The changing epidemiologic scene: malnutrition versus chronic diseases in India.
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Biomedical subjects
Publications and source records attributed to K Krishnaswamy.
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The effect of smoking on DNA adduct formation in lymphocytes was analysed in individuals with low (deficient) and high (non-deficient) glutathione S-transferase (class Mu) activity. DNA adduct levels in lymphocytes were determined by the highly sensitive nuclease P1-enhanced 32P-postlabeling assay. The lymphocyte DNA adducts/10(8) nucleotides of smokers deficient in glutathione S-transferase Mu activity (n = 12) were significantly higher than those of smokers non-deficient (n = 9) in glutathione S-transferase Mu activity. The DNA adduct levels of the lymphocytes inversely correlated with glutathione S-transferase Mu activity. A correlation was found between DNA adduct levels and daily cigarette consumption. Results of the present study suggest that individuals deficient in glutathione S-transferase Mu activity may be at greater risk of DNA damage.
OBJECTIVE: To develop and test a food frequency questionnaire (FFQ) for use in rural areas of Kerala, India. DESIGN: Based on food use and market surveys of the study area, a quantitative 81-item interviewer-administered FFQ was developed. A validation study was conducted consisting of 24-h diet recalls (24HR) administered on 8 days randomly selected over an entire year and two administrations of the FFQ, one at the beginning of the 1-year period and the other at the end. FFQ and 24HR-derived nutrient scores were compared using correlation and regression analyses and by examining differences in the nutrient scores. SETTING: Rural villages in Ernakulum district, Kerala, South India. SUBJECTS: In each of 30 households, the male head of household and female food preparer were enrolled. RESULTS: Pearson (parametric) correlation coefficients (r(p)) averaged about 0.50 in comparing nutrient scores derived from the 24HR with those from the first FFQ and about 0.55 in comparing the second FFQ. On average, Spearman correlation coefficients (r(s)) were slightly lower than the r(p) in comparing the scores derived from the first FFQ, but virtually identical for the second FFQ. Regression analyses indicated better agreement in the comparison of the 24HR-derived scores with the first FFQ than the second FFQ. Difference scores, however, tended to be larger in comparing the first FFQ scores with the 24HR. CONCLUSIONS: This FFQ produces results broadly comparable to those used in Europe and North America, indicating its suitability for comparing exposures within a study population in reference to health-related endpoints.
Turmeric and its active principle curcumin have been extensively investigated for their antimutagenic and antioxidant effects in bacterial and animal systems. Because oral cancers are common in India, an experimental model of 7,12-dimethylbenzanthracene-induced buccal pouch tumors in Syrian Golden hamsters was used to evaluate the tumor retardation effects of turmeric and curcumin. Turmeric and/or curcumin was administered in the diet and/or applied locally for 14 weeks along with 7,12-dimethylbenzanthracene. After the experimental period, the animals were sacrificed and oral pouches were examined for tumor number and size. DNA adducts were estimated by 32P postlabel assay in the cheek pouches. Neoplastic changes were graded by histopathology. The results of the study suggest that turmeric or curcumin in the diet and/or applied locally significantly reduced DNA adducts at the target site. Tumor number and tumor burden were significantly lower (p < 0.05) in the animals that received turmeric in the diet and applied locally. The histopathological examinations suggested that the neoplastic grading was least in the animals fed or painted with curcumin (p < 0.05). The current study demonstrates that turmeric or curcumin administered in the diet or applied as paint may have a plausible chemopreventive effect on oral precancerous lesions.
Diet can modify the pathophysiological processes of various metabolic disorders and can be an effective preventive strategy for various disease processes most of which are known to involve oxidative damage. Both nutrient and non-nutrient components of the diet have been recognized for their anti-oxidant and other potential benefits. Plant foods contain phytochemicals such as flavonoids, phenolic acids, etc., which show biological activity. Some common foods used in Indian culinary practices were assessed for their anti-oxidant, anti-mutagenic and anti-carcinogenic effects and vitamin D activity and evaluated for their plausible biological effects. Green leafy vegetables had the highest anti-oxidant activity followed by wheat and rice. Cooking decreased this activity. Eugenol, the active principle of clove, was shown to offer protection against CCl4 induced hepatotoxicity in rats. It also showed anti-peroxidative activity in addition to decrease in O2 formation. Studies on the anti-carcinogenic effect of turmeric/curcumin revealed that both are potent anti-mutagens in vivo and reduce the adducted DNA levels in liver of rates challenged with B(a)P. In another study, Syrian hamsters receiving turmeric/curcumin through diet or local paint on cheek pouch had lower tumour burden as well as adducted DNA level against 7-12-DMBA challenge. Turmeric/curcumin were found to be better anti-tumour agents when given in the post initiation phase of carcinogenesis. The beneficial effect of turmeric was found to be due to its anti-oxidant potential. Studies on humans at risk of palatal cancer due to reverse smoking showed that turmeric (1 g/day) for 9 months had a significant impact on the regression of precancerous lesions. Onion and garlic also possess anti-mutagenic principle. Further studies on the bioactive phytochemicals in plants showed that certain plants belonging to Solanaceae (Cestrum diurnum, Lycopersicon esculentum and Solanum melongena) have calcinogenic potential and vitamin D like activity. In view of the vast data on bioactive principles from plants, it is suggested that dietary prevention coupled with other life-style changes in perhaps the right answer for prevention of cancer and other chronic diseases in India.
As a novel approach to tackle the problems of iron deficiency anaemia and iodine deficiency disorders (IDDs), which often coexist, the National Institute of Nutrition has developed iron and iodine fortified common salt (double fortified salt-DFS) as a public health measure. This salt has undergone a battery of laboratory and field tests to evaluate its feasibility for use in a national programme. The DFS is designed to provide 1 mg of iron and 15 micrograms of iodine per gram of common salt. This was made possible by the inclusion of a polyphosphate stabilizer, sodium hexametaphosphate (SHMP) at 1 per cent level. The stability of iron and iodine was found to be good up to 6 months. However, the stability of iodine depended upon the quality of the salt used for fortification. The biological effects of long-term consumption of DFS were evaluated in experimental rats and in field trials. Both iron and iodine from the salt were found to be biologically available in regenerating haemoglobin and in increasing excretion of iodine in urine. When this salt was tested in tribal villages endemic for goitre and iron deficiency anaemia, the bioresponse was good with regard to the iodine status but was not uniform in all segments with regard to iron, probably due to confounding variables. In a study carried out in residential school children where such variables did not exist, DFS was found to have significant impact on haemoglobin status in anaemic children and improved their urinary iodine excretion. The consumption of DFS for 2 yr did not have any adverse effects in school children as well as in the tribal population. Parameters related to calcium homeostasis were not altered in children receiving DFS. Histopathological examination of tissues and radiological examination of bone did not reveal any abnormality in DFS fed rats. Similarly serum and urinary parameters related to calcium and phosphorus were not altered in DFS fed rats. Therefore, DFS is presented as a feasible and effective strategy to control the double deficiency of iron and iodine in our community.
Naturally occurring substances of plant origin are known to possess antimutagenic potential. Garlic (Allium sativum) was fed to rats in dried powdered form at 0.1%, 0.5% and 1% concentrations in their diet for 4 weeks. At the end of the experiment benzo[a]pyrene (1 mg/rat) was injected intraperitoneally and 24-h urine was collected from the rats. Urinary mutagens were quantitated by the Salmonella typhimurium assay. There was a significant reduction in the excretion of urinary mutagens by carcinogen-exposed rats fed garlic. Further, there was a stimulation in the activities of liver cytosolic glutathione-S-transferase and liver and lung quinone reductases. The study suggested that the antimutagenic potential of garlic may be mediated through induction of detoxification enzymes in target tissues.
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Tobacco chewing and/or smoking are strongly related to several cancers, mainly of the upper aerodigestive tract. Several studies on diet and cancer links suggest that micronutrients, particularly antioxidant vitamins and minerals, are risk modifiers of cancers of epithelial origin. This study looks at the impact of micronutrients such as vitamin A, riboflavin, zinc and selenium as intervention agents in subjects with and without precancerous lesions in a high risk group (reverse smokers of chutta-rolled tobacco leaf). Reverse smokers from four villages were enrolled in the study. 150 subjects were supplemented with four nutrients, namely vitamin A, riboflavin, zinc and selenium in the form of a capsule twice a week for 1 year. 148 controls received a placebo capsule containing lactose for the same period. Clinical history and anthropometric data were collected from all the subjects and a clinical photograph of the palate was taken. Micronutrients were estimated in random blood collected from a sub-sample before and after the study. Micronutrients improved the vitamin A, riboflavin and selenium nutriture in the supplemented group with a concomittant regression of precancerous lesions present on the palate. Clinically complete remission of white, red and combination lesions was seen in 57% of subjects on supplements whereas 8% on placebo showed a positive response. Further progression of these lesions was seen in 10% of the supplemented group compared with 47% in the placebo group (P < 0.001). In the non-lesion group, new lesions appeared in 12% on supplements while more than 38% on the placebo developed new lesions (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
In cancer chemoprevention trials, biomarkers as intermediate end points have gained importance. A variety of biomarkers have been proposed as intermediate end points for upper aerodigestive tract cancers. This study was aimed at studying the frequency of micronucleated cells and carcinogen DNA adducts as indicators of DNA damage and intervention end points in chemoprevention trials. Reverse smokers of chutta (rolled tobacco) from four villages numbering 298 in total were selected. Out of these, 150 were supplemented with four nutrients (vitamin A, riboflavin, zinc and selenium) and 148 controls received placebo, one capsule twice a week for 1 year. Slides of buccal smears were prepared and stained with Fuelgen reaction and counterstained with Fast Green and examined microscopically for the presence of micronucleated cells. Oral cell washings were collected and centrifuged. The DNA adducts were evaluated by the 32P post-labelling assay method. Protein and RNA free DNA (adducted) isolated from the cells was digested with MN/SPD and the DNA adducts isolated by the butanol enrichment procedure. The DNA adducts were identified and quantitated by multidimensional chromatography on PEI-TLC sheets by screen enhanced autoradiography and presented as RAL (relative adduct labelling) values. Both the micronuclei and DNA adducts were significantly elevated in subjects with lesions. At the end of 1 year the frequency of micronuclei decreased significantly (P < 0.001) in the supplemented subjects with or without lesions. The DNA adducts in the supplement group at the end of 1 year also reduced significantly. The adducts decreased by 95% in subjects with all categories of lesions and by 72% in subjects without lesions. No such effects were noted in the placebo group. The two biomarkers investigated in the case study appear to be modifiable by the administration of micronutrient supplements.(ABSTRACT TRUNCATED AT 250 WORDS)
Glutathione S-transferase isozyme class mu from human leukocytes has been shown to be dominantly inherited and can be determined by activity measurement directed toward the substrate trans-stilbene oxide. The activity distribution of leukocyte glutathione S-transferase class mu was determined from control healthy nonsmokers, smokers, and smoking-related cancer patients. In a control healthy nonsmoker population, 54% (n = 50) of the subjects showed high levels of glutathione S-transferase class mu activity. In patients with cancers known to be related to smoking, 46% (n = 50) showed higher levels of glutathione S-transferase class mu. Noncancer smokers matched for age and smoking history with cancer patients showed an increased likelihood of having glutathione S-transferase (GST) class mu activity (76%). These results suggest that GST mu may be a cancer susceptibility marker in the case of smokers. In rats, benzo[a]pyrene (1 mg/kg, ip) administration daily for 3 d produced a significant increase in liver glutathione S-transferase class mu. Although these induction studies in experimental animals may not be relevant to humans, there is a possibility that, as in rats, this enzyme may be inducible in humans by polycyclic aromatic hydrocarbons.
Information on pharmacoepidemiology is particularly important in developing countries where a rational drug policy has not been adopted. In the present study, a profile of 1769 doctors' prescriptions and 763 self-orders were monitored at pharmacy outlets in the twin cities of Hyderabad and Secunderabad and 4 rural areas of Andhra Pradesh with the aim of identifying urban and rural differences, if any, in the self-medication rate, prescription costs, types of drugs purchased and factors influencing self-medication. Self-medication, expressed as the percentage of the total population that self-medicates, was found to be high in urban areas (37%) compared with rural areas (17%), and the majority of the over-the-counter sales were for prescription-only drugs. The majority of physicians' prescriptions were incomplete with respect to diagnosis and dosage regimen. The mean cost of the drugs purchased on doctors' prescriptions was 2-fold higher than the cost of drugs sold over the counter. A higher proportion of patients from rural areas (80%) purchased all the prescribed drugs compared with those from urban areas (54%). Financial constraints in urban areas were a major determinant in the partial purchase of prescribed drugs. In addition, the urban elite (i.e. professional people with high incomes, who comprise 18% of the total population) considered that all of the prescribed drugs were not necessary for their present disease. Nutritional products, potent compounds with analgesic, antipyretic and anti-inflammatory effects, and broad spectrum antibiotics constituted a high proportion of prescriptions in both urban and rural areas. The consumption of food supplements was higher in rural areas than in urban areas. Based on WHO criteria, most of the drugs (60%) prescribed in rural areas were nonessential, compared with 47% in urban areas. The results of this study emphasise the need for comprehensive measures, including information, training, legislation and education at all levels of the drug delivery system, to rationalise drug therapy by improving prescribing patterns and influencing self-medication.
Automotive use of leaded gasoline continues to be an important source of occupational exposure to lead in India and other countries. The present study assessed the renal function and markers of early renal damage of 22 mechanics at three automobile garages. Urinary N-acetyl-3-D-glucosaminidase activity and beta-2-microglobulin levels were significantly increased in auto garage mechanics with blood leads of 30-69 micrograms/dL. A significant correlation was observed between blood lead levels and urinary N-acetyl-3-D-glucosaminidase activity but not with urine beta-2-microglobulin levels. A marginal impairment in creatinine clearance was not statistically significant. Urinary N-acetyl-3-D-glucosaminidase activity offers a sensitive monitor of blood lead and renal tubular injury.
Cancer continues to be a major health problem despite advances in medical technology for its diagnosis and treatment. Hence prevention strategies are needed to decrease the burden of the disease. Of all the environmental factors, dietary components appear to play an important role in the initiation/progression of the disease. Nutrients and non-nutrients in the diet can influence the carcinogenic process at various stages, from initiation to overt manifestation. The National Institute of Nutrition has conducted studies on several aspects of diet-cancer inter-relationships. These include studies on metabolic susceptibility, case-control approach to determine the risk factors and intervention studies to determine the role of nutrients and non-nutrient components on preneoplastic events. Extensive work has been carried out demonstrating the antimutagenic/anticarcinogenic potential of some commonly consumed spices and vegetables such as turmeric, mustard, green leafy and allium species of vegetables. Dietary intervention for cancer prevention is needed to control the disease besides avoiding risk factors such as smoking and alcoholism and exposure to genotoxicants. Public education and awareness about the beneficial effects of consuming a healthy diet including plenty of fresh vegetables and fruits with spices such as turmeric in adequate amounts to prevent cancer are required.
Male rats were given diets containing Brassica nigra (mustard seed) powder at 0, 1, 5 or 10% for 1 month and then exposed to benzo[a]pyrene (B[a]P. 1 mg by ip injection). The antimutagenic effect due to mustard was assessed by testing the urine of rats fed diets with and without mustard. There was a significant (P < 0.001) reduction in reversion frequency of the TA98 and TA100 strains of Salmonella typhimurium in mustard-fed groups. This protective effect was seen with all three doses of mustard. The study demonstrated that mustard (Brassica nigra) can be a potent antagonist of the adverse biological effects of the ultimate metabolites of B[a]P, a ubiquitous environmental genotoxicant.