Biomedical subjects

M Mishra

Publications and source records attributed to M Mishra.

At least 19 recordsLinked to original sources

PubMed2003

Single-dose liposomal amphotericin B in the treatment of visceral leishmaniasis in India: a multicenter study.

Widespread antimony resistance renders conventional amphotericin B the only option for the treatment of visceral leishmaniasis (VL) in North Bihar, India. Because of its excellent safety profile, a large dose (7.5 mg/kg) of liposomal amphotericin B (L-AmB) was given to each of 203 patients with VL at 4 treatment centers, and the patients were discharged the next day. At initial clinical and parasitological follow-up, performed on day 30 after treatment, evidence of a cure was seen in 195 (96%) of 203 patients (95% CI, 92-98); 4 patients experienced treatment failure. Two patients were lost to follow-up, 2 died (one due to progressive disease and another, 5 months after treatment, due to an unrelated illness), and 12 experienced relapses during follow-up. Thus, 183 patients (90%; 95% CI, 85-94) had obtained final cure 6 months after treatment. Very few adverse events (fever with rigor, in 9.8% of patients) were seen. Single-dose L-AmB (7.5 mg/kg) treatment is safe and effective, and it may be used for the mass treatment of VL in India.

Adolescent↗

PubMed2003

Lead acetate induced cytotoxicity in male germinal cells of Swiss mice.

Single intraperitoneal injection of lead acetate (200 mg/kg b.w) to Swiss mice stimulated testicular weight loss with a constant increase in the incidence of abnormal sperm population and decrease in the total sperm count. Testicular ascorbic acid also declined significantly during the post-treatment phase with significant rise in Lipid Peroxidation Potential (LPP) of the tissue. Elevated LPP is indicative of oxidative stress in treated mice testes. The possible role of lead-induced oxidative stress in culminating increased sperm abnormality and decreased sperm count have been discussed. Further, possible antioxidative role of testicular ascorbic acid in minimizing oxidative stress in lead-treated mice has been demonstrated.

Animals↗

PubMed2002

Phylogenetic relationships and genetic polymorphisms in wild Indian mice.

Randomly amplified polymorphic DNA (RAPD) analysis was used to examine the extent of variability in 11 Indian wild derived commensal house mice (Mus musculus) populations and compared with inbred strains of musculus and domesticus subspecies as well as commonly used laboratory inbred strains C57BL/6J and DBA/2J. Arbitrary designed 10 mer oligonucleotide primers with 60-70% (G+C) content were used to amplify DNA template. Out of 52 primers screened initially on the laboratory strains, 20 were selected for analysis on the basis of amplification product in the size range of 200-1400 bp. Among 353 total polymorphic bands, 220 bands (64%) were found to be polymorphic in Indian wild mice, 85 bands (25%) in wild derived inbred strains and 37 bands (11%) in laboratory mice strains. The amplification patterns produced by primers were statistically analysed by Jaccard's similarity coefficient the value of which ranged from 0.56 to 0.80. High level of genetic diversity was seen in the Indian wild mice populations as compared to the controls. The UPGMA phenogram grouped mice population into two major clusters except Bikaner [BIK], Bilaspur [BIL] and Ranikhet [RK] populations which were placed outside the close-knit clusters. Inspite of low values of bootstrap estimates obtained by Wagner and Dollo parsimony analysis, the results were comparable with UPGMA phenogram when constitution of the populations in the major cluster was considered. Indian mice populations appeared to be diverse from laboratory inbred mice strains.

Animals↗

PubMed2002

Low-dose liposomal amphotericin B in refractory Indian visceral leishmaniasis: a multicenter study.

In this randomized, double-blind, dose-ranging, multicenter trial, 84 patients with visceral leishmaniasis refractory to antimony therapy were administered liposomal amphotericin B (AmBisome) at cumulative doses of 3.75, 7.5, and 15.0 mg/kg for 5 consecutive days. Posttreatment apparent cure and definite cure were assessed at 2 weeks and 6 months after the end of therapy, respectively. Mild to moderate infusion-related fever and rigors were seen in 29 and 44% of patients, respectively. One patient each in the 3.75- and 7.5-mg groups had detectable parasites on splenic smear at posttreatment evaluation. At 6 months' follow-up, however, 2, 1, and 1 patients relapsed in the 3.75-, 7.5-, and 15.0-mg groups, resulting in definite cure rates of 89, 93, and 97%, respectively. There was no significant difference in the cure rates of the 3 groups. Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar.

Adolescent↗

PubMed2001

Enhanced activity of antisense phosphorothioate oligos against leishmania amastigotes: augmented uptake of oligo, ribonuclease H activation, and efficient target intervention under altered growth conditions.

Leishmania, a parasitic protozoan, infects human macrophages, often causing severe morbidity and mortality. The pathogenic form of this parasite, the amastigote, lives inside the acidic phagolysosomes of infected macrophages. In our attempt to develop anti-miniexon phosphorothioate oligodeoxyribonucleotides (S-oligos) as an alternative chemotherapy against Leishmania, we found that intracellular as well as 'axenic' amastigotes were more susceptible to these S-oligos than were the cultured promastigotes. Lower pH (4.5) and elevated temperature (35 degrees) of the medium were among the direct enhancing factors for killing. Addition of the cationic polypeptide poly-l-lysine (PLL) to the growth medium further enhanced the killing effect of the S-oligo at pH 4.5. The enhancement of specific ablation of mRNA expression was directly correlated to the increased leishmanicidal activity of the S-oligo. This was shown by the increased inhibition of luciferase activity expressed in transgenic Leishmania amazonensis promastigotes by anti-miniexon S-oligo or anti-luciferase S-oligo at acidic pHs and in the presence of PLL. The leishmanicidal effects of S-oligos at acidic pH and in the presence of PLL were related to increased uptake of the S-oligos under these conditions. The rate of S-oligo uptake was enhanced up to 15-fold at pH 4.5. The addition of PLL to the assay medium at acidic pH further enhanced the uptake of S-oligo up to 80-fold. RNase H is known to accentuate the antisense action of S-oligos. We found that at an elevated temperature RNase H activity in Leishmania cell extracts increased about 5-fold. Thus, enhanced uptake of S-oligos at the acidic pH of macrophage phagolysosomes and activation of RNase H may explain the efficient killing of the parasite in macrophages, both in tissue culture and in the animal model, by antisense miniexon oligonucleotide/PLL, when targeted directly to the parasite-containing phagolysosomes.

Animals↗

PubMed2001

Increased efficacy of antileishmanial antisense phosphorothioate oligonucleotides in Leishmania amazonensis overexpressing ribonuclease H.

Ribonuclease H (RNase H), an enzyme that cleaves an RNA sequence base-paired with a complementary DNA sequence, is proposed to be the mediator of antisense phosphorothioate oligonucleotide (S-oligo) lethality in a cell. To understand the role of RNase H in the killing of the parasitic protozoan Leishmania by antisense S-oligos, we expressed an episomal copy of the Trypanosoma brucei RNase H1 gene inside L. amazonensis promastigotes and amastigotes that constitutively express firefly luciferase. Our hypothesis was that S-oligo-directed degradation of target mRNA is facilitated in a cell that has higher RNase H activity. Increased inhibition of luciferase mRNA expression by anti-luciferase S-oligo and by anti-miniexon S-oligo in these stably transfected promastigotes overexpressing RNase H1 was correlated to the higher activity of RNase H in these cells. The efficiency of killing of the RNase H overexpressing amastigotes inside L. amazonensis-infected macrophages by anti-miniexon S-oligo was higher than in the control cells. Thus, RNase H appears to play an important role in the antisense S-oligo-mediated killing of Leishmania. Chemical modification of S-oligos that stimulate RNase H and/or co-treatment of cells with an activator of RNase H may be useful for developing an antisense approach against leishmaniasis. The transgenic Leishmania cells overexpressing RNase H should be a good model system for the antisense-mediated gene expression ablation studies in these parasites.

Animals↗

PubMed2001

Expression of cGMP-dependent protein kinase in human atrium.

We have shown that cGMP-dependent protein kinase (PKG) mediates stimulation of L-type calcium current by cGMP in rabbit atrial myocytes. The human atrium may have similar PKG-dependent regulation of calcium current. To elucidate the significance of PKG in cardiac function, we have isolated human PKG type I alpha cDNA (+1 to 2016), determined the nucleotide sequence and analyzed specific expression of PKG in human atrium. We obtained full-length cDNA of PKG type I alpha from human atrial RNA using reverse transcriptase-polymerase chain reaction (RT-PCR). The coding region of human cardiac PKG I alpha showed 99.9% homology to previously published human PKG I alpha except for base No. 1983. At this position G was substituted for T and this resulted in an amino acid substitution from Leu649 to Phe649. The cloned PKG I alpha cDNA was expressed in COS cells and the expressed PKG showed cGMP-stimulated PKG enzyme activity and immunoreactivity. Ribonuclease protection assay, Western blot analysis, and PKG enzyme activity assays in homogenates from human atrial tissue demonstrated the presence of PKG mRNA and protein in human atrial tissue. Immunofluorescence staining confirmed that PKG is highly expressed in human atrial myocytes. These findings suggest that PKG is highly expressed in human atrium and that PKG-dependent phosphorylation may be important in regulation of calcium channel activity in human atrial myocytes.

Adult↗

PubMed2001

Further reduction in stroke after off-pump coronary artery bypass grafting: a 10-year experience.

BACKGROUND: Perioperative stroke is a devastating complication after coronary artery bypass grafting (CABG). The reported incidence of neurologic complications after conventional CABG is 3% to 7%. With improved monitoring and surgical techniques, we have been able to achieve a drastic reduction in the stroke rate in our institution. This study evaluates the incidence of neurologic sequelae in patients who underwent off-pump CABG. METHODS: Over a 10-year period from January 1990 to September 2000, off-pump coronary artery bypass (OPCAB) operation was performed on 2,800 patients of the 18,037 patients undergoing CABG during that time frame at the Escorts Heart Institute and Research Centre. Initially, OPCAB was performed selectively in the high-risk group of patients (atheromatous aorta, renal impairment, chronic obstructive pulmonary disease, octogenarians, etc). Lately we performed multivessel OPCABs electively in about 60% to 65% of the patients undergoing CABG. Results. Mean age of the patients was 58.0 +/- 9.91 years (range 27 to 85 years) and mean number of grafts was 2.9 per patient. Neurologic complications (stroke/transient ischemic attack) occurred in 0.14% of patients. Overall hospital mortality in OPCAB patients was 2.14%, whereas mortality from neurologic complications was 0.07%. Predicted mortality (National Society of Thoracic Surgeons Cardiac Surgery Database Risk Model for CABG) for the entire patient group was 3.86% (p < 0.001). Conclusions. Although current techniques of monitoring and surgical procedures have significantly reduced the risk of stroke from CABG, our data strongly support OPCAB as a technique to further reduce stroke after CABG, especially in the high-risk group of patients.

Adult↗

PubMed2000

Pyronaridine: an effective antimalarial against multidrug-resistant malaria.

Pyronaridine, administered intramuscularly (im) to Swiss mice infected with the lethal multidrug-resistant Plasmodium yoelii nigeriensis, was found to exert high blood schizontocidal activity. The efficacy of doses of pyronaridine ranging from 0.625 to 30 mg (base/kg) was evaluated using a 4 day treatment schedule (drug was administered at 0, 24, 48 and 72 hrs). It was found that doses of 2.5mg/ kg and higher protected animals completely from the lethal effects of the parasite. The same degree of protection was found when the treatment duration was reduced to 3 days. This study shows that pyronaridine is a potentially useful antimalarial drug that could be exploited for the control of multidrug-resistant malaria infection.

Animals↗

PubMed2000

Plasmodium yoelii nigeriensis (MDR)-efficacy of oral pyronaridine against multidrug-resistant malaria in Swiss mice.

A multidrug-resistant strain of Plasmodium yoelii nigeriensis (MDR) showing a wide spectrum of resistance to chloroquine, amodiaquine, mepacrine, mefloquine, halofantrine, quinine, and quinidine was used in this study for in vivo evaluation of the blood schizontocidal activity of pyronaridine, a topoisomerase II inhibitor, in Swiss mice. The parasite produces 100% lethal infection in mice. The drug was administered orally once a day from day 0 onward. The initial studies showed that low doses of pyronaridine (0.625 to 5.0 mg base/kg x9 days) did not completely control blood-induced P. yoelii nigeriensis infection. Finally a series of doses of pyronaridine ranging from 1.25 to 30.0 mg/kg administered orally for 7 consecutive days were evaluated and in spite of high level of resistance to standard antimalarials, the parasite P. yoelii nigeriensis has shown complete susceptibility to pyronaridine (15 mg/kg dose x7 days). The present paper also compares the merits of a single MDR strain vs a battery of different resistant lines for quick antimalarials screening.

Animals↗

PubMed2000

Surgical strategies in patients at high risk for stroke undergoing coronary artery bypass grafting.

BACKGROUND: Perioperative stroke represents one of the major complications following coronary artery bypass grafting (CABG). The present study was designed to evaluate the use of an individualized surgical approach for reducing neurological injury in patients undergoing CABG at high risk of stroke from aortic atherosclerosis or carotid disease. METHODS: Between January 1993 and June 1999, 6,138 patients undergoing elective CABG were evaluated by intraoperative transesophageal echocardiography. Patients were screened preoperatively for internal carotid artery disease. Based on the intraoperative transesophageal echocardiography findings the surgical technique was individualized: hypothermic circulatory arrest with aortic atherectomy, CABG combined with transmyocardial laser revascularization on the beating heart, off-pump CABG by midsternotomy, ministernotomy, minimally invasive direct CABG, hybrid procedure, and so on. Patients were divided into four groups: a low-risk group (no significant aortic or carotid disease); an aortic atheromatous disease group (A.ATH); a carotid disease group (CD); and a carotid disease combined with aortic atheromatous disease group (CD + A.ATH). RESULTS: The incidence of stroke in the low-risk group (n = 5,043) was 0.92% compared with 0.96% in the A.ATH group (n = 918). In the CD group (n = 166) the incidence of stroke was 0.6% whereas it was 0% in the CD + A.ATH group (n = 11). CONCLUSIONS: Preoperative and intraoperative screening can detect extensive atherosclerosis of the proximal aorta and internal carotid artery. Selective use of surgical techniques in this group of high-risk patients can prevent adverse neurologic sequelae while achieving complete myocardial revascularization.

Aged↗

PubMed2000

Reduced neurological injury during CABG in patients with mobile aortic atheromas: a five-year follow-up study.

BACKGROUND: Mobile atheromas of the thoracic aorta have been identified as a major cause of stroke after coronary artery bypass grafting (CABG). This prospective study was undertaken to identify mobile atheromas and to determine the incidence of immediate postoperative embolic events after suitable surgical modifications. Late clinical events attributable to embolization were also studied. METHODS: Between January 1993 and July 1997, 3,660 patients scheduled for CABG underwent intraoperative transesophageal echocardiography to identify aortic atheromatous disease. The disease was graded as follows: grade I, plaques extending less than 5 mm into the aortic lumen; grade II, plaques extending more than 5 mm into the aortic lumen; and grade III, plaques with a mobile element. Only patients with grade III atheromas were included in the study. Various surgical modifications were done depending on the location of the lesion, eg, aortic arch atherectomy, CABG combined with transmyocardial laser revascularization, off-pump CABG by median sternotomy, and minimally invasive direct coronary artery bypass. Measured outcomes were death, stroke, and other vascular events, both early (within 1 week) and late (1 to 5 years) after operation. RESULTS: Of the 3,660 patients, 104 (2.84%) had mobile atheromas. The perioperative stroke rate was 0.96%, and the incidence of other vascular events was 1.92% at 1 week. There was no embolic event in the group of 88 patients who underwent off-pump CABG. Of the study group, 98.07% are in regular follow-up. At 5 years, 1 patient had had a nonfatal stroke, and 2 patients had died of causes unrelated to atheromatous disease. CONCLUSIONS: The stroke rate was very low in patients with mobile aortic atheromas who underwent CABG after modification in surgical technique, especially off-pump CABG. A follow-up of 5 years showed that patients with mobile atheromas have a very low incidence of spontaneous embolization.

Adult↗

PubMed2000

Euphane triterpenoid and lipid constituents from Butea monosperma.

Besides stigmasterol, stigmasterol-betaD-glucopyranoside and nonacosanoic acid, two new compounds isolated from the stems of Butea monosperma have been characterised as 3alpha-hydroxyeuph-25-ene and 2,14-dihydroxy-11,12-dimethyl-8-oxo-octadec-11-enylcyclohexane+ ++ by spectral data and chemical studies.

Molecular Structure↗

PubMed1999

Development of a cold resistant mutant of plant growth promoting Pseudomonas fluorescens and its functional characterization.

A cold resistant mutant of plant growth promoting Pseudomonas fluorescens GRS(1), was isolated following N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment. The mutant was able to grow and promote root and shoot elongation of wheat both at 25 and 10 degrees C, a temperature at which the wild type was unable to proliferate and function. In an effort to determine the mechanistic basis for this behavior, it was observed that following growth at 10 degrees C, the mutant synthesized some new proteins. SDS-polyacrylamide gel electrophoresis of the protein synthesized by the mutant revealed the presence of one major protein with a molecular mass of 13.5 kDa. However, at this point the function of this protein in not known.

Journal Article↗

PubMed1999

Density of Pure, Associating Fluids near the Solid-Liquid Interface.

In the present letter, we study the role of hydrogen bonds on the density of a pure, associating liquid in the solid-liquid interfacial region. The approach followed by us is to treat the liquid phase as comprising (i) oligomers/clusters of various sizes formed between the molecules of associating components present in the liquid/solid phases and (ii) holes. The interfacial properties of the resulting multicomponent system are then obtained using the monolayer theory proposed earlier by us (Suresh and Naik, 1996, 1997). The resulting expressions are found to be remarkably simple. To clearly demonstrate the accuracy of the proposed theory, results for the density of water-like molecules (each possessing two proton donor and two proton acceptor sites) near a hard wall are compared against those of available Monte-Carlo simulations (Segura and Chapman, 1995) and the density functional theory (Segura et al., 1997). Copyright 1999 Academic Press.

Journal Article↗

PubMed1998

Real-time intraoperative transesophageal echocardiography--how useful? Experience of 5,016 cases.

OBJECTIVE: To evaluate transesophageal echocardiography (TEE) as an intraoperative monitoring modality and to assess its safety, reliability, and overall utility in real-time use during cardiac surgery. DESIGN: Prospective, observational cohort study performed from January 1993 to June 1997. SETTING: Operating room of a tertiary care hospital for cardiology and cardiovascular surgery. PARTICIPANTS: Five thousand and sixteen adult patients with acquired heart disease, who underwent 1,356 valve procedures and 3,660 coronary artery bypass graftings (CABGs). INTERVENTIONS: All patients were monitored with radial artery and pulmonary artery catheters, along with continuous TEE monitoring with a multiplane transducer. MEASUREMENTS AND MAIN RESULTS: Prebypass imaging yielded unsuspected findings that either helped or modified the surgical plan in 158 of 1,356 valve procedures (11.65%) and in 993 of 3,660 CABGs (27.13%). There were 3,217 TEE-guided hemodynamic interventions in 944 patients (25.79%) in the CABG group and 629 in 142 patients (10.47%) in the valve group. TEE was the sole guiding factor in initiating therapy in 23.53% of events, whereas it was supportive to other monitoring modalities in 76.46% of events. Postbypass TEE identified the need for graft revision in 29 patients (0.8%), intra-aortic balloon pump (IABP) requirement in 29 patients (0.8%), and inadequate valve repair in 28 patients (2.08%). For the entire series, 38.78% of patients benefited from prebypass and 39.16% from postbypass use of TEE. There were no complications attributable to the use of TEE in the entire series. There was 87% concordance between online interpretation by a trained anesthesiologist and offline analysis by a cardiologist. CONCLUSION: Intraoperative TEE is useful in formulating the surgical plan, guiding various hemodynamic interventions, and assessing the immediate results of surgery. It is safe and the results are reliable in the hands of trained anesthesiologists.

Cardiac Surgical Procedures↗

PubMed1998

Rapid detection of enteric fever by coagglutination and countercurrent immunoelectrophoresis.

A total of 463 patients clinically suspected of enteric fever and 100 healthy individuals were investigated by coagglutination (COAG) and countercurrent immunoelectrophoresis (CIEP) for rapid diagnosis of enteric fever. The S. typhi was grown in blood culture in 32 (6.91%) and Widal test was positive in 126 (27.21%) cases. The serum COAG with local antiserum was positive in 165 (35.64%), serum COAG with standard antiserum in 163 (35.21%), Blood culture supernatant (BCS) COAG in 153 (33.05%), serum CIEP for antigen (Ag) in 118 (25.09%), BCS CIEP in 99 (21.39%) while serum CIEP for antibody (Ab) was positive in 34 (7.34%) cases. Only two healthy controls revealed positive COAG result with local antiserum. The sensitivity of all antigen detection tests was 100% except BCS CIEP (98.25%) in the first week of fever and declined rapidly to 75.79% for serum COAG tests, 69.47% for BCS COAG and dramatically to 37.89% for serum CIEP for Ag and 22.11% for BCS CIEP tests during the second week whereas the sensitivity of serum CIEP for Ab detection rose from 17.54% to 23.16% from first to second week of illness. In view of the resulting data, it is suggested that both COAG and CIEP may be employed for the rapid diagnosis of enteric fever in the routine clinical setup.

Agglutination Tests↗

PubMed1997

Polyamine metabolism in various tissues during pathogenesis of chloroquine-susceptible and resistant malaria.

The pathophysiological impact of infections with chloroquine-susceptible (CQS) and chloroquine-resistant (CQR) strains of Plasmodium berghei in Mastomys natalensis was studied with respect to changes in polyamine profiles in various tissues. Both CQS and CQR infections produced similar changes in polyamine profiles of various tissues. Maximum increase was recorded in spleen followed by liver and lungs. Renal, cardiac and cerebral tissues did not register significant changes. An increase in spermidine level was more prominent as compared to putrescine and spermine, leading to an overall increase in spermidine/spermine ratio. This ratio is an important index of cellular proliferation. Liver did not show considerable change in the activities of ornithine decarboxylase and S-adenosyl methionine decarboxylase, the regulatory enzymes of the polyamine biosynthetic pathway. Spleen however, registered marked induction of both the enzymes which was more prominent in the CQS infection than CQR. Normal erythrocytes contained traces of polyamine while the erythrocytes loaded with P. berghei parasites exhibited appreciably higher polyamine levels. Spermidine was detected in about five-fold higher concentrations than putrescine and spermine which were detected in equimolar levels. Again, CQS as well as CQR P. berghei, exhibited qualitatively and quantitatively similar polyamine profiles thus ruling out a role of polyamines in CQ-resistance in malaria.

Adenosylmethionine Decarboxylase↗