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Biomedical subjects

B Sivakumar

Publications and source records attributed to B Sivakumar.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of vitamin A supplementation on haemoglobin and vitamin A levels during pregnancy.

About 450 pregnant women from a low-income group were recruited to study the effect of vitamin A supplementation on plasma vitamin A levels in the mother and cord and on the birth weights of the neonates. Results showed that supplementation with 1800 micrograms vitamin A/d for more than 12 weeks prevented the decline in plasma vitamin A that otherwise occurs during the last few weeks of pregnancy. This improvement in maternal values for vitamin A at a critical time of development favourably affected availability to the fetus, as reflected by the marked elevation in cord levels. Supplementation for a period of 12 weeks was found to be sufficient, since subsequent discontinuation did not alter the beneficial response. Apart from increasing maternal and cord vitamin A levels, vitamin A supplementation along with iron prevented, in this study, the significant decline in haemoglobin occurring at 26-28 weeks of gestation. The birth weights were not altered by vitamin A supplementation.

Birth Weight↗
PubMed1990

Plasma levels of estradiol & progesterone at different gestational ages in Indian women.

Plasma levels of estradiol and progesterone were determined at different gestational ages in Indian pregnant women from the low socio-economic group. The levels of estradiol and progesterone progressively increased with gestation and reached maximum values (14.35 +/- 1.092 and 145.9 +/- 7.69 ng/ml, respectively) by term. Though the estradiol values were comparable to those reported in literature, the term values of progesterone were found to be lower (145.9 +/- 7.69 ng/ml) than those reported from Western countries (160 +/- 7.5 ng/ml) at 34-38 wk of gestation. These low progesterone values may have physiological implication in placental function.

Estradiol↗
PubMed1989

Effect of vitamin A deficiency on nitrogen balance and hepatic urea cycle enzymes and intermediates in rats.

After 12 wk of feeding a 4-d nitrogen balance was carried out in 8 vitamin A--deficient and 8 pair-fed control rats to understand the effect of vitamin A deficiency on protein metabolism. Urea nitrogen (UN) was lower and amino nitrogen (AN) was higher in plasma of deficient animals than in pair-fed controls. No significant alteration in the nitrogen retention or in the general pattern of other nitrogen metabolites in plasma and urine was observed in vitamin A--deficient rats as compared to controls. However, there was a significant increase in the excretion of urinary ammonium nitrogen (Am-N) in relation to creatinine (CR). Activities of hepatic carbamoylphosphate synthase-I (CPS-I) and ornithine transcarbamoylase (OTC) were significantly lower in vitamin A--deficient animals than in control rats at the end of 13 wk of feeding. While the liver levels of ornithine and polyamines were significantly greater, that of glutamine was lower in vitamin A--deficient rats than in pair-fed controls. The results suggest that vitamin A deficiency leads to a reduced efficiency of urea synthesis pathway, thus accounting for the increased Am-N excretion seen in vitamin A deficiency.

Amino Acids↗
PubMed1989

Evaluation of a colorimetric method for vitamin A estimation.

A simple colorimetric procedure for plasma vitamin A is evaluated, which does not require sophisticated or expensive equipment. Vitamin A values obtained with 30 human plasma samples and 11 liver samples obtained from lactating rabbits, using a colorimetric procedure based on Carr-Price reaction with ferric chloride and acetyl chloride were compared with those obtained with spectrophotometric and spectrofluorimetric micro methods. With widely varying plasma samples, the values showed a high degree correlation and good agreement. The intraassay variation was 3% which is in the acceptable range. The plasma samples could be analysed within 4 weeks and the reagents, were found to be stable, unlike some batches of trifluoro acetic acid (TFA).

Animals↗
PubMed1986

Bioavailability of levonorgestrel from intravaginal rings in women of low income groups.

Two types of intravaginal rings (IVR) containing 50-128 mg of levonorgestrel (LNOG) and 28-60 mg of estradiol were inserted in 18 apparently normal subjects belonging to the low socioeconomic group on day 5 of the cycle. A total of 120 cycles were studied with cyclic insertion and withdrawal. Data on menstrual cycle changes were noted. For bioavailability study, blood samples were collected twice weekly for a period of one month in the first cycle in 8 women. All the plasma samples were analysed for LNOG and progestrone by RIA. Cycle control was excellent in IVR users. Expulsion of the ring was noted in 4 instances. The plasma LNOG levels were found to reach a peak level ranging from 2.7-7.5 ng/ml within 4 days after the IVR insertion. In between day 9 to 24, the plasma levels appeared to be almost steady, and once the ring was removed, the levels dropped off rapidly. The mean plasma LNOG calculated during the steady-state period of the cycle ranged from 1.6-5.1 ng/ml. These mean LNOG levels were found to be inversely correlated with skin-fold at triceps. In all the subjects ovulation was found to be inhibited, as reflected by plasma progesterone values. The range of release rates calculated from plasma steady-state values was 51-119 micrograms/day. The average release rates over the entire period of observation based on area under curve were 102-200 micrograms/day. On the other hand, the release rates obtained from the residual drug in the ring after a period of use ranged from 184-259 micrograms/day.

Adolescent↗
PubMed1986

Interleukin-1 in malnutrition.

The effect of malnutrition on the in vitro production of interleukin-1 by lipopolysaccharide stimulated circulating monocytes has been investigated in children suffering from kwashiorkor and marasmus. The interleukin-1 activity was significantly lower in children with severe malnutrition. Furthermore, macrophages from children with kwashiorkor produced factors that suppressed mouse thymocyte proliferation. These observations show a significant impairment of macrophage function and provide a mechanism for the suppression of cellular immunity in malnutrition.

Cells, Cultured↗
PubMed1985

Pharmacokinetics of norethisterone and levonorgestrel in experimental iron deficiency anemia in rabbits.

Mild-moderate anemia (hemoglobin, 10-12 g/100 ml) was induced in eight female rabbits by feeding a purified diet with low iron content over a period of 4 months and it could be maintained for a further period of 7 months. Nine control animals received the same diet supplemented with iron. Pharmacokinetics of intravenously administered contraceptive steriods, norethindrone and levonorgestrel, were determined in both control and anemic rabbits at the end of 150 and 171 days, respectively. No significant alterations were observed in the disposition of these steroids in deficient rabbits as compared to controls, indicating that mild-moderate forms of iron deficiency anemia may not influence the metabolic handling of either norethindrone or levonogestrel.

Anemia, Hypochromic↗
PubMed1983

Pharmacokinetics of levonorgestrel in Indian women.

A low dose combination pill containing levonorgestrel 150 micrograms and ethynylestradiol 50 micrograms was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The pi t1/2 was lower in Group A women and the alpha-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (beta t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.

Adult↗
PubMed1981

Plasma levels of norethidrone in Indian women receiving norethidrone enanthate (20 mg) injectable.

Plasma norethindrone (NET) and progesterone were estimated by radioimmunoassay in seven Indian women after intramuscular administration of 20 mg NET enanthate. One subject had intermenstrual bleeding throughout the cycle. Out of the six subjects considered for analysis, three subjects showed ovulation suppression, two had delayed ovulation and the remaining one exhibited normal ovulatory pattern. Post-peak average plasma NET values ranged from 1.0 to 2.1 ng/ml. These values showed a significant positive correlation with the anthropometric indices such as body weight and mid-arm-circumference. The subjects with lower anthropometry showed exponential decline of plasma NET. A possible role for nutritional status of an individual in drug disposition is indicated from this study.

Adult↗
PubMed1981

Effect of food restriction (undernutrition) on pharmacokinetics of levonorgestrel in rabbits.

Twelve female rabbits aged about 3-4 months were randomly divided into two groups (group A and group B) and were individually matched for their initial body weights. Animals of group A received a stock diet ad libitum while each of the animals in group B were fed 50% of the diet consumed by the corresponding matched control from group A. Pharmacokinetics of levonorgestrel were determined in all animals between 1 1/2-2 months after these diets were started, using an intravenous dose of 8-20 /uCi of 3H-levonorgestrel and 15-20 /ug of levonorgestrel per kg body weight. Urinary excretion of radioactivity was also measured in all the animals for a period of 5 days following the dose. The body weights of animals on the restricted diet were 17% lower than those of the ad lib fed animals. Haemoglobin levels and plasma albumin concentration were found to be in the normal range in both groups. There was a significant increase in Metabolic Clearance Rate (MCR) and t 1/2 pi and a decrease in elimination half-life in animals of group B as compared to those seen in animals of group A. The urinary excretion of label was found to be slightly increased in group B animals as compared to that in group A controls.

Animals↗
PubMed1981

Effect of food restriction (undernutrition) on plasma sex hormone binding globulin (SHBG) capacity, liver drug metabolizing enzymes and uterine cytosol progesterone receptor levels in rabbits.

The present investigation was designed to understand the mechanism underlying the altered pharmacokinetic and pharmacodynamic properties of norethindrone and levonorgestrel observed in undernourished rabbits. Eighteen albino rabbits aged 3-4 months were divided into two groups. One group received a stock diet ad libitum and the other group was individually fed half the food consumed by the matched animal in ad lib group. Three pairs of animals were sacrificed at the end of three months and the remaining at the end of five months. Liver and uterine tissues were dissected out and processed for analysis. For both sets of animals, whether killed at the end of three months or 5 months, the trend of results obtained were similar. The capacity and affinity characteristics of plasma sex hormone binding globulin were found to be not significantly different between control and experimental animals. The specific activities of liver microsomal glucuronyl transferase and cytochrome P-450 were significantly higher in undernourished rabbits. The increase observed in the activity of sulfuryl transferase was, however, not statistically significant. Uterine cytosol progesterone receptor levels were found to be higher in food restricted animals though there were no changes in the affinity properties of the receptors. Thus, it appears that imposition of food restriction leads to increased drug metabolism as a result of increased drug metabolizing enzyme activities and that the animals appear to adapt by enhanced target organ response in terms of elevated receptor concentration.

Animals↗
PubMed1981

The rabbit as an animal model to study pharmacokinetics of levonorgestrel in women.

In an attempt to develop an animal model to facilitate investigations on the effects of various nutritional and environmental factors on the metabolism of the contraceptive steroid levonorgestrel, the pharmacokinetics of levonorgestrel were investigated in rabbits. Six adult female rabbits received an intravenous bolus dose of 3H-levonorgestrel, 8-20 microCi, with 15-20 micrograms of carrier cold levonorgestrel per kg body weight. Blood samples were drawn at different intervals of time after the dose and the plasma drug concentration was determined both by radioisotopic dilution method and by radioimmunoassay. Plasma concentrations of levonorgestrel as assayed by radioimmunoassay agreed very closely with those obtained by isotope counting. The decline in plasma radioactivity attributable to unchanged levonorgestrel followed a triexponential pattern. Plasma radioactivity data were therefore analysed according to a three-compartment open model by graphical and regression analysis. The half-lives of the three phases pi, alpha and beta representing the shallow, deep peripheral and the terminal elimination compartment, respectively, were in close agreement with those reported in women. The metabolic clearance rate (MCR) and volume of distribution (VB) of levonorgestrel expressed per unit of body weight were comparable to values reported in women. The overall observed trend of pharmacokinetics of levonorgestrel in rabbits resemble closely those seen in women. It would therefore appear that the rabbit is a suitable animal model for studying the effects of nutritional factors on the pharmacokinetics of the drug.

Animals↗
PubMed1981

Effect of food restriction (undernutrition) on pharmacokinetics of norethindrone in rabbits.

Our previous studies have shown that the plasma norethindrone (NET) elimination is faster in women of low socio-economic group as compared to those of high socio-economic group. Undernutrition being very common in low socio-economic group, using an animal model, efforts were made to determine whether these differences were due to differences in the nutritional status of these two group of women. The experimental animals consisted of a set of twelve female rabbits, divided equally into two groups. One group (A) was fed on a stock diet ad libitum while the second group (B) received the diet in restricted amounts (half of that consumed by animals of group A). At the end of three months, radiolabelled NET was administered intravenously and plasma drug levels were determined at frequent intervals up to 24 hours. The plasma values were subjected to pharmacokinetic analysis. Food restriction to the extent of 50% resulted in a 20% deficit of body weight as compared to controls. The half-lives of alpha and beta phases were shortened in the restricted group resulting in an enhanced metabolic clearance rate of NET in this group. Though the differences were not statistically significant, the volume of distribution tended to be lower and the dose excreted in urine higher when food restriction was imposed.

Animal Nutritional Physiological Phenomena↗
PubMed1979

Pharmacokinetics of norethindrone in Indian Women.

Pharmacokinetics of norethindrone (NET) was evaluated in eleven women belonging to a low socio-economic group and in five womem belonging to the high socio-economic group after the administration of an oral dose of 0.35 mg NET minipill on an empty stomach. Blood samples were collected at different intervals of time over a period of 24 hours. Plasma NET was estimated by radioimmunoassay. In all women, peak levels of NET occurred within 1-2 hours and a semi-log plot of plasma NET levels showed a biexponential decline. The half-life of plasma NET clearance was relatively shorter in women of low socio-economic group with poor nutritional status as indicated by anthropometric indices, as compared to that in well nourished women of high socio-economic group. There was a significant positive correlation between weight/(height) 2x 100 index on the one hand and t1/2 (beta) on the other in all the women studied, thereby suggesting a role for nutritional status in the metabolic handling of NET.

Absorption↗
PubMed1979

The rabbit as an animal model to study pharmacokinetics of norethindrone in women.

The pharmacokinetics of norethindrone (NET) were studied in adult female rabbits and rhesus monkeys with a view to developing an animal model closely resembling humans in the handling of NET. Plasma levels of NET were determined in rabbits and monkeys after administering either labelled NET or a NET minipill. Pharmacokinetic parameters were evaluated by using a two-compartment open model and by graphical and regression analysis of plasma NET data. In rabbits, the drug absorption was found to be rapid and NET peak levels were attained within 0.5 to 1.0 hour. The clearance half-lives were 1.3 hours for 'alpha' and 10.0 hours for 'beta'. In monkeys, plasma NET values showed an inconsistent pattern and the approximate t 1/2 was found to lie between 4 and 6 hours. The observed pharmacokinetics of NET in rabbits rather than in monkeys were closer to those in humans. On this basis, it would appear that the rabbit is a suitable animal model for studying effects of nutritional factors on the pharmacokinetics of NET.

Animals↗