Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypolipidemic activity of tiadenol-disulfoxide, the major metabolite of 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) in man and in the rat was assessed in various experimental models versus the corresponding activity of tiadenol. Tiadenol-disulfoxide in the normolipidemic rats lowers total serum cholesterol and serum and liver triglycerides in an extent comparable to that of the reference compound. Likewise, it is equally effective as tiadenol in preventing Triton-induced hyperlipidemia and Nath diet induced hypercholesterolemia; in addition tiadenol-disulfoxide is slightly more effective than tiadenol in increasing HDL-cholesterol in hypercholesterolemic rats. At hypolipidemic doses the compound causes no hepatomegaly, no induction of peroxisomal catalase and palmitoyl-CoA oxidase activities, no smooth endoplasmic reticulum proliferation and no induction of microsomal cytochrome P-450 and of cytochrome P-450 dependent enzyme activities: aminopyrine (aminophenazone) N-demethylase, aniline hydroxylase, zoxazolamine hydroxylase and hexobarbital oxidase. At the suprapharmacological dose of 300 mg/kg tiadenol-disulfoxide, if compared to the reference compound, shows a generally lower order of toxicity on these hepatic parameters. Orally administered tiadenol-disulfoxide is well absorbed by the gastrointestinal tract and is eliminated in urine at 45% of the dose in unchanged form, and the remaining being: glucuron-conjugated tiadenol-disulfoxide (10%), S-oxidized metabolites (15%) and sulfoxidized carboxylic metabolites (15%). The compound is well tolerated both in mice and rats. The results of this comparative study demonstrate that: 1. tiadenol-disulfoxide is a substance with promising hypolipidemic properties; 2. tiadenol-disulfoxide is largely responsible for the hypolipidemic activity of tiadenol; 3. hepatomegaly consequent to tiadenol administration is the consequence of the response of the liver cell to the increased functional demand of the mixed function oxidase (MFO) system involved in the metabolism of the drug; 4. peroxisomal enzyme activities induction observed with both drugs at non-pharmacological doses does not play any role in their hypolipidemic action and is not associated with hepatomegaly.
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PMID:Experimental studies on pharmacology, metabolism and toxicology with tiadenol-disulfoxide. Dissociation of lipid lowering effects and the induction of peroxisomal and microsomal drug-metabolizing enzymes. 366 66

Aniline is widely used as an intermediate in the synthesis of dyes. It is also used in the manufacture of pharmaceuticals, photographic developers, shoe polish, etc. Exposure to aniline is toxic because it produces methemoglobin. In humans, blood methemoglobin levels are often measured as an index of exposure to aniline. Here a method is described for identification and quantification of aniline by gas chromatography-mass spectrometry after extraction from human serum and derivatization with 2,2,2-trichloroethyl chloroformate. Aniline, along with the internal standard N-methylaniline, were extracted from alkaline serum using chloroform. Aniline and the internal standard were derivatized with 50 microl 2,2,2-trichloroethyl chloroformate. After evaporating excess derivatizing reagent, the residue was reconstituted in 50 microl chloroform and injected into the gas chromatographic-mass spectrometry (GC-MS) system. A positive identification of derivatized aniline can be made by observing strong molecular ions at m/z 267 and 269. Similarly, the derivatized internal standard showed strong molecular ions at m/z 281 and 283. The within-run and between-run precisions of the assay were 3.61 and 5.92%, respectively, at an aniline concentration of 5 mg/l. The assay was linear for serum aniline concentrations of 0.5-25.0 mg/l. The detection limit was 0.1 mg/l. The assay was not affected by lipemia, hemolysis or high bilirubin concentration in serum.
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PMID:Gas chromatographic-mass spectrometric identification and quantification of aniline after extraction from serum and derivatization with 2,2,2-trichloroethyl chloroformate, a novel derivative. 982 51

Aniline, widely used as an intermediate in the synthesis of dye, is also used in the manufacture of pharmaceuticals, photographic developers, shoe polish, and other common substances. Exposure to aniline is toxic because it produces methemoglobin. Aniline levels are usually not measured in serum; in humans, blood methemoglobin levels are often measured as an index of exposure to aniline. In this article, we describe a method for the identification and the quantification of aniline by gas chromatography/mass spectrometry (GC/MS) after its extraction from human serum and derivatization with 4-carbethoxyhexafluorobutyryl chloride. Aniline, as well as the internal standard N-methyl aniline, was extracted from alkaline serum using chloroform. Aniline and the internal standard were derivatized with 50 microL of 4-carbethoxyhexafluorobutyryl chloride. After evaporating the excess derivatizing reagent, the residue was reconstituted in 50 microL of ethyl acetate and injected into the GC/MS. A positive identification of derivatized aniline can be made from the strong molecular ion at m/z 343. Similarly, derivatized internal standard showed a strong molecular ion at m/z 357. The within-run and between-run precisions of the assay were 3.8% and 5.8%, respectively, at an aniline concentration of 5 mg/L. The assay was linear for serum aniline concentrations of 0.5 mg/L to 25.0 mg/L. The detection limit was 0.1 mg/L. The assay was not affected by lipemia, hemolysis, or high bilirubin concentration in serum, and the assay was applicable to whole blood. We also fed mice (C57bl/6) with various concentrations of aniline and measured methemoglobin and blood concentrations of aniline. The methemoglobin percentage and aniline concentrations in blood increased with increasing aniline doses.
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PMID:Gas chromatographic/mass spectrometric identification and quantification of aniline after extraction from serum and derivatization with 4-carbethoxyhexafluorobutyryl chloride, a new derivative. 1021 46

Benzothiophene carboxamide derivatives of aminobenzophenone, aminopyridine, aminobenzimidazole, and aniline derivatives (compounds 1-9) were synthesized and compounds 3, 6, 7, 8, and 9 tested in vivo for their hypolipidemic activity. Compounds 1-8 were prepared adopting the fusion process at 130-150 degrees C between benzothiophene-2-carbonyl chloride and aminobenzophenones, aminopyridine, and anilines, respectively, and were obtained in high yield, while compound 9 was obtained from the reaction of benzothiophene acyl chloride with aminobenzimidazole in DMF at 160 degrees C. At a dose of 15 mg/kg body weight compounds 6, 7, and 9 significantly reduced plasma triglyceride levels in Triton WR-1339-induced hyperlipidemic rats in comparison to control rats. Furthermore, they significantly increased high-density lipoprotein levels. It is therefore reasonable to assume that compounds 6, 7, and 9 may have a promising potential in the treatment of hyperlipidemia and atherosclerosis.
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PMID:Synthesis of benzothiophene carboxamide derivatives and their pharmacological evaluation as potent antihypertriglyceridemic agents in rats. 2163 May 82