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Biomedical subjects

S Seth

Publications and source records attributed to S Seth.

At least 19 recordsLinked to original sources
PubMed1999

CD and NMR investigations on trifluoroethanol-induced step-wise folding of helical segment from scorpion neurotoxin.

A 14 amino acid residue peptide from the helical region of Scorpion neurotoxin has been structurally characterized using CD and NMR spectroscopy in different solvent conditions. 2,2,2-Trifluoroethanol (TFE) titration has been carried out in 11 steps from 0 to 90% TFE and the gradual stabilization of the conformation to form predominantly alpha-helix covering all of the 14 residues has been studied by 1H and 13C NMR spectroscopy. Detailed information such as coupling constants, chemical shift indices, NOESY peak intensities and amide proton temperature coefficients at each TFE concentration has been extracted and analysed to derive the step-wise preferential stabilization of the helical segments along the length of the peptide. It was found that there is a finite amount of the helical conformation in the middle residues 5-11 even at low TFE concentrations. It was also observed that > 75% TFE (v/v) is required for the propagation of the helix to the N and C termini and for correct packing of the side chains of all of the residues. These observations are significant to understanding the folding of this segment in the protein and may throw light on the inherent preferences and side chain interactions in the formation of the helix in the peptide.

Circular Dichroism↗
PubMed1997

Characterization of a 22-residue peptide derived from a designed ion channel.

We have designed a four-helix protein that is expected to tetramerize in the membrane to form an ion channel with a structurally well-defined pore. This should serve as a model system to study the structural requirements of voltage-sensitive, ion-selective transmembrane channels. We have synthesized the peptide corresponding to the channel-lining helix. Circular dichroism (CD) spectroscopy shows that this peptide is helical in the membrane. Fluorescence resonance energy transfer (FRET) shows that this peptide, at low concentrations, forms aggregates in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) liposomes and facilitates ion transport across liposomal membranes. Our data indicate that a component of the designed four-helix protein, i.e., the channel-lining helix, behaves as per design.

Alamethicin↗
PubMed1997

The crystal and molecular structure of (HgL2)n (L = 4,6-dimethylpyrimidine-2-thiolate)--an unusual helical supramolecular assembly in solid phase: in search of a new antidote to mercury poisoning.

An X-ray crystallographic study reveals that in solid phase, 4,6-dimethylpyrimidine-2-thiol (4,6Me2 Pm2SH) forms a multinuclear complex with mercury, containing an open HgN3S2 core and exhibiting a helix-like polymerization through repetitive distant Hg(sp3d) ... N(sp2) interactions along the b axis of the lattice. The complex, therefore, exemplifies a supramolecular assembly, generated by successive vacant ligand site promoted self-associations. It crystallizes in the monoclinic space group P2(1)/c, a = 11.808(2), b = 9.198(2), and c = 14.702(3) A, beta = 112.19(3)0, Z = 4 (monomers). Such self-associative distant interactions are absent in solution phase, as observed from the 1H NMR spectrum (acetone-d6, TMS). A preliminary toxicological study of the pyrimidinethiol ligand reveals a high toxicity at substantially higher doses and appreciably low toxic effects at lower doses. The ligand is also highly potent in inhibiting all common gram negative bacteria (except the acid fast group, which was not tested) and this property may endow it with some side therapeutic uses when considered as an antidote to mercury poisoning following some functional modifications in order to reduce the toxic effects, even when administered at higher doses.

Animals↗
PubMed1997

Protective actions of a thromboxane receptor antagonist, SQ 29548 on the ischemic myocardium: morphologic and hemodynamic effects.

The effects of thromboxane A2 (TXA2)/prostaglandin endoperoxide receptor blockade on myocardial infarct size and cardiac dynamics were determined in a canine model of 24 h acute myocardial infarction. Anesthetized open-chest dogs were subjected to left anterior descending (LAD) coronary artery occlusion. Twenty minutes post-occlusion the dogs were given i.v. saline (0.9% NaCl solution) (n = 12) or the TXA2 receptor antagonist SQ 29548 (0.2 mg/kg i.v. loading dose +0.2 mg/kg/h i.v. for 4 h) (n = 10). SQ 29548 treatment resulted in a significant (P < 0.01) reduction in infarct size. Heart rate (HR) and systolic blood pressure (SAP) were not markedly affected by the drug. The sharp rise in the left ventricular end diastolic pressure (LVEDP) in the saline-treated animals was significantly lowered by SQ 29548 treatment and the correction of this variable was maintained till 24 h post-occlusion. The lowered maximal rate of rise of left ventricular pressure (LVdP/dt max) in the saline-treated animals was corrected albeit non-significantly by the drug treatment. Thus, SQ 29548 treatment resulted in a significant salvage of myocardial tissue and marked alterations in left ventricular dynamics. The study suggests a deleterious role for thromboxane A2 in ischemia; indicating that TXA2 blockade may have potential as a mode of therapy for ischemic heart disease.

Animals↗
PubMed1996

Biological activity of 4-(4-bromophenyl)-thiosemicarbazide.

The two molecules (A and B) in the asymmetric unit of the title compound, C7H8BrN3S, display different conformation. In both molecules, the S atom is trans to the NH2 group. The Br atoms of the two molecules approach each other at a distance of 3.573(2) A. The crystal structure of the bromine compound is isomorphous with that of its chlorine analogue. In the crystal structure, intramolecular N-H...N and intermolecular N-H...S hydrogen bonds help stabilize the molecular packing. The increased antibacterial activity of the title compound compared to that of its chlorine analogue may be attributed to the increase in electron density on the hydrazinic end of the thiosemicarbazide chain.

Anti-Bacterial Agents↗
PubMed1996

Serial blood phosphine levels in acute aluminium phosphide poisoning.

Serial blood phosphine (PH3) levels were done in patients with severe (Group I, n = 30), mild (Group 2, n = 10) and minimal or nil toxicity due to aluminium phosphide compound. Blood phosphine levels were significantly higher (p < 0.001) in patients of Group I than other two groups. Phosphine was not detectable in Group 3 patients. Therefore, blood phosphine levels were positively correlated to clinical grades of toxicity and to dose of active pesticide consumed. Higher the blood phosphine, higher was the mortality. Patients having blood phosphine levels equal to or less than 1.067 +/- 0.16 mg% survived, hence, it appeared to be limit of phosphine toxicity.

Adult↗
PubMed1995

Comparative bioavailability of two brands of norfloxacin.

Twelve adult healthy volunteers participated on two occasions in a cross-over study with an interval of 30 days. The bioavailability of norfloxacin 400 mg administered as single oral dose was compared in an Indian preparation A (Torrent) and imported preparation B (Merck Sharp and Dohme (MSD), USA). Plasma was separated from the blood and stored at -20 degrees C for analysis by High Performance Liquid Chromatography. Time taken to achieve mean peak plasma concentration (Tmax) was 2.00 +/- 0.74 hours in case of Torrent (A) and 1.70 +/- 0.49 hours in case of Merck Sharp and Dohme, USA (B). The maximum plasma concentration (Cmax) ranged from 1.60 to 2.87 ug/ml in Torrent (A) and 1.18 to 2.28 ug/ml in case of MSD (B). Area under plasma concentration curve (AUCO-12hr) was 12.70 +/- 3.2 ug/ml/hour for 'A' and 14.80 +/- 2.80 ug/ml/hr for 'B'. Elimination half life (t1/2) for Torrent (A) was 9.25 +/- 5.10 hours and for MSD (B) it was 12.05 +/- 1.05 hours. There was no significant difference in the pharmacokinetic parameters between the two brands (Student's 't' test). Increased elimination half life and large bioavailability (AUC) with both the preparations in the present study suggest the need to be cautious while treating patients with renal problems and to use lower doses in Indian population to achieve desirable kinetics of norfloxacin.

Administration, Oral↗
PubMed1995

Comparative bioavailability of two brands of ciprofloxacin.

Twelve adult healthy volunteers participated on two occasions in a cross-over study with an interval of 30 days. The bioavailability of ciprofloxacin 500 mg administered as single oral dose was compared in preparation A (Indian, Torrent) and preparation B (Imported, Bayer). The drug was administered early morning on an empty stomach. Blood samples were collected at 1/2,1,2,4,6,8,12 and 24 hours. Plasma levels of ciprofloxacin were determined by HPLC. Time taken to achieve peak plasma concentration (Tmax) was 2 hours (A) and 1.67 +/- 0.49 hours (B). Maximum plasma concentration (Cmax) ranged from 1.8 to 5.1 ug/ml (mean 3.08 +/- 0.99 ug/ml) for 'A' and 2.08 to 5.5 mu g/ml (mean 3.58 +/- 1.37 mu g/me for 'B'. Area under plasma concentration time curve ranged from 30.91 to 118.27 ug/ml/hr (mean 59.97 +/- 26.68 ug/ml/hr) in 'A' and 36.52 to 108.05 (mean 62.80 +/- 22.33 ug/ml/hr) in 'B' which is more than reported in Western literature. Large bioavailability of ciprofloxacin in the present study suggests the need to be cautious while treating patients with renal problems and to use lower doses in Indian patients to achieve desirable results. However, there was no significant difference in the pharmacokinetic parameters between the two brands (Paired 't' test and Wilcoxon Sign Rank test). It is therefore, concluded that both the preparations are comparable in terms of bioavailability.

Administration, Oral↗
PubMed1994

Alteration in blood gases in tetanus.

Tetanus is an important cause of patient mortality. Hypoxia is an important determinant of poor prognosis in tetanus. Oxygen saturation (Sa02) determines effectiveness of muscle relaxants. We performed arterial blood gas (ABG) studies in 20 patients with tetanus and 20 controls. All patients had hypoxemia and metabolic acidosis at admission. The mortality rate in patients with admission PaO2 < 70mm Hg was higher compared to those with PaO2 > 70mm Hg (P < 0.01). Patient with pH < 7.2 had higher mortality compared to those with pH > 7.2 (p < 0.05). Severe hypoxemia and severe metabolic acidosis connoted poor prognosis.

Acidosis↗
PubMed1993

Effect of atenolol and labetalol on serum lipids.

Adverse alterations in lipid profile suggesting higher atherogenicity were observed following 12 weeks treatment with atenolol in patients of hypertension. No significant alterations in lipid profile were observed with labetalol therapy.

Atenolol↗
PubMed1992

Evidence for verapamil-induced functional inhibition of noradrenergic neurotransmission in vivo.

Contractions of the cat nictitating membrane have been used to explore the effects of calcium channel blockers on neurotransmission in vivo, by comparing the effects of verapamil and nifedipine on contractions of nictitating membrane following either electrical stimulation of the superior cervical ganglion or intravenous injection of the alpha-adrenoceptor agonist phenylephrine. Verapamil (0.3, 0.6 and 1.2 mg/kg, iv) produced a dose related and reversible inhibition of stimulation induced contractions but did not affect phenylephrine responses of nictitating membrane. Intravenous nifedipine (10, 20 and 40 micrograms/kg) produced inconsistent effects on both stimulation- and phenylephrine-induced contractions of the nictitating membrane. Thus only verapamil appears to selectively affect noradrenergic neurotransmission in this model, possibly by altering the neurotransmitter release from the terminals innervating the nictitating membrane in the cat.

Adrenergic Fibers↗
PubMed1992

Gastrointestinal endoscope disinfection practices in India: results of a national survey.

A questionnaire was sent to 435 endoscopy centers in the country to obtain information regarding current endoscopic disinfection practices. Of these, 133 (30.6%) centers responded. Adequate disinfection (a minimum exposure to 1% glutaraldehyde for 2 minutes) before the start of endoscopy sessions and between procedures was practised in 61 (46%) and 45 (34%) centers respectively. The proportion of centers practising adequate disinfection was similar among those performing < 1500 and > 1500 endoscopies/year (50% vs 36%; p = ns). Twenty two (17%) centers used some additional precautions in patients with hepatitis B virus infection or immunocompromised states. Two (1.5%) of the 133 centers performing upper GI endoscopies and eight (18%) of the 44 centers performing ERCP examinations reported occurrence of infections following these procedures. Allergic reactions to disinfectants were reported by five (4%) centers. We conclude that only about a third of the gastroenterology centers in the country are practising adequate endoscope disinfection routinely.

Cross Infection↗