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Biomedical subjects

C M Singh

Publications and source records attributed to C M Singh.

At least 19 recordsLinked to original sources
PubMed2000

Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila.

BACKGROUND: Drugs of abuse have a common property in mammals, which is their ability to facilitate the release of the neurotransmitter and neuromodulator dopamine in specific brain regions involved in reward and motivation. This increase in synaptic dopamine levels is believed to act as a positive reinforcer and to mediate some of the acute responses to drugs. The mechanisms by which dopamine regulates acute drug responses and addiction remain unknown. RESULTS: We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced negative geotaxis assay and a locomotor tracking system to measure the effect of psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through convergent pathways. In addition, we found that dopamine is involved in the acute locomotor-activating effect, but not the sedating effect, of ethanol. CONCLUSIONS: We show that in Drosophila, as in mammals, dopaminergic pathways play a role in modulating specific behavioral responses to cocaine, nicotine or ethanol. We therefore suggest that Drosophila can be used as a genetically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.

Animals↗
PubMed2000

Functional ethanol tolerance in Drosophila.

In humans, repeated alcohol consumption leads to the development of tolerance, manifested as a reduced physiological and behavioral response to a particular dose of alcohol. Here we show that adult Drosophila develop tolerance to the sedating and motor-impairing effects of ethanol with kinetics of acquisition and dissipation that mimic those seen in mammals. Importantly, this tolerance is not caused by changes in ethanol absorption or metabolism. Rather, the development of tolerance requires the functional and structural integrity of specific central brain regions. Mutants unable to synthesize the catecholamine octopamine are also impaired in their ability to develop tolerance. Taken together, these data show that Drosophila is a suitable model system in which to study the molecular and neuroanatomical bases of ethanol tolerance.

Animals↗
PubMed2000

Genetic control of acute ethanol-induced behaviors in Drosophila.

BACKGROUND: In most organisms in which acute ethanol exposure has been studied, it leads to similar changes in behavior. Generally, low ethanol doses activate the central nervous system, whereas high doses are sedative. Sensitivity to the acute intoxicating effects of ethanol is in part under genetic control in rodents and humans, and reduced sensitivity in humans predicts the development of alcoholism (Crabbe et al., 1994; Schuckit, 1994). We have established Drosophila melanogaster as a model organism to study the mechanisms that regulate acute sensitivity to ethanol. METHODS: We measured the effects of ethanol vapor on Drosophila locomotor behaviors by using three different assays. Horizontal locomotion was quantified in a locomotor chamber, turning behavior was assayed in narrow tubes, and ethanol-induced loss of postural control was measured in an inebriometer. Mutants with altered sensitivity to the acute effects of ethanol were generated by treatment with ethyl methane sulfonate and isolated by selection in the inebriometer. We ascertained the effects of these mutations on ethanol pharmacokinetics by measuring ethanol levels in extracts of flies at various times during and after ethanol exposure. RESULTS: Among nearly 30,000 potentially mutant flies tested, we isolated 19 mutant strains with reduced and 4 strains with increased sensitivity to the acute effects of ethanol as measured in the inebriometer. Of these mutants, four showed changes in ethanol absorption. Two mutants, named barfly and tipsy to reflect their reduced and increased ethanol sensitivity in the inebriometer, respectively, were analyzed for locomotor behaviors. Both mutants exhibited ethanol-induced hyperactivity that was indistinguishable from wild type. However, barfly and tipsy displayed reduced and increased sensitivity to the sedative effects of ethanol, respectively. Finally, both mutants showed an increased rate of ethanol-induced turning behavior. CONCLUSIONS: The effects of acute ethanol exposure on Drosophila locomotor behaviors are remarkably similar to those described for mammals. The analysis of mutants with altered sensitivity to ethanol revealed that the genetic pathways which regulate these responses are complex and that single genes can affect hyperactivity, turning, and sedation independently.

Absorption↗
PubMed1998

Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for regulation by the cAMP signaling pathway.

Upon exposure to ethanol, Drosophila display behaviors that are similar to ethanol intoxication in rodents and humans. Using an inebriometer to measure ethanol-induced loss of postural control, we identified cheapdate, a mutant with enhanced sensitivity to ethanol. Genetic and molecular analyses revealed that cheapdate is an allele of the memory mutant amnesiac. amnesiac has been postulated to encode a neuropeptide that activates the cAMP pathway. Consistent with this, we find that enhanced ethanol sensitivity of cheapdate can be reversed by treatment with agents that increase cAMP levels or PKA activity. Conversely, genetic or pharmacological reduction in PKA activity results in increased sensitivity to ethanol. Taken together, our results provide functional evidence for the involvement of the cAMP signal transduction pathway in the behavioral response to intoxicating levels of ethanol.

Adenylyl Cyclases↗
PubMed1995

Growth and differentiation in the Drosophila eye coordinated by hedgehog.

Differentiation of the Drosophila retina is asynchronous: it starts at the posterior margin of the eye imaginal disc and progresses anteriorly over two days. During this time the disc continues to grow, increasing in size by approximately eightfold. An indentation in the epithelium, the morphogenetic furrow, marks the front edge of the differentiation wave. Anterior progression of the furrow is thought to be driven by signals emanating from differentiating photoreceptor cells in the posterior eye disc. A good candidate for such a signal is the product of the hedgehog (hh) gene; it is expressed, and presumably secreted, by differentiating photoreceptors and its function is required for continued furrow movement. Here we show that ectopic expression of hedgehog sets in motion ectopic furrows in the anterior eye disc. In addition to changes in cell shape, these ectopic furrows are associated with a tightly orchestrated series of events, including proliferation, cell cycle synchronization and pattern formation, that parallel normal furrow progression. We propose that the morphogenetic furrow coincides with a transient boundary that coordinates growth and differentiation of the eye disc, and that hedgehog is necessary and sufficient to propagate this boundary across the epithelium.

Animals↗
PubMed1979

Typhoid perforation of the bowel. Experiences in 78 cases.

Seventy-eight patients ranging from four to 65 years of age were treated for typhoid perforation of the bowel. Sixty-one patients (78%) were males. The average time from perforation to admission was 56 hours. The mortality rate was 32% and was adversely influenced by the duration of illness, duration of perforation, shock, uremia, encephalopathy and fecal peritonitis. Forty-nine patients were treated by closure of the perforation, resection or miscellaneous procedures; the other 29 by closure of the perforation combined with an end-to-end ileotransverse colostomy. Although mortality was the same in both groups, those undergoing bypass had a significantly smoother postoperative course.

Adolescent↗
PubMed1979

Management of thoracic amebiasis.

The thoracic complications of amebiasis frequently necessitate surgical intervention. Experience with 28 patients is presented. Involvement included the pleura in 19 patients, the lungs in 10, and the pericardium in five. In 25%, more than one site was involved. Treatment consisted of measures designed to obliterate the pleural space or widely drain the pericardial sac, as indicated. Concurrent drainage of the associated amebic liver abscess was done in half the cases. The mortality rate was 36%, generally related to the poor general condition of the patients and their delay in seeking hospitalization.

Adolescent↗
PubMed1977

Cricotracheal disruption owing to strangulation. A report of two cases with successful surgical repair.

Two patients with cricotracheal disruption resulting from accidental strangulation of the neck were treated. The first patient had severe respiratory obstruction. In the second patient, a fascial tube maintained airway continuity between the separated larynx and trachea, and she had no difficulty breathing. A preoperative diagnosis of tracheal injury was based on the findings of respiratory obstruction, bloody secretions in the endotracheal tube, and subcutaneous emphysema in the neck. In both cases, an endotracheal tube was easily passed and entered the distal tracheal lumen. This relieved the respiratory obstruction in the first case and allowed administration of general anesthesia and control of ventilation during the operation. Prompt repair with cricotracheal anastomosis was followed by excellent results in both cases.

Accidents, Occupational↗
PubMed1976

Serum hormone levels in women undergoing abortion with intra-amniotic, extra-amniotic or intra-muscular administration of 15(S) 15-methyl-prostaglandin F2alpha.

The serum levels of estradiol-17beta, progesterone and HPL have been estimated by specific radioimmunoassay in thirty women undergoing abortion with 15-methyl-PGF2alpha given by intra-amniotic, extra-amniotic or intra-muscular route. A significant decline in the levels of these hormones was observed in 27 cases in which the pregnancy was terminated. However, in the remaining three cases, 15-methyl-PGF2alpha was found to be unsuccessful, and no significant change in the hormone levels was evident. The decline in these hormones was more marked by intra-muscular route, than that observed by the other routes. The pattern of estradiol-17beta decline was more consistent when compared with progesterone and HPL. The levels of progesterone and HPL, in a few cases, rather showed an increase in the initial hours of 15-methyl-PGF2alpha administration before the decline began and this pattern was more prominent on extra-amniotic administration. In general, the decline in the hormone levels was slower in cases which took longer time for abortion than cases with shorter induction-abortion time (IAT). The decline in estradiol-17beta levels was about 65% at six hour of intra-muscular administration of 15-methyl-PGF2alpha, whereas the corresponding fall with intra-amniotic and extra-amniotic routes was 29 and 22%, respectively. However, the net drop in its levels during IAT was not significantly different (range 70 to 80%) by the three routes. About 38% fall in progesterone levels was observed at six hour of intra-muscular administration whereas, by intra-amniotic the fall was 19%. The net decline in progesterone levels, during IAT, was in the range of 46 to 60% by the three routes. Similarly, intra-muscular 15-methyl-PGF2alpha evoked a sharper decline in HPL levels as compared with other routes. The total decline during IAT was 58 to 66%. The results, thus indicated that the abortion with 15-methyl-PGF2alpha was associated with a fall in the serum hormone levels, which could be resultant effect of alterations in the hormone production by the foeto-placental unit. This along with the uterine contractions may play a significant role in the abortifacient action of 15-methyl-PGF2alpha.

Abortion, Induced↗
PubMed1976

Arterial injuries of the extremities.

Fifty-eight patients with arterial injuries of the extremities were treated during the past 8 years. Fifty-one had acute injuries and seven had nonacute injuries. Blunt trauma or shotgun wounds caused 74% of the injuries, and 55% were associated with skeletal trauma. All the acute injuries endangered the limb; the average ischemic time was 8.5 hours. Brachial, popliteal, and superficial femoral arterial injuries were seen most frequently. Repair was accomplished with autogenous saphenous vein grafts in 47% and end-to-end anastomosis in 41%. Six patients died, four due to injuries of other organs. The most alarming complication of arterial repair was secondary hemorrhage which occurred in three patients and was caused by local infection. Six patients (13.3% required amputations; the highest number (three) after injuries of the popliteal artery. The injuries leading to amputations had associated prolonged ischemia, severity of injury, and associated venous, soft tissue, and skeletal injury. The nonacute injuries were in the form of false aneurysms, pulsating hematomas, AV fistula, and delayed bleeding. These were easily managed without any significant complication.

Adolescent↗
PubMed1975

End-to-side splenorenal shunt for treatment of portal hypertension.

Twenty-eight patients with portal hypertension were treated with splenectomy and end-to-side splenorenal shunt. Nineteen had cirrhosis and nine had portal vein thrombosis. Among the patients with cirrhosis, there was one hospital death due to recurrent bleeding in a patient in whom shunt could not be constructed and only splenectomy was done. During the follow-up period, one patient developed encephalopathy and later died of liver failure. There were three additional deaths, one due to an unrelated causes and two due to liver failure. All the remaining patients are well and none has had recurrent bleeding. All the patients with portal vein thrombosis survived the operation and are well. None has had recurrent bleeding. Encouraged by these results, we continue to use end-to-side splenorenal shunt in all patients except small children.

Adolescent↗