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Biomedical subjects

Kamala Krishnaswamy

Publications and source records attributed to Kamala Krishnaswamy.

10 recordsLinked to original sources
PubMed2006

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Animals↗
PubMed2006

Effect of micronutrient supplement on health and nutritional status of schoolchildren: study design.

OBJECTIVE: We tested the hypothesis that supplementation with a micronutrient-fortified beverage improves micronutrient status and physical and mental development in apparently healthy schoolchildren. METHODS: The study was carried out in middle-income students in two residential schools that catered to children from a semi-urban population near Hyderabad, India. Included were 869 children who were 6 to 16 y of age in grades 1 to 10. Because children at each grade were distributed across two classrooms (clusters) and were homogeneous, each grade was considered to consist of a matched pair. There were thus 10 pairs available for the study. Classes in each grade were randomized to receive a micronutrient-enriched beverage or a placebo without added micronutrients. The study was double blinded and the duration was 14 mo, with supervised feeding of the micronutrient-enriched beverage. The effect of the micronutrients on the outcome variables growth, biochemical status, mental function, and bone health were assessed. RESULTS: The number of matched pairs varied between seven and eight, and the required number of children per treatment group ranged from 32 in the case of bone heath to 177 for body weight. The power of the outcome variables ranged from 74% to 100% and was adequate for successful pairing. The effect assessed at the end of supplementation showed that the intervention was beneficial. CONCLUSIONS: Designing an intervention, choosing outcome variables, and implementing the protocol in a typical Indian school setting were achieved.

Adolescent↗
PubMed2006

Effect of micronutrient supplement on health and nutritional status of schoolchildren: bone health and body composition.

OBJECTIVE: We investigated the effect of a micronutrient-enriched beverage on body composition, bone mineral content (BMC), bone area, and bone mineral density (BMD) at various sites in schoolchildren. METHODS: A double-blind, placebo-controlled, matched-pair, cluster, randomization study was carried out in residential schoolchildren 6 to 16 y of age who lived near Hyderabad, India. Children (n = 268) were selected randomly from two classes of each grade (1 to 9) and were provided a micronutrient-enriched beverage (n = 146) or a placebo drink (n = 122). Bone parameters such as BMC, BMD, and bone area at various sites and the entire body were measured with dual-energy X-ray absorptiometry at the beginning and end of the study. Increments of outcome variables were subjected to paired t test with appropriate corrections to assess the effect of the supplement on bone health. RESULTS: After 14 mo, increments for height, weight, fat-free mass, percentage of fat, whole-body BMC, whole-body bone area, and BMD at the neck of the femur were significantly greater (P < 0.05) in the supplemented group than in the placebo group. CONCLUSIONS: The micronutrient-rich supplement increased tissue growth and skeletal shell in apparently normal children in the 14-mo period. It did not increase whole-body or site-specific BMD except at the neck of the femur. Amounts of calcium and other nutrients contained in the supplement were inadequate for tissue growth with density increases. This study raises important questions about the nutrient requirements of Indian children who consume a diet of cereals and pulses.

Absorptiometry, Photon↗
PubMed2005

Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats.

PURPOSE: The purpose of this study was to investigate the effect of curcumin and its source, turmeric, on streptozotocin-induced diabetic cataract in rats. METHODS: Wistar-NIN rats were selected and diabetes was induced by streptozotocin (35 mg/kg body weight, intraperitoneally) and divided into four groups (group II-V). The control (group I) rats received only vehicle. Group I and II animals received an unsupplemented AIN-93 diet, and those in groups III, IV, and V received 0.002% and 0.01% curcumin and 0.5% turmeric, respectively, in an AIN-93 diet for a period of 8 weeks. Cataract progression due to hyperglycemia was monitored by slit lamp biomicroscope and classified into four stages. At the end of 8 weeks, the animals were killed and the biochemical pathways involved in the pathogenesis of cataract such as oxidative stress, polyol pathway, alterations in protein content and crystallin profile in the lens were investigated, to understand the possible mechanism of action of curcumin and turmeric. Blood glucose and insulin levels were also determined. RESULTS: Although, both curcumin and turmeric did not prevent streptozotocin-induced hyperglycemia, as assessed by blood glucose and insulin levels, slit lamp microscope observations indicated that these supplements delayed the progression and maturation of cataract. The present studies suggest that curcumin and turmeric treatment appear to have countered the hyperglycemia-induced oxidative stress, because there was a reversal of changes with respect to lipid peroxidation, reduced glutathione, protein carbonyl content and activities of antioxidant enzymes in a significant manner. Also, treatment with turmeric or curcumin appears to have minimized osmotic stress, as assessed by polyol pathway enzymes. Most important, aggregation and insolubilization of lens proteins due to hyperglycemia was prevented by turmeric and curcumin. Turmeric was more effective than its corresponding levels of curcumin. CONCLUSIONS: The results indicate that turmeric and curcumin are effective against the development of diabetic cataract in rats. Further, these results imply that ingredients in the study's dietary sources, such as turmeric, may be explored for anticataractogenic agents that prevent or delay the development of cataract.

Animals↗
PubMed2003

Effect of curcumin on galactose-induced cataractogenesis in rats.

PURPOSE: Curcumin, the active principle of turmeric, has been shown to have both antioxidant and hypoglycemic activity in vitro and in vivo. The purpose of this study was to investigate the effect of curcumin on the onset and maturation of galactose induced cataract. METHODS: Sprague-Dawley rats (21 days old) were divided into 5 groups. The control group (A) received an AIN-93 diet, the galactose group (B) received 30% galactose in the diet, the test groups (C and D) received the B group diet plus 0.002% and 0.01% curcumin respectively, and group (E) received the control diet plus 0.01% curcumin, all for a period of 4 weeks. Cataract progression due to galactose feeding was monitored by slit lamp microscope and classified into 4 stages. At the end of the experiment biochemical parameters such as lipid peroxidation, aldose reductase (AR), sorbitol dehydrogenase (SDH), reduced glutathione, protein content, and protein carbonyls were measured in the lens. Advanced glycated end products (AGE) and protein oxidation were measured by AGE and tryptophon fluorescence respectively. Crystallin profile was analyzed by size exclusion chromatography (HPLC). RESULTS: Slit lamp microscope observations indicated that curcumin at 0.002% (group C) delayed the onset and maturation of cataract. In contrast even though there was a slight delay in the onset of cataract at the 0.01% level (group D), maturation of cataract was faster when compared to group B. Biochemical analysis showed that curcumin at the 0.002% level appeared to exert antioxidant and antiglycating effects, as it inhibited lipid peroxidation, AGE-fluorescence, and protein aggregation. Though the reasons for faster onset and maturation of cataract in group D rats was not clear, the data suggested that under hyperglycemic conditions higher levels of curcumin (0.01%) in the diet may increase oxidative stress, AGE formation, and protein aggregation. However, feeding of curcumin to normal rats up to a 0.01% level did not result in any changes in lens morphology or biochemical parameters. CONCLUSIONS: These results suggest that curcumin is effective against galactose-induced cataract only at very low amounts (0.002%) in the diet. On the other hand at and above a 0.01% level curcumin seems to not be beneficial under hyperglycemic conditions, at least with the model of galactose-cataract.

Aldehyde Reductase↗
PubMed2003

Validation of hemoglobin estimation using Hemocue.

OBJECTIVE: This piece of work is an attempt to compare Hemocue and Cyanmethemoglobin methods for hemoglobin estimation. METHODS: In 100 apparently healthy children of 1-6 years of age, Hb was estimated using Hemocue and cyanmethemoglobin methods from finger prick blood sample. The results obtained by the two methods were compared using appropriate statistical methods. RESULTS: Mean +/- SD values for hemoglobin (g/dl) were 9.33 +/- 2.719 by Hemocue and 8.14 +/- 2.448 by cyanmethemoglobin method. When assessed by Hemocue method the proportion of children with anemia was 66% while it was 88% with cyanmethemoglobin method. The sensitivity of Hemocue method was 0.75 and specificity 1.0 considering cyanmethemoglobin method as gold standard. The corresponding values by cyanmethemoglobin method for a given Hemocue value fell within the Mean difference +/- 2 SD with correlation coefficient being r = 0.922. Despite the good association, the two methods agreed, the magnitude of difference being -1.19 g/dl (CI: -1.40 to -0.98) thus suggesting an overestimate of hemocue values ranging from 10 to 15%. A correction factor was arrived for converting Hb values obtained by Hemocue method to arrive at the expected value by the reference method, this factor being 0.389 + 0.831 Hb (Hemocue). CONCLUSION: As there are limitations expressed for both the methods in accurately estimating Hb, it is difficult to decide whether one is an overestimate or the other an underestimate. By virtue of the principle involved in estimating Hb, cyanmethemoglobin method may be taken as an indirect indicator of iron status. However, it is not clear whether such a principle is involved in estimating Hb by Hemocue. Therefore, these two methods need to be further validated against a sensitive and specific indicator for iron status like circulating transferrin receptor to decide which of the methods can be used to accurately determine the prevalence of iron deficiency anemia in the community.

Anemia, Iron-Deficiency↗
PubMed2003

Safety and impact of vitamin A supplementation delivered with oral polio vaccine as part of the immunization campaign in Orissa, India.

A study was carried out in Orissa, India, to evaluate the impact on vitamin A status of vitamin A supplementation integrated with an immunization campaign. Data were collected from a representative sample of 1,811 children, aged 12 to 48 months, at baseline and then at 4 and 16 weeks following implementation of vitamin A supplementation. The primary outcome indicator was serum retinol. The coverage of vitamin A supplementation was 97%. There was a significant decline in the prevalence of Bitot's spots from 2.9% to 1.9% at 4 weeks, but the prevalence increased to 3.6% by 16 weeks. Serum retinol concentrations increased between baseline and 4 weeks (from 0.62 +/- 0.32 to 0.73 +/- 0.23 mumol/L, p < .001) but then decreased to 0.50 +/- 0.19 mumol/l at 16 weeks, which was significantly lower than at baseline (p < .001). The greatest increase in serum retinol from baseline to 4-week follow-up was among children with lowest baseline serum retinol and children with Bitot's spots at baseline. This study demonstrates the short-term benefits of vitamin A supplementation to be significant, especially for those whose status is most compromised. At the same time, the benefit of vitamin A supplementation in this population was transient. The impact of the vitamin A could not be sustained for the full 16 weeks in the study population. This finding calls for exploration of other means to improve vitamin A status, perhaps by adjusting the vitamin A supplementation schedule with more aggressive measures to improve intake of foods rich in bioavailable vitamin A, such as small amounts of animal foods or fortified foods. The study demonstrates the feasibility of integrating vitamin A supplementation with immunization campaigns.

Child, Preschool↗
PubMed2002

Role of nutritional supplementation in reducing the levels of homocysteine.

Elevated plasma homocysteine level is a risk factor for atherosclerotic disease. Plasma homocysteine levels are influenced by genetic, physiological and lifestyle factors. Among the lifestyle factors, diet plays a significant role. Dietary intakes of folate, vitamins B12, B6 and B2 have been reported to be inversely related to plasma homocysteine concentration. Prevalence of subclinical deficiencies of these vitamins is high in Indian population. Folate status is the major determinant of plasma homocysteine level and there is a strong inverse correlationship between plasma homocysteine level and serum or erythrocyte folate levels. A combination therapy with B vitamins--folate, vitamins B12 and B6 is an effective means to reduce elevated homocysteine levels in general people and in patients with myocardial infarction. To maintain low plasma homocysteine concentration, people should be advised to increase their consumption of pulses, eggs, green leafy vegetables and fruits which are rich in B vitamins.

Dietary Supplements↗