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Biomedical subjects

C K Nain

Publications and source records attributed to C K Nain.

At least 55 records · Page 3Linked to original sources

Disposition of chloramphenicol in young rhesus monkeys with protein-energy malnutrition.

The disposition of chloramphenicol was studied in young rhesus monkeys at three levels of nutrition: control, protein-energy deficiency, and following nutritional rehabilitation. During the malnutrition phase, the plasma elimination half-life was prolonged and the plasma clearance was reduced. Simultaneously there was a decrease in the activity of chloramphenicol-specific UDP-glucuronyl transferase. These changes were reversible following nutritional rehabilitation.

Animals↗

Pharmacokinetic profile of antipyrine in young rhesus monkeys (Macaca mulatta) with protein energy malnutrition.

An experimental model of protein energy malnutrition was produced in five young rhesus monkeys and the pharmacokinetics of antipyrine were studied at three points, initially, during protein energy malnutrition and following nutritional rehabilitation. In a separate group of animals, the estimation of hepatic enzyme aminopyrine N-demethylase was performed. There was a significant decrease in the elimination kinetics, the half life was increased, and the clearance rate was decreased in the malnourished animals, which correlated with a corresponding decrease in aminopyrine N-demethylase activity.

Aminopyrine N-Demethylase↗

Disposition of acetaminophen in children with protein calorie malnutrition.

Acetaminophen disposition was studied in 11 children suffering from Protein Calorie Malnutrition (PCM) and 5 (age matched) control subjects using the time plasma concentration curve obtained after a single oral administration of 10 mg/kg of the drug. Absorption rate constant (Ka) was not altered in PCM. Elimination rate constant (Ke) was decreased significantly. PCM children had Ke 0.108 +/- 0.015 h-1 in comparison to the control value of 0.170 +/- 0.022 h-1. Plasma half-life (t1/2) was increased in PCM (8.14 +/- 1.30 h) in comparison of the control (4.33 +/- 0.52 h). Area under the curve (AUC) was also significantly increased in PCM (88.88 +/- 21.36 ug h/ml/kg) compared to the control (25.05 +/- 2.99 ug h/ml/kg). Time of drug disappearance was 44.7 +/- 7.1 hours in PCM compared to 24.6 +/- 3.3 hours in the control. Five PCM subjects could be restudied after rehabilitation and they demonstrated the return of elimination parameters towards control values. Drug therapy needs revision in light of these findings.

Acetaminophen↗

Lipid composition of the peripheral nerves in malnutrition: an experimental study in young rhesus monkeys.

An experimental model of protein calorie malnutrition (PCM) was created in young rhesus monkeys. Ulnar and tibial nerves from six monkeys with PCM, six rehabilitated and 12 control monkeys were studied for lipid composition and activity of myelin marker enzyme. Total lipids, myelin marker lipids and activity of myelin marker enzyme, 2', 3'-cyclic nucleotide 3' - phosphohydrolase were decreased, while esterified cholesterol and free fatty acids were increased in PCM as compared to controls. There was partial recovery in myelin marker lipids and complete restoration of other lipids on nutritional rehabilitation.

Animals↗

In vitro incorporation of (U-C14)-glucose and (1-C14)-sodium acetate in peripheral nerves of malnourished young rhesus monkeys.

The effect of protein calorie malnutrition (PCM) on synthesis of lipids in peripheral nerves was studied by in vitro incorporation of (U-C14)-glucose and (1-C14)-sodium acetate. Ulnar and tibial nerves obtained from five young rhesus monkeys with PCM, five rehabilitated monkeys, and five control monkeys were incubated for 2 h with the radioactive precursors. Uptake of both radioactive precursors in whole peripheral nerves as well as myelin marker lipids was significantly decreased in animals with PCM. However, uptake returned to normal in rehabilitated monkeys.

Acetates↗

Disposition of four drugs in malnourished children.

Pharmacokinetic studies on antipyrine, chloramphenicol, acetaminophen, and sulphadiazine have been carried out in infants and children suffering from protein-energy malnutrition (PEM). Increased antipyrine plasma half-life in PEM indicated altered mixed oxidative microsomal enzyme activity in hepatocytes. Chloramphenicol was absorbed (ka) as well as eliminated (ke) at slower rates in PEM. The net result was that the comparative bioavailability of the drug was higher in PEM as compared to the control. Observations were similar in the case of sulphadiazine. The rate of absorption (ka) of acetaminophen was not affected in children with PEM, but the elimination rate constant was slower and plasma half-life prolonged. Noticeable improvement was observed within 6-8 weeks of nutritional rehabilitation with respect to chloramphenicol, antipyrine, and acetaminophen pharmacokinetics.

Acetaminophen↗

Metabolism of sulfadiazine in children with protein calorie malnutrition.

6 children with protein calorie malnutrition (PCM) and 5 control children received a single dose of sulfadiazine (25 mg/kg body weight). Absorption rate constant in the control group was 0.735 +/- 0.058 h-1 and in PCM 0.519 +/- 0.03 h-1. Peak blood levels of the drug were similar in both groups. However, the time to reach the peak was shorter in the control than in the PCM group. Elimination rate constant and half life of the drug were 0.0233 +/- 0.0026 h-1 and 31.78 +/- 3.82 h, respectively, in the PCM group and 0.0332 +/- 0.0022 h-1 and 21.27 +/- 1.51 h, respectively, in the control group. These values differ significantly from each other. The area under the blood concentration-time curve was more than double in the PCM group as compared to the control group. Urinary excretion of the drug in 48 h was significantly more in control (19.3 +/- 1.4 mg/kg body weight) in comparison to the PCM group (13.6 +/- 1.7 mg/kg body weight). However, the free drug concentration in urine/kg body weight was not altered in the PCM group. There was a significant decrease in quantity of acetylated drug in the PCM group as compared to the controls. In view of these observations, therapy with sulfadiazine in children suffering from PCM requires reconsideration.

Acetylation↗

Energy metabolism of the brain in malnutrition. An experimental study in young rhesus monkeys.

An experimental model of protein-calorie malnutrition (PCM) has been successfully produced in young rhesus monkeys. The model showed close resemblance to the energy kinetics of the brain as observed in human PCM inasmuch as oxygen consumption was decreased while glucose uptake was increased. The cerebral blood flow was also diminished. The observations suggest that a significant part of glucose is perhaps diverted to long-chain fatty acids, etc.

Animals↗

Primate model of sprue-like syndrome.

An experimental model resembling so-called tropical sprue has been produced in young, growing rhesus monkeys kept on a protein-deficient diet. At a 2% level of protein intake, the animals became frankly diseased after two months, but at a 5% protein intake the symptoms appeared after five months. The animals lost weight, their skin became brittle, the fur lost luster, and facial edema appeared. The hematocrit, and serum folate, protein and albumin were significantly decreased, and intestinal absorption of fat, D-xylose, radioactive vitamin B12 and folic acid showed marked depression. The jejunal mucosa showed moderate villous atrophy. Histochemical and electron microscopy changes were consistent with those seen in the human tropical sprue syndrome. It appears, therefore, that protein malnutrition plays an important role in the experimental tropical-sprue-like syndrome in monkeys.

Animals↗

Hypogammaglobulinaemic sprue in tropics: Report of an Indian patient.

Acquired hypogammaglobulinaemia is a rare disease and has not been reported from tropical regions before. A fourteen year old boy, who had symptoms of intestinal malabsorption since the age of seven years, was investigated and found to be suffering from severe hypogammaglobulinaemic sprue which ended fatally. The problems in diagnosis and management of this rare disorder have been highlighted.

Adolescent↗

Energy metabolism of brain in human protein-calorie malnutrition.

Cerebral blood flow (CBF) and carbohydrate metabolism were studied in 5 normal children and 25 children, aged 40 months or less, with varying degrees of protein-calorie malnutrition (PCM). CBF in normal children and those suffering from grade I PCM was 90.3 +/- 5.7 ml/100 g/min, a value comparable with that obtained by other investigators, but the proportion of glucose taken up by the brain which combined with oxygen, the oxygen/glucose index (OGI), was 65.8%, indicating significant conversion of glucose into lactic acid. Cerebral lactic acid production was 45.3 micronM/100 g/min, and the respiratory quotient (R.Q.) was 1.00. With increasing severity of PCM, there was increased glucose utilization and a progressive reduction in the OGI. In grade IV PCM, CBF was 68.7 +/- 5.4ml/100g/min, and the OGI was 34.7%. Cerebral lactic acid production was 27.4 micronM/100 g/min, and the R.Q. rose to 1.52. These findings suggest that in severe human PCM the proportion of glucose undergoing aerobic oxidation is reduced, and that in addition to being converted to lactic acid, a significant proportion of glucose is transformed by the brain into long chain fatty acids.

Blood Glucose↗