtained, and these fractions were found to have distinct acidic polysaccharides as characterized by their molecular weight and sugar content. NMR spectral analysis revealed the presence of (1→4) linked b-d-Xylofuranose moiety in these polysaccharides. Using these polysaccharide fractions F1 and F2, anti-inflammatory and anticancer activities were evaluated against cancer cells in vitro and the mechanism of action of the polysaccharides in inducing apoptosis in cancer cells via intrinsic pathway was also proposed. Two different reproductive cancer cells such as Siha and LNCap were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation, changes in mitochondrial membrane potential, and profiles of gene and protein expression in response to treatment of cells by the polysaccharide fractions. These polysaccharide fractions exhibited potential cytotoxic and apoptotic effects on carcinoma cells, and they induced apoptosis in these cells through the events of up-regulation of caspase 3, down-regulation of bcl-2 family genes followed by cytochrome c release.

Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor-α (TNF- α) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF-α gene, the data published so far indicate the possible existence of TNF-α gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 (PADI4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), signal transducer and activator of transcription (STAT4), cluster of differentiation 244 (CD244) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease.

HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population

To investigate the presence of the ‘shared epitope’ (SE) in the HLA‐DRB1 alleles in patients with RA and to ascertain the frequency of the HLA‐DRB1 alleles with autoantibodies (anti‐cyclic citrullinated peptide [anti‐CCP] rheumatoid factor [RF]) and disease severity.

Heat stress and inadequate sanitary facilities at workplaces – an occupational health concern for women?

Background Health concerns unique to women are growing with the large number of women venturing into different trades that expose them to hot working environments and inadequate sanitation facilities, common in many Indian workplaces. Objective The study was carried out to investigate the health implications of exposures to hot work environments and inadequate sanitation facilities at their workplaces for women workers. Design A cross-sectional study was conducted with 312 women workers in three occupational sectors in 2014-2015. Quantitative data on heat exposures and physiological heat strain indicators such as core body temperature (CBT), sweat rate (SwR), and urine specific gravity (USG) were collected. A structured questionnaire captured workers perceptions about health impacts of heat stress and inadequate sanitary facilities at the workplace. Results Workplace heat exposures exceeded the threshold limit value for safe manual work for 71% women (Avg. wet bulb globe temperature=30°C±2.3°C) during the study period. Eighty-seven percent of the 200 women who had inadequate/no toilets at their workplaces reported experiencing genitourinary problems periodically. Above normal CBT, SwR, and USG in about 10% women workers indicated heat strain and moderate dehydration that corroborated well with their perceptions. Observed significant associations between high-heat exposures and SwR (t=-2.3879, p=0.0192), inadequate toilet facilities and self-reported adverse heat-related health symptoms (χ 2=4.03, p=0.0444), and prevalence of genitourinary issues (χ 2=42.92, p=0.0005×10-7) reemphasize that heat is a risk and lack of sanitation facilities is a major health concern for women workers. Conclusions The preliminary evidence suggests that health of women workers is at risk due to occupational heat exposures and inadequate sanitation facilities at many Indian workplaces. Intervention through strong labor policies with gender sensitivity is the need of the hour to empower women, avert further health risks, and also enhance productivity for the few million women workers who contribute largely to the countrys economy.Background Health concerns unique to women are growing with the large number of women venturing into different trades that expose them to hot working environments and inadequate sanitation facilities, common in many Indian workplaces. Objective The study was carried out to investigate the health implications of exposures to hot work environments and inadequate sanitation facilities at their workplaces for women workers. Design A cross-sectional study was conducted with 312 women workers in three occupational sectors in 2014–2015. Quantitative data on heat exposures and physiological heat strain indicators such as core body temperature (CBT), sweat rate (SwR), and urine specific gravity (USG) were collected. A structured questionnaire captured workers perceptions about health impacts of heat stress and inadequate sanitary facilities at the workplace. Results Workplace heat exposures exceeded the threshold limit value for safe manual work for 71% women (Avg. wet bulb globe temperature=30°C±2.3°C) during the study period. Eighty-seven percent of the 200 women who had inadequate/no toilets at their workplaces reported experiencing genitourinary problems periodically. Above normal CBT, SwR, and USG in about 10% women workers indicated heat strain and moderate dehydration that corroborated well with their perceptions. Observed significant associations between high-heat exposures and SwR (t=−2.3879, p=0.0192), inadequate toilet facilities and self-reported adverse heat-related health symptoms (χ 2=4.03, p=0.0444), and prevalence of genitourinary issues (χ 2=42.92, p=0.0005×10−7) reemphasize that heat is a risk and lack of sanitation facilities is a major health concern for women workers. Conclusions The preliminary evidence suggests that health of women workers is at risk due to occupational heat exposures and inadequate sanitation facilities at many Indian workplaces. Intervention through strong labor policies with gender sensitivity is the need of the hour to empower women, avert further health risks, and also enhance productivity for the few million women workers who contribute largely to the countrys economy.

Leptin-Melanocortin Pathway and childhood obesity

Childhood obesity is a major health epidemic caused by both genetic and environmental factors. Evidence suggests a strong role of genetic factors in the predisposition to obesity. Several monogenic forms of obesity have also been reported. Mutations in the genes involved in the leptin-melanocortin pathway have been found to cause these forms of obesity mainly by increasing the energy intake. Genes involved in the leptin-melanocortin pathway play a crucial role in human energy homeostasis. In this review we discuss the role of the leptin-melanocortin pathway in the regulation of energy balance with special reference to the association between the genetic variants in the genes involved in the pathway and childhood obesity.

Oral candidal carriage, salivary lysozyme levels, and their relationship with CD4 count in HIV-infected patients.

AIM The aim of the present study was to compare the lysozyme concentration and candidal count in saliva between HIV-seropositive and HIV-negative individuals, and to correlate the relationship between lysozyme concentrations, candidal count, and CD4 count in HIV patients. METHODS A study was conducted in 90 HIV-seropositive patients (subgroups: 1 [CD4 ≥ 500 cells/μL], 2 [CD4 200-499 cells/μL], and 3 [CD4 ≤ 200 cells/μL] and 30 HIV-negative individuals. A total of 6 mL unstimulated saliva was collected and stored at -80°C. Samples were centrifuged and divided into two portions of 600 μL each. One portion was used for the candidal assay and the other for the lysozyme assay using ready-made kits. Students independent t-test and Karl Pearson correlation coefficient were used for the statistical analysis. RESULTS There was a significant increase (P < 0.001) in lysozyme levels and the candidal count in the saliva of HIV-positive individuals compared with the HIV-negative individuals. A significant increase (P < 0.004) in the salivary candidal count was observed in the HIV subgroups 1-3. There was a significant negative correlation (P < 0.01) between the CD4 and candidal counts in subgroup 1 (P < 0.02) and between the lysozyme concentration and CD4 count in subgroup 3. There was no correlation between the lysozyme concentration and oral candidal carriage. CONCLUSIONS An association exists between the lysozyme concentration and specific immunity. Yeast colonization serves as a marker of immunodeficiency in HIV disease progression.

Cysteine Cathepsins: In Health and Rheumatoid Arthritis

Proteases are enzymes which catalyze the irreversible hydrolysis of peptide bonds in proteins. Cysteine cathepsins belonging to proteases have also been termed as papain-like proteases because they resemble the overall fold of papain. The present chapter aims to focus on the historical aspects, structure, cellular distribution, biosynthesis, mechanism of catalysis, its regulation, physiological functions, and its association with rheumatoid arthritis. As these enzymes are also new therapeutic drug targets, information on available assays of cysteine cathepsins and their inhibitors are also highlighted which will help in the development of therapies in various diseases.