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1.  Carbon Black Particle Exhibits Size Dependent Toxicity in Human Monocytes 
Increased levels of particulate air pollution are associated with increased respiratory and cardiovascular mortality and morbidity. Some epidemiologic and toxicological researches suggest ultrafine particles (<100 nm) to be more harmful per unit mass than larger particles. In the present study, the effect of particle size (nano and micro) of carbon black (CB) particle on viability, phagocytosis, cytokine induction, and DNA damage in human monocytes, THP-1 cells, was analysed. The cells were incubated with nanosize (~50 nm) and micron (~500 nm) size of CB particles in a concentration range of 50–800 µg/mL. The parameters like MTT assay, phagocytosis assay, ELISA, gene expression, and DNA analysis were studied. Exposure to nano- and micron-sized CB particles showed size- and concentration dependent decrease in cell viability and significant increase in proinflammatory cytokines IL-1β, TNF-α and IL-6 as well as chemokine IL-8 release. Gene expression study showed upregulation of monocyte chemoattractant protein-1 gene while cyclooxygenase-2 gene remained unaffected. Nano CB particles altered the phagocytic capacity of monocytes although micron CB had no significant effect. CB particles did not show any significant effect on DNA of monocytes. The investigations indicate that CB particles in nanosize exhibit higher propensity of inducing cytotoxicity, inflammation, and altered phagocytosis in human monocytes than their micron size.
doi:10.1155/2014/827019
PMCID: PMC3941121  PMID: 24669321
2.  Nanosized Zinc Oxide Induces Toxicity in Human Lung Cells 
ISRN Toxicology  2013;2013:316075.
Zinc oxide nanoparticles (ZnO-NPs) are increasingly used in sunscreens, biosensors, food additives, pigments, rubber manufacture, and electronic materials. With the wide application of ZnO-NPs, concern has been raised about its unintentional health and environmental impacts. This study investigates the toxic effects of ZnO-NPs in human lung cells. In order to assess toxicity, human lung epithelial cells (L-132) were exposed to dispersion of 50 nm ZnO-NPs at concentrations of 5, 25, 50, and 100 μg/mL for 24 h. The toxicity was evaluated by observing changes in cell morphology, cell viability, oxidative stress parameters, DNA damage analysis, and gene expression. Exposure to 50 nm ZnO-NPs at concentrations between 5 and 100 μg/mL decreased cell viability in a concentration-dependent manner. Morphological examination revealed cell shrinkage, nuclear condensation, and formation of apoptotic bodies. The oxidative stress parameters revealed significant depletion of GSH level and increase in ROS levels suggesting generation of oxidative stress. ZnO-NPs exposure caused DNA fragmentation demonstrating apoptotic type of cell death. ZnO-NPs increased the expression of metallothionein gene, which is considered as a biomarker in metal-induced toxicity. To summarize, ZnO-NPs cause toxicity in human lung cells possibly through oxidative stress-induced apoptosis.
doi:10.1155/2013/316075
PMCID: PMC3749605  PMID: 23997968
3.  Effectiveness of physical activity promotion in blood pressure and blood sugar reduction: A community–based intervention study in rural south India 
Context:
Physical activity of moderate intensity for 30 minutes a day, on most days substantially reduces the risk of many chronic diseases.
Aim:
To assess the effect of regular physical activity on blood pressure and blood sugar levels in a rural Indian community
Settings and Design:
This community-based study was carried out in Periakattupalayam and Rangareddipalayam in south India, with 485 subjects, aged 20 to 49 years.
Materials and Methods:
The study was done in five phases: Awareness campaign, baseline assessment of participants, intervention phase (10 weeks), interim, and final assessment. Physical activity of moderate intensity (brisk walking for 30 minutes on four days / week) was promoted by forming 30 small walking groups, in a home-based setting, with professional supervision. Village leaders and Self-Help Group members were the resource people for the promotion of physical activity.
Statistical Analysis:
Analysis was done by using paired ‘t’ test; the ‘Intention-to-Treat’ approach was utilized for the interpretation of the findings of the study.
Results:
Of the 485 subjects, 265 (54.6%) complied with walking on more than four days / week, while 156 (32.2%) walked on one to four days / week, and 64 (13.2%) dropped out during the intervention period. This study has shown that a 10-week intervention to promote physical activity was effective in significantly decreasing the population's BP by 1.56 / 0.74 mm Hg, fasting blood sugar levels by 2.82 mg%, body weight by 0.17 kg, and BMI by 0.06 kg / m2.
Conclusions:
This study has proved the functional feasibility of enabling people to undertake physical activity in a rural Indian community, and the effectiveness of using physical activity, to significantly reduce the population's mean BP and blood sugar levels.
doi:10.4103/2230-8229.98284
PMCID: PMC3410184  PMID: 22870410
Blood pressure; chronic diseases; community intervention; physical activity
4.  Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology 
Biological psychiatry  2010;68(12):1172-1181.
Background
Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human Disrupted-In-Schizophrenia-1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders.
Methods
Pregnant mice were treated with saline or polyinosinic:polycytidylic acid (Poly I:C) at gestation day 9. Levels of inflammatory cytokines were measured in fetal and adult brains, expression of mhDISC1, endogenous DISC1, LIS1, NDEL1, gp130, Grb2, and GSK-3β were assessed in cortical samples of newborn mice. Tissue content of monoamines, volumetric brain abnormalities, dendritic spine density in the hippocampus and various domains of the mouse behavior repertoire were evaluated in adult male mice.
Results
Prenatal interaction produced anxiety, depression-like responses, and altered pattern of social behavior. These behaviors were accompanied by decreased reactivity of the HPA axis, attenuated 5-HT neurotransmission in the hippocampus, reduced enlargement of lateral ventricles, decreased volumes of amygdala and periaqueductal gray matter and density of spines on dendrites of granule cells of the hippocampus. Prenatal interaction modulated secretion of inflammatory cytokines in fetal brains, levels of mhDISC1, endogenous mouse DISC1, and GSK-3β. The behavioral effects of GEI were observed only if mhDISC1 was expressed throughout the life span.
Conclusions
Prenatal immune activation interacted with mhDISC1 to produce the neurobehavioral phenotypes that were not seen in untreated mhDISC1 mice and that resemble aspects of major mental illnesses, including mood disorders. We propose that our DISC1 mouse model is a valuable system to study the molecular pathways underlying GEI relevant to mental illnesses.
doi:10.1016/j.biopsych.2010.09.022
PMCID: PMC3026608  PMID: 21130225
schizophrenia; mood disorders; DISC1; gene-environment interactions; mouse models; Tet-off system
5.  Safety and efficacy of nicotinamide in the management of hyperphosphatemia in patients on hemodialysis 
Indian Journal of Nephrology  2011;21(4):245-249.
Hyperphosphatemia is an important modifiable risk factor for death and cardiovascular events in patients on hemodialysis (HD). As nicotinamide has been shown as an inhibitor of sodium–dependent phosphate co–transport in rat renal tubule and small intestine, we examined whether nicotinamide reduces hyperphosphatemia in patients undergoing HD. The study was conducted in 30 end-stage renal disease (ESRD) patients [20 (66.7%) males and 10 (33.3%) females; mean age 54 ± 14.9 years] undergoing twice/thrice weekly HD for more than 3 months. Patients on other phosphate binders were given a 2-week wash-out period. Nicotinamide 250 mg capsules were given twice daily for 25 patients with serum phosphorus greater than 5 mg/dL and thrice daily for 5 patients with serum phosphorus greater than 8 mg/dL immediately after food for 8 weeks. Serum phosphate and calcium levels were estimated every month prior to HD session, and complete blood count, blood sugar, renal profile, liver function tests were estimated at beginning and end of the study. Patients were regularly monitored for side effects. There were significant decreases in the serum phosphate (6.85 ± 1.35 mg/dL at the baseline to 5.74 ± 1.18 mg/dL at the 4th week and to 4.54 ± 0.86 mg/dL at the 8th week), the serum calcium-phosphorus product (57.8 ± 12.21 at the baseline to 48.3 ± 10.71 on 4th week and to 38.201 ± 8.21 at the 8th week), and alkaline phosphatase levels (130.23 ± 50.13 IU/L at the baseline to 116.40 ± 48.27 IU/L after 8 weeks) on treatment with nicotinamide (P < 0.001). Other parameters remained unchanged. Watery stools reported by seven patients resolved during the course of the therapy. Nicotinamide is safe, cheap and effective in controlling serum phosphorus, Ca × P product and alkaline phosphatase levels in patients on maintenance HD.
doi:10.4103/0971-4065.83735
PMCID: PMC3193667  PMID: 22022084
Hemodialysis; hyperphosphatemia; nicotinamide; phosphate; renal disease
6.  Pharmacokinetic Evaluation of Paclitaxel in South Indian Cancer Patients: A Prospective Study 
Paclitaxel is a promising drug in the treatment of different solid tumors. It exhibits nonlinear pharmacokinetics, particularly when administered as a constant rate infusion for shorter duration (e.g., 3 h). Because of the nonlinearity, relatively small changes in dose may lead to large changes in peak plasma concentration and total drug exposure. The study was conducted to evaluate the pharmacokinetics of different doses of paclitaxel administered intravenously as an infusion. A prospective study was conducted in 23 cancer patients aged between 28 and 74 years, treated with paclitaxel (130, 200, 230, and 260 mg/m2) over 3 h as constant rate infusion. Plasma samples were collected from all patients at 0, 1, and 3 h and for five patients at 5 and 13 h and paclitaxel concentrations were determined using high-performance liquid chromatography method. The overall mean clearance was found to be 47.5847 ± 142.028 l/h; the mean volume of distribution was 142.028 ± 73.438 l; mean elimination rate constant was 0.336 ± 0.002/h; mean half-life was 2.086 ± 0.009 h; mean area under the curve (AUC) was 5.5917 ± 2.707 mg/ml*h; and the mean of mean residence time was 2.980 ± 0.0131 h. Paclitaxel showed nonlinear kinetics and the pharmacokinetic parameters calculated were similar to those quoted in the literature. The peak plasma concentration at 130 mg dose level was 2 μ/ml, but an increase in dose was not associated with proportional increase in plasma concentration. No significant difference was found between pharmacokinetic parameters such as clearance, volume of distribution, and AUC at different dose levels.
doi:10.4103/0975-1483.90245
PMCID: PMC3249746  PMID: 22224040
Non-linear; pharmacokinetics; plasma concentrations; optimization; taxane
7.  Prediction of Malnutrition Using Modified Subjective Global Assessment-dialysis Malnutrition Score in Patients on Hemodialysis 
Malnutrition is widely prevalent among patients on hemodialysis. Malnutrition can be estimated using a fully quantitative scoring system Subjective Global Assessment-Dialysis Malnutrition Score which is simple, reliable and dynamic. The primary objective of the study was to assess the severity of malnutrition in patients with end stage renal disease and undergoing hemodialysis in a tertiary care teaching hospital in Chennai, using Subjective Global Asses sment-Dialysis Malnutrition Score and correlate it with standard indicators of malnutrition like anthropometric and biochemical parameters of the study population by Pearson's correlation. Anthropometric assessment included height, body weight, triceps skin fold thickness, mid arm circumference, mid arm muscle circumference % and biochemical parameters included serum albumin, transferrin, ferritin, total protein, total cholesterol, blood urea nitrogen and creatinine. Based on the scores, of the 66 patients, 91% were moderately malnourished. There was a significant negative correlation between modified Subjective Global Assessment-Dialysis Malnutrition Score and anthropometric measures such as triceps skin fold thickness, mid arm circumference, mid arm muscle circumference; biochemical markers such as albumin, transferrin and ferritin. The data obtained from this study confirm that a high degree of malnutrition was prevalent in patients on hemodialysis, as shown by anthropometric assessment, biochemical markers of malnutrition and Subjective Global Assessment-Dialysis Malnutrition Score. Nutritional status as determined by Subjective Global Assessment-Dialysis Malnutrition Score is a useful and reliable index for identifying patients at risk for malnutrition and it correlates well with anthropometric and biochemical assessment. may be integrated in regular assessment of malnutrition in patients on maintenance hemodialysis.
doi:10.4103/0250-474X.89755
PMCID: PMC3224408  PMID: 22131620
Anthropometry; hemodialysis; malnutrition; protein energy
8.  Drug Usage Evaluation of Dapsone 
Dapsone has been the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. It is also widely used by dermatologists in varied skin conditions like dermatitis herpetiformis, bullous pemphigoid, Behcet's disease, lupus erythematous and a host of other skin diseases. Hence an attempt has been made to review the utilization and qualitative evaluation of dapsone over a period of 6 months in a tertiary care teaching hospital. The study consisted of 80 patients (54 leprosy and 26 non-leprosy patients), prescribed with dapsone 100 mg oral once daily. The prescribing patterns of dapsone in leprosy and other dermatological conditions (non-leprosy) were analyzed and the safety, efficacy and appropriateness of the doses prescribed were reviewed. The adverse drug reactions observed in the study population were type I Lepra reactions, gastrointestinal side effects (abdominal pain and anorexia), peripheral neuropathy, other nervous side effects (insomnia, headache and vertigo) and other adverse reactions (fever and tinnitus). Patient information leaflets were distributed to patients to educate on the appropriate use of dapsone.
doi:10.4103/0250-474X.57301
PMCID: PMC2865824  PMID: 20502558
Dapsone; drug usage evaluation; adverse effects; patient education

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