Biomedical subjects

M Hashmi

Publications and source records attributed to M Hashmi.

21 records · Page 2Linked to original sources

PubMedDate not supplied

Bioactivation of [13C]dichloromethane in mouse, rat, and human liver cytosol: 13C nuclear magnetic resonance spectroscopic studies.

Dichloromethane is tumorigenic in lungs and liver of B6C3F1 mice, but is not tumorigenic in rats or hamsters, and its toxicity is associated with glutathione-dependent bioactivation. The objective of the present studies was to investigate the glutathione-dependent bioactivation of [13C]dichloromethane in mouse, rat, and human liver cytosol and the fate of dichloromethane-derived reactive intermediates with 13C NMR. [13C]Formaldehyde hydrate, [13C]S-(hydroxymethyl)glutathione, and [13C]methanol were identified as metabolites of [13C]dichloromethane. [13C]S-(Chloromethyl)glutathione, a putative intermediate in the glutathione-dependent bioactivation of dichloromethane, or derived adducts were not observed. Moreover, no evidence for the formation of S,S'-methylenebis[glutathione] by reaction of glutathione and formaldehyde under physiological conditions was obtained, although methanol was observed as a product. S,S'-Methylenebis[glutathione] was, however, formed by reaction of glutathione and formaldehyde at pH 1. S-(Chloromethyl)-N-acetyl-L-cysteine methyl ester, a surrogate for S-(chloromethyl)glutathione, was prone to hydrolysis. These results corroborate the finding that formaldehyde is a reactive intermediate formed during the glutathione-dependent bioactivation of dichloromethane that may be involved in the observed tumorigenicity of dichloromethane in susceptible species. The results also indicate that S-(chloromethyl)glutathione is an intermediate in the glutathione-dependent bioactivation of dichloromethane and may also play a role in its mutagenicity and carcinogenicity.

Animals↗

PubMedDate not supplied

Fourier-transform ion cyclotron resonance mass spectrometric evidence for the formation of alpha-chloroenethiolates and thioketenes from chloroalkene-derived, cytotoxic 4-thiaalkanoates.

The cytotoxicity of chloroalkene-derived cysteine S-conjugates is thought to be associated with the formation of alpha-chloroenethiolates and thioketenes as reactive intermediates. Recent studies indicate that the formation of 1,2-dichloroethenethiolate, which may give rise to chlorothioketene, is a key step in the bioactivation of 5,6-dichloro-4-thia-5-hexenoic acid (Fitzsimmons et al. (1995) Biochemistry 34, 4276-4286). We report here the use of Fourier-transform ion cyclotron resonance mass spectrometry to provide the first direct evidence for the formation of alpha-chloroenethiolate and thioketene species from a cytotoxic 4-thiaalkanoate. The bioactivation of 5,6-dichloro-4-thia-5-hexenoic acid involves conversion to the corresponding CoA thioester 5,6-dichloro-4-thia-5-hexenoyl-CoA and subsequent processing by the fatty acid beta-oxidation pathway. It has been proposed that the bioactivation of 5,6-dichloro-4-thia-5-hexenoyl-CoA involves loss of 1,2-dichloroethenethiolate, followed by loss of chloride to form chlorothioketene. 1,2-Dichloroethenethiolate and related alpha-chloroalkenethiolates have not been observed directly in aqueous solution. Fourier-transform ion cyclotron resonance mass spectrometric experiments show that S-propyl 5,6-dichloro-4-thia-5-hexenethioate reacts in the gas phase with base (hydroxide ion) to release 1,2-dichloroethenethiolate, which is observed directly in the mass spectrum of the products of the gas-phase reaction. Furthermore, the elimination of chloride from 1,2-dichloroethenethiolate on collision-induced decomposition is facile and provides evidence for chlorothioketene formation. Preliminary evidence for the formation of 1,2-dichloroethenethiolate and chlorothioketene from S-(1,2-dichlorovinyl)-N-acetyl-L-cysteine methyl ester was also obtained. These observations support the intermediacy of alpha-chloroenethiolates and chlorothioketenes in the bioactivation of cytotoxic, chloroalkene-derived 4-thiaalkanoates and cysteine S-conjugates and demonstrate the utility of Fourier-transform ion cyclotron mass spectrometry in studying the formation of reactive intermediates.

Acetylcysteine↗

PubMedDate not supplied

Post-laparoscopic cholecystectomy bile leak secondary to an accessory duct of Luschka.

Intraperitoneal bile collection following laparoscopic cholecystectomy has been reported to occur in 0.2-2% of cases and appears to be slightly higher than when the open technique is used. When the injuries of the common bile duct, technical problems with the cystic duct, diathermic injuries to the biliary tree, and iatrogenic interruption of congenital anomalous of the biliary tree are excluded, the iatrogenic transaction of the cholecystohepatic ducts commonly known as the 'Ducts of Luschka' should be considered as the cause of the biliary leak. This article reports a case of bile leakage due to an unrecognized division of a large duct of Luschka within the gall bladder fossa during laparoscopic cholecystectomy and reviews clinical diagnosis, radiological confirmation, and the appropriate treatment for this uncommon complication of laparoscopic cholecystectomy.

Adult↗