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Biomedical subjects

M Singh

Publications and source records attributed to M Singh.

At least 163 records · Page 9Linked to original sources
PubMed2001

Role of vagal afferents in the reflex effects of capsaicin and lobeline in monkeys.

Reflex effects of pulmonary C-fiber receptor stimulation by right atrial injections of capsaicin and lobeline were investigated in conscious monkeys (n=17). Capsaicin injection (15.0+/-1.4 microg/kg) produced apnea mostly (n=15, latency-1.7+/-0.2 s) and bradycardia, which were abolished by vagotomy (n=4). Lobeline administration (142+/-6 microg/kg) produced either apnea (n=7, latency -2.0+/-0.3 s) or excitation of breathing (n=8, latency -3.5+/-0.3 s) and no change in heart rate. After vagotomy (n=4), the apneic response was abolished, but the respiratory excitation persisted. Neither capsaicin nor lobeline produced cough. In the anesthetized monkey also (n=7), lobeline injection (50-150 microg/kg) did not produce any cardiovascular response. However, it produced excitation of breathing, which persisted after vagotomy but was abolished by carotid sinus denervation. It is concluded that in the non-human primate, it is capsaicin that produces reflexes typical of pulmonary C-fiber receptor stimulation, and cough is not a part of this reflex.

Afferent Pathways↗
PubMed2001

Does the presence of thrombus seen on a coronary angiogram affect the outcome after percutaneous coronary angioplasty? An Angiographic Trials Pool data experience.

OBJECTIVES: This study aimed to determine whether pre-existing angiographic thrombus was associated with adverse in-hospital and six-month outcomes after percutaneous coronary interventions. BACKGROUND: There are conflicting data about whether pre-existing thrombus is an independent predictor of adverse in-hospital and short-term outcome after coronary interventions. METHODS: The Angiographic Trials Pool, a data set derived from eight prospective randomized trials, was analyzed. The study population consisted of 7,917 patients who underwent coronary interventions between 1986 and 1995. Two trials were excluded because they did not collect information regarding thrombus. Patients from the other six trials were divided on the basis of the presence or absence of thrombus. RESULTS: In patients with (n = 2,752) and without (5,165) thrombus, in-hospital mortality following angioplasty was low (0.8 vs. 0.6%, p = 0.207). Several adverse outcomes were higher in patients with thrombus: death/myocardial infarction (8.4 vs. 5.5%, p < or = 0.001), in-hospital abrupt closure (5.9 vs. 3.9%, p < or = 0.001) and an in-hospital composite of death, myocardial infarction and/or repeat revascularization (15.4 vs. 11.2%, p < or = 0.001). Six-month mortality was low and comparable between the two groups (2.1 vs. 1.8%, p = 0.34), but the incidence of six-month death/myocardial infarction was higher in patients with thrombus (11.7 vs. 8.7%, p < or = 0.0001). CONCLUSIONS: Percutaneous coronary angioplasty can be performed with low mortality in patients with pre-existing thrombus, although these patients are at higher risk of in-hospital and six-month death/myocardial infarction. Continued efforts are required to optimize the outcome in these high risk patients.

Aged↗
PubMed2001

Antithrombotic and thrombolytic therapy for ischemic stroke.

Antithrombotic and thrombolytic agents form the cornerstone of stroke prevention and treatment. Large, randomized trials have also highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Aspirin is the antiplatelet treatment standard against which several other antiplatelet agents (ticlopidine, clopidogrel, aspirin-dipyridamole) have been shown to be more effective. The prevention of cardioembolic stroke is best accomplished with oral anticoagulation, barring any contraindications. The thrombolytic agent, rt-PA, improves outcome in ischemic stroke patients treated within 3 hours of onset. The risk-benefit ratio is narrow because of an increased risk for bleeding but studies do not support a higher risk in the geriatric population.

Acute Disease↗
PubMed2001

Evaluation of skin sensitization potential of melatonin and nimesulide by murine local lymph node assay.

Melatonin is a good candidate for transdermal delivery considering its short plasma half life, low molecular weight and a favorable octanol:water partition coefficient. Nimesulide is a nonsteroidal anti-inflammatory agent used orally and rectally for inflammatory disorders. The objective of this study was to investigate the skin sensitization potential of melatonin and nimesulide using the standard murine local lymph node assay (LLNA). Melatonin (0.5, 2.5, 5.0 and 10.0%, w/v) and nimesulide (0.5, 2.5, 5.0 and 10.0%, w/v) dissolved in acetone:olive oil (4:1, AOO) was applied (25 microl) on the dorsal surface of each ear of female CBA/Ca mice for three consecutive days. On the sixth day, [3H]methyl thymidine was administered intravenously and the uptake of [3H]methyl thymidine (dpm) by the draining lymph nodes was determined by established methods. Dinitrochlorobenzene (DNCB, 0.25%, w/v) and para-aminobenzoic acid (PABA, 2.5%, w/v) were used as positive and negative control, respectively. The mean dpm obtained with melatonin and nimesulide treatment at all concentrations were not significantly different (P>0.05) from that of AOO. The stimulation index (SI) values of melatonin and nimesulide at different concentrations were close to 1. The results of the present study using the standard LLNA approved by US Interagency Coordinating Committee in the Validation of Alternative Methods (ICCVAM) indicate that melatonin and nimesulide are not skin sensitizers. However, since LLNA has shown false negatives with many drugs, clinical trials are certainly needed to exclude the possibility of a weak or delayed type skin sensitization reaction. Further studies using modified LLNA procedures (extended exposure, alternative vehicle systems, pre-abrasion, etc.) may be useful in identifying the weak or delayed type skin sensitization reactions.

Animals↗
PubMed2001

Stealth monensin immunoliposomes as potentiator of immunotoxins in vitro.

Stealth monensin liposomes (SML) were prepared using dipalmitoyl phosphatidylcholine, cholesterol, distearoyl glycerophosphoethanolamine coupled to polyethylene glycol, stearylamine, and N-succinimidyl pyridodithiopropionate linked to stearyl amine, in the molar ratio of 10:5:1.4:1.4:1.5. SML was conjugated to the anti-MY9 antibody by a disulfide linkage to form stealth monensin immunoliposomes (SMIL) by an already established procedure. The encapsulation concentrations of monensin in SML and SMIL were 10(-7) and 4.9x10(-8) M, respectively. More than 20% of monensin remained in circulation after 24 h in BALB/c mice. The ability of SML and SMIL to potentiate the effect of anti-MY9 immunotoxin (anti-MY9-IT) was tested against human leukemia HL-60 sensitive and resistant tumor cells in vitro. SML and SMIL potentiated the activity of anti-MY9-IT by 10-20 times against HL-60 sensitive tumor cell lines. However, greater potentiation of anti-MY9-IT was observed in combination with SML and SMIL against HL-60 resistant tumor cells, found to be 200 and 500 times, respectively. The potentiation of anti-MY9-IT by SMIL was more than two-fold compared with SML against both HL-60 sensitive and resistant tumor cells. Transmission electron microscopy studies conducted with HL-60 resistant cells incubated with anti-MY9-IT and monensin liposomes showed significant dilation of the golgi, which was reversible after re-incubation in fresh medium. Our studies show that SML and SMIL can be successfully used to potentiate the activity of ricin based anti-MY9-IT in vitro, and further in vivo studies will demonstrate the usefulness of this approach.

Animals↗
PubMed2001

Crop residue addition effects on myriad forms and sorption of phosphorus in a Vertisol.

Crop residues are a vital organic resource and their extensive use in soil management for sustainable agriculture is widely advocated. The effects of soybean residue (SR) and wheat residue (WR) applied alone or in combination with fertilizer P (FP) on dynamics of labile P, distribution of P fractions and P sorption in a Vertisol (Typic Haplustert) were assessed in a 16 week long incubation study. The amount of P added through crop residues, FP or their combination was kept constant at 10 mg P kg(-1) soil. Addition of SR or WR resulted in net increase of labile inorganic (Pi) and organic (Po) P, and microbial P throughout the incubation period, except that the WR decreased labile Pi during the first two weeks due to Pi immobilization. Integration of FP with SR had no added benefit compared to SR alone, while use of FP + WR proved better in ensuring short-term P availability by offsetting initial P immobilization associated with WR alone. Sequential fractionation of soil P at the end of 16 weeks showed that addition of SR and WR alone or in combination with FP favoured a build-up in labile Pi and Po (NaHCO3-Pi and Po), and moderately labile Po (NaOH-Po) fractions at the expense of recalcitrant P (HCl-P). The P sorption capacity of soil and P required to maintain optimum solution P concentration of 0.2 mg P 1(-1) also decreased with addition of these crop residues. The implication of the results of this study is that soybean and wheat residues can potentially improve soil P fertility by increasing labile Pi and Po, and moderately labile Po fractions, decreasing P sorption and concomitantly causing dissolution of recalcitrant P in soil.

Crops, Agricultural↗
PubMed2001

Microwave assisted solid support synthesis of novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines as potent antimicrobial agents.

An environmentally benign and economic synthesis of 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines is described from readily accessible substituted 2-mercapto-1-amino triazoles and substituted chalcones on basic alumina that are accelerated by exposure to microwaves. The reaction time has been brought down from hours to seconds with improved yield as compared to conventional heating. The method reported herein is devoid of the hazards of solution phase reactions. All the synthesised compounds were tested for their in vitro antibacterial and antifungal activity. Some compounds showed significant antimicrobial properties. The best activity was observed with compounds 3a, 3c, 4a and 4d.

Anti-Bacterial Agents↗
PubMed2001

CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines.

The 70 kDa mycobacterial heat shock protein (Mtb HSP70) stimulates mononuclear cells to release CC-chemokines. We now show that this function of Mtb HSP70, but not human HSP70, is dependent on the cell surface expression of CD40. Deletion of the CD40 cytoplasmic tail abolished, and CD40 antibody inhibited, Mtb HSP70 stimulation of CC-chemokine release. Mtb HSP70 stimulated THP1, KG1 cells, and monocyte-derived dendritic cells to produce RANTES. Specific binding of CD40-transfected HEK 293 cells to Mtb HSP70 was demonstrated by surface plasmon resonance. Coimmunoprecipitation of Mtb HSP70 with CD40 indicates a physical association between these molecules. The results suggest that CD40 is critical in microbial HSP70 binding and stimulation of RANTES production.

Bacterial Proteins↗
PubMed2001

Programmed cell death in a human intestinal parasite, Blastocystis hominis.

Although programmed cell death (PCD) has been associated with multicellular organisms, there have been more reports of its presence in some protozoans. Our study shows the existence of PCD in an intestinal protozoan, Blastocystis hominis. Light and electron microscopy, biochemical and flow cytometry studies showed apoptosis-like death in B. hominis cells exposed to a cytotoxic monoclonal antibody (MAb 1D5). B. hominis cells displayed key morphological and biochemical features of apoptosis, namely, nuclear condensation and in situ fragmentation, reduced cytoplasmic volume, some externalization of phosphatidylserine and maintenance of plasma membrane integrity. No oligonucleosomal DNA laddering was observed in gel electrophoresis. This study supports earlier observations that the cellular machinery that is required to carry out PCD may have existed before the advent of multicellularity. Our study also ascribes a novel function for the B. hominis central vacuole in apoptosis; it acts as a repository where apoptotic bodies are stored before being released into the extracellular space.

Animals↗
PubMed2001

Protein kinase C activation and cardioprotective effect of preconditioning with oxidative stress in isolated rat heart.

The present study is designed to investigate the effect of myocardial preconditioning with oxidative stress induced by pyrogallol or H2O2, on ischaemia-reperfusion induced myocardial injury. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of preconditioning induced by pyrogallol or hydrogen peroxide (H2O) or ischaemia markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. Administration of polymyxin B, a protein kinase C (PKC) inhibitor, during pyrogallol, H2O2 or ischaemic preconditioning markedly attenuated the cardioprotective effect of preconditioning produced with oxidative stress or ischaemia. These results suggest that preconditioning with oxidative stress may provide cardioprotection similar to ischaemic preconditioning, against ischaemia-reperfusion injury and this cardioprotective effect may be mediated through activation of PKC.

Animals↗
PubMed2001

Amino acid composition and biological evaluation of the protein quality of high lysine barley genotypes.

The protein quality of high lysine barley genotypes Notch1 Notch2, Riso-1508 and Hiproly grown in Indian soil was evaluated by determining amino acid composition and also by rat growth and nitrogen balance studies. Protein and fat contents were found to be highest in Riso-1508. Lysine concentration (5.26 g/16g N) of Riso-1508 was also highest compared to the other high lysine genotypes. Rat feeding trials indicated that the growth promoting qualities of the proteins of genotype Riso-1508 were significantly (p < 0.05) higher than the low lysine barley genotype. The comparatively low lysine barley diet had more digestible protein than the high lysine barley diet. However, the BV and NPU of the high lysine barley were significantly (p < 0.05) higher. This improvement is of importance in meeting the essential amino acid requirements of man as well as other monogastric animals. The study showed that the high lysine barley harvested in Indian agroclimatic conditions retained high lysine quality.

Amino Acids↗
PubMed2001

Predicting anti-HIV activity: computational approach using a novel topological descriptor.

The discriminating power of a novel topological descriptor termed as eccentric adjacency index in the estimation of anti-HIV activity, for a data set of 107 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives was investigated in the present study. The value of eccentric adjacency index of each derivative was computed and active range was identified using moving average analysis. Subsequently, each derivative was assigned a biological activity which was then compared with the reported anti-HIV activity. The accuracy of prediction was found to be more than ninety percent in the active range using eccentric adjacency index. The proposed index offers a vast potential for structure-activity/property studies.

Anti-HIV Agents↗
PubMed2001

Superovulation and intrauterine insemination in cases of treated mild pelvic disease.

PURPOSE: Our purpose was to examine the effect of treated mild pelvic disease on the outcome of superovulation with intrauterine insemination (SO/IUI). METHODS: Three hundred cycles of SO/IUI were retrospectively reviewed for 118 women with laparoscopically treated minimal/mild endometriosis and 67 cycles for 28 women with minimal/mild distal tubal disease/adnexal adhesions and compared with 265 cycles in 111 couples with idiopathic infertility. RESULTS: The monthly fecundity rate (MFR) of 6.8% and live birth rate (LBR) of 6% in the endometriosis group were significantly lower (P = 0.002) than those in the idiopathic infertility group (MFR = 13.5%, LBR = 12.1%). The 10.9% MFR and 7.5% LBR in the minimal/mild tubal/adnexal disease were not significantly different from those in the other two groups. CONCLUSIONS: MFR and LBR were higher after SO/IUI in idiopathic infertility compared to those for treated mild/minimal endometriosis or mild/minimal tubal/adnexal adhesions. However, SO/IUI still remains a reasonable option for both these groups prior to IVF-ET.

Adnexal Diseases↗
PubMed2001

L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated pregnant rat uterine strips in vitro.

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.

Animals↗