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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 217 records · Page 12Linked to original sources
PubMed1999

Morphine synergizes with lipopolysaccharide in a chronic endotoxemia model.

Emergent or elective surgical procedures may be complicated by sepsis, resulting in critical illness that can lead to organ failure and death. The opioid drug, morphine is widely used to alleviate pain in post-surgical patients; however, it is well documented that chronic treatment of mice with morphine affects the proliferation, differentiation and function of immune cells. Thus, morphine might be expected to exacerbate the effects of sepsis, which also compromises the immune system. To test this notion, we investigated the effect on several immune functions of a clinical dose of morphine (4 mg/kg) superimposed upon a lipopolysaccharide (LPS)-induced infection model. Our results show that this relatively low dose of morphine, though generally having no effects on immune parameters by itself, significantly augmented LPS responses. A clinical dose of morphine (4 mg/kg body weight) superimposed upon an animal model of sepsis resulted in a significant increase in mortality at 48 h. In the absence of the drug, most septic animals died after 96 h. Phenotypic responses such as, decreased thymic cellularity, compromised mitogenic response and inhibition of IL-2 synthesis that are evident at 48-72 h after LPS injection appear as early as 24 h in animals that receive morphine in addition to LPS. In addition, our results show that in T cells there is a shift from TH1 type cytokine elaboration to a TH2 type cytokine elaboration in animals that receive both LPS and morphine.

Animals↗
PubMed1999

A phosphorylation-induced major structural change in the N-terminal domain of the P protein of Chandipura virus.

It has previously been shown that phosphorylation of P protein of vesicular stomatitis virus as well as Chandipura (CHP) virus is required for transcription activation and replication switch. The structural nature of this crucial conformational change, however, is largely unknown. We have studied the phosphorylation-associated conformational change in the P protein of Chandipura (CHP) virus using chemical modification, fluorescence, and circular dichroism spectroscopy. Sulfhydryl groups of unphosphorylated CHP-P protein are unreactive to DTNB under nondenaturing conditions. Upon phosphorylation, one sulfhydryl group becomes reactive. We have identified this sulfhydryl group as cysteine 57. The two tryptophan residues (105 and 135) become significantly more buried in the phosphorylated protein. Circular dichroism spectra show significant enhancement in the far-UV region upon phosphorylation. Anisotropy decay of AEDANS-labeled C57 CHP-P protein shows rapid rotation of the probe, suggesting significant mobility of the N-terminal domain in the phosphorylated P protein. The results suggest a global conformational change in the N-terminal domain of the P protein is induced by phosphorylation and yet the phosphorylated N-terminal domain shows significant flexibility.

Anilino Naphthalenesulfonates↗
PubMed1999

Immunoprophylaxis and immunotherapy against experimental visceral leishmaniasis.

The ability of the Leishmanial parasite, UR6 (MHOM/IN/1978/UR6) to act as a immunoprophylactic and immunotherapeutic agent against experimental visceral leishmaniasis in a hamster model was tested. The Leishmanial parasite, UR6, lacked LPG but possessed abundant message for kinetoplastid membrane protein-11 (KMP-11), and failed to induce visceral infection when given through the intracardiac route, unlike the virulent Leishmania donovani, AG83 (MHOM/IN/1983/AG83), the causative agent of Kala-azar. Priming of macrophage with UR6 in vitro, induced superoxide (O2-) generation whereas a similar experiment with virulent AG83 inhibited O2- generation. This observation prompted us to test the efficacy of UR6 as a immunoprophylactic and immunotherapeutic agent. It was observed that priming of hamsters with either live or sonicated UR6 in the absence of any adjuvant provided strong protection against subsequent virulent challenge. The UR6 mediated protection was also observed in hamsters having established infection. Furthermore, UR6 primed infected hamsters displayed a greatly extended life span as compared to infected hamsters. To our knowledge, this is the first report concerning the use of an atypical Leishmanial parasite, UR6 in immunoprophylaxis and immunotherapy in the absence of any adjuvant.

Animals↗
PubMed1999

Mass spectral study of substituted allyl aryl and allyl alkyl selenides and some analogous sulfides

The electron impact (EI) mass spectra of allyl aryl selenides showed abundant molecular ions and many fragment ions containing the selenium atom. alpha-Cleavage is the dominant process in the fragmentation of selenides, and cleavage product ions are characteristic of the substituents. In the case of 3-methyl allyl and related aryl selenides, characteristic delta-hydrogen migration to the selenium atom is observed. A McLafferty-type rearrangement is found in benzyl allyl selenides and substituted alkyl allyl selenides. The charge on the rearrangement products preferably remains on the fragments containing the phenyl group. The [M - SeH](+), [M - CH(3)](+) and [M - C(2)H(4)](+) ions are found only in the EI mass spectrum of allyl phenyl selenide, and are attributed to a Claisen rearrangement in the source of the mass spectrometer. All structurally informative fragmentation processes are supported by collision induced dissociation spectra of molecular ions. The fragmentation patterns found in methane chemical ionization (CI) spectra of the selenides were significantly different from those observed in EI. The EI and CI mass spectra of analogous sulfides showed similar behaviour to that observed in the corresponding selenides. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗
PubMed1999

Muscle pattern diversification in Drosophila: the story of imaginal myogenesis.

There are two phases of somatic muscle formation in Drosophila. During embryonic development, one phase of myogenesis generates larval muscle elements that mediate the relatively simple behavioural repertoire of the larva. During pupal metamorphosis, a diverse pattern of muscle fibres are assembled, and these facilitate the more elaborate behavioural patterns of the adult fly. In this review, we discuss the current status of understanding of the cellular, genetic, and molecular mechanisms of pattern formation during the second phase, imaginal muscle development. We briefly compare aspects of embryonic and adult myogenesis in Drosophila and muscle development in vertebrates and highlight conserved themes and disparities between these diverse myogenic programmes.

Animals↗
PubMed1999

Inhibition of early DNA-damage and chromosomal aberrations by Trianthema portulacastruml. In carbon tetrachloride-induced mouse liver damage.

The underlying molecular mechanisms of the antihepatotoxic activity of Trianthema portulacastrum by monitoring its effect on mouse liver DNA-chain break, sugar-base damage and chromosomal aberrations, during chronic or acute treatment with carbon tetrachloride (CCl(4)) have been studied. Daily oral feeding with the ethanolic extract (150 mg/kg basal diet, per os) was given 2 weeks before CCl(4)treatment and continued until the end of the experiment (13 weeks). T. portulacastrum extract offer unique protection (P< 0.05-0. 001) against the induction of liver-specific structural-type chromosomal anomalies 15, 30 or 45 days after the last CCl(4)insult, compared to control mice. This was further evidenced by extract-mediated protection (15 days prior feeding following a single necrogenic dose of CCl(4)) of the generation of DNA chain-break and Fe-sugar-base damage assays. The observed hepatoprotective mechanism could be due to its ability to counteract oxidative injury to DNA in the liver of mouse.

Acute Disease↗
PubMed1999

Atorvastatin and simvastatin have distinct effects on hydroxy methylglutaryl-CoA reductase activity and mRNA abundance in the guinea pig.

The effects of atorvastatin and simvastatin on hydroxy methylglutaryl (HMG)-CoA reductase activity and mRNA abundance were studied in guinea pigs randomized to three groups: untreated animals and those treated with 20 mg/kg of atorvastatin or simvastatin. Guinea pigs were fasted for 0, 6, 12, or 18 h in an attempt to remove the drug from their systems. Reductase activity and mRNA levels were analyzed after each time point. Reductase inhibitor treatment resulted in 50-62% lower cholesterol concentrations compared to untreated guinea pigs (P < 0.0001), while plasma triacylglycerol (TAG) concentrations did not differ among groups. Plasma cholesterol and TAG were 50-70% lower after 18 h fasting in the three groups (P < 0.001). In the nonfasting state, simvastatin and atorvastatin treatment did not affect HMG-CoA reductase activity compared with untreated animals. However, after 6 h of fasting, simvastatin-treated guinea pigs had higher HMG-CoA reductase activity than untreated animals (P < 0.01), suggesting that the drug had been removed from the enzyme. In contrast, atorvastatin-treated guinea pigs maintained low enzyme activity even after 18 h of fasting. Further, HMG-CoA reductase mRNA abundance was increased by sevenfold after atorvastatin treatment and by twofold after simvastatin treatment (P < 0.01). These results suggest that simvastatin and atorvastatin have different half-lives, which may affect HMG-CoA reductase mRNA levels. The increase in reductase activity by simvastatin during fasting could be related to an effect of this statin in stabilizing the enzyme. In contrast, atorvastatin, possibly due to its longer half-life, prolonged inhibition of HMG-CoA reductase activity and resulted in a greater increase in mRNA synthesis.

Animals↗
PubMed1999

Effects of smoking on prostacyclin formation and platelet aggregation in users of oral contraceptives.

OBJECTIVE: The aim of this review was to determine which subgroups within the population of smokers and oral contraceptive users are at especially elevated risk for thromboembolic events. STUDY DESIGN: This review covers 10 articles published between 1981 and 1996 that examined the effects of smoking and oral contraceptive use, in conjunction or independently, on factors affecting the coagulation pathway, particularly the expressions of prostacyclin and thromboxane. RESULTS: Heavy, prolonged, or current nicotine use was associated with a reduction in the urinary metabolite of prostacyclin (prostaglandin I2) in oral contraceptive users. Smoking and increased excretion of thromboxane were also linked, and in 1 study the effect was dose related. These changes were associated with increased platelet aggregation. Oral contraceptive use and concurrent smoking increased the risk of acute myocardial infarction by a ratio of 10.1. Although most of this risk was seen among smokers who used second-generation oral contraceptives (odds ratio 11.1), with a much reduced odds ratio for smokers who used third-generation oral contraceptives (odds ratio 3.1), the study was not controlled for estrogen dose. A reduction in myocardial infarction risk compared with that in the 1970s was seen for all oral contraceptive users, probably because of the reduced hormonal doses in current preparations. CONCLUSION: Smoking, not oral contraceptive use, constitutes the greater cardiovascular risk. However, cigarette smoking and oral contraceptive use act synergistically to increase the risk of thromboembolic events. Differences in oral contraceptive formulations may mitigate the increased risk resulting from concurrent smoking and use of oral contraceptives, but whether the progestin component or the lowered estrogen dose is responsible is unclear.

Cardiovascular Diseases↗
PubMed1999

Flow cytometric determination of cellular thiols.

Several biochemical techniques are based on chromatography or electrophoresis for the determination of thiols from biological samples. These techniques are indispensable for the accurate and sensitive detection of specific thiols. Flow cytometric determination of cellular thiols is a powerful technique that is perhaps best suited for clinical application, particularly for cells in blood or other body fluids. Information can be obtained from a small sample amount with a relatively little and quick sample treatment. This technique offers an unique advantage to study the thiol status of a subset of cells because data are collected from individual cells. Multiparameter flow cytometry allows the study of different subsets of immunotyped cells. A major drawback of the flow cytometric method is the lack of specificity for the determination of distinct thiols. The reaction between MBB and thiols is not specific for any particular intracellular thiol, although almost all of the entire thiol-reacted bimane emission is specific for thiols in general. This limitation can be partly overcome by the treatment of cells with known thiol regulatory agents as described in the section on the differential assessment of cellular thiols.

Bridged Bicyclo Compounds↗
PubMed1999

Incidence of abnormal laryngeal findings in asymptomatic singing students.

OBJECTIVE: Abnormalities in the mucosal lining of the vocal folds may interfere with the normal vibratory patterns and result in vocal limitations, especially for singers whose demands are great. A prospective, longitudinal study was undertaken to investigate the incidence of laryngeal abnormalities in asymptomatic singing students. METHODS: Sixty-five singing students at the school of music underwent videostroboscopic evaluation and completed a comprehensive questionnaire. Videos were rated by 3 experienced clinicians, and interrater reliability was calculated. Results were correlated with demographic factors, background medical history, and singing history. RESULTS: Five students (8.3%) exhibited early signs of benign vocal fold lesions (2 with nodules and 3 with cysts). A high incidence of posterior erythema (n = 44; 73.4%), suggesting possible reflux, was found. CONCLUSIONS: A surprisingly high number of otherwise asymptomatic singing students demonstrated abnormal laryngeal findings. Their relationship with vocal performance will be addressed as well as implications for preventative measures.

Adolescent↗
PubMed1999

Ultrasound-assisted ankle arthrocentesis.

Difficulty is frequently encountered in performing ankle arthrocentesis. This report describes an ultrasound-assisted technique that can be readily learned by emergency physicians. It involves using the ultrasound beam to accurately locate the tibiotalar joint, thereby increasing the probability of obtaining joint fluid on aspiration.

Adult↗
PubMed1999

Neuroprotective effects of alpha-lipoic acid and its positively charged amide analogue.

Elevated levels of extracellular glutamate have been linked to reactive oxygen species mediated neuronal damage and brain disorders. Lipoic acid is a potent antioxidant that has previously been shown to exhibit neuroprotection in clinical studies. A new positively charged water soluble lipoic acid amide analog, 2-(N,N-dimethylamine) ethylamido lipoate HCl (LA-plus), with a better cellular reduction and retention of the reduced form was developed. This novel antioxidant was tested for protection against glutamate induced cytotoxicity in a HT4 neuronal cell line. Glutamate treatment for 12 h resulted in significant release of LDH from cells to the medium suggesting cytotoxicity. Measurement of intracellular peroxides showed marked (up to 200%) increase after 6 h of glutamate treatment. Compared to lipoic acid, LA-plus was more effective in (1) protecting cells against glutamate induced cytotoxicity, (2) preventing glutamate induced loss of intracellular GSH, and (3) disallowing increase of intracellular peroxide level following the glutamate challenge. The protective effect of LA-plus was found to be independent of its stereochemistry. The protective function of this antioxidant was synergistically enhanced by selenium. These results demonstrate that LA-plus is a potent protector of neuronal cells against glutamate-induced cytotoxicity and associated oxidative stress.

Animals↗