Substituting brown rice for white rice on diabetes risk factors in India: a randomised controlled trial.

India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25-65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (-0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.

Nutritional and sensory profile of two Indian rice varieties with different degrees of polishing.

Traditional hand-pounded rice has been replaced today with highly polished white rice in the Asian Indian diets. The study aimed to evaluate the nutritional as well as the sensory differences between the brown (0% polish) and the rice milled to different degrees of polish (2.3, 4.4 and 8.0%). Bapatla and Uma (red pigmented) varieties in both raw and parboiled forms were used. The protein, fat, dietary fibre, γ-oryzanol, polyphenols, vitamin E, total antioxidant activity and free radical scavenging abilities of the brown rice decreased while the available carbohydrates increased with polishing. Sensory attributes of the cooked rice samples (whiteness, grain intactness, fluffiness, firmness, stickiness, chewiness and the cooked rice aroma) were evaluated by trained panelists. Scores for branny taste and chewiness decreased with polishing. On the whole, brown rice of both the varieties was readily accepted by the well-informed sensory trained panelists.

Antiallodynic and Antihyperalgesic Activities of Fentanyl-Loaded Dermal Clay Dressings in Rat Model of Second-Degree Burn Injury.

Second-degree burn injury is the most common type of burn injury, which usually takes 2-3 weeks for complete healing. However, such patients suffer with intense pain associated with development of hyperalgesia and allodynia. Here, we prepare a silver clay patch using montmorillonite clay, betaine, and silver nitrate. Later, the silver clay patches were loaded with fentanyl. Furthermore, the patches were fabricated into burn wound dressings. The dressings were first subjected to ex vivo skin penetration studies and were later evaluated for thermal hyperalgesia and mechanical allodynia using second-degree burn injury rodent model. Our results show that application of fentanyl-loaded dermal clay (FLDC) dressings for 3 h showed significant increase of paw withdrawal latency (p <0.001) against hyperalgesia starting from 30 min after removal of patch to up to 6 h. Similarly, the FLDC dressings also potentiated the paw withdrawal threshold for up to 4 h after application (p <0.001). From these studies, we can conclude that FLDC dressings are ideal topical formulations for better management of pain in second-degree burns.

Metabolism of drugs and carcinogens in man: antipyrine elimination as an indicator.

The suitability of the most commonly used "prototype" drug, viz, antipyrine, in predicting drug and carcinogen metabolism was evaluated, by studying in vivo antipyrine elimination rate (Ke) and in vitro metabolism of drugs and carcinogens in liver preparations in the same individuals. Our subjects were 20 adult males undergoing abdominal surgery for gastrojejunostomy, although antipyrine Ke could be studied in only 16 subjects. Correlations of the various in vito--in vivo parameters were positive between the parameter pairs: in vivo antipyrine Ke--in vitro benzopyrene hydroxylase; benzopyrene hydroxylase--aniline hydroxylase; and benzopyrene hydroxylase--gamma-glutamyl transferase. Aminopyrine demethylase did not correlate with any of the parameters studied. The degree of correlation between antipyrine Ke and benzopyrene hydroxylase was statistically significant but was not satisfactory for predictive purposes. Our study indicates some of the problems and limitations of in vivo--in vitro comparisons and confirms earlier doubts on the usefulness of antipyrine as a "prototype" drug for predicting drug and carcinogen metabolism in man.

Vitamin B6 nutritional status of pellagrins and their leucine tolerance.

Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required.

Effect of vitamin B6 on leucine-induced changes in human subjects.

Distrubances in the tryptophan-niacin pathway seen in endemic pellagra among sorghum eaters have been ascribed to high dietary intake of leucine. Vitamin B6 plays an important role in several steps of this pathway. Therefore, studies on possible metabolic interrelations between excess dietary leucine and vitamin B6 were undertaken in normal healthy human subjects. The results indicated that vitamin B6 could successfully counteract the effects of leucine on quinolinic acid excretion in urine, and on in vitro nicotinamide nucleotide synthesis by erythrocytes, and also could correct the abnormalities of 5-hydroxytryptamine metabolism induced by excess leucine. These observations suggest that vitamin B6 nutritional status may have a contributory role in the pathogenesis of endemic pellagra.

Serotonin metabolism is pellagra.

Altered mental status is common in pellagrins. We evaluated the mental status of pellagrins in relation to the neurohormone, serotonin or 5-hydroxytryptamine (5-HT). Levels of 5-hydroxyindoleacetic acid (5-HIAA), an end product of serotonin in the urine and cerebrospinal fluid (CSF), and of platelet 5-HT were determined in a group of pellagrins and in normal subjects. The results indicated that the 5-HT concentration was reduced in platelets and 5-HIAA excretion in urine was below normal levels. The 5-HIAA concentration in CSF was also reduced, suggesting a decrease in 5-HT functional activity in the brain.

Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet.

Accelerated atherosclerotic lesions are observed in genetic defects characterised by marked homocystinaemia as a result of low levels of cystathionine synthase, a pyridoxal phosphate-dependent enzyme. Attempts were therefore made to induce atherosclerosis in Macaca radiata, maintained on a high-protein, high-methionine and high-fat diet by inducing pyridoxine deficiency with deoxypyridoxine. Pyridoxine deficient monkeys failed to show any biochemical or pathological evidence of atherosclerosis, despite a significant decrease in the activity of hepatic cystathionine synthase.

Drug metabolism and pharmacokinetics in malnourished children.

Malnutrition is a complex condition in which many deficiencies occur simultaneously. Protein-energy malnutrition is a major public health and clinical problem in paediatric practice that accounts for high child mortality and morbidity. It includes many different clinical syndromes with protean manifestations. The malnourished often have several concomitant diseases; drugs are therefore as widely used as in the well-nourished. The pathophysiological profile in malnutrition can alter pharmacokinetic processes, drug responses and toxicity. This review summarizes the available knowledge on nutrient-drug interactions in malnourished children. Although there is much evidence in the literature that diet and nutritional status are 2 important environmental variables determining the pharmacotoxicological properties of chemicals, there are few data on humans. Recently, intense effort has been initially directed at studying drug kinetics in grade III malnutrition, namely kwashiorkor and marasmus. Studies on drugs and nutrients indicate delayed or decreased absorption, reduced protein binding of several drugs, fluctuations in volume of distribution, altered hepatic oxidative drug biotransformations and conjugations, reduced elimination of conjugates and reduced elimination of renally excreted drugs. The estimated steady-state levels of a few drugs suggest accumulation. Bioavailability problems with certain drugs are due to divergent effects of pharmacokinetic processes. Clinical risk of toxicity appears to be higher in malnourished children. Rehabilitation studies suggest that a number of these pharmacological abnormalities can be reversed. The majority of studies have concentrated on single-dose pharmacokinetics in severely malnourished children. A number of abnormalities seen in drug disposition during the acute phase of malnutrition need to be confirmed for other grades of malnutrition. For practical purposes, it is important to consider steady-state levels and data in mild and moderate forms of growth-retarded children; drug-induced nutritional deficiencies can occur more easily in these populations. Although some of the drugs described in this review have been in use for many years, knowledge on drug response and toxicity is still only approximate. There is at present enough evidence to support monitoring plasma drug concentrations in malnourished children, particularly for those drugs which have dose-dependent kinetics and narrow margins of safety. The metabolism and disposition of xenobiotics seem to vary widely in children with protein-energy malnutrition. Therapeutic inadequacies and toxicities need careful evaluation in malnourished children.

The effect of malnutrition on the pharmacokinetics of phenylbutazone.

The pharmacokinetics of phenylbutazone were studied after a single oral dose of 6 mg/kg bodyweight in 35 adult male subjects with differing nutritional status. The elimination half-life was significantly shorter and plasma clearance accelerated in undernourished patients who had significant weight deficit and low serum albumin concentration. Plasma protein binding was only 86% compared with 95 to 96% in normal subjects (smokers and non-smokers). The apparent volume of distribution was also higher in undernourished patients. Significant correlations were observed between serum albumin, protein binding and bodyweight. Multiple regression analysis of the data indicated that altered drug protein binding partially contributed towards variation in half-life and clearance; and the plasma albumin concentration significantly influenced the amount of drug bound in plasma. The results indicate that nutritional status is one of the important environmental variables that can alter drug kinetics and disposition in man. Further studies, including measurement of steady-state plasma concentrations of various other drugs, are necessary to elucidate drug kinetics in malnourished subjects.

Reduction of urinary mutagen excretion in rats fed garlic.

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.

Fetal malnutrition and adult chronic disease.

Since the fetal origins of adult disease hypothesis was put forward, more than 30 studies around the world have indicated low-birth-weight (LBW) infants have a higher incidence of hypertension and impaired glucose tolerance. India ranks second in incidence of LBW among South East Asian countries and is experiencing a transition of disease pattern from communicable disease to non-communicable disease. Whether this could be explained in part by LBW infants who experienced better nutrition at a later age is explored here. An earlier cohort with accurate birth weights was traced and enrolled into the study. A sample of 50 LBW and 78 normal birth weight (NBW) individuals are reported on here. Though the odds ratio (OR) estimates of risk factors for coronary heart disease and diabetes tended to be higher in LBWs who were better nourished at the time of the study, they were not statistically different. Similarly, OR estimates for risk factors tended to be higher in LBWs who put on more weight than the median of NBWs, but they were not significant. Logistic regressions with several variables indicated significant influence of body mass index on systolic (P <0.007) and diastolic (P <0.004) blood pressures. Since the risk associations are weak, more studies are needed to put the hypothesis on a firm footing.

Effect of food on bioavailability of rifampicin.

The area under the plasma concentration-time curve of rifampicin was determined with and without food administration in six healthy male volunteers. Rifampicin (10 mg/kg) was administered orally in the fasting state on one occasion and following a wheat-based breakfast on another. Administration of rifampicin with food reduced mean peak plasma concentration and prolonged the time to reach peak concentration (2 versus 4 hours). Total area under the concentration-time curve from 0 to 8 hours and the rate of absorption were also significantly reduced when rifampicin was administered with food.

Role of vitamin B6 on leucine-induced metabolic changes.

Administration of leucine at 3% level in the diet has been shown to increase tryptophan oxygenase activity and to decrease kynureninase activity in the liver and to increase quinolinic acid excretion in the urine of rats fed low amounts of vitamin B6 (0.5 mug/g diet). Vitamin B6 at 3 mug/g of diet was able to reverse the effects of leucine on enzyme activities, but not on quinolinic acid excretion. Isoleucine at 0.2% level could counteract the leucine effect on kynureninase but not on tryptophan oxygenase. Administration of leucine also decreased the 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. Simultaneous administration of isoleucine could counteract the effects of leucine on brain 5-HT and 5-HIAA partially at low amount of vitamin B6 but completely at higher levels of vitamin B6 in the diet.

Undernutrition and tetracycline half life.

The plasma half life of tetracycline hydrochloride was determined in groups of well-nourished and undernourished subjects employing two dosage schedules and two routes of administration, namely oral and parenteral. Protein binding of the drug was estimated and relative volume distribution was calculated. The results indicated that in undernourished subjects, the half life of tetracycline hydrochloride, protein binding and relative volume distribution were all significantly low as compared to well-nourished subjects. The elimination rate was considerably higher in the undernourished groups, which accounted for the shorter half life. These data suggest that to maintain adequate serum concentrations of the drug in undernourished subjects, tetracycline needs to be given at more frequent intervals.

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.

Glutathione S-transferase Mu (GST Mu) deficiency and DNA adducts in lymphocytes of smokers.

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.

Hepatic drug metabolising enzymes in undernourished men.

The influence of the nutritional status of the individual on the hepatic drug metabolising enzymes in human wedge-biopsy liver samples was investigated. The aryl hydrocarbon hydroxylase (AHH) was found to be elevated although there was no change in the cytochrome P-450 levels in the undernourished groups. Conjugating enzymes viz. UDP glucuronyl transferase (UDPGT) and glutathione-S-transferase (GST) were not found to be different. The increase in AHH activity as compared to UDPGT and GST activities suggests that the activation processes may possibly be increased in the undernourished segment of the population.

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.

Phrynoderma: is it an EFA deficiency disease?

The clinical response to various therapeutic agents was evaluated in 31 patients with phrynoderma. A complete clinical response with vitamin B-complex was noted in an average period of 5.7 weeks. In patients treated with vitamin E, partial or total improvement was seen in an average period of 12.3 and 10.7 weeks respectively. Patients treated with safflower oil showed a partial improvement in an average period of 13.2 weeks. The essential fatty acid (EFA) nutriture of 30 patients was compared with 7 controls. Plasma phospholipid fatty acid composition was used as an indicator of EFA nutriture. The patients with phrynoderma fell into two groups. In the 23 children in one group (pattern A), the mean levels of linoleic (18:2 omega 6), arachidonic (20:4 omega 6) and eicosatrienoic (20:3 omega 9) acids were similar to the levels in the controls. The ratio of eicosatrienoic to arachidonic acids (20:3 omega 9/20:4 omega 6), which is considered an accurate measure of EFA nutritional status, was 0.12 and in the normal range, suggesting that the EFA nutriture is normal in phrynoderma. The ratio of linoleic to arachidonic acids (18:2 omega 6/20:4 omega 6) was also found to be normal, suggesting that the metabolism of linoleic to arachidonic acid is not affected in phrynoderma. In seven children in a second group (pattern B), the fatty acid profile was different from patients with pattern A. In these two groups no obvious differences were noted in clinical features and severity. In patients treated with safflower oil, the mean levels of vitamin E were elevated. On all the three treatment schedules, the levels of other fatty acids were not altered. The biochemical and clinical evidence obtained indicate that phrynoderma may not be directly associated with EFA deficiency but that vitamin B-complex may have an important role. The plasma phospholipid fatty acid profile seems to reflect neither the clinical situation nor the response to therapy.