The effect of fat intake and antihypertensive drug therapy on serum lipid profile: a cross-sectional survey of serum lipids in male and female hypertensives.

The present study aimed to investigate the effect of betablocker with diuretics therapy on serum cholesterol and high density lipoprotein (HDL-C) lipids in cross-sectional data (age, sex, weight, and body mass index (BMI), smoking/alcoholic consumption) and supplemented vegetarian low-fat diet with daily low fat energy intake, salt intake, duration of drug therapy, and serum protein as effective measures of lowering blood pressure among hypertensives in both males and females. Hypertensive patients on betablocker and/or thiazide therapy were compared in cross-section study with their age, blood pressure, fat intake, serum lipid profile, BMI, and serum albumin in males and females. Dietary fat intake and serum lipid profile were income related. Betablocker and diuretics therapy in combination with dietary fat intervention was beneficial for prolonged dyslipidemia control. Serum cholesterol level was main contributing factor dependent on BMI, duration of drug, and socio-economic factors. Fat intake contributed in hypertension and serum cholesterol levels. A cross-sectional data analysis showed beneficial effects of "low fat-salt-smoking-alcohol consumption and combined polyunsaturated fatty acid with antihypertensive therapy approach" to keep normal dyslipidemia and hypertension. Low fat intake, low salt, smoking, alcohol consumption, and combination of dietary oil supplements with lipid betablockers and diuretic modulators were associated with low hypertension and controlled dyslipidemia in Asian sedentary population.

Nutritional significance of rice bran oil.

India is the second largest producer of rice in the world and has the high potential to produce rice bran oil (RBO), a by-product of the rice milling industry. Since RBO is, an unconventional oil, the chemical composition, nutrient evaluation and toxicological safety were assessed. The fatty acid composition RBO is very close to that of groundnut oil (GNO). Though RBO has high unsaponifiable matter (4.2%), it is rich In minor constituents such as phytosterols, triterpene alcohols, tocopherols and tocotrienols. Experimental as well as human studies have demonstrated the hypolipidaemic effects of RBO. Further, It was established that minor constituents present in unsaponifiable fraction of RBO were responsible for its hypolipidaemic effects. Nutritional evaluation studies, carried out with 10 per cent RBO and 20 per cent protein, indicated that growth, feed efficiency and mineral balance were comparable to GNO-fed animals. Toxicological studies had shown that there were no abnormalities In animals fed either RBO or GNO. The reproductive performance was also found to be normal as compared with that of GNO-fed animals in all three generations. In addition, neither RBO nor the foods deepfried in it showed any mutagenicity as judged by Ames test. In view of its safety and hypolipidaemic activity, RBO could be considered as an alternative source of edible oil.

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.

Accidental acute fatal sodium nitrite poisoning.

An accidental food poisoning outbreak occurred resulting in the death of 14 of the 22 affected persons. Chemical analysis of food materials revealed the presence of sodium nitrite and potassium arsenate. Analysis of urine, gastric contents, liver and kidney, collected at the time of autopsy, confirmed the presence of these chemical substances in high concentrations. Epidemiological data indicated that the food poisoning occurred due to the accidental use of sodium nitrite and potassium arsenate instead of table salt in the preparation of tamarind (Tamarindus indica) soup.

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.

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.

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.

Nutritional and biochemical aspects of the hypolipidemic action of rice bran oil: a review.

In this paper, we review the effects of rice bran oil (RBO), an unconventional oil recently introduced onto the Indian market for human use. RBO contains oleic acid (38.4%), linoleic acid (34.4%), and linolenic acid (2.2%) as unsaturated fatty acids, and palmitic (21.5%) and stearic (2.9%) acids as saturated fatty acids. The unsaponifiable fraction (4.2%) has total tocopherols (81.3 mg%), gamma-oryzanol (1.6%), and squalene (320 mg%). Oryzanol is a mixture of ferulic acid esters of triterpene alcohols such as cycloartenol (CA) (106 mg%) and 24-methylene cycloartanol (494 mg%). Studies on experimental rats demonstrated a hypolipidemic effect of RBO. The unsaponifiable fraction of RBO lowers cholesterol levels. Feeding phytosterols, CA, and 24-methylene cycloartanol in amounts present in RBO to hypercholesterolemic rats for 8 weeks indicates that CA alone reduces cholesterol and triglyceride levels significantly. Endogenous sterol excretion increases in animals given CA. The accumulation of CA in the liver inhibits cholesterol esterase activity, which in turn leads to reduction in circulating cholesterol levels. CA is structurally similar to cholesterol and may compete with the binding sites of cholesterol and sequestrate cholesterol, which is metabolized to its derivatives. RBO, which is rich in tocopherols and tocotrienols, may improve oxidative stability. Tocotrienols inhibit HMG CoA reductase, resulting in hypocholesterolemia. The hypolipidemic effect of RBO has also been established in human subjects. Thus, RBO could be a suitable edible oil for patients with hyperlipidemia.

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.

Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes.

The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes.

Polymorphic ability to metabolize propranolol alters 4-hydroxypropranolol levels but not beta blockade.

The ability to hydroxylate debrisoquine is known to be polymorphically distributed, with about 8% to 9% of the North American Caucasian population being poor metabolizers. We have shown that the ability to 4-hydroxylate propranolol is also polymorphically determined and that it cosegregates with ability to metabolize debrisoquine, such that poor debrisoquine metabolizers produce much less 4-hydroxypropranolol (4-OH propranolol) than do extensive metabolizers. There was no significant difference, however, between plasma propranolol concentrations after either single or multiple doses in the two groups. Despite the substantial difference in production of the pharmacologically active 4-OH metabolite, no difference was seen in the extent of beta-blockade induced in the extensive and poor metabolizers, which implies that 4-OH propranolol does not contribute substantially to beta-blockade.

Pharmacokinetics and plasma steady state levels of doxycycline in undernutrition.

1 The kinetics of doxycycline were studied in well nourished and undernourished male subjects. 2 The area under the curve after an intravenous dose was reduced and total body clearance was significantly elevated with a shorter/beta-phase half life of the drug in undernourished subjects. 3 The percentage of total drug excreted in urine in 48 h and renal clearance of the drug were similar in both groups. 4 Plasma protein binding was significantly reduced and gamma-glutamyltransferase levels tended to be higher in the undernourished as compared to normals. 5 Increased total body clearance of the drug appeared therefore to be due to higher metabolism of drug in undernourished subjects. This increased metabolism is probably due to lower protein binding of the drug and/or induction of drug metabolism. 6 Plasma Cmin concentrations of doxycycline determined at steady state were lower in undernourished subjects. However, they were within the therapeutic range. 7 The observed alterations in kinetics of doxycycline therefore do not warrant a change in dosage regimen in undernourished subjects.

Influence of dietary restriction and protein deficiency on plasma half-life and tissue distribution of tetracycline in rats.

1. The effects of dietary restriction and protein deficiency on plasma half-life and tissue distribution of tetracycline were studied in rats by feeding either a 20% protein diet in restricted quantity or a 9% protein diet ad lib and compared with rats given a 20% protein diet ad lib (control group). 2. It was observed that half-life of tetracycline was shortened and that plasma and tissue Cmin levels at steady-state were lower in undernourished rats. Tissue concentrations in liver, kidney, muscle and bone correlated well with plasma levels. A high degree of correlation was also observed between plasma and tonsillar concentrations of tetracycline in human subjects. 3. These studies indicate that undernourished subjects may require an altered dosage regimen of tetracycline to maintain effective steady-state concentrations of the drug.

Pharmacokinetics of tetracycline in nutritional edema.

Tetracycline pharmacokinetics were studied in a group of normal subjects and in patients with nutritional oedema. Though both groups of subjects received similar dose per kilogram body weight, plasma concentrations and area under the curve (AUC) were significantly higher in nutritional oedema patients. The total body clearance of the drug was reduced due to significant reductions in renal and non-renal clearance of drug. The volume of distribution (VB) was low, with significant increase in rate of transfer of drug from peripheral to central compartment (K21), indicating poor tissue sequestration of the drug in nutritional-oedema patients. In some respects, these alterations in kinetics of tetracycline in nutritional-oedema patients are different from our earlier observations made in undernourished subjects who had mild and moderate forms of malnutrition. These results suggest that changes in disposition of drugs are also influenced by the severity of malnutrition, and demand suitable alterations in dosage regimen.

Tetracycline kinetics in undernourished subjects.

The pharmacokinetics of tetracycline were studied in eight normal healthy adult male volunteers and six undernourished adult males, ages 25-40 years, after an intravenous dose of 10 mg/kg body wt. The post-intravenous tetracycline time curve was found to decline in a biphasic manner in both well-nourished and undernourished subjects. However, significant differences were observed in alpha and beta phase with significant alterations in microscopic rate constants and apparent volume of distribution. The kinetic constants suggested a rapid distribution with a faster rate of transfer of drug between compartments followed by a significant increase in total body clearance in undernourished subjects. The apparent volume of distribution was significantly reduced. It is concluded that due to alterations in kinetics undernourished subjects may require altered dosage regimens to maintain tetracycline concentrations above the recommended minimum inhibitory concentration in both plasma/tissue for effective therapy.

Tetracycline absorption in malnutrition.

Tetracycline absorption was studied in a group of normal healthy subjects and in adult male patients suffering from various nutritional disorders such as protein-calorie malnutrition, pellagra, anaemia, and vitamin B-complex deficiency. Tetracycline hydrochloride in doses of 10 mg/kg body weight was administered in a crossover design by oral and intravenous routes at an interval of one week. Absorption of tetracycline was determined from total 48-hour urinary excretion of the drug following each dose. It was observed that tetracycline absorption was significantly reduced in subjects with undernutrition and pellagra but not in patients with orolingual lesions due to vitamin B-complex deficiency and in patients with severe anaemia. Comparative studies on absorption of tetracycline, given in the form of capsule and solution, indicated that impaired absorption of tetracycline in undernourished subjects was not due to inadequate dissolution of the capsule.