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Biomedical subjects

R B Roy

Publications and source records attributed to R B Roy.

At least 37 records · Page 2Linked to original sources
PubMed1989

Dietary choline intake modulates benzodiazepine receptor binding and gamma-aminobutyric acidA receptor function in mouse brain.

Several lines of evidence suggest that dietary choline intake influences the metabolism of membrane phospholipids with possible effects on GABAergic neurotransmission. Based on these findings, the present experiments determined whether chronic choline supplementation or deficiency alters GABAergic function at the level of the gamma-aminobutyric acid (GABA)/benzodiazepine-chloride channel complex. To accomplish this, mice were fed diets containing 0% (deficient), 0.2% (basal) or 2.0% (supplemented) choline chloride for 28 days, and behavior, ligand binding at several sites in the complex and chloride uptake were determined in various brain regions. For both rotarod ataxia and open-field activity, mice receiving choline supplementation had a decreased response to clonazepam compared to those receiving basal and deficient diets. Choline supplementation significantly increased the in vivo binding of [3H]Ro15-1788 to cortex and cerebellum by 19% and 24%, respectively, and in vitro studies in cortical membranes indicated a significant 36% increase in the maximal number of [3H]flunitrazepam binding sites without a change in affinity, as compared to basal controls. In contrast, [3H]Ro15-1788 binding in vivo in all brain regions from mice fed the deficient diet decreased significantly to 20 to 58% of control values. Dietary choline intake did not alter GABA levels in brain, the binding of [35S]t-butylbicyclophosphorothionate to the chloride channel or the coupling between GABA and either the t-butylbicyclophosphorothionate site or the benzodiazepine site. However, the function of the GABAA receptor, determined by muscimol-stimulated chloride uptake into cortical synaptoneurosomes, was increased significantly in tissue from the supplemented group as compared to both control and deficient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Chronic benzodiazepine administration. III. Upregulation of gamma-aminobutyric acidA receptor binding and function associated with chronic benzodiazepine antagonist administration.

Chronic administration of a benzodiazepine agonist appears to downregulate benzodiazepine receptors and gamma-aminobutyric acid (GABA) receptor function. To examine the effects of chronic treatment with a benzodiazepine antagonist, we administered Ro15-1788, 1, 2 and 5 mg/kg/day to mice via implanted s.c. osmotic pumps for 1 to 14 days. Plasma and cortex (CX) concentrations of Ro15-1788 remained constant between days 1 and 7, indicating no change in pharmacokinetics. Open-field activity studies showed no change in distance traveled or ambulatory time at days 1, 2 and 4, but an increase in both parameters at days 7 and 14 in mice receiving Ro15-1788, 2 mg/kg/day. Benzodiazepine receptor binding was unchanged in CX, cerebellum (CB), hypothalamus, hippocampus and ponsmedulla at 1, 2 and 4 days at a dose of 2 mg/kg/day. Binding was increased in CX, CB and hippocampus at day 7 compared to days 1 and 2, and remained elevated at day 14. Similar results were observed at Ro15-1788 doses of 1 and 5 mg/kg/day. Benzodiazepine binding assessed in vitro in CX and CB also was increased at day 7 compared to day 1, due to an increase in receptor number rather than a change in apparent affinity. Binding of t-[35S]butylbicyclophosphorothionate to the chloride channel site in CX after Ro15-1788, 2 mg/kg/day, was increased at days 7 and 14 compared to days 1, 2 and 4 and controls due to an increase in number of binding sites. t-Butylbicyclophosphorothionate binding in CB was unchanged throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Chronic clonazepam administration decreases gamma-aminobutyric acidA receptor function in cultured cortical neurons.

Chronic benzodiazepine administration has been reported to decrease gamma-aminobutyric acidA (GABAA) receptor function in animals and may alter benzodiazepine binding in neuronal cultures. To assess GABAA receptor function in neuronal cultures exposed to chronic clonazepam, we measured muscimol-stimulated chloride uptake in chick cerebral cortical cultures treated acutely and for 2, 4, and 10 days. Acute clonazepam administration (1 microM) led to an increase in GABA-related chloride uptake at lower doses of muscimol. After chronic clonazepam (1 microM), maximal uptake was markedly decreased at day 10, but maximal uptake was unchanged after 2- and 4-day treatments. Benzodiazepine receptor binding was decreased by approximately 60% after 10 days due to a decrease in receptor number. Decreases in chloride uptake were also observed after 10 days of treatment with 0.1 and 10 microM clonazepam. Concomitant treatment with 0.1 microM Ro15-1788 abrogated the effect of 0.1 microM clonazepam on chloride uptake. Chronic clonazepam treatment (1 microM) did not alter total cellular protein, cellular protein synthesis or degradation or percentage of neuronal cells, as determined morphologically and by [3H]ouabain binding.

Animals↗
PubMed1989

Prenatal lorazepam administration is associated with GABAA receptor alterations in late embryonic and mature chicks.

Prenatal benzodiazepine administration has been associated with alterations in behavior in young and mature animals. Prior studies of neurochemical changes in animals treated in utero have produced conflicting results. We used a chick embryo system to assess the effects of chronic lorazepam administration on binding and function at the GABAA receptor in late embryos and in mature animals. Administration of lorazepam for 10 days of embryonic development (E8-E18) led to decreases in binding of the chloride channel ligand TBPS and in muscimol-stimulated chloride uptake in late embryos (E18). Similar alterations were observed in mature animals after the same regimen of prenatal lorazepam. Persistent alterations in GABAA receptor binding and function after prenatal lorazepam may be due to effects of neuronal differentiation or on receptor regulation. These neurochemical effects may underlie the behavioral abnormalities associated with prenatal benzodiazepine administration.

Animals↗
PubMed1988

Lorazepam administration during embryonic development alters GABAA receptor binding and function.

Prenatal exposure to diazepam has been reported to lead to behavioral alterations in young and mature animals, but the neurochemical basis of this effect is uncertain. To examine effects of embryonic benzodiazepine exposure on the gamma-aminobutyric acidergic (GABA)ergic) system, we assessed binding and function at the GABAA receptor complex in chick embryos treated with lorazepam, 2 mg/kg, for 2-10 days. There was no change in benzodiazepine receptor binding in cortex after lorazepam administration, but a decrease in the number of chloride channel sites was observed. Overall function at the GABAA receptor complex as assessed by chloride uptake into cortical synaptoneurosomes was decreased after 10 days of lorazepam, and possibly increased after 4 days of lorazepam. Similar results were obtained when embryos were treated for 2- and 4-day periods beginning on day 8. These results indicate that chronic lorazepam administration to embryos alters binding and function in the GABA system measured soon before hatching. These alterations, if persistent, may contribute to the behavioral changes seen in animals exposed prenatally.

Animals↗
PubMed1988

Chronic benzodiazepine administration. II. Discontinuation syndrome is associated with upregulation of gamma-aminobutyric acidA receptor complex binding and function.

A "withdrawal" or "rebound" syndrome may follow the abrupt discontinuation of chronic treatment with benzodiazepines. To assess the neurochemical basis of this syndrome, mice were treated with lorazepam, 2 mg/kg/day for 7 days, a course which produces tolerance and downregulation of receptor binding and function. Behavioral studies indicated that open-field activity in lorazepam-treated mice was similar to controls at 1 day postlorazepam. Activity was increased at 4 days postlorazepam, and had returned to control levels by day 7. Benzodiazepine receptor binding as measured by specific uptake of [3H]Ro15-1788 in several brain regions returned to control levels by day 2 postbrazepam but had increased above controls at day 4 postlorazepam. Binding returned to control levels by day 7. Similar results were observed using [3H]flunitrazepam in membrane preparations. A similar time course was also observed for the maximum binding of the chloride channel ligand t-[35S]butylbicyclophosphorothionate during this period. The IC50 value for muscimol inhibition of t-butylbicyclophosphorothionate binding was decreased at day 4, suggesting increased coupling between gamma-aminobutyric acid and the chloride channel. Muscimol-stimulated [36Cl-] up-take in cortical synaptoneurosomes was increased at day 4 postlorazepam. These results indicate that the benzodiazepine discontinuation syndrome is associated with upregulation of receptor binding and function at the gamma-aminobutyric acidA receptor complex.

Animals↗
PubMed1988

Structural specificity of MIF-1 and Tyr-MIF-1 in augmenting GABA-stimulated benzodiazepine receptor binding.

The possibility of a linkage between endogenous peptides and the GABA-benzodiazepine system has been greatly strengthened by reports that the brain peptides MIF-1(Pro-Leu-Gly-NH2) and Tyr-MIF-1(Tyr-Pro-Leu-Gly-NH2) augment GABA-stimulated benzodiazepine binding. We evaluated the actions of fragments and analogs of these small peptides on GABA-stimulated benzodiazepine binding in mouse cortical brain membranes. Fragments of Tyr-MIF-1, several compounds related to MIF-1, or several analogs of Tyr-MIF-1 had no effect on binding. These results demonstrate the specificity of the effects of MIF-1 and Tyr-MIF-1 on GABA-stimulated benzodiazepine binding.

Animals↗
PubMed1987

Effects of Tyr-MIF-1 and MIF-1 at the GABAA receptor chloride channel site.

The peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and, to a lesser extent, MIF-1 (Pro-Leu-Gly-NH2) recently have been found to augment the effects of gamma-aminobutyric acid (GABA) on benzodiazepine receptor binding at the GABAA receptor complex. To assess their interaction with the chloride channel binding site on the GABAA receptor, we evaluated the effects of these two peptides on [35S]-t-butylbicyclophosphorothionate (TBPS) binding in mouse brain membranes. In cortex, neither peptide altered [35S]-TBPS binding over a broad dose range, but Tyr-MIF-1 significantly augmented displacement of radioligand binding by the GABA analog muscimol at peptide concentrations of 10(-10) to 10(-7) M; MIF-1 had little effect on muscimol displacement of [35S]-TBPS binding. In cerebellum and brainstem, neither peptide was active in altering muscimol displacement of binding. Thus, Tyr-MIF-1 augments the displacement of [35S]-TBPS binding by the GABA analog muscimol in mouse brain cortical membranes, indicating that this peptide enhances the effects of GABA at the chloride channel as well as at the benzodiazepine receptor.

Animals↗
PubMed1985

Are we failing our teenagers? Value of a family planning service for teenagers within the sexually transmitted disease clinic.

Out of 100 teenage girls attending a sexually transmitted disease clinic for the first time, 77 were found to be using a reliable method of contraception and had similar characteristics to teenage girls attending a family planning clinic. The 23 girls not using any reliable contraception exhibited a different pattern of sexual behaviour and were at high risk of unplanned pregnancy. Subsequently, another group of 23 girls not using contraception when seen at the sexually transmitted disease clinic were actively encouraged to attend a family planning clinic. Their risk of unplanned pregnancy was much reduced, although their pattern of sexual activity was unchanged. Ready availability of contraceptive advice for unprotected teenagers in sexually transmitted disease clinics would reduce their high risk of unplanned pregnancy.

Adolescent↗
PubMed1984

Thymus derived lymphocytes (T cells) in patients with genital warts.

Thymus derived lymphocytes (T cells) were counted in the peripheral blood of 30 patients with genital warts and in 20 healthy controls. The control group was made up of 10 healthy patients with no history of warts and 10 who had been cured of warts for at least 12 months. We found that patients with genital warts had a significantly lower number of T cells despite an adequate number of circulating lymphocytes in the peripheral blood. We therefore suggest that a functional defect of lymphocytes ("dyslymphocytosis") could be the cause of genital warts either in their primary or recurrent form. These abnormal lymphocytes return to their normal function after the disappearance of genital warts.

Adolescent↗
PubMed1983

Evaluation of urea-acid system as medium of extraction for the B-group vitamins. Part II. Simplified semi-automated chemical analysis for niacin and niacinamide in cereal products.

Efficiency of a urea-acid system was evaluated as a medium of extraction for niacin and niacinamide from cereals and other selected food products. Samples were treated with 1N HCl in the presence of urea and autoclaved 30 min at 15 psi. Extracts were diluted to a known volume, filtered, and analyzed. The analytical results obtained for niacin were compared with values obtained by AOAC method 43.044. In general, the urea-acid extraction system was simple and straightforward with an efficiency comparable to the AOAC method. The analytical manifold designed uses fewer modules, gives net absorbance readings from sample and blank, and is capable of analyzing 50 samples per hour.

Autoanalysis↗