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Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 415 records · Page 23Linked to original sources
PubMed1994

Serotonergic properties of cocaine: effects on a 5-HT2 receptor-mediated behavior and on extracellular concentrations of serotonin and dopamine.

The present study examined the ability of cocaine to produce behavioral and neuropharmacological effects through serotonin (5-HT) systems. Pretreatment with fluoxetine or cocaine potentiated the head-shake response to the 5-HT precursor, 5-hydroxytryptophan (5-HTP; 75 mg/kg), a behavior mediated by the activation of 5-HT2 receptors. This effect was antagonized by the selective 5-HT2 receptor antagonist ketanserin (1 mg/kg). In contrast, pretreatment with the selective norepinephrine uptake inhibitor desipramine (10 mg/kg) or the selective dopamine (DA) uptake inhibitor GBR 12909 (32 mg/kg) failed to potentiate the head-shake response. The effects of cocaine on extracellular concentrations of DA and 5-HT in the nucleus accumbens were examined using in vivo microdialysis in a separate group of anesthetized rats. Cocaine (10 mg/kg) increased the extracellular concentrations of DA and 5-HT by 300-350% over baseline levels. Cocaine's ability to increase the head-shake response and to increase extracellular concentrations of 5-HT may be due to its ability to block 5-HT uptake.

5-Hydroxytryptophan↗
PubMed1994

Antidepressant-like behavioral effects of serotonin receptor agonists.

The clinical discoveries that drugs that stimulate 5-HT neurotransmission, either by inhibiting 5-HT uptake or by stimulating postsynaptic receptors directly, have antidepressant properties has stimulated interest in defining the role of the 5-HT receptor system in the clinical effects of antidepressant drugs. Two approaches are reviewed in this paper that address the neurochemical mediation of the therapeutic effects of antidepressant drugs from the standpoint of animal behavior. The first approach utilizes a behavioral response in rats, the forced swimming test, that correlates well with predicting antidepressant drugs in humans. Studies are reviewed that examined serotonergic compounds in the forced swimming test, from the standpoint of identifying better serotonergic mechanisms involved in the antidepressant response. Both 5-HT uptake inhibitors and 5-HT1A receptor agonists produce effects in the forced swimming test that are similar to those of other classes of antidepressant drugs. In contrast, agonists at other 5-HT receptors or 5-HT receptor antagonists do not produce antidepressant-like behavioral effects. Evidence for an important role of 5-HT1A receptors in the antidepressant response is supported by findings that antagonists of 5HT1A receptors prevent the ability of 5-HT1A receptor agonists to reduce immobility in the forced swimming test. The results of studies interfering with 5-HT neurotransmission, either by inhibition of 5-HT synthesis or by the destruction of 5-HT neurons, favor the idea that the effects of 5-HT1A receptor agonists are produced by the stimulation of postsynaptic 5-HT1A receptors. The second approach for studying the behavioral effects of antidepressant drugs employs drug discrimination studies, conducted using a discriminated taste aversion procedure, to provide a method for studying the discriminative stimulus effects of the antidepressant 5-HT uptake inhibitor sertraline. Rats were trained to discriminate the effects of sertraline (10 mg/kg) from saline. Other 5-HT uptake inhibitors, such as fluoxetine, fluvoxamine and paroxetine, substituted for the sertraline stimulus. High doses of norepinephrine uptake inhibitors, such as desipramine or maprotiline, were required to produce similar effects. These two behavioral approaches promise to be useful for defining the important pharmacological effects associated with the behavioral effects of antidepressant drugs.

Animals↗
PubMed1994

Supine and upright radionuclide esophageal transit before and after treatment for achalasia.

The authors hypothesized that radionuclide esophageal transit (RET) studies performed in the upright position and aided by gravity would provide better objective evaluation of achalasia than supine scanning and would correlate better with the degree of symptomatic relief after treatment. Radionuclide esophageal transit studies were prospectively performed in both the supine and upright positions in four symptomatic patients before treatment, after simple dilation, and after pneumatic dilation in patients who did not respond to simple dilation. After simple dilation, two patients reported near resolution of symptoms. Supine RET revealed little improvement, but upright esophageal emptying was markedly improved at 2, 5, and 10 minutes. In the two patients who had no relief after simple dilation. RET failed to show improvement while they were in either the supine or the upright position. These patients subsequently underwent pneumatic dilation that resulted in resolution of symptoms and marked improvement in upright RET only. In the supine position, the esophageal emptying at 2 minutes in the four patients after successful dilation improved from 0% baseline to a mean of 14% (+/- 18%). However, in the upright position, esophageal emptying improved from 3% (+/- 3%) to 73% (+/- 17%) and better correlated with symptomatic relief. The difference in improvement in esophageal emptying in the upright versus the supine position was statistically significant (P = 0.0033). The authors conclude that only upright esophageal emptying provides objective evidence that correlates well with symptomatic relief.(ABSTRACT TRUNCATED AT 250 WORDS)

Dilatation↗
PubMed1994

A hypercellulolytic mutant of Fusarium oxysporum.

Multiple mutagenesis of Fusarium oxysporum DSM 841 resulted in enhanced yields of cellulases. The hypercellulolytic mutant (NTG-19) secretes high levels of extracellular cellulases on different cellulosic substrates. Addition of surfactant, Tween-80, further increased enzyme secretion by about 30%. The results on hydrolysis of wheat straw by parent strain, DSM 841 and mutant NTG-19 cellulases also revealed a significant improvement in the hydrolytic potential of the cellulolytic enzymes from the mutant NTG-19.

Cellulase↗
PubMed1994

Lack of circadian variation in the sensitivity of rat terminal 5-HT1B autoreceptors.

The sensitivity of terminal 5-HT1B autoreceptors in the cerebral cortex and hippocampus to both agonist and antagonist was determined at four different time points in the light:dark cycle of the rat to evaluate whether changes in their responsiveness underlie the circadian rhythm in 5-hydroxytryptamine (5-HT) release. No significant circadian differences were evident in the apparent pIC50 values calculated for 5-HT to inhibit K(+)-evoked tritium efflux or in the apparent pA2 values calculated for methiothepin to antagonize the effect of 5-HT, at the different time points, in either brain region. These findings suggest that the sensitivity of terminal 5-HT1B autoreceptors in rat cerebral cortex and hippocampus does not change in a circadian pattern, during the light:dark cycle, and argues against such a change influencing the circadian variation in 5-HT release.

Animals↗
PubMed1994

Exercise-induced changes in immune function: effects of zinc supplementation.

To examine the effect of zinc (Zn) supplementation on exercise-induced changes in immune function, five male runners were randomly assigned in a double-blind crossover design to take a supplement (S; 25 mg of Zn and 1.5 mg of copper) or placebo (P) twice daily for 6 days. On morning 4 of each phase, 1 h after taking S or P, subjects ran on a treadmill at 70-75% of maximal oxygen uptake until exhaustion (approximately 2 h). Blood samples were obtained before (Pre), immediately after (Post), and 1 (Rec1) and 2 (Rec2) days after the run. [3H]thymidine incorporation by mitogen-treated mononuclear cell cultures was significantly lower (P < 0.05) Post than Pre, Rec1, or Rec2 for both S and P. Respiratory burst activity of isolated neutrophils was enhanced after exercise with P but not with S (P: Pre 12.0 +/- 1.1 vs. Post 17.6 +/- 2.3 nmol O2-/10(6) cells; S: Pre 11.7 +/- 0.3 vs. Post 12.1 +/- 1.2 nmol O2-/10(6) cells). Thus supplemental Zn blocked the exercise-induced increase in reactive oxygen species. Whether this antioxidant effect of Zn will benefit individuals exposed to chronic physical stress remains to be determined.

Adult↗
PubMed1994

Indices of morbidity and control of asthma in adult patients exposed to environmental tobacco smoke.

The study was undertaken to compare the indices of morbidity and control of asthma in 100 adult patients exposed to environmental tobacco smoke (ETS) inhalation (group 2), with 100 asthmatics not exposed (group 1). Exposure was established from the history of smoking by the patient's spouse and other close contacts. Asthma control and morbidity were assessed during their follow-up visits in the chest outpatient clinic by inquiring into the emergency department (ED) visits, hospitalization, acute episodes, requirement of parenteral drugs at home, corticosteroids, and maintenance bronchodilators in the preceding 1-year period. Index per patient was also calculated. Lung function was recorded by the measurement of forced expiratory flows on the same day of the follow-up visit. The mean age and disease duration were comparable, but the expiratory flows were lower in the patients exposed to ETS. More patients in group 2 required daily bronchodilators (66 percent) and intermittent corticosteroids (56 percent). The number of ED visits, acute episodes, and parenteral bronchodilators per patient were significantly more (p < 0.01) in group 2 patients. Similarly, the number of weeks of absence from work and of corticosteroid requirement were more (p < 0.01) in the ETS-exposed patients. We conclude that the control of asthma is poor and morbidity greater in adult patients with asthma exposed to ETS at home and/or at work.

Adult↗
PubMed1994

Lack of circadian variation in the responsiveness of alpha 2-heteroreceptors regulating serotonin release.

We have previously shown that the circadian variation in 5-HT release is not the consequence of a variation in the activity of terminal 5-HT1B autoreceptors. However, recently identified alpha 2-adrenoceptors located on 5-HT nerve terminals may be important in regulating the release of 5-HT from serotonergic neurons. The sensitivity of hippocampal alpha 2-heteroreceptors to both agonist and antagonist was determined at different time points in the light:dark cycle of the rat. No significant circadian differences were evident in either the apparent pD2 values calculated for noradrenaline to inhibit potassium-evoked tritium efflux or in the apparent pA2 values calculated for phentolamine to antagonize the effect of noradrenaline. The corollary of the lack of a circadian rhythm in sensitivity to the alpha 2-heteroreceptor is that this receptor population will accurately reflect any circadian variation in noradrenaline release and in the available concentration of noradrenaline at the receptor sites.

Analysis of Variance↗
PubMed1994

Guinea pig terminal 5-HT1D autoreceptors do not display a circadian variation in their responsiveness to serotonin.

Many of the components involved in the synthesis and release of serotonin (5-HT) display a circadian variation in their activity. Autoreceptors located on nerve terminals were recently suggested to underlie some of these circadian variations. The aim of this study was to examine whether terminal 5-HT1D autoreceptors in the cerebral cortex of the guinea pig exhibit a circadian variation in their responsiveness. The responsiveness of these autoreceptors was assessed by the ability of exogenously applied 5-HT to inhibit the potassium-evoked release of [3H]5-HT from slices of guinea pig cortex. Identical experiments were conducted at four different, equally spaced time points during the light:dark cycle of the guinea pig. The results presented here demonstrate that terminal 5-HT1D autoreceptors do not exhibit a circadian variation in their responsiveness. Therefore, terminal 5-HT1D autoreceptors bear similarity to terminal 5-HT1B autoreceptors identified in rat brain in being devoid of a significant rhythm in their responsiveness.

Animals↗
PubMed1994

Effect of polycations on permeability of glomerular epithelial cell monolayers to albumin.

Polycations can interact with the surface negative charges of the glomerular epithelial cells in the kidney and give rise to metabolic alterations. This study examined whether charge neutralization can affect intercellular junctions and increase macromolecular permeability across epithelial monolayers. We examined this question by studying the effect of polycations on the leakage of albumin across monolayers of glomerular epithelial cells. Cells were grown to confluency on filter-lined cups. They were treated apically with cationic bovine gamma globulin or protamine (100 micrograms/ml) for 2 hours at 37 degrees C. After washing the cells, the monolayers were tested for leakage of albumin by the addition of radioactive bovine serum albumin on the apical side and determining the time course of its appearance on the basal side. Polycation treatment caused significant leakage of albumin in the absence of any toxic effect on viability or lactate dehydrogenase release. The leakage was shown to be through the tight junctions of the monolayer. Permeability alterations were compared at 4 degrees C and 37 degrees C to determine whether impairment was due to the membrane ruffling effect of charge neutralization or due to intracellular metabolic changes. Despite equal bindings of polycations at 4 degrees C and 37 degrees C, significant leak occurred only at 37 degrees C, suggesting the role of active processes in the maintenance of permselectivity. This was consistent with the rapid interiorization of the polycation at 37 degrees C after membrane binding. Further substantiation of this point was obtained by studying the protective effect of removing bound polycation with heparin. Removal of polycation after initial binding failed to protect the monolayer from albumin leakage. The conclusion was that neutralization of glomerular epithelial cell surface charges results in subtle impairment of tight junction control of permeability to macromolecules across the monolayer. The impairment was due to active intracellular processes that ensue after polycation binding to cell surface charges and their subsequent internalization.

Animals↗
PubMed1994

Expression of pokeweed lectin binding in murine intestinal Paneth cells.

Pokeweed (Phytolacca americana) lectin was found to stain the secretory granules in epithelial Paneth cells of small intestine in mice and rats. The distribution of Paneth cells stained with this lectin was identical to that obtained by another immunohistochemical marker for lysozyme. However, in comparison with other immunohistochemical markers, Pokeweed lectin is a more robust method for identifying Paneth cells in histological sections and for studying their secretory granules. Co-expression of the Pokeweed lectin binding sites in some oligomucous cells within the crypts suggested a close developmental link between these two cell types. Only one other non-epithelial cell type was stained by this lectin, and these were migratory lymphocytes found within the villus epithelium and lamina propria. Approximately 20% of these lymphocyte cells were also positive for the expression of CD3+. Pokeweed lectin was therefore used to study changes in the frequency of Paneth cells and intra-epithelial lymphocytes in normal and immunologically compromised animals (following infection with a parasite worm Trichuris muris and in a model of graft-versus-host rejection). This study confirmed that the population of Paneth cells turns over slowly even during conditions of inflammation.

Animals↗
PubMed1994

Goldenhar's syndrome--a case report.

A case of Goldenhar's syndrome in a three months old male child with epibulbar dermoid (Fig. 1), accessory auricular appendages (Fig. 2), transverse facial cleft (Figs. 1 and 3), pedunculated mass on the left cheek (Figs. 2 and 3), asymmetry of skull (Fig. 4) and imperforate anus (already operated) is presented. Literature is reviewed briefly and aetiopathogenesis discussed in short.

Goldenhar Syndrome↗