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Biomedical subjects

D Sadava

Publications and source records attributed to D Sadava.

At least 19 recordsLinked to original sources
PubMed1997

Effect of methadone addiction on glucose metabolism in rats.

Female albino rats were exposed to methadone over a 35-day period by addition of the drug in their drinking water. The final dose of the drug was 1.8 mg/kg body weight per day. After this period, the drug was withdrawn from some animals for 30 days (postexposure). Compared to unexposed controls, serum glucose levels rose during exposure and returned to control levels postexposure. Oral glucose tolerance tests showed impairment in 35-day drug-exposed animals compared to controls and postexposure. The activities of three key enzymes of glycolysis and three key enzymes of gluconeogenesis were measured in liver during and at the end of the exposure period, as well as postexposure. Compared to unexposed controls and postexposure, specific activities of two glycolytic enzymes in livers of exposed animals-hexokinase and phosphofructokinase 1-were significantly reduced, whereas the activity of a third glycolytic enzyme-pyruvate kinase-was unchanged. The specific activities of two gluconeogenic enzymes-glucose-6-phosphatase and fructose-1,6-biphosphatase-were significantly elevated in the drug-exposed animals compared to controls, whereas the activity of a third enzyme-phosphoenolpyruvate carboxykinase-was unchanged. These data indicate that methadone addiction produces a metabolic state similar to insulin-resistant diabetes.

Animals↗
PubMed1996

Hyperplasia, hyperproliferation and decreased migration rate of colonic epithelial cells in mice fed a diet deficient in vitamin D.

Low serum levels of vitamin D metabolites have been associated with an increased risk for colon cancer. To investigate the effects of vitamin D deficiency on the colon, 4-week-old mice were fed a diet either containing (100,000 IU/kg diet) or lacking this vitamin for 3 weeks. Food consumption and body weight gain were similar in both groups. Following injection with 3H-thymidine to label dividing cells, cellular proliferation and migration up the colonic crypt were determined autoradiographically. Although overall crypt lengths were similar in both groups, there was hyperplasia and hyperproliferation in crypts of the deficient animals. Also, their epithelial cells migrated up the crypt at a significantly slower rate (maximum 0.78 micron/h) than did those from control mice (1.42 microns/h). There was no difference in cellularity, proliferation or migration in duodenal epithelium. These results indicate that vitamin D deficiency significantly alters colonic but not duodenal epithelial cells.

Animals↗
PubMed1992

Development of enzymes of glycolysis and gluconeogenesis in human fetal liver.

The activities of two key enzymes of glycolysis and two key enzymes of gluconeogenesis were measured in liver samples from 44 human fetuses ranging in gestational age from 20 weeks to term, from infants to 10 years and from adults from 21 to 58 years. Specific activities of both gluconeogenic enzymes, fructose-1,6-biphosphatase and phosphoenolpyruvate carboxykinase, increased throughout the period of fetal development examined, and rose to near adult levels after birth. The activities of both glycolytic enzymes, phosphofructokinase 1 and pyruvate kinase, were lower in fetal than in pediatric and adult samples. For both of these enzymes, there was a significant reduction in activity of livers from fetuses of 34-37 weeks' gestation. Both enzymes showed hyperbolic kinetics at 24 weeks' gestation, but this changed to sigmoid kinetics during the 34-37 weeks' period of low activity. The data indicate that during the last weeks of gestation, inhibition of the activities of these two glycolytic enzymes, coupled with the rise in the two gluconeogenic enzymes, may reflect a change in liver from a primarily glycolytic role in the first two trimesters to a gluconeogenic role shortly before birth.

Adult↗
PubMed1990

Transition from cytosolic to mitochondrial thymidine kinase during development in human fetal tissues.

The transition from cytosolic ("fetal") to mitochondrial ("adult") thymidine kinase, as detected by electrophoresis, was examined in six human fetal tissues of gestational ages 11-40 weeks. In all tissues there was an early period during development in which only the fetal form was detected, followed by a transitional period in which both fetal and adults forms were present, followed by a later period in which only the adult enzyme occurred. Transitional periods were 23-25 wk. gestational age for colon, 13-15 wk. for kidney, 18-20 wk. for liver, 14-18 wk. for lung, 34-36 wk. for serum, and 25-28 wk. for thyroid. In all cases, only the adult form was present by the time of birth and persisted during the first 18 months of extrauterine life. The adult form, but not the fetal form, was inhibited by dCTP.

Adult↗
PubMed1988

The effects of maternal hyperphenylalaninemia on learning in mature rats.

Pregnant rats were given a diet supplemented with 0.5% alpha-methyl-phenylalanine and 3% phenylalanine from the 12th day of gestation to term. Compared to unsupplemented controls, maternal serum phenylalanine was elevated 8-10-fold. Experimental litters did not differ from controls in number of offspring, birth weight, or subsequent growth on an unsupplemented diet. At 8 weeks of age, animals were tested for latent learning on a 4-arm maze, and at 10 weeks, they were tested for observational learning with littermates in a food preference paradigm. In both tests, experimental animals did learn, but significantly less than controls. The data suggest that maternal hyperphenylalaninemia, induced as a model for the inborn error, phenylketonuria, can lead to learning deficits later in the lives of offspring.

Animals↗
PubMed1987

Glycerol metabolism in higher plants: glycerol kinase.

Glycerol kinase activity was identified in extracts of higher plant seeds and seedlings, and was partially purified and characterized from cucumber radicle tissue. The enzyme was localized in the post-mitochondrial supernatant of the cell, and catalyzed the formation of glycerol-3-phosphate. The pH optiumum was 9.0. ATP, CTP, GTP or UTP could be used as the phosphoryl group donor. The Km for glycerol was 55 microM and Km values for the nucleoside triphosphates were 145-620 microM. The Vmax for the reaction was 40-78 pmol product per min. Kinetic data indicate that the enzyme has a sequential mechanism.

Glycerol↗
PubMed1987

Development of enzymes of glycerol metabolism in human fetal liver.

The activities of three key enzymes of glycerol metabolism were measured in liver samples from 37 human fetuses ranging in gestational age from 18 weeks to term, from neonates (1-3 days) and from infants to 2 years. Glycerol kinase specific activity was constant throughout the period of fetal development examined, and was comparable to that measured in neonates and infants. However, the subcellular distribution of the activity changed markedly, being predominantly particulate in fetal samples and cytoplasmic in postnatal samples. The particulate activity had an elevated Km for glycerol. Cytoplasmic glycerol-3-phosphate dehydrogenase activity was very low in the fetal period, and then rose to adult levels during infancy. There were no kinetic differences between the fetal and postnatal activities. Mitochondrial glycerol-3-phosphate dehydrogenase activity rose somewhat after birth to near adult levels. The data indicate that glycerol can be metabolized by human fetal, neonatal and infant liver.

Cytoplasm↗
PubMed1986

The effect of methadone addiction on cyclic nucleotide levels in regions of rat brain.

Studies of tissue culture cells and tissue slices have implicated the nucleotides, cyclic AMP and cyclic GMP, in the mechanism of action of opiates. However, there are little in vivo data to corroborate this hypothesis. We addicted rats to the synthetic opiate, methadone, by providing the drug in their drinking water (dosage 2.1 mg./kg./day). The two cyclic nucleotides were measured in four brain areas which contain a high concentration of opiate receptors: amygdala, neostriatum, periventricular grey, and thalamus. Data were obtained after acute exposure of the drug (1 day), tolerance (35 days), withdrawal (35 days on drug then 1 day off drug), and readjustment (35 days on drug then 21 days off drug). Cyclic GMP levels were low (0.03 pmol./mg. tissue) in the four regions and did not differ significantly during the experiment. Cyclic AMP levels were higher (1-3 pmol./mg.) and fluctuated consistently in the four regions. After acute methadone treatment, there was a reduction in cyclic AMP, which continued at lower levels after tolerance. One day of withdrawal led to increased cAMP, which rose to near control levels. After readjustment, the levels were reduced. These data indicate an involvement of cyclic AMP in the addiction and withdrawal processes in the intact animal.

Amygdala↗
PubMed1984

Tricyclic antidepressant drugs affect histamine receptors in human leukocytes.

Tricyclic antidepressant drugs bind to histamine receptors in rodent and other mammalian tissues. However, a readily accessible, normal human tissue for studies of these drugs has not been available. We showed that freshly isolated human leukocytes can be used for this purpose. Following isolation by dextran sedimentation, leukocytes were incubated for 30 sec. in histamine concentrations from 1.0 nM to 1.0 mM. A dose-related increase in intracellular cyclic AMP was observed. When the cells were preincubated for 10 min. in the tricyclic, nortriptyline, and then challenged with histamine, the concentration of histamine needed for a comparable cyclic AMP increase was elevated 100-fold over non-preincubated cells. These results indicate that the tricyclic drug interacts with histamine receptors on leukocytes, and that these cells may be used for biochemical and clinical studies of these drugs.

Adult↗
PubMed1982

Human glycerol kinase deficiency: enzyme kinetics and fibroblast hybridization.

Glycerol kinase deficiency has been associated with neuromuscular, skeletal and adrenal abnormalities and has also been seen in individuals without these clinical findings. Examination of residual enzyme activity in patients' liver, kidney, leukocytes and fibroblasts showed a generalized, heritable defect: the apparent Km for glycerol was increased 5-200-fold over control values, whereas the apparent Km for ATP was not significantly altered. This kinetic defect was similar in fibroblasts from clinically different individuals with this inborn error of metabolism. Hybridization of fibroblasts from these individuals showed no evidence of complementation for glycerol kinase activity.

Adenosine Triphosphate↗
PubMed1982

The effect of vitamin C on the rapid induction of aortic changes in rabbits.

Male rabbits were injected intraperitoneally for five consecutive days with one of the following: (A) 0.3 ml/kg dimethyl ethylene glycol (solvent); (B) 40 mg/kg cholesterol and 8 mg/kg ergocalciferol in solvent; (C) same regimen as B with the addition of 150 mg/kg ascorbic acid in water. Daily blood samples were taken for determination of cholesterol and triglycerides, and for lipoprotein electrophoresis. After 5 days of injections, histological sections were made of the aorta at the arch. After 5 days, group B, as compared with group A, had higher serum cholesterol (150 ng/dl vs. 50 mg/dl, p less than 0.005), higher serum triglycerides (650 mg/dl vs. 150 mg/dl, p less than 0.01), and lower high-density lipoprotein (16% vs. 35%, p less than 0.05). On autopsy, discontinuous elastic fibers and intimal damage were seen in sections of the aortas from group B, but not from group A. After 5 days, group C had control levels of cholesterol (55 mg/dl) and triglycerides (160 mg/dl), and no significant difference from the control lipoprotein profile. Injections of cholesterol alone showed a slight induction of aortic lesions and blood chemistry changes. No alterations in these parameters were induced by ergocalciferol alone. The data indicate a prophylactic effect of vitamin C on the biochemical and histological changes rapidly induced by cholesterol and ergocalciferol.

Animals↗
PubMed1980

Effect of prematurity on the developmental progression from fetal to adult thymidine kinase in human serum.

The developmental progression of thymidine kinase from the electrophoretically slow-migrating 'fetal' forms to the fast-migrating 'adult' form was examined weekly in the serum of 5 premature infants. Only the fetal forms were present up to 32 weeks after conception. The adult form appeared along with the fetal forms until 39 weeks post-conception; thereafter, only the adult form was detected. With respect to post-conceptional age, the timing of the changeover from fetal to adult serum, thymidine kinase was the same in the prematurely born infants as in stillborn infants at an equivalent gestational age.

Electrophoresis, Polyacrylamide Gel↗
PubMed1977

Multiple forms of thymidine kinase during human development.

The developmental progression of thymidine kinase from the electrophoretically slow-migrating 'fetal' forms to the fast-migrating 'adult' form was examined in human serum and fetal liver. In fetal liver, only the fetal forms of the enzyme were present at 17 weeks' gestation. A transitional period followed in that both enzyme forms were identified and by 24 weeks only the adult form was detected in fetal liver. This same enzyme changeover pattern--fetal to transitional to adult--occurred at a later time in human serum as it took place between 30 and 40 weeks' gestation.

Adult↗
PubMed1977

Effect of maternal methadone addiction on offspring in rats.

Female rats were addicted to methadone via small dosages in their drinking water. The addicted animals were impregnated, and continued to receive the drug during pregnancy and lactation. Offspring were examined at birth and at age 21 days. Compared to controls whose mothers did not receive the drug, pups of addicted mothers at birth had significantly lower weight, brain weight and brain protein; litter size, brain DNA and brain acetylcholinesterase activity were not significantly different between the two groups. At age 21, pups of addicted mothers had significantly lower brain protein and brain acetylcholinesterase than did controls; body weight and brain DNA were not significantly different.

Animals↗
PubMed1976

Effect of methadone addiction on N-demethylation activity of rat liver microsomes.

Adult male rats were addicted to methadone via small dosages in their drinking water. The N-demethylation activity of microsomal mixed function oxidase in liver was determined for partially addicted (25 days of drug consumption) and fully addicted (38 days of drug consumption) rats. Compared to controls which did not receive the drug, enzyme activity expressed on a microsmal protein basis was increased in partially addicted, but not increased in fully addicted animals. Enzyme activity expressed on a liver weight basis was decreased in partially addicted animals but unchanged from contro levels in fully addicted animals. Brief (three-day) exposures to phenobarbital or high dosages of methadone led to an increase in N-demethylation activity.

Animals↗