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Biomedical subjects

R Ramakrishnan

Publications and source records attributed to R Ramakrishnan.

At least 37 records · Page 2Linked to original sources

An institutional outbreak of leptospirosis in Chennai, South India.

The emergence of an outbreak of leptospirosis in a nurses' hostel in Chennai presented a challenge to identify and control the source of the outbreak. Sixty-nine residents and staff members were interviewed to assess exposure factors. Blood samples from the acute and convalescent patients were tested with the Microscopic Agglutination Test using the serovars prevalent in Chennai. Polymerase Chain Reaction (PCR) was conducted on serum and water samples. Based on preliminary investigation, control measures with standard hygienic measures were instituted. The attack rate was 35%. The epidemic curve suggested continuous or intermittent exposure to infection over a five-week period. Twenty residents (three asymptomatic) developed laboratory confirmed Leptospira icterohemorrhagiae. Residents collected water from an underground storage tank that was filled twice weekly from a mobile water tanker with a bucket on a rope, and the tank was usually left open. PCR tests confirmed the presence of leptospires from this water. Other control measures included cleaning the large backyard with its many stray dogs and rats, chlorinating water supplies, boiling drinking water and health education. No further cases occurred twelve days after implementing control measures. Access to clean water, not only for drinking but also for bathing, brushing and washing is essential to prevent water-borne outbreaks.

Adult↗

A population based eye survey of older adults in Tirunelveli district of south India: blindness, cataract surgery, and visual outcomes.

AIMS: To assess the prevalence of vision impairment, blindness, and cataract surgery and to evaluate visual acuity outcomes after cataract surgery in a south Indian population. METHODS: Cluster sampling was used to randomly select a cross sectional sample of people > or =50 years of age living in the Tirunelveli district of south India. Eligible subjects in 28 clusters were enumerated through a door to door household survey. Visual acuity measurements and ocular examinations were performed at a selected site within each of the clusters in early 2000. The principal cause of visual impairment was identified for eyes with presenting visual acuity <6/18. Independent replicate testing for quality assurance monitoring was performed in subjects with reduced vision and in a sample of those with normal vision for six of the study clusters. RESULTS: A total of 5795 people in 3986 households were enumerated and 5411 (93.37%) were examined. The prevalence of presenting and best corrected visual acuity > or =6/18 in both eyes was 59.4% and 75.7%, respectively. Presenting vision <6/60 in both eyes (the definition of blindness in India) was found in 11.0%, and in 4.6% with best correction. Presenting blindness was associated with older age, female sex, and illiteracy. Cataract was the principal cause of blindness in at least one eye in 70.6% of blind people. The prevalence of cataract surgery was 11.8%-with an estimated 56.5% of the cataract blind already operated on. Surgical coverage was inversely associated with illiteracy and with female sex in rural areas. Within the cataract operated sample, 31.7% had presenting visual acuity > or =6/18 in both eyes and 11.8% were <6/60; 40% were bilaterally operated on, with 63% pseudophakic. Presenting vision was <6/60 in 40.7% of aphakic eyes and in 5.1% of pseudophakic eyes; with best correction the percentages were 17.6% and 3.7%, respectively. Refractive error, including uncorrected aphakia, was the main cause of visual impairment in cataract operated eyes. Vision <6/18 was associated with cataract surgery in government, as opposed to that in non-governmental/private facilities. Age, sex, literacy, and area of residence were not predictors of visual outcomes. CONCLUSION: Treatable blindness, particularly that associated with cataract and refractive error, remains a significant problem among older adults in south Indian populations, especially in females, the illiterate, and those living in rural areas. Further study is needed to better understand why a significant proportion of the cataract blind are not taking advantage of free of charge eye care services offered by the Aravind Eye Hospital and others in the district. While continuing to increase cataract surgical volume to reduce blindness, emphasis must also be placed on improving postoperative visual acuity outcomes.

Age Distribution↗

In-vitro efficacy of antibacterials against bacterial isolates from corneal ulcers.

PURPOSE: To analyse the in-vitro efficacy of commonly used antibacterials against bacterial pathogens from corneal ulcers. METHODS: We evaluated 596 patients seen over 18 months, period, September 1999 through March 2001. Corneal scrapings were subjected to microscopy and cultures using standard protocols. Antibacterial susceptibility of isolated bacteria were determined by the Kirby-Bauer disc-diffusion method. RESULTS: 626 bacterial pathogens were isolated from 596 corneal ulcer cases. 411(65.65%) were gram positive cocci Streptococcus pneumoniae (41.85%) was the predominant bacterial species. The antibacterial susceptibility was: 451(72.04%) to cefazolin, 471(75.24%) to chloramphenicol; 321(51.28%) to cephaloridine; 430(68.69%) to vancomycin; 564(90.09%) to ciprofloxacin; 429(68.53%) to norfloxacin; 464(74.12%) to gentamicin and 202(32.27%) to co.trimoxazole. CONCLUSION: This study provides information on the efficacy of ocular antibacterials commonly used against bacterial pathogens of keratitis. It is hoped that this information will help decision-making in empiric initial treatment of bacterial keratitis.

Anti-Bacterial Agents↗

Vitamin E kinetics in smokers and nonsmokers.

Does cigarette smoking increase vitamin E utilization in vivo? A trial was carried out in 6 smokers and 5 nonsmokers of comparable ages and serum lipids. Subjects consumed 75 mg each d(3)-RRR and d(6)-all rac-alpha-tocopheryl acetates (natural and synthetic vitamin E, respectively) daily for 7 d with a standardized breakfast. Fasting blood samples were drawn on days -7, -6, -5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 9, 14, 21 (negative days indicate supplementation). In both groups, plasma d(3)-alpha-tocopherol concentrations were approximately double of d(6)-alpha-tocopherol. At day 0, the %d(3) alpha-tocopherols (d(3)-alpha-tocopherol/total-alpha-tocopherol x 100) were similar in both smokers and nonsmokers. Subsequently, there was a trend toward a faster exponential disappearance of the plasma %d(3) alpha-tocopherol in smokers compared with nonsmokers (0.30 +/- 0.04 compared with 0.24 +/- 0.05, p =.0565). The calculated %d(3) half-lives were 55.6 +/- 7.4 h in smokers and 72.1 +/- 17.3 h in nonsmokers (p =.0630). By day 21, the %d(3) in smokers had decreased to 1.4% +/- 0.3% while it was 2.2% +/- 0.7% (p =.0418) in the nonsmokers. These data suggest that smoking increases plasma vitamin E disappearance, but further studies are needed to confirm this finding and to assess its cause.

Adult↗

Interactions of aspirin and salicylic acid with prednisolone for inhibition of lymphocyte proliferation.

The anti-inflammatory properties of salicylates and prednisolone were investigated using inhibition of in vitro phytohemagglutinin-stimulated lymphocyte proliferation in human whole blood from healthy male and female subjects. Steroids and salicylates are used in conjunction for the treatment of inflammatory disorders such as rheumatoid arthritis and inhibit the proinflammatory transcription factor, NFKB, by different mechanisms. Data generated using various combinations of these drugs were analyzed using isobolograms and the universal surface response approach based on the Loewe additivity principle. The interaction between aspirin and prednisolone was mildly antagonistic while that between salicylic acid and prednisolone was modestly synergistic at therapeutic concentrations. Further, aspirin was slightly more potent in males, but the nature of the steroid-salicylate interaction was similar across genders. This study helps rationalize part of the beneficial effects of steroids and salicylates in treatment of inflammatory disorders.

Adult↗

Retinol binding protein as a surrogate measure for serum retinol: studies in vitamin A-deficient children from the Republic of the Marshall Islands.

BACKGROUND: Serum retinol is transported by retinol binding protein (RBP), which has one high-affinity binding site for retinol; consequently, the molar ratio of retinol to RBP in the circulation is approximately 1 to 1. In vitamin A deficiency (VAD), both serum retinol and RBP decline. However, the retinol-RBP relation has not been well studied in populations with a high incidence of severe VAD. OBJECTIVE: The purpose of this study was to determine whether RBP is a good surrogate for serum retinol at the very low retinol concentrations encountered in VAD. DESIGN: The stoichiometric relation between retinol and RBP was studied in 239 Marshallese children: 65 with severe VAD (< or = 0.35 micromol retinol/L), 94 with moderate VAD (0.36-0.70 micromol retinol/L), and 80 with vitamin A sufficiency (> 0.70 micromol retinol/L). RESULTS: Excellent correlation between retinol and RBP (r = 0.94) was observed across all retinol concentrations. Severe VAD was predicted with 96% sensitivity and 91% specificity on the basis of an RBP cutoff of < or = 0.48 micromol/L, whereas moderate VAD was predicted with 87% sensitivity and 98% specificity on the basis of an RBP cutoff of < or = 0.70 micromol/L. CONCLUSIONS: The use of RBP results in the classification of essentially the same children with VAD as does retinol, and RBP is an excellent surrogate for serum retinol. Considering the relative ease of measuring RBP with immunodiagnostic kits compared with that of serum retinol by HPLC, the use of RBP concentrations to assess VAD may be particularly advantageous in field settings. Consequently, measuring RBP concentrations may be a practical alternative to measuring serum retinol in population surveys assessing the prevalence of VAD.

Acute-Phase Proteins↗

Effects of quality of energy intake on growth and metabolic response of enterally fed low-birth-weight infants.

Carbohydrate and fat may vary in their ability to support protein accretion and growth. If so, variations in the source of nonprotein energy might be used to therapeutic advantage in enterally fed low-birth-weight infants. To test the hypothesis that high-carbohydrate diets are more effective than isocaloric high-fat diets in promoting growth and protein accretion, low-birth-weight infants weighing 750-1600 g at birth were randomized in a double blind study to receive one of five formulas differing only in the quantity and quality of nonprotein energy. Groups 1, 2, and control received 130 kcal x kg(-1) x d(-1) with 35, 65, and 50% of the nonprotein energy as carbohydrate. Groups 3 and 4 received energy intake of 155 kcal x kg(-1) x d(-1) with 35 and 65% of the nonprotein energy as carbohydrate. Protein intake of all groups was 4 g x kg(-1) x d(-1). Growth and metabolic responses were followed weekly, and macronutrient balances including 6-h indirect calorimetry were performed biweekly. Greater rates of weight gain and nitrogen retention were observed at high-carbohydrate intake compared with high-fat intake at both gross energy intakes. Greater rates of energy storage and an increase in skinfold thickness were observed in group 4 (high-energy high-carbohydrate diet) despite higher rates of energy expenditure. These data support the hypothesis that at isocaloric intakes, carbohydrate is more effective than fat in enhancing growth and protein accretion in enterally fed low-birth-weight infants. However, a diet with high-energy and high-carbohydrate content also results in increased fat deposition.

Body Weight↗

Antihyperglycaemic effect of Diamed, a herbal formulation, in experimental diabetes in rats.

Diamed is a herbal formulation composed of the aqueous extracts of three medicinal plants (Azardirachta indica, Cassia auriculata and Momordica charantia). We have investigated Diamed for its possible antihyperglycaemic action in rats with alloxan-induced experimental diabetes. Oral administration of Diamed (1.39 (0.25 g), 1.67 (0.30 g) or 1.94 (0.35 g) mL kg(-1)) for 30 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin, and an increase in plasma insulin and total haemoglobin. The effect was highly significant after administration of the 1.94 mL (0.35 g) g(-1) body weight dose. Diamed also prevented a decrease in body weight. An oral glucose tolerance test was performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in the animals treated with Diamed. The effect was compared with 600 microg kg(-1) glibenclamide. The results showed that Diamed had antihyperglycaemic action in experimental diabetes in rats.

Animals↗

Effect of systemic lupus erythematosus (SLE) treatment drugs on GI-101A breast tumor cell growth.

The effect of systemic lupus erythematosus (SLE) treatment drugs on PKC (protein kinase C) activity and cell growth was studied using GI-101A breast tumor cells. Both hydroxychloroquine (HCQ) and prednisone treatments significantly increased the PKC activity in GI-101A cells after 60 min. Treatment of cells with a combination of HCQ/prednisone also produced the highest increase in PKC activity following 60 min incubation. When the GI-101A cells were treated with the same drugs, HCQ (10 ng/ml) prednisone (10 ng/ml) and HCQ/prednisone combination (10 ng/ml of each), for 72 hr the total PKC activity in the cells was significantly elevated and consequently the GI-101A cell growth was stimulated. As a result of drug induced cell growth stimulation the total number of cells in the treatment groups increased significantly compared to the non-treated controls. Interestingly HCQ and prednisone treatment induced cell growths were completely blocked by PKC specific inhibitor chelerythrine (50 microM). Our results suggest that HCQ and prednisone treatment can induce GI-101A cell growth via activating PKC.

Breast Neoplasms↗

Expression of vascular endothelial growth factor mRNA in GI-101A and HL-60 cell lines.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that has a strong association with growth and metastasis of various cancers. We analyzed the expression of VEGF mRNA levels in human breast-tumor derived GI-101A cells and in human promyelocytic leukemia derived HL-60 cells using RT-PCR technique. During our RT-PCR analysis we detected the expression of three splice variants of VEGF mRNA at 400, 520 and, 650 bp lengths, which were amplified by a single set of VEGF specific forward and reverse primers. The three RT-PCR products detected by us in these cells correspond to the mRNA splice variants coding for the three isoforms of VEGF respectively, VEGF(121), VEGF(165), and VEGF(189). Treatment of GI-101A and HL-60 cells with phorbol 12, 13-dibutyrate (PDB) or diethylstilbestrol (DES) resulted in a significant increase of VEGF mRNA levels in a dose dependent manner. Both treatments increased the levels of all three splice variants of VEGF mRNA and a maximum increase was detected with 10 microM concentrations of PDB or DES treatments after 2 h. Interestingly, both PDB and DES mediated stimulation of VEGF mRNA expression was completely blocked by the PKC inhibitor chelerythrine. Quantitation of VEGF levels by ELISA technique confirmed that changes seen in mRNA levels following different treatments altered the release of VEGF. Our results suggest that PDB and DES mediated effects on VEGF expression in GI-101A and HL-60 cells occur at the gene transcription level.

Alkaloids↗

4-Hydroxynonenal, an end-product of lipid peroxidation, induces apoptosis in human leukemic T- and B-cell lines.

4-Hydroxynonenal (HNE) is the major aldehydic product resulting from lipid peroxidation and has been implicated as involved in several pathological conditions. In our continuing studies on the role of membranes and lipid peroxidation in the induction of apoptosis, we investigated the effect of HNE on cultured human malignant immune system cells. Two cell lines were utilized; MOLT-4, a human T-cell leukemia cell line, and Reh, a human B-cell lymphoma cell line. A 10 min treatment with 0.01 mM HNE resulted in the apoptotic death, as determined by flow cytometric and morphological analyses, of both cell lines within 24 h. MOLT-4 cells exhibited the manifestations of impending apoptotic death much sooner than did Reh cells, indicating that MOLT-4 cells were more sensitive or not as efficient at detoxifying HNE than were Reh cells. These results suggest that peroxidative damage to cellular membranes resulting in the production of HNE may be a trigger for the induction of apoptosis in immune system cells.

Aldehydes↗

Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice.

We used wild-type (WT) mice and mice engineered to express either apoB-100 only (B100 mice) or apoB-48 only (B48 mice) to examine the effects of streptozotocin-induced diabetes (DM) on apoB-100- and apoB-48-containing lipoproteins. Plasma lipids increased with DM in WT mice, and fat tolerance was markedly impaired. Lipoprotein profiles showed increased levels and cholesterol enrichment of VLDL in diabetic B48 mice but not in B100 mice. C apolipoproteins, in particular apoC-I in VLDL, were increased. To investigate the basis of the increase in apoB-48 lipoproteins in streptozotocin-treated animals, we characterized several parameters of lipoprotein metabolism. Triglyceride and apoB production rates were normal, as were plasma lipase activity, VLDL glycosaminoglycan binding, and VLDL lipolysis. However, beta-VLDL clearance decreased due to decreased trapping by the liver. Whereas LRP activity was normal, livers from treated mice incorporated significantly less sulfate into heparan sulfate proteoglycans (HSPG) than did controls. Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG. Western blots of livers from diabetic mice showed a decrease in the HSPG core protein, perlecan. Delayed clearance of postprandial apoB-48-containing lipoproteins in DM appears to be due to decreased hepatic perlecan HSPG.

Animals↗

Feeding inhibition and mortality in Reticulitermes flavipes (Isoptera: Rhinotermitidae) after exposure to imidacloprid-treated soils.

Feeding inhibition and mortality of Reticulitermes flavipes (Kollar) exposed to sand, sandy loam, loam, and silty clay loam soils treated with several concentrations of imidacloprid were studied using bioassay techniques under laboratory conditions. Termite workers stopped feeding after exposure to treated soils. Differences in feeding reduction varied among the soil types. Based on the magnitude of the F-statistics, the effect of imidacloprid on the reduction of termite feeding was greatest in sand followed by sandy loam, loam, and silty clay loam soils. Soil properties such as organic matter content, silt and clay proportions, pH, and cation exchange capacity were suggested to affect the bioavailability of imidacloprid. Similar soil effects on mortality were observed in termites continuously exposed to treated soil for 21 d. In three of four soils tested, susceptibility to imidacloprid was not affected by the source of the termites tested.

Animals↗

Kearns Sayre syndrome: an atypical presentation.

Kearns Sayre syndrome is a rare presentation which usually involves a triad of factors: external ophthalmoplegia, retinal pigmentary degeneration, and heart block. We present a clinically and histopathologically confirmed case of Kearns Sayre syndrome that involved no retinal pathology.

Adolescent↗

Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile.

The clearance of free cholesterol from plasma lipoproteins by tissues is of major quantitative importance, but it is not known whether this is passive or receptor-mediated. Based on our finding that scavenger receptor BI (SR-BI) promotes free cholesterol (FC) exchange between high density lipoprotein (HDL) and cells, we tested whether SR-BI would effect FC movement in vivo using [(14)C]FC- and [(3)H]cholesteryl ester (CE)-labeled HDL in mice with increased (SR-BI transgenic (Tg)) or decreased (SR-BI attenuated (att)) hepatic SR-BI expression. The initial clearance of HDL FC was increased in SR-BI Tg mice by 72% and decreased in SR-BI att mice by 53%, but was unchanged in apoA-I knockout mice compared with wild-type mice. Transfer of FC to non-HDL and esterification of FC were minor and could not explain differences. The hepatic uptake of FC was increased in SR-BI Tg mice by 34% and decreased in SR-BI att mice by 22%. CE clearance and uptake gave similar results, but with much slower rates. The uptake of HDL FC and CE by SR-BI Tg primary hepatocytes was increased by 2.2- and 2.6-fold (1-h incubation), respectively, compared with control hepatocytes. In SR-BI Tg mice, the initial biliary secretion of [(14)C]FC was markedly increased, whereas increased [(3)H]FC appeared after a slight delay. Thus, in the mouse, a major portion of the clearance of HDL FC from plasma is mediated by SR-BI.

Animals↗

An immunologically active arabinogalactan from Tinospora cordifolia.

An arabinogalactan of mean M(r) 2.2 x 10(6) has been isolated from the dried stems of Tinospora cordifolia and examined by methylation analysis, partial hydrolysis and carboxyl reduction. Purified polysaccharide showed polyclonal mitogenic activity against B-cells, their proliferation did not require macrophages.

Adjuvants, Immunologic↗

Basic pharmacodynamic models for agents that alter production of natural cells.

Basic indirect pharmacodynamic models for agents which alter the generation of natural cells based on a life-span concept are introduced. It is assumed that cells (R) are produced at a constant rate (kin), survive for a specific duration TR, and then are lost. The rate of cell loss must equal the production rate but is delayed by TR. A therapeutic agent can stimulate or inhibit the production rate according to the Hill function: 1 +/- H(C(t)) where H(C(t)) contains capacity (Smax) and sensitivity (SC50) constants and C(t) is a pharmacokinetic function. Thus an operative model is [equation: see text] with the baseline condition R0 = kin.TR. One- and two-compartment catenary cell models were examined by simulation to describe the role of pharmacokinetics and cell properties. The area under the effect curve (AUCE) was derived. The models were applied to literature data to describe the stimulatory effects of single doses of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) on neutrophils, thrombopoietin (TPO) on platelets, and erythropoietin (EPO) on reticulocytes in blood. The models described experimental data adequately and provided cell life-spans and SC50 values. The proposed cell production/loss models can be readily used to analyze the pharmacodynamics of agents which alter cell production yielding realistic physiological parameters.

Algorithms↗

HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects.

BACKGROUND: Little information is available about HDL subpopulations during dietary changes. OBJECTIVE: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations. DESIGN: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat,15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat). RESULTS: HDL(2)-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 +/- 0.21, 0.53 +/- 0.19, and 0.48 +/- 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL(3) cholesterol decreased (P < 0.01) less: 0.76 +/- 0.13, 0.73 +/- 0.12, and 0.72 +/- 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL(2b) subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL(3a, 3b), and (3c) subpopulations (P < 0.01). HDL(2)-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = -0.46, -0.37, and -0.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL(2b), whereas HDL(3a, 3b), and (3c) correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL(2) and HDL(2b) cholesterol. CONCLUSIONS: A reduction in dietary total and saturated fat decreased both large (HDL(2) and HDL(2b)) and small, dense HDL subpopulations, although decreases in HDL(2) and HDL(2b) were most pronounced.

Adult↗