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Biomedical subjects

S K Sharma

Publications and source records attributed to S K Sharma.

At least 91 records · Page 5Linked to original sources

Neuroprotective actions of pyridoxine.

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.

Animals↗

Role of endoscopic retrograde cholangiopancreatography in the management of suspected choledocholithiasis.

BACKGROUND: Indications for endoscopic retrograde cholangiopancreatography (ERCP) are not precisely defined. With the increasing availability of magnetic resonance cholangiopancreatography (MRCP) and several prospective studies proving the accuracy of this modality, it is important to select appropriate criteria for invasive testing when common bile duct (CBD) pathology is suspected. METHODS: We reviewed 200 consecutive ERCPs performed for jaundice, pancreatitis, noninvasive visualization of CBD stones, radiologic evidence of CBD dilatation, elevated liver function tests, or biliary colic. Diagnostic and therapeutic yields are determined for each indication and various combinations thereof. RESULTS: Of the 180 ERCPs performed for suspected choledocholithiasis, 97 (53.8%) were performed for multiple indications, whereas 83 (46.2%) were performed for only one indication. One hundred two patients (56.6%) had CBD pathology, whereas 78 explorations (43.4%) were negative. If multiple indications for ERCP were present, the diagnostic yield was 85.6%. When there was only one indication, the diagnostic yield decreased to 25.3%. CONCLUSIONS: ERCP is an invasive procedure with significant morbidity that should be used selectively. MRCP may be a more appropriate initial evaluation of suspected CBD pathology in many patients.

Cholangiopancreatography, Endoscopic Retrograde↗

Separation of the components of type A botulinum neurotoxin complex by electrophoresis.

Clostridium botulinum neurotoxins (BoNTs) are the most toxic substances known. They exert potent neuroparalysis on vertebrates. C. botulinum produces seven serotypes of neurotoxin (A-G). BoNT/A, found in bacterial cultures of C. botulinum type A, is produced as a complex with a group of neurotoxin associated proteins (NAPs). Botulinum neurotoxin complex is the only known example of a protein complex where a group of proteins (NAPs) protect another protein (BoNT) against the acidity and proteases of the stomach. Here, we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for separation and identification of the constituent proteins of BoNT/A complex. A range of homogenous and gradient SDS-PAGE gels was used to resolve the BoNT/A complex. These gels were run under constant voltage and constant current conditions. The molecular weight and relative amount of each protein band were determined. On a 12.5% homogenous SDS-PAGE under reducing conditions, seven protein bands were identified with average molecular weights of 118, 106, 90, 56, 36, 23 and 17 kDa. The relative amounts of these seven proteins were determined densitometrically as 10, 6, 13, 27, 22, 13 and 8%, respectively. The separation and identification of BoNT/A complex will help in understanding the molecular structure and function of BoNT/A NAPs and their interaction with the toxin, in the toxico-infection process of the botulism diseased state. In particular, the stoichiometry of the individual components is established for a typical preparation of BoNT/A complex. Furthermore, the studies reported here identify the most favorable conditions for the baseline resolution of BoNT/A NAPs proteins for other workers in this field.

Botulinum Toxins, Type A↗

Lithium inhibits a late step in agrin-induced AChR aggregation.

Agrin activates an intracellular signaling pathway to induce the formation of postsynaptic specializations on muscle fibers. In myotubes in culture, this pathway has been shown to include autophosphorylation of the muscle-specific kinase MuSK, activation of Src-family kinases, tyrosine phosphorylation of the acetylcholine receptor (AChR) beta subunit, a decrease in receptor detergent extractability, and the accumulation of AChRs into high-density aggregates. Here we report that treating chick myotubes with lithium prevented any detectable agrin-induced change in AChR distribution without affecting the number of AChRs or the agrin-induced change in AChR tyrosine phosphorylation and detergent extractability. Lithium treatment also increased the rate at which AChR aggregates disappeared when agrin was removed. The effects of lithium developed slowly over the course of approximately 12 h. Thus, sensitivity to lithium identifies a late step in the agrin signaling pathway, after agrin-induced MuSK and AChR phosphorylation, that is necessary for the recruitment of AChRs into visible aggregates.

Agrin↗

Reninoma treated with nephron-sparing surgery.

A 14-year-old hypertensive boy was evaluated in our clinic. The physical examination was essentially normal except for his high blood pressure. Laboratory findings showed increased plasma renin activity. Abdominal ultrasonography detected a hypoechoic, 2-cm mass in right kidney. Contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion in the middle of the right kidney. Magnetic resonance angiography documented bilateral normal renal arteries. With a preoperative diagnosis of reninoma, the patient underwent nephron-sparing surgery. Intraoperative frozen section analysis revealed a benign lesion. Subsequently, histopathologic examination and electron microscopy confirmed the diagnosis of juxtaglomerular cell tumor. The patient remained normotensive in the postoperative period. Follow-up intravenous urography showed bilateral normally functioning kidneys.

Adenocarcinoma↗

Biomethanation under psychrophilic conditions: a review.

Anaerobic digestion of animal manure, sewage and other agricultural wastes at psychrophilic temperatures has not been explored as extensively as either mesophilic or thermophilic digestion, probably due to little anticipation of the development of economically attractive systems using this technology. This review article discusses psychrophilic anaerobic digestion studies reported by various researchers using different substrates. The effect of operational parameters such as type of substrate, size of inoculum, concentration of volatile fatty acids, hydraulic retention time and loading rate, on reduction of TS/VS, BOD/COD and biogas yield is discussed in detail.

Agriculture↗

Clinical and genetic risk factors for the development of multi-drug resistant tuberculosis in non-HIV infected patients at a tertiary care center in India: a case-control study.

Genetic susceptibility of the host to multi-drug resistant tuberculosis (MDR-TB) is not fully understood. We undertook a case-control study at a tertiary care center at New Delhi, India to identify the clinical and genetic predictors of MDR-TB as compared to the drug sensitive TB cases. Patients with multi-drug resistant tuberculosis were identified on the basis of drug sensitivity testing by the proportion method. Treatment was initiated according to standard norms and all patients were followed up during the period. Genomic DNA extracted from the peripheral blood mononuclear cell pellet was used for amplification of HLA class II region (second exon) with a set of forward (5') and reverse (3') primers. A sequence specific 5' biotinylated probes were used to determine 12 DRB1, 8 DQA1 and 13 DQB1 alleles by the PCR-SSOP method. Past history of disease, higher severity of illness, inadequacy of drug treatment and presence of HLA-DRB1*14, DQB1*0503 and DQB1*0502 alleles were found to be significant risk factors for MDR-TB. Multivariate analysis identified poor past compliance to treatment (odds ratio, OR=6.6; 95% confidence interval, CI [2.0-21.5]), higher number of cavities (OR=6; 95% CI [2.1-17.3]) in chest radiographs and the presence of the HLA-DRB1*14 allele (OR=8.2; 95% CI [2.1-31.3]) as independent predictors of MDR-TB. Our results suggest that a combination of clinical and immunogenetic parameters could provide better information on drug resistance in tuberculosis with implications in therapy.

Adult↗

Soil properties and crop productivity as influenced by flyash incorporation in soil.

Field experiments were carried out during 1996-97 at Gulawathi, Muthiani and Salarpur Villages, IARI Farm, New Delhi and NCPP Campus, Dadri to evaluate changes in soil characteristics and growth of wheat (Triticum aestivum L.), mustard (Brassica juncea L.), lentil (Lence esculenta Moench.), rice (Oryza sativa L.) and maize (Zea mays L.) by varying amounts of flyash addition (up to 50t ha(-1)) in soils at sowing/transplanting time of crops. Flyash addition in areas adjoining NCPP Thermal Power Plant, Dadri, Ghaziabad, U.P. ranged from 5-12 t ha(-1)] yr(-1) in 1995-96. Shoot and root growth and yield of test crops at different locations after flyash incorporation resulted in beneficial effects of flyash addition in most cases. The silt dominant texture of flyash improved loamy sand to sandy loam textures of the surface soils at the farmers' fields. The increased growth in yield of crops with flyash incorporation was possibly due to modifications in soil moisture retention and transmission characteristics, bulk density, physico-chemical characters such as pH and EC and organic carbon content. The response of flyash addition in the soil on soil health and crop productivity needs to be evaluated on long-term sustainable aspects.

Agriculture↗

Estimation of thyroid mass in Graves' disease by a scintigraphic method.

scintigraphic method for the estimation of the thyroid mass in patients with Graves' disease is described. The method was first standardized using thyroid phantoms with eight different volumes ranging from 5 to 110 cm(3). The planar and single photon emission computed tomography (SPECT) images of each phantom were acquired with four different activities [3.7 MBq (100 microCi), 11.1 MBq (300 microCi), 22.2 MBq (600 microCi) and 37 MBq (1.0 mCi) of 99mTc-pertechnetate] with a 20% window symmetrically placed over the photopeak of 99mTc. The thyroid lobes were enclosed with the help of regions of interest (ROI) tools and a threshold was selected to identify the thyroid boundaries. The same threshold was used in all slices of an image. In the phantom study, a 20% threshold for planar images and a 30% threshold for SPECT were found to be optimum for measuring the thyroid volume. The volume from planar images was calculated by the formula described by Allen and Goodwin (The scintillation counter as an instrument for in-vivo determination of thyroid weight. Radiology 1952; 58: 68-79), whereas, in SPECT images, the sum of the slice areas was multiplied by the slice thickness. The estimated volume of each phantom was compared and correlated with its actual volume. After standardization of the technique with phantom studies, planar scintigraphy (with 20% threshold) in 51 patients and SPECT (with 30% and 35% threshold) in 40 patients with Graves' disease were performed to estimate the thyroid size. The thyroid size was also estimated by ultrasonography, which showed good agreement with the scintigraphic method, particularly with SPECT.

Graves Disease↗

Plasmodium falciparum infection elicits both variant-specific and cross-reactive antibodies against variant surface antigens.

Naturally acquired antibodies to Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1), the variant surface antigens expressed on the surface of infected erythrocytes, are thought to play a role in protection against P. falciparum malaria. Here, we have studied the development of antibodies to PfEMP-1 in adult malaria patients living in Rourkela, India, an area with a low malaria transmission rate, and prevalence of antibodies to PfEMP-1 in residents of San Dulakudar, India, a village in which P. falciparum malaria is hyperendemic. Convalescent-phase sera from adult malaria patients from Rourkela agglutinate homologous P. falciparum isolates as well as some heterologous isolates, suggesting that they develop partially cross-reactive antibodies to PfEMP-1 following infection. Adult sera from San Dulakudar agglutinate diverse P. falciparum isolates, suggesting that they have antibodies with wide recognition of diverse PfEMP-1. Mixed-agglutination assays using pairs of P. falciparum isolates confirm the presence of both variant-specific and partially cross-reactive antibodies in convalescent-phase sera from Rourkela and adult sera from San Dulakudar. Analysis of PfEMP-1 sequences suggests a molecular basis for the observed cross-reactivity.

Adult↗

Rapid detection of mutations in rpoB gene of rifampicin resistant Mycobacterium tuberculosis strains by line probe assay.

BACKGROUND & OBJECTIVES: Multidrug resistant (MDR) tuberculosis (TB) is a problem of increasing importance in the world due to limited treatment options. Resistance to rifampicin results from nucleotide changes in the gene encoding the beta subunit of the RNA polymerase (rpoB) of Mycobacterium tuberculosis. Rifampicin resistance is considered as a marker for MDR TB. The nature and frequency of mutations in the rpoB gene of rifampicin resistant clinical isolates vary considerably according to the geographical location and very little information is available on specific mutational patterns in India. This study was undertaken to detect and characterize the rpoB gene mutation associated with rifampicin resistance in M. tuberculosis by line probe assay. METHODS: A total of 36 strains of M. tuberculosis were analysed by INNO-LiPA Rif TB and compared with the results of conventional susceptibility testing method. After PCR amplification of the region of RNA polymerase involved in rifampicin resistance, the amplified product was hybridized with a set of 10 oligonucleotides immobilized onto a membrane strip. From the pattern obtained, the presence or absence of rifampicin resistance in the M. tuberculosis strains was assessed. RESULTS: It was found that the M. tuberculosis probe was 100 per cent specific; the most frequently observed mutation was His-526-Tyr in the rpoB gene; and correlation between the results of the LiPA and those obtained by the classical susceptibility testing was excellent (100%). INTERPRETATION & CONCLUSION: INNO LiPA was found to be a reliable, simple, rapid and informative tool for the early detection and characterization of rpoB mutation associated with rifampicin resistance in M. tuberculosis in the clinical laboratory setting and may constitute an important molecular method for the control of tuberculosis.

Antibiotics, Antitubercular↗

Scientific basis of directly observed treatment, short-course (DOTS).

The introduction of rifampicin, pyrazinamide and ethambutol ushered in the era of "short course chemotherapy". Multidrug resistance TB (MDR-TB) is threatening to destabilise the best efforts of TB control. Treatment of MDR-TB is difficult, expensive and toxic and is often unsuccessful. DOTS is an interventional strategy designed to effectively diagnose and treat TB. The fundamental principles in the DOTS strategy are: Polititical will, diagnosis by sputum microscopy, directly observed standardised short-course treatment, adequate supply of good quality drugs, systematic monitoring and accountability. Patients with HIV infection and TB disease respond well to antituberculosis treatment if they are given short-course chemotherapy in the programme of DOTS.

Antitubercular Agents↗

Increasing HIV seropositivity among adult tuberculosis patients in Delhi.

We report the HIV seropositivity among adult TB patients from our hospital, a tertiary care hospital in north India between 2000-2002. Of the 555 patients with various forms of tuberculosis, 52 were found to be seropositive (9.4%). In 1994-1999, the HIV seropositivity in this hospital was only 0.4 per cent (2 of 500 patients). This communication describes a dramatic increase in seropositivity and highlights the importance of continued HIV serosurveillance in patients with TB.

Adolescent↗