Biomedical subjects

A S Kulkarni

Publications and source records attributed to A S Kulkarni.

At least 19 recordsLinked to original sources

PubMed2004

Novel S-substituted aminoalkylamino ethanethiols as potential antidotes against sulfur mustard toxicity.

Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, aryl, and heterocyclic substituents, have been designed and synthesized as candidate antidotes against SM toxicity. These compounds were screened for their protective efficacy through the oral route against dermally applied sulfur mustard in female mice measured on the basis of percent survival following percutaneous administration of SM. A number of compounds demonstrated significant protection.

Animals↗

PubMed2002

In vivo protection by amifostine and DRDE-07 against sulphur mustard toxicity.

The study was aimed at investigating the prophylactic efficacy of orally administered amifostine and a newly synthesized compound, S-2(2-amino-ethylamino)ethyl phenyl sulphide (DRDE-07), against dermally applied sulphur mustard (SM) in mice and rats. The LD50 values of amifostine and DRDE-07 were determined following oral and intraperitoneal routes and the LD50 of SM diluted in PEG-300 was determined following dermal route. Amifostine or DRDE-07 (equivalent to their 0.05 LD50, 0.10 LD50 and 0.20 LD50) dissolved in water was fed to mice and rats and, after 30 min, various doses of SM were applied to the hair-clipped area of the skin and were observed for 14 days for mortality. The protection index (PI) was calculated as a ratio of LD50 with treatment to LD50 without treatment. The estimated percutaneous LD50 of SM was found to be 8.1 and 2.4 mg/kg for female mice and male rats, respectively. A dose-related protection was observed with all the three doses of both compounds. Thirty minutes prior, the administration of amifostine in female mice offered a PI of 3.0 at the lowest pretreatment dose (52.5 mg/ kg) followed by PI of 6.7 and 9.5 at 105 and 210 mg/kg pretreatment doses, respectively. DRDE-07 offered better protection against SM in female mice, i.e., a PI of 4.8 at pretreatment dose of 62.5 mg/kg, a PI of 12.0 at the dose of 124.7 mg/kg and a PI of 27.0 at the dose of 249.4 mg/kg. In male rats, DRDE-07 gave a PI of about 3.0 at all the three pretreatment doses (80, 160 and 320 mg/kg), whilst amifostine offered a PI of 3.1 at the highest pretreatment dose (452 mg/kg). The present study showed that oral administration of both amifostine and DRDE-07 was effective as a prophylactic agent for protecting against SM toxicity, and that DRDE-07 offered better protection.

Administration, Cutaneous↗

PubMed1999

Membrane-interaction QSAR analysis: application to the estimation of eye irritation by organic compounds.

PURPOSE: The purpose of this study was to explore a potential mechanism of eye irritation, and to construct a corresponding general quantitative structure-activity relationship (QSAR) model, in terms of diversity of irritant chemical structure, based on the Draize eye irritation ECETOC data set. METHODS: Molecular dynamic simulation (MDS) was used to generate intermolecular membrane-solute interaction properties. These intermolecular properties were combined with intramolecular physicochemical properties and features of the solute (irritant) to construct QSAR models using multi-dimensional linear regression and the Genetic Function Approximation (GFA) algorithm. RESULTS: Significant QSAR models for estimating eye irritation potential were constructed in which solute aqueous solvation free energy and solute-membrane interaction energies are the principle correlation descriptors. These physicochemical descriptors were selected from a trial set of 95 descriptors for 18 structurally diverse compounds fully representative of the ECETOC set of 38 compounds. CONCLUSIONS: Combining intermolecular solute-membrane interaction descriptors with intramolecular solute descriptors yields statistically significant eye irritation QSAR models. The resultant QSAR models support an eye irritation mechanism of the action in which increased aqueous solubility of the irritant and its strength of binding to the membrane both increase eye irritation.

Animals↗

PubMed1989

Single dose therapy of ascariasis--a randomized comparison of mebendazole and pyrantel.

A multicentre, randomized trial was carried out to compare the efficacy of two single-dose treatments for ascariasis: mebendazole 200 mg, and pyrantel 10 mg/kg. Each centre enrolled 200 patients with a suspected diagnosis of ascariasis, 100 for each treatment, and the treatments were randomized for each centre. To confirm the diagnosis, stools were examined for eggs of Ascaris lumbricoides by Kato's thick smear method. Efficacy was evaluated by stool examination repeated three weeks after treatment by a "blind" technician using two methods, viz. Kato's thick smear method and the zinc sulfate flotation method. Cure was defined as absence of ascaris eggs in the stools by both methods. Of the 600 enrolled patients, 32 were excluded from analysis as their initial stool examination was negative, and 568 completed the trial: 284 on each treatment. The cure rate was 80 per cent in the mebendazole group and 90 per cent in the pyrantel group (P less than 0.01). Thus pyrantel was found to be significantly more efficacious than mebendazole for single-dose treatment of ascariasis.

Adolescent↗

PubMed1978