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Biomedical subjects

B Mishra

Publications and source records attributed to B Mishra.

At least 19 recordsLinked to original sources

Foundations of a query and simulation system for the modeling of biochemical and biological processes.

The analysis of large amounts of data, produced as (numerical) traces of in vivo, in vitro and in silico experiments, has become a central activity for many biologists and biochemists. Recent advances in the mathematical modeling and computation of biochemical systems have moreover increased the prominence of in silico experiments; such experiments typically involve the simulation of sets of Differential Algebraic Equations (DAE), e.g., Generalized Mass Action systems (GMA) and S-systems. In this paper we reason about the necessary theoretical and pragmatic foundations for a query and simulation system capable of analyzing large amounts of such trace data. To this end, we propose to combine in a novel way several well-known tools from numerical analysis (approximation theory), temporal logic and verification, and visualization. The result is a preliminary prototype system: simpathica/xssys. When dealing with simulation data simpathica/xssys exploits the special structure of the underlying DAE, and reduces the search space in an efficient way so as to facilitate any queries about the traces. The proposed system is designed to give the user possibility to systematically analyze and simultaneously query different possible timed evolutions of the modeled system.

Biochemical Phenomena↗

Primary splenic flexure volvulus--a case report with review of literature.

Splenic flexure is a rare site for volvulus. Very few cases have been reported in the literature. Cases mostly present with recurrent attacks of obstruction with distension of the abdomen. A case of a young female who had primary splenic plexure volvulus due to absence of ligamental attachment has been presented here. Resection of the volvulus segment with end to end anastomosis is the curative surgical treatment.

Adult↗

Transfusion associated infections: a threat to life.

Blood transfusion is indispensable in the management of many haematological diseases and has become the mainstay in major surgical procedures. Transfusion-transmitted infections have been a major threat to life since the dawn of transfusion therapy. The authors have highlighted the different viral, parasitic and bacterial infections associated with transfusion and have focussed on the precautionary measures that can be implemented for prevention of the infections along with a brief review of the literature.

Bacterial Infections↗

Itih-4, a serine protease inhibitor regulated in interleukin-6-dependent liver formation: role in liver development and regeneration.

Inter-alpha-trypsin inhibitor-4 (Itih-4) is a liver-restricted member of the serine protease inhibitor family with diverse functions as an anti-apoptotic and matrix stabilizing molecule that are important throughout development. We investigate the functional role of Itih-4 in liver formation, regeneration (LR) and examine its role in calcium and hyaluronic acid binding. Itih-4 expression is prominent in early liver development at E9 and later at E16, being restricted to hepatoblasts, immature hepatocytes, and differentiated hepatocytes. We note a marked and differential increase in Itih-4 labeling in proliferating hepatocytes, compared with bile duct cells in liver explant cultures treated with interleukin-6 (IL-6). After partial hepatectomy, maximal Itih-4 expression occurs in a bimodal manner at 30 min and at 12 hr, with a predominant centrizonal distribution. There is no detectable binding of glutathione transferase-fusion Itih-4 protein to calcium and hyaluronic acid, indicating a possible requirement for posttranslational modifications for these functions. These results suggest that in LR, Itih-4 expression corresponds to that of immediate early genes and may contribute to the entry of normally quiescent hepatocytes into the early stages of the cell cycle. The markedly high expression of Itih-4 in early liver development and in explants treated with IL-6 suggests a prominent role for Itih-4 at key points in liver formation.

Animals↗

Catheter associated urinary tract infections in neurology and neurosurgical units.

OBJECTIVE: Catheter associated bacteriuria is the most common infection acquired in hospitals. The objective of the study was (1) to study the incidence of bacteriuria following indwelling urethral catheterization in patients with short-term vs long-term catheterization (2) to define the antibiotic resistance pattern among these isolates so that the study can provide guidelines for choosing an effective antibiotic against infections in catheterized patients. METHODS: This is a prospective study carried out over a period of 18 months in Neurology/Neurosurgical patients who had indwelling catheters for > or =48 h. RESULTS: In this study, 68 out of 800 (8.5%) adult inpatients acquired urinary tract infection following indwelling bladder catheterizations. The risk was significantly higher for female, elderly patients, critically ill and patients on prolonged catheterization. Among the bacterial pathogens, Escherichia coli was the commonest organism isolated (32.9%) followed by Pseudomonas sp. (15.1%) and Staphylococcus aureus (12.3%). Candida sp. comprised 13.7% of all isolates. Among Gram negative bacterial pathogens maximum number of isolates were sensitive to Amikacin (sensitivity of 42%). All Gram positive organisms were however sensitive to Vancomycin. CONCLUSIONS: Our results provide guidelines for choosing salvage therapy against hospital resistant strains causing infection in catheterized patients. However, antibiotics seem to prevent urinary tract infections but primarily in patients catherized for short duration, i.e. 3-14 days and not in patients with long-term catheterization.

Aged↗

Plasticizer effect and comparative evaluation of cellulose acetate and ethylcellulose-HPMC combination coatings as semipermeable membranes for oral osmotic pumps of naproxen sodium.

The objective of this study was to compare the performance of cellulose acetate (CA) and ethylcellulose (EC)-HPMC combination coatings as semipermeable membranes (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions. Osmotic pump tablets were designed with different coating variables and optimized in terms of nature of plasticizer, membrane thickness, and orifice diameter. The effect of insertion of an inner microporous film around the NPS core to minimize deformation of the SPM due to peristaltic movement of the gut was also studied. Osmotic pump tablets composed of membranes with water-soluble plasticizer, propyleneglycol (PG), released drug mainly through diffusion, whereas those designed with CA and EC-HPMC (4:1) coats containing water-insoluble plasticizer, castor oil, released their contents by perfect zero-order kinetics over a prolonged period of time, though the average release rate that could be achieved with the EC-HPMC (4:1) membrane was only about half the rate achieved with the CA membrane for the same membrane thickness. Release rates for both the membranes decreased with increasing membrane thickness and were found to be independent of orifice diameter, agitation intensity, and pH of the dissolution medium.

Administration, Oral↗

Metabolism and excretion of centbutindole (neuroleptic) in rats after oral administration.

The metabolism and excretion of centbutindole was studied in Sprague-Dawley rats after oral administration. The percentage of dose excreted was monitored over 4 days. Efforts were also directed towards evaluating the stability of centbutindole in various in-vitro biomatrices. Centbutindole was found to be metabolised in rats and only a negligible amount of parent drug was excreted. The percentage of the dose excreted in bile and faeces was 0.2% and 0.6%, respectively. No drug was found in urine after oral administration, but after an intravenous dose only 0.0012% of the dose was eliminated through urine. Two metabolites, dealkylated metabolite and hydroxy metabolite, were identified by ion spray LC/MS/MS, using a combination of parent ion and product ion scanning techniques. The major routes of metabolism of centbutindole include reduction of the carbonyl functional group in the butyrophenone side chain and N-dealkylation of the butyrophenone side chain attached to the pyrazinopyridoindole ring nitrogen at position 2. The hydroxy metabolite was excreted negligibly in bile, although it was present in the form of glucuronide conjugates more in comparison to its free form.

Administration, Oral↗

Studies on solubility and hypoglycemic activity of gliclazide beta-cyclodextrin-hydroxypropylmethylcellulose complexes.

This study was undertaken with an objective to increase the dissolution rate and bioavailability of a poorly water soluble drug gliclazide (Gz) by complexation with beta-cyclodextrin (CD) in the presence of hydroxypropylmethylcellulose (HPMC). Phase solubility studies of Gz were performed in aqueous solutions of different concentrations of CD alone and in the presence of some water soluble polymers. Gz-CD complexes were prepared in 1:1 and 1:2 drug:CD molar ratios by autoclaving, neutralization and kneading methods. The complexes were also prepared in the presence of 0.05% w/w HPMC. Physical mixtures of Gz-CD in 1:1 and 1:2 molar ratios were also prepared. Complexes and physical mixtures were characterized and evaluated for in vitro dissolution in distilled water and hypoglycemic activity in rats. CD enhanced the dissolution of Gz to 1.5 to 2.0 fold. Presence of water soluble polymer HPMC in Gz-CD complexes further enhanced the rate and extent of drug dissolution to 2.5 fold. Gz-CD-HPMC complexes were found to be more promising as they produced not only an early onset but also more intense hypoglycemic effect as compared to pure drug powder and commercial tablets.

Animals↗

Mitral valve endocarditis following balloon mitral valvotomy.

The case of a patient who developed fungal valve endocarditis due to Candida albicans following balloon mitral valvotomy is presented. The patient did not have any obvious predisposing factors which led to the development of fungal endocarditis.

Candida albicans↗

Shotgun optical maps of the whole Escherichia coli O157:H7 genome.

We have constructed NheI and XhoI optical maps of Escherichia coli O157:H7 solely from genomic DNA molecules to provide a uniquely valuable scaffold for contig closure and sequence validation. E. coli O157:H7 is a common pathogen found in contaminated food and water. Our approach obviated the need for the analysis of clones, PCR products, and hybridizations, because maps were constructed from ensembles of single DNA molecules. Shotgun sequencing of bacterial genomes remains labor-intensive, despite advances in sequencing technology. This is partly due to manual intervention required during the last stages of finishing. The applicability of optical mapping to this problem was enhanced by advances in machine vision techniques that improved mapping throughput and created a path to full automation of mapping. Comparisons were made between maps and sequence data that characterized sequence gaps and guided nascent assemblies.

Contig Mapping↗

Chitosan based pentazocine microspheres for intranasal systemic delivery: development and biopharmaceutical evaluation.

Bioadhesive chitosan microspheres (Ms) of pentazocine (Pz) for intranasal systemic delivery were prepared with the aim of avoiding the first pass effect, and thus improving the bioavailability and achieving sustained and controlled blood level profiles, as an alternative therapy to injection and to obtain improved therapeutic efficacy in the treatment of chronic pain such as cancer, trauma and post-operative pain, etc. The formulation variables were drug loading, polymer concentration, stirring rate during crosslinking and oils. The microspheres (Ms) were subjected to evaluation for physical characteristics, such as particle size, incorporation efficiency, swelling ability, in vitro bioadhesion, in vitro drug release characteristics and in vivo performance in rabbits. Application of in vitro data to various kinetic equations indicated matrix diffusion controlled drug delivery from chitosan Ms. Drug loading, polymer concentration and stirring speed influenced the drug release profiles significantly while oils had negligible effect. In vivo studies indicated significantly improved bioavailability of Pz from Ms with sustained and controlled blood level profiles as compared to i.v., oral and nasal administration of drug solution. Good correlation was observed between in vitro and in vivo data.

Adhesiveness↗

Design and evaluation of osmotic pump tablets of naproxen sodium.

Osmotic pump tablets (OPTs) deliver a constant, predetermined amount of drug in solution form over a fixed span of time, independent of external environmental conditions. OPTs of naxopren sodium (NPS) were made and evaluated with the principal aim of limiting the drug's frequently experienced gastrointestinal side effects, by preventing the undissolved drug from coming in to contact with the gastric mucosa. OPTs with and without the osmotic driving agent, sodium chloride (SCL), with different membrane thicknesses, and with and without an orifice were designed. In vitro release profiles of the OPTs, when compared to a conventional marketed tablet (Xenobid 275), were highly controlled and exhibited an almost perfect zero-order release pattern. The magnitudes of lag times and average release rates were found to depend on the amount of SCL present in the formulation which decreased the drug's solubility within the system. The release rates were found to be independent of stirring rate and decreased with increasing membrane thickness. Release profiles of the OPTs with and without an orifice were found to be comparable.

Anti-Inflammatory Agents, Non-Steroidal↗

Osmotically controlled oral drug delivery.

It is advantageous to deliver some drugs with short half-life, and which are to be given frequently for chronic ailments, in the form of controlled-release (CR) formulations. The orally administered drugs, in the form of conventional matrix or reservoir type formulations, pose problems of bioavailability fluctuations due to gastric pH variations. Moreover, the release of drug(s) from these systems is affected by the hydrodynamic conditions of the body. Osmotically controlled drug delivery systems utilize the principles of osmotic pressure for the controlled delivery of active agent(s). The release rate of drug(s) from these systems is independent of the physiological factors of the gastrointestinal (GI) tract to a large extent. In the present review, theory underlying the delivery of drugs from osmotic systems is presented. Different types of oral osmotic systems, their advantages over conventional matrix and reservoir types of systems, and their applications are also discussed. Finally, some of the limitations, adverse effects, and patent and market status of these systems are reviewed. These systems form a major segment of drug delivery products. Because of their advantages and strong market potential, it appears that the future of osmotic systems in rate-controlled oral drug delivery is promising.

Administration, Oral↗

Optical mapping of BAC clones from the human Y chromosome DAZ locus.

The accurate mapping of clones derived from genomic regions containing complex arrangements of repeated elements presents special problems for DNA sequencers. Recent advances in the automation of optical mapping have enabled us to map a set of 16 BAC clones derived from the DAZ locus of the human Y chromosome long arm, a locus in which the entire DAZ gene as well as subsections within the gene copies have been duplicated. High-resolution optical mapping employing seven enzymes places these clones into two contigs representing four distinct copies of the DAZ gene and highlights a number of differences between individual copies of DAZ.

Chromosome Mapping↗