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Biomedical subjects

S K Sharma

Publications and source records attributed to S K Sharma.

At least 235 records · Page 13Linked to original sources
PubMed1998

Species diversity and interspecific associations among mosquitoes in rice agro-ecosystem of Kheda district, Gujarat.

Rice agro-ecosystem of Kheda district in Central Gujarat was inhabited by 14 species of anophelines and 15 species of culicines. Anopheles subpictus and Culex vishnui gr dominated the respective groups. Species diversity in rice fields as well as in associated habitats remained high during non-monsoon (rabi) period. There existed several positive and negative interspecific associations. Malaria vector An. culicifacies showed positive association with An. subpictus, An. annularis, An. pallidus and Cx. quinquefasciatus but was found negatively associated with An. nigerrimus, Cx. vishnui and Cx. tritaeniorhynchus.

Animals↗
PubMed1998

Influence of Escherichia coli endotoxin induced fever on the pharmacokinetics and dosage regimen of oxytetracycline in cross-bred calves.

The pharmacokinetics and dosage regimen of oxytetracycline were determined in healthy and febrile cross-bred calves following its single intravenous administration (10 mg kg-1). Fever was induced by a single intravenous injection of E. coli endotoxin (1 microgram kg-1 i.v.). The elimination half-life (t1/2 beta) and the apparent volume of distribution [vd(area)] were slightly increased in febrile calves, as compared to healthy animals. The values of t1/2 beta and Vd(area) were 3.22 +/- 0.20 h and 0.49 +/- 0.02 L. kg-1 in healthy calves and 4.06 +/- 0.32 h and 0.70 +/- 0.09 L kg-1, respectively, in febrile calves. An intravenous dosage regimen suitable for maintaining the minimum therapeutic plasma concentration of > or = 2 micrograms/ml in febrile animals would be 10 mg kg-1 repeated at 12-h intervals.

Animals↗
PubMed1998

Hemagglutinin binding mediated protection of botulinum neurotoxin from proteolysis.

Type A Clostridium botulinum, the causative agent of the food poisoning botulism disease, secretes botulinum neurotoxins along with seven neurotoxin associated proteins (NAPs). The function of NAPs has been shown to protect the neurotoxin from acidity, heat, and proteolytic attack in the environmental and gastrointestinal tract during the toxicogenesis of the botulism disease. One of the NAPs, purified from type A botulinum neurotoxin complex, showed hemagglutination activity. A direct interaction has been demonstrated between purified NAP, a 33-kDa hemagglutinin or Hn-33, and the neurotoxin by using Sephadex G-200 column chromatography. Furthermore, Hn-33 has complete resistance against proteolytic attack at pH 2.0 as well as at normal physiological pH. We have investigated digestion of the neurotoxin in the presence and absence of Hn-33. The neurotoxin alone has been found to be more susceptible to the enzymatic digestion than neurotoxin with Hn-33. The presence of Hn-33 changes the proteolytic fragmentation pattern of the neurotoxin. It seems that Hn-33 protects the neurotoxin from proteolysis either by structural modification of the neurotoxin or by blocking the protease accessible sites of the neurotoxin.

Botulinum Toxins, Type A↗
PubMed1997

Nucleotide-induced stable complex formation by HIV-1 reverse transcriptase.

Nondenaturing gel electrophoresis was used to study the nucleotide substrate-induced conformational change in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). Dead-end complex was formed between HIV-1 RT, dideoxynucleotide chain-terminated primer, and DNA template in the presence of deoxynucleotide triphosphate (dNTP) complementary to the next position on the template. Complexes which form in the absence of the next complementary dNTP were disrupted by adding excess poly(rA)/oligo(dT) or heparin just prior to electrophoresis. Dead-end complex formation by noncomplementary dNTP's or ribonucleotides was at least 2000-fold less efficient than with the complementary nucleotide. When dA was the next nucleotide on the template, analogues of dTTP supported dead-end complex formation with increased apparent Kd (dTTP < dideoxy-TTP approximately alpha-thio-dTTP < dUTP < 3'-azidothymidine triphosphate). A similar relationship was observed for dGTP analogues across from dC on the template (dGTP < dideoxy-GTP < alpha-thio-dGTP << dITP < dideoxy-ITP). The optimal length of the primer/template duplex region for dead-end complex formation was between 20 and 32 base pairs. Primer-template with a mismatched primer terminus did not support dead-end complex formation, and primer terminated with 3'-azidothymidine formed dead-end complex with 25-fold elevated apparent Kd. By contrast, dead-end complex formation on primer terminated with dideoxy-IMP base paired with dC on the template was more efficient than on primer terminated with dideoxy-GMP. Implications for the mechanisms of discrimination between nucleotide analogues by HIV-1 RT are discussed.

DNA Primers↗
PubMed1997

Angiographic evolution of intracoronary thrombus and dissection following percutaneous transluminal coronary angioplasty (the Thrombolysis and Angioplasty in Unstable Angina [TAUSA] trial).

The evolution and progression of thrombus and dissection after percutaneous transluminal coronary angioplasty (PTCA) are unknown. As part of the protocol of the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial, 1 and 15 minutes post-PTCA angiograms were routinely performed and evaluated by the core laboratory for the presence of thrombus and either minor or major dissection. Thrombus was present at 1 minute in 4.4% of culprit lesions. This increased to 16% at 15 minutes (p < 0.005) and was equally seen in patients receiving both urokinase and placebo. Any dissection was noted in 25.2% at 1 minute versus 30.5% at 15 minutes (p < 0.08), and this trend was mainly related to an increase in major dissection with urokinase at 15 minutes versus 1 minute (10.1% vs 5.9%, respectively, p = 0.10). The in-hospital clinical outcome of patients with lesions that did or did not have thrombus or major dissection at 1 and 15 minutes was retrospectively assessed in the placebo group. The presence of either thrombus or major dissection at 1 minute was associated with a subsequent incidence of acute closure of 14% and an incidence of emergency bypass surgery of 11% (p < 0.01 compared with no thrombus or major dissection at 1 minute). The absence of thrombus and major dissection at 15 minutes (n = 173) was associated with no subsequent acute closure or emergency bypass surgery, (p < 0.05 for acute closure vs thrombus or major dissection at 15 minutes). Thrombus evolves progressively over 15 minutes after PTCA in unstable angina, whereas dissection is usually present immediately after PTCA. The absence of thrombus and major dissection at 15 minutes is associated with very low-acute in-hospital complications. Delayed angiograms following standard balloon angioplasty for unstable angina may be predictive of low complications and our study suggests a possible role for their use.

Acute Disease↗
PubMed1997

A single-step stent delivery, deployment, and expansion system.

Placement of intracoronary stents now comprises a significant number of the percutaneous coronary revascularization procedures being performed in high-volume interventional laboratories in the United States. Stents have become popular because of the reliable acute results, and decreased restenosis. The most common stent currently in use in the United States is the Palmaz-Schatz balloon-expandable stent (PS stent). This stent delivery system (SDS) usually requires predilatation with a balloon and another dilatation, after stent deployment, with a high-pressure balloon in order to adequately expand the stent. We report on a new hybrid stent-delivery system using the PS stent, the sheath from the SDS, and an NC Bandit balloon. This new hybrid system is safe and significantly decreases the procedure time, fluoroscopy time, and need for additional stents due to angiographic dissection resulting from inexact positioning of the high-pressure balloon within the initially deployed stent, and/due to inadequate placement of the first stent. This may be an ideal delivery system for single stent deployment using currently approved FDA equipment.

Angioplasty, Balloon, Coronary↗
PubMed1997

Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial.

Antibody-directed enzyme prodrug therapy (ADEPT) was administered to ten patients in a phase I clinical trial. The aim was to measure plasma levels of the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl) amino] benzoyl-L-glutamic acid (CMDA) and the bifunctional alkylating drug (CJS11) released from it by the action of tumour-localised carboxypeptidase G2 (CPG2) enzyme. New techniques were developed to extract the prodrug and drug from plasma by solid-phase absorption and elution and to measure CPG2 activity in plasma and tissue. All extracts were analysed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). CPG2 activity was found in metastatic tumour biopsies but not in normal tissue, indicating that localisation had been successful. The clearing agent SB43-gal, given at 46.5 mg/m2, achieved the aim of clearing non-tumour-localised enzyme in the circulation, indicating that conversion of prodrug to drug could take place only at the site of localised conjugate. Plasma prodrug did not always remain above its required threshold of 3 microM for the "therapeutic window" of 120 min after dosing, but the presence of residual prodrug after the first administration of each day indicated that this could be achieved during the remaining four doses over the following 8 h. Despite considerable inter-patient prodrug plasma concentration variability, the elimination half-life of the prodrug was remarkably reproducible at 18 +/- 8 min. Rapid appearance of the drug in plasma indicated that successful conversion from the prodrug had taken place, but also undesirable leakback from the site of localisation into the bloodstream. However, drug plasma levels fell rapidly by at least 50% at between 10 and 60 min with a half-life of 36 +/- 14 min. Analysis of the plasma extracts by LC/MS indicated that this technique might be used to confirm qualitatively the presence of prodrug, drug and their metabolites.

Antibodies, Monoclonal↗
PubMed1997

Biodistribution of an antibody-enzyme conjugate for antibody-directed enzyme prodrug therapy in nude mice bearing a human colon adenocarcinoma xenograft.

The enzyme carboxypeptidase G2 (CPG2) can be targeted to tumors by antibodies and used to activate prodrugs in a treatment called antibody-directed enzyme prodrug therapy (ADEPT). Different doses of CPG2 conjugated to the anti-CEA antibody A5B7 were administered i.v. to nude mice bearing the LS174T human colon adenocarcinoma xenograft, and the biodistribution of conjugate activity 48 and 72 h later was determined using a novel high-performance liquid chromatography (HPLC) method. Conjugate doses of 2,500 and 625 U/kg gave tumor enzyme levels of 0.5-0.6 U/g. Lower doses of 300 and 150 U/kg gave tumor enzyme levels of 0.1-0.3 U/g. Intriguingly, the best tumor:blood ratio of conjugate activity at both 48 and 72 h was achieved after administration of the 625-U/kg dose, not the 2,500-U/kg dose. After 48 h this ratio was 3.8, whereas after 72 h the value was 5.5. This conjugate dose also gave the greatest tumor:tissue ratios in all other tissues examined. After 72 h the tumor:colon ratio was 105, whereas the tumor:kidney ratio was 36. In ADEPT, to obtain maximal tumor damage to LS174T xenografts in nude mice with minimal systemic toxicity using the A5B7-CPG2 conjugate, prodrug should therefore be administered at least 72 h after a conjugate dose of 625 U/kg.

Adenocarcinoma↗
PubMed1997

A rapid and quantitative assay for inhibition of 3' cleavage activity of HIV-1 integrase.

The human immunodeficiency virus-1 (HIV-1) integrase catalyzes the specific removal of two nucleotides at either 3' end of each long terminal repeat (LTR) sequence of the proviral DNA duplex. The most commonly used in vitro assays for integrase employ 5' end 32P-labeled double-stranded oligonucleotides and the product of integrase-associated endonuclease activity is visualized by denaturing gel electrophoresis followed by autoradiography. We report here a simple assay system based upon the liberation of [35S]GT dinucleotide from the 3' end of a double-stranded U5 LTR sequence derived from HIV-1. The uncleaved labeled substrate and the unlabeled large product are removed by adsorption to polyethyleneimine cellulose followed by centrifugation. The small labeled GT dinucleotide product released in the supernatant is quantitated in terms of counts released as a function of time. Since the method is rapid and quantitative, it should be useful in the kinetic evaluation of inhibitors of the 3' cleavage activity of HIV-1 integrase.

HIV Integrase↗
PubMed1997

Immunomodulatory effects of NIM-76, a volatile fraction from Neem oil.

The immunomodulatory properties of NIM-76 have been described in this paper. Pre-treatment of rats with a single i.p. injection of NIM-76 resulted in an increase in polymorphonuclear (PMN) leukocytes with a concomitant decrease in lymphocyte counts. The immunomodulatory activity of NIM-76 was found to be concentration-dependent. At 120 mg/kg body weight, there was an enhanced macrophage activity and lymphocyte proliferation response, while the humoral component of immunity was unaffected. At higher concentrations of NIM-76 (300 mg/kg body weight), there was a stimulation of mitogen-induced lymphocyte proliferation, while macrophage activity remained unaffected. However, a fall in primary and secondary antibody titres was observed. The study indicates that NIM-76 acts through cell-mediated mechanisms by activating macrophages and lymphocytes.

Adjuvants, Immunologic↗
PubMed1997

Management of a postpartum coagulopathy using thrombelastography.

Thrombelastography (TEG), which evaluates the elastic properties of whole blood and provides a global assessment of hemostatic function, is useful in managing peripartum coagulopathy. A case of severe bleeding after vaginal delivery, in which TEG was used successfully to manage hemostatic defects, is presented.

Adult↗
PubMed1997

Anti-invasive activity of alkaloids and polyphenolics in vitro.

Invasiveness, the ability of certain tumour cells to migrate beyond their natural tissue boundaries, often leads to metastasis, and usually determines the fatal outcome of cancer. The need for anti-invasive agents has led us to search for possibly active compounds among alkaloids and polyphenolics. One hundred compounds were screened in an assay based on the confrontation of invasive human MCF-7/6 mammary carcinoma cells with fragments of normal embryonic chick heart in vitro. Anti-invasive activity was frequently found among chalcones having a prenyl group. Six compounds were found to inhibit invasion when added to the culture medium at concentrations as low as 1 microM. For at least three of them the anti-invasive effect could be associated with a cytotoxic effect on the MCF-7/6 cells, but not on the heart tissue. This selective cytotoxicity was substantiated by different methods, such as histology and growth assays (volume measurements, cell counts, MTT and sulforhodamine B assays). The anti-invasive effects of the compounds could neither be ascribed to induction of apoptosis nor to the promotion of cell-cell adhesion. Our data indicate that among the alkaloids and polyphenolics a number of molecules can inhibit growth and invasion of human mammary cancer cells via selective cytotoxicity.

Alkaloids↗