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Biomedical subjects

S Ahmad

Publications and source records attributed to S Ahmad.

At least 55 records · Page 3Linked to original sources
PubMed2002

Prevalence of S315T mutation within the katG gene in isoniazid-resistant clinical Mycobacterium tuberculosis isolates from Dubai and Beirut.

OBJECTIVE: To determine the prevalence of S315T mutation within the katG gene that confers clinically significant resistance to isoniazid in isoniazid-resistant Mycobacterium tuberculosis isolates recovered from tuberculosis patients in Dubai and Beirut. METHOD: A total of 28 and 17 isoniazid-resistant and seven and six susceptible clinical M. tuberculosis isolates from Dubai and Beirut, respectively, were tested. The presence of S315T mutation in the katG gene was detected by amplification of the DNA region around codon 315 by polymerase chain reaction followed by restriction digestion with Msp I to generate restriction fragment length polymorphism. The genotyping of the isolates carrying S315T mutation was carried out by touchdown double-repetitive-element PCR (DRE-PCR). RESULTS: The mutation S315T was detected in 18 (64%) of 28 isoniazid-resistant isolates from Dubai and in six (35%) of 17 resistant strains from Beirut. None of the susceptible strains contained this mutation. The genotyping studies showed that the majority of the isolates carrying the S315T mutation exhibited unique DNA banding patterns. CONCLUSION: The data show a varying prevalence of S315T mutation within the katG gene in M. tuberculosis strains isolated from the two geographical locations, Dubai and Beirut.

Antitubercular Agents↗
PubMed2001

Design and synthesis of 4-substituted benzamides as potent, selective, and orally bioavailable I(Ks) blockers.

Multiple delayed rectifier potassium currents, including I(Ks), are responsible for the repolarization and termination of the cardiac action potential, and blockers of these currents may be useful as antiarrhythmic agents. Modification of compound 5 produced 19(S) that is the most potent I(Ks) blocker reported to date with >5000-fold selectivity over other cardiac ion channels. Further modification produced 24A with 23% oral bioavailability.

Administration, Oral↗
PubMed2001

Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1.

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.4 microM). Structure-activity relationships are used to optimize the affinity of various acyl guanidines for NHE-1 by screening the effect of substituents at both aryl and cyclopropyl rings. It is demonstrated that introduction of appropriate hydrophobic groups at the phenyl ring and a gem-dimethyl group at the cyclopropane ring enhances the NHE-1 inhibitory activity by up to 3 orders of magnitude (compound 7f, IC(50) = 0.003 microM). In addition, the gem-dimethyl series of analogues seem to display improved oral bioavailability and longer plasma half-life in rats. Furthermore, the lead benzodihydrofuranyl analogue 1 (BMS-284640) shows over 380-fold increased NHE-1 inhibitory activity as well as improved selectivity for NHE-1 over NHE-2 compared to cariporide.

Administration, Oral↗
PubMed2001

Transition from the C3-dominated discharge to the sooting plasma.

Mass spectrometry and photoemission spectroscopy of a graphite hollow cathode source identify the parameters of the transition from the C3-dominated discharge to the sooting plasma. The transition is a function of the shape and profile of a special cusp magnetic field B(z)(r, theta), the geometry of the source, the discharge current, and pressure. Characteristic atomic and molecular emission lines and bands in the C3 discharge transform into broad bands emitted by the excited soot. We identify four prominent emission bands between 300-400 nm to be the hallmark of the sooting plasma.

Journal Article↗
PubMed2001

Inhibition of tissue factor-activated platelets by low-molecular-weight heparins and glycoprotein IIb/IIIa receptor antagonist.

Thrombotic disorders can lead to vascular distress and platelet activation eventually resulting in the rupture of the lesions where a sizable amount of tissue factor (TF) is generated during the pathogenesis of arterial diseases. Since low-molecular-weight heparins (LMWHs) and platelet glycoprotein (GP) IIb/IIIa inhibitors are clinically used for the management of acute coronary syndrome (ACS), studies were taken to determine the effects of these agents on TF-mediated activation of platelets. Freshly drawn native whole blood (WB) from normal healthy volunteers (n = 6) supplemented with a predetermined amount of TF was incubated with equivalent anti-Xa adjusted amounts of various LMWHs at 0.01-1.0 U/ml and tirofiban from 10 to 100 ng/ml. Platelet activation was assessed by measuring the expression of P-selectin (CD62) and the generation of platelet aggregates. At 0.01 U/ml, enoxaparin exhibited a stronger inhibition of TF-induced platelet activation compared to ardeparin and dalteparin. At 0.1 U/ml, these LMWHs produced a comparable inhibition of total P-selectin expression, and at 1.0 U/ml, a marked inhibition was noted. Since enoxaparin produced the best concentration-dependent inhibition of P-selectin expression (saline: 76 +/- 10% vs. 1.0 U/ml enoxaparin: 18 +/- 7%; P < .02) and platelet aggregate formation (saline: 63 +/- 7% vs. 1.0 U/ml enoxaparin: 35 +/- 6%, P < .035), this agent was used for additional studies. Unlike enoxaparin, tirofiban produced a weak concentration-dependent inhibition of platelet activation. At 100 ng/ml, tirofiban produced a 40% inhibition of P-selectin expression and about 60% inhibition of platelet aggregate formation. To elucidate the potential interaction between tirofiban and enoxaparin, the effect of 10 and 100 ng/ml tirofiban was studied with enoxaparin-supplemented WB in a 0.01-1.0 U/ml range. Additive effects between these two agents were noted only at lower concentrations. Thus, at therapeutic concentrations (0.8-1.2 U/ml), enoxaparin itself was capable of inhibiting TF-mediated activation of platelets to > 70%; whereas tirofiban failed to produce such concentration-dependent inhibition. This suggests that the simultaneous administration of GPIIb/IIIa receptor antagonist with LMWH may not have any added benefit in the clinical management of patients with ACS.

Blood Platelets↗
PubMed2001

Elliptic flow in Au+Au collisions at square root(S)NN = 130 GeV.

Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at square root(S)NN = 130 GeV using the STAR Time Projection Chamber at the Relativistic Heavy Ion Collider. The elliptic flow signal, v2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.

Journal Article↗
PubMed2001

Performance of stochastic approaches for forecasting river water quality.

This study analysed water quality data collected from the river Ganges in India from 1981 to 1990 for forecasting using stochastic models. Initially the box and whisker plots and Kendall's tau test were used to identify the trends during the study period. For detecting the possible intervention in the data the time series plots and cusum charts were used. The three approaches of stochastic modelling which account for the effect of seasonality in different ways. i.e. multiplicative autoregressive integrated moving average (ARIMA) model. deseasonalised model and Thomas-Fiering model were used to model the observed pattern in water quality. The multiplicative ARIMA model having both nonseasonal and seasonal components were, in general, identified as appropriate models. In the deseasonalised modelling approach, the lower order ARIMA models were found appropriate for the stochastic component. The set of Thomas-Fiering models were formed for each month for all water quality parameters. These models were then used to forecast the future values. The error estimates of forecasts from the three approaches were compared to identify the most suitable approach for the reliable forecast. The deseasonalised modelling approach was recommended for forecasting of water quality parameters of a river.

Environmental Monitoring↗
PubMed2001

Screening for primary aldosteronism without discontinuing hypertensive medications: plasma aldosterone-renin ratio.

The traditional workup for primary aldosteronism is cumbersome and requires discontinuing antihypertensive medications, which is inconvenient and potentially dangerous. A simple and accurate screening test that can be used without modifying medications is needed. The plasma aldosterone-renin ratio (ARR) is a valid screening assay for primary aldosteronism, but antihypertensives are usually discontinued before obtaining this ratio, limiting its utility. The present prospective study is designed to examine the validity of the ARR as a screening test for primary aldosteronism if the ratio is measured randomly while patients continue antihypertensive therapy. During the 18-month study period, 90 patients were referred to the hypertension clinic with poorly controlled hypertension. ARR was measured in random blood samples in all 90 patients while maintaining their prescribed antihypertensive medications. Those with elevated ARRs (>100 ng/dL / ng/mL/h) underwent further diagnostic workup, including adrenal computed tomography and/or magnetic resonance imaging and adrenal iodine 131 norcholesterol uptake scan. Fifteen patients (17%) had elevated ARRs greater than 100:1. Ten of 15 patients were found to have adrenal adenoma on diagnostic workup, and adenoma was later confirmed by histological examination after surgical removal in these 10 patients. Five patients were found to have adrenal hyperplasia; all 5 patients responded to antialdosterone treatment. Thus, all 15 patients had good control of blood pressure after surgery and/or antialdosterone medications. No patient showed a falsely elevated ARR. Data suggest that the ARR is a valid screening assay for primary aldosteronism in patients with poorly controlled blood pressure, and discontinuation of antihypertensive medications is not needed for this test.

Adenoma↗
PubMed2001

Immobilization and stabilization of invertase on Cajanus cajan lectin support.

Use of lectins as ligands for the immobilization and stabilization of glycoenzymes has immense application in enzyme research and industry. But their widespread use could be limited by the high cost of their production. In the present study preparation of a novel and inexpensive lectin support for use in the immobilization of glycoenzymes containing mannose or glucose residues in their carbohydrate moiety has been described. Cajanus cajan lectin (CCL) coupled covalently to cyanogen bromide activated Seralose 4B could readily bind enzymes such as invertase, glucoamylase and glucose oxidase. The immobilized and glutaraldehyde crosslinked preparations of invertase exhibited high resistance to inactivation upon exposure to enhanced temperature, pH, denaturants and proteolysis. Binding of invertase to CCL-Seralose was however found to be readily reversible in the presence of 1.0 M methyl alpha-D mannopyranoside. In a laboratory scale column reactor the CCL-Seralose bound invertase was stable for a month and retained more than 80% of its initial activity even after 60 days of storage at 4 degrees C. CCL-Seralose bound invertase exhibited marked stability towards temperature, pH changes and denaturants suggesting its potential to be used as an excellent support for the immobilization of other glycoenzymes as well.

Bioreactors↗
PubMed2001

Assembly of gap junction channels: mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants.

The assembly of connexins (Cxs) into gap junction intercellular communication channels was studied. An in vitro cell-free synthesis system showed that formation of the hexameric connexon hemichannels involved dimeric and tetrameric connexin intermediates. Cx32 contains two putative cytoplasmic calmodulin-binding sites, and their role in gap junction channel assembly was investigated. The oligomerization of Cx32 into connexons was reversibly inhibited by a calmodulin-binding synthetic peptide, and by W7, a naphthalene sulfonamide calmodulin antagonist. Removing the calmodulin-binding site located at the carboxyl tail of Cx32 limited connexon formation and resulted in an accumulation of intermediate connexin oligomers. This truncation mutant, Cx32Delta215, when transiently expressed in COS-7 cells, accumulated intracellularly and had failed to target to gap junctions. Immunoprecipitation studies suggested that a C-terminal sequence of Cx32 incorporating the calmodulin-binding site was required for the formation of hetero-oligomers of Cx26 and Cx32 but not for Cx32 homomeric association. A chimera, Cx32TM3CFTR, in which the third transmembrane and proposed channel lining sequence of Cx32 was substituted by a transmembrane sequence of the cystic fibrosis transmembrane conductance regulator, did not oligomerize in vitro and it accumulated intracellularly when expressed in COS-7 cells. The results indicate that amino-acid sequences in the third transmembrane domain and a calmodulin-binding domain in the cytoplasmic tail of Cx32 are likely candidates for regulating connexin oligomerization.

Animals↗
PubMed2001

Triterpenes from Mimusops elengi.

Pentacyclic triterpenes (1) and (2) have been isolated from Mimusops elengi and assigned structures 3beta,6beta,19alpha,23-tetrahydroxy-urs-12-ene and 1beta-hydroxy-3beta-hexanoyllup-20 (29)-ene-23, 28-dioic acid, respectively, on the basis of spectroscopic studies including 2D-NMR. The compound 1 showed moderate inhibiting activity against beta-glucuronidase enzyme

Animals↗
PubMed2001

Vaccinia virus vectors with an inactivated gamma interferon receptor homolog gene (B8R) are attenuated In vivo without a concomitant reduction in immunogenicity.

The vaccinia virus (VV) B8R gene encodes a secreted protein with homology to the gamma interferon (IFN-gamma) receptor. In vitro, the B8R protein binds to and neutralizes the antiviral activity of several species of IFN-gamma, including human and rat IFN-gamma; it does not, however, bind significantly to murine IFN-gamma. Here we report on the construction and characterization of recombinant VVs (rVVs) lacking the B8R gene. While the deletion of this gene had no effect on virus replication in vitro, rVVs lacking the B8R gene were attenuated for mice. There was a significant decrease in weight loss and mortality in normal mice, and nude mice survived significantly longer than did controls inoculated with parental virus. This is a surprising result considering the minimal binding of the B8R protein to murine IFN-gamma and its failure to block the antiviral activity of this cytokine in vitro. Such reduction in virulence could not be determined in rats, since they are considerably more resistant to VV infection than are mice. Finally, deletion of the B8R gene had no detectable effects on humoral immune responses. Mice and rats vaccinated with the rVVs showed identical humoral responses to both homologous and heterologous genes expressed by VV. This study demonstrates that the deletion of the VV B8R gene leads to enhanced safety without a concomitant reduction in immunogenicity.

Animals↗
PubMed2001

Demographic and behavioural profile of adults infected with chlamydia: a case-control study.

OBJECTIVES: To determine which demographic and behavioural parameters are independently associated with chlamydial infection in adults. METHODS: Subjects were recruited prospectively from male and female attendees at a large clinic for sexually transmitted infections (STI). All subjects were tested for chlamydia and gonorrhoea and asked to complete a questionnaire addressing demography, sexual and non-sexual (including drug taking) behaviour, and history of STI. Cases were those attending with a new clinical episode and found to be infected with chlamydia, but who did not have gonorrhoea. A control group was selected randomly from those found to be negative on screening for both infections. RESULTS: 986 cases and 1212 controls were recruited over one calendar year. The following were found to be independent risk factors for chlamydial infection on multivariate analysis (odds ratios with 95% confidence intervals in parentheses): being unmarried (1.8; 1.1-3.1); black Caribbean ethnicity (2; 1.5-2.7). Increasing age, fewer partners, and higher reported use of condoms were associated with a lower risk of infection. CONCLUSION: Black Caribbeans are at increased risk from chlamydia after controlling for sexual behaviour and socioeconomic status. Future research should seek an explanation elsewhere-for example, in terms of differences in sexual mixing or effectiveness of healthcare interventions.

Adolescent↗
PubMed2001

Glutamine protects mitochondrial structure and function in oxygen toxicity.

Glutamine is an important mitochondrial substrate implicated in the protection of cells from oxidant injury, but the mechanisms of its action are incompletely understood. Human pulmonary epithelial-like (A549) cells were exposed to 95% O2 for 4 days in the absence and presence of glutamine. Cell proliferation in normoxia was dependent on glutamine, and glutamine deprivation markedly accelerated cell death in hyperoxia. Glutamine significantly increased cellular ATP levels in normoxia and prevented the loss of ATP in hyperoxia seen in glutamine-deprived cells. Mitochondrial membrane potential as assessed by flow cytometry with chloromethyltetramethylrosamine was increased by glutamine in hyperoxia-exposed A549 cells, and a glutamine dose-dependent increase in mitochondrial membrane potential was detected. Glutamine-supplemented, hyperoxia-exposed cells had a higher O2 consumption rate and GSH content. Electron and fluorescence microscopy revealed that, in hyperoxia, glutamine protected cellular structures, especially mitochondria, from damage. In hyperoxia, activity of the tricarboxylic acid cycle enzyme alpha-ketoglutarate dehydrogenase was partially protected by its indirect substrate, glutamine, indicating a mechanism of mitochondrial protection.

Adenosine Triphosphate↗
PubMed2001

Anticoagulant and antiprotease effects of a novel heparinlike compound from shrimp (Penaeus brasiliensis) and its neutralization by heparinase I.

Heparin is usually obtained from mammalian organs, such as beef lung, beef mucosa, porcine mucosa, and sheep intestinal mucosa. Because of the increased use of heparin in the production of low-molecular-weight heparin (LMWH), there is a growing shortage of the raw material needed to produce LMWHs. A previous report described the structural features of a novel LMWH from the shrimp (Penaeus brasiliensis). In order to compare anticoagulant and antiprotease effects of this heparin, global anticoagulant tests, such as the prothrombin time, activated partial thromboplastin time, thrombin time, and Heptest, were used. Amidolytic anti-Xa and anti-IIa activities were also measured. The relative susceptibility of this heparin to flavobacterial heparinase was also evaluated. The United States Pharmacopeia (USP) potency of shrimp heparin (SH) was found to be 28 U/mg. SH produced a concentration-dependent prolongation of all of the clotting tests and exhibited marked inhibition of FXa and FIIa. Heparinase treatment resulted in a marked decrease of the anticoagulant effects and neutralized the in vitro anti-IIa actions. However, the anti-Xa activities were only partially neutralized. Protamine sulfate was only partially effective in neutralizing the anticoagulant and antithrombin effects of SH. SH also produced marked prolongation of activated clotting time, which was neutralized by heparinase but not by protamine sulfate. These results suggest that SH is a strong anticoagulant with comparable properties to mammalian heparins and can be used in the development of clinically useful antithrombotic-anticoagulant drugs.

Animals↗