Biomedical subjects

K Krishnaswamy

Publications and source records attributed to K Krishnaswamy.

At least 37 records · Page 2Linked to original sources

PubMed1995

Human leukocyte glutathione S-transferase isozyme (class mu) and susceptibility to smoking-related cancers.

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.

Adult↗

PubMed1995

Profile of drug use in urban and rural India.

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.

Anti-Bacterial Agents↗

PubMed1995

Detection of occupational lead nephropathy using early renal markers.

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.

Adult↗

PubMed1995

Diet, nutrition & cancer--the Indian scenario.

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.

Carcinogens↗

PubMed1994

Effect of Brassica nigra on benzo[a]pyrene mutagenicity.

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.

Animals↗

PubMed1994

N-nitrosamines in Indian beers.

Presence of volatile N-nitrosamines in beer and other alcoholic drinks are well documented in developed countries. Analysis of 120 beer samples of various brands/batches showed positivity for N-nitrosodimethylamine (NDMA) in more than 100 samples. The overall mean of 3.6 ppb of NDMA is higher than those currently found in Western countries. Since N-nitrosamines are proven carcinogens in animals at several sites it is necessary to keep their levels of exposure to as low as possible.

Beer↗

PubMed1993

Effect of turmeric on xenobiotic metabolising enzymes.

Diet contains several substances capable of inhibiting chemical carcinogenesis. It is known that such inhibitors may either act directly by scavenging the reactive substances or indirectly by promoting mechanisms which enhance detoxification. Turmeric which contains curcumin both in vitro and in vivo is an active antimutagen. Studies were therefore conducted to evaluate the effects of turmeric on xenobiotic metabolising enzymes in hepatic tissue of rats fed turmeric ranging from 0.5-10% in the diet. Enzymes such as aryl hydrocarbon hydroxylase, UDP glucuronyl transferase and glutathione-S-transferase were assayed after four weeks of turmeric fed diets. No significant differences were seen in the activating enzyme AHH. However, UDPGT was significantly elevated in rats fed 10% turmeric while GSHT registered a significant increase in 5 and 10% turmeric fed diet as compared to controls and 0.5-1.0% turmeric fed animals. The results suggest that turmeric may increase detoxification systems in addition to its anti-oxidant properties. Curcumin perhaps is the active principle in turmeric. Turmeric used widely as a spice would probably mitigate the effects of several dietary carcinogens.

Animals↗

PubMed1993

Effects of riboflavin deficiency and riboflavin administration on carcinogen-DNA binding.

A study was conducted to assess the effects of riboflavin deficiency and riboflavin supplementation on carcinogen-DNA binding. After 12 wk on a riboflavin-sufficient or a riboflavin-deficient diet male Wistar rats were administered 3H-labelled benzo[a]pyrene (BP) ip. [3H]BP was given either at a uniform dose of 450 muCi/rat irrespective of body weight or at a dose adjusted to body weight. After 17 hr the animals were killed, various organs were dissected and the level of [3H]BP bound to DNA was quantified in organs that are known to be the seats of drug metabolism (i.e. the liver, lungs and intestinal mucosa). In a separate experiment, the effect of riboflavin supplementation on BP-DNA binding was also investigated. When [3H]BP was administered at 450 microCi/rat, BP-DNA binding was markedly increased in the livers and intestinal mucosae of the pair-fed and deficient groups compared with controls. With the administration of [3H]BP adjusted to body weight, no differences in BP-DNA binding between groups were observed in any tissue. However, on administration of riboflavin there was a decrease in the level of [3H]BP bound to DNA in almost all tissues, especially in the lungs, where the reduction was significant. The results suggest that undernutrition/riboflavin deficiency may increase the risk of carcinogenesis by way of an increase in carcinogen binding, which however can be reversed by riboflavin supplementation.

Animals↗

PubMed1993

Effect of turmeric and curcumin on BP-DNA adducts.

Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention.

Animals↗

PubMed1993

A case control study of selenium in cancer.

As selenium has been shown to be a risk modifier of cancer at several sites in a case-control approach, selenium nutriture was studied in oral and oesophageal cancer patients. The mean selenium level in oral cancer patients was 102.6 ng/ml and in oesophageal cancer 103.3 ng/ml, while in the matched controls it was 117.5 and 116.2 ng/ml respectively. Relative risk estimates were 3.16 (P < 0.02) and 16.0 (P < 0.01) in oral and oesophageal cancer patients respectively. The risk appears to increase with selenium levels lower than 115 ng/ml.

Case-Control Studies↗

PubMed1992

Esophageal cancer and diet--a case-control study.

It has been estimated that approximately 40% of human cancers may be associated with dietary factors. The relationship is more significant in esophageal cancers. Case-control studies involving 35 subjects of early-diagnosed esophageal cancers showed low mean blood levels of retinol, zinc (p less than 0.001), folic acid (p less than 0.01), and albumin (p less than 0.05). Relative risk was significantly higher for low levels of retinol and zinc. Diet, in general, in both groups reflected poor intake of several nutrients.

Case-Control Studies↗

PubMed1992

Effect of turmeric on urinary mutagens in smokers.

Curcumin, the active principle of turmeric, is known to act as an anti-oxidant, anti-mutagen and anti-carcinogen in experimental animals. In the present study, anti-mutagenic effects of turmeric were assessed in 16 chronic smokers. It was observed that turmeric, given in doses of 1.5 g/day for 30 days, significantly reduced the urinary excretion of mutagens in smokers. In contrast, in six non-smokers, who served as control, there was no change in the urinary excretion of mutagens after 30 days. Turmeric had no significant effect on serum aspartate aminotransferase and alanine aminotransferase, blood glucose, creatinine and lipid profile. These results indicate that dietary turmeric is an effective anti-mutagen and it may be useful in chemoprevention.

Adult↗

PubMed1992

Detection of rifampicin-induced nephrotoxicity by N-acetyl-3-D-glucosaminidase activity.

The objective of the present study was to assess renal damage, if any, by non-invasive technique, viz NAG activity in urine and GFR in patients on continuous and intermittent rifampicin therapy. Eighty-four tuberculosis patients for cross-sectional study and six subjects for longitudinal study on antitubercular therapy and ten patients on withdrawal of rifampicin participated in the investigation; 13 leprosy patients intermittently treated with rifampicin were also included. Twenty-seven normal subjects served as controls. Rifampicin on continuous use resulted in a progressive increase in enzymuria with no change in GFR. An additive toxic effect was obvious in patients receiving streptomycin; when the treatment was withdrawn the urinary NAG activity stabilized within 15-21 days. However, patients receiving rifampicin intermittently did not show any evidence of renal damage. The results suggest that there is a need for monitoring renal damage, particularly on antitubercular therapy, when nephrotoxic agents are administered together.

Acetylglucosaminidase↗

PubMed1992

Bioavailability of different brands of tetracycline in undernourished subjects.

Chemical estimation of seven different marketed brands of tetracycline/Hcl capsules for tetracycline content showed six brands were not meeting the Indian pharmacopia 1985 prescribed standards. However, their dissolution rate and disintegration time were in accordance with United States pharmacopia 1985 specifications. One standard and one substandard brand of tetracycline were selected and their bioavailability, after single dose and plasma steady-state levels after multiple dosing in well nourished and undernourished subjects were determined. The bioavailability of substandard product as determined from 48 h urinary tetracycline excretion was significantly lower as compared to standard product both in well-nourished and undernourished subjects. The plasma steady-state concentrations with the substandard product were below the generally recommended minimum inhibitory concentrations, more so in undernourished subjects. These results indicate that the use of sub-standard tetracycline products in undernourished subjects may lead to therapeutic failures and/or result in the development of resistant microorganisms.

Adult↗

PubMed1992

Basic concepts of clinical pharmacokinetics.

Clinical pharmacology is now a well established discipline. Unlike the yester years when dosage schedules were determined by trial and error, in the present day selection of dose, dosage interval and route of administration are based on pharmacokinetic and pharmacodynamic principles. The primary utility of pharmacokinetics is to study the process of absorption, distribution, metabolism and elimination of drugs, fundamental for drug action. Individuals show a wide variation in kinetic parameters due to internal and external factors. Sometimes change in one variable may be compensated by change in another variable so that dose need not be altered e.g. metabolism of some drugs is increased in thyrotoxicosis but due to increased protein binding overall dose adjustment may not be required. On the other hand sometimes variations in these parameters can markedly affect the plasma concentrations of and the pharmacological response to drugs e.g. anticonvulsant treatment in oral contraceptive users, phenylbutazone addition in warfarin therapy. Drug concentrations can be measured in plasma, urine or saliva. Equipped with this knowledge the modern physician will be able to make a wiser use of drugs under altered physiological conditions like pregnancy, lactation, infancy, old age and pathological states like renal and liver failure and shock.

Absorption↗

PubMed1991

Antipyrine kinetics in undernourished diabetics.

In developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits. The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.

Adult↗

PubMed1991

Turmeric (Curcuma longa)-induced reduction in urinary mutagens.

Rats were fed turmeric at various levels in the diet for up to 3 months and then exposed to benzo[a]pyrene (B[a]P) or 3-methylcholanthrene (3-MC) by ip injection. Urinary mutagens were detected using the Salmonella typhimurium assay. Turmeric fed at 0.5% and above inhibited B[a]P- and 3-MC-mediated mutagenicity. Turmeric did not adversely affect the food intake, or weight gain of the rats and no histological changes were detected. These findings are significant in view of the widespread exposure of humans to polycyclic aromatic hydrocarbons. The study has also revealed a useful in vivo model for testing the antimutagenicity.

Administration, Oral↗

PubMed1989

Effect of food restriction on benzo(a)pyrene binding to DNA in Wistar rats.

A study was carried out to assess the binding of the carcinogen benzo[a]pyrene to DNA in different tissues under in vivo and in vitro conditions in Wistar rats which have been subjected to different levels of food restriction. The results showed that there was a significant increase in the binding of benzo[a]pyrene to hepatic DNA in food restricted animals in in vivo experimentation although this was not observed under in vitro conditions. There was a decrease in binding to pulmonary DNA and no change for renal DNA.

Animals↗