ABSTRACT
OBJECTIVES: We report the efficacy of alteplase (a recombinant tissue plasminogen activator) with heparin or heparin alone in the treatment of acute thrombosis of the portal venous system. METHODS: Ten consecutive patients with acute portal venous system thrombosis were studied. Five patients were treated with alteplase and heparin, and the remaining 5 patients, who were asymptomatic or had a contraindication to alteplase, were treated with heparin alone. RESULTS: In 3 of the 5 patients treated with alteplase, ultrasonography showed total resolution of the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the 5 patients treated with heparin alone, ultrasonography showed total resolution of the thrombus, and no change in one. No bleeding occurred. CONCLUSION: Treatment with heparin can result in complete recanalisation of acute portal venous system thrombosis. These data suggest that combined therapy with systemic alteplase does not increase the efficacy of heparin.
Subject(s)
Anticoagulants/therapeutic use , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Portal System , Thrombosis/drug therapy , Tissue Plasminogen Activator/therapeutic use , Acute Disease , Adult , Aged , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
A case of obstructive intramural hematoma of the esophagus post variceal sclerotherapy is reported in a 44-year-old man who presented retrosternal pain and complete dysphagia. Endoscopy showed a bluish submucosal mass occupying the esophageal lumen. Diagnosis was confirmed by Computed Tomography. A favorable outcome was observed with symptomatic treatment.
Subject(s)
Esophageal Diseases/etiology , Hematoma/etiology , Sclerotherapy/adverse effects , Adult , Esophageal and Gastric Varices/therapy , Humans , MaleABSTRACT
The urinary metabolites of n-nonane in male Fischer 344 rats, after administering the hydrocarbon by gavage, included gamma-valerolactone, delta-hexanolactone, 2,5-hexanedione, delta-heptanolactone, 1-heptanol, 2-nonanol, 3-nonanol, 4-nonanol, 4-nonanone and 5-methyl-2-(3-oxobutyl)furan. Metabolism strongly favored the formation of monoalcohols and lactones, which are the products of appropriately substituted hydroxy carboxylic acids. The metabolites were identified using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). High pressure liquid chromatography (HPLC) permitted the detection of the dicarboxylic acids malonic acid and glutaric acid in the n-nonane dosed rat urines.
Subject(s)
Alkanes/metabolism , Alcohols/urine , Alkanes/urine , Animals , Chromatography, High Pressure Liquid , Furans/urine , Gas Chromatography-Mass Spectrometry , Hexanones/urine , Lactones/metabolism , Lactones/urine , Male , Rats , Rats, Inbred F344Subject(s)
Carcinoma, Squamous Cell/complications , Deglutition Disorders/drug therapy , Endoscopy, Digestive System/methods , Esophageal Neoplasms/complications , Ethanol/therapeutic use , Adenocarcinoma/complications , Adolescent , Adult , Aged , Aged, 80 and over , Deglutition Disorders/etiology , Ethanol/administration & dosage , Ethanol/adverse effects , Female , Humans , Male , Middle AgedABSTRACT
Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests.
Subject(s)
Acidosis/chemically induced , Indicators and Reagents/toxicity , Picrates/toxicity , Administration, Oral , Animals , Biological Availability , Blood Gas Analysis , Dose-Response Relationship, Drug , Female , Half-Life , Indicators and Reagents/administration & dosage , Indicators and Reagents/pharmacokinetics , Injections, Intravenous , Intestinal Absorption , Lethal Dose 50 , Male , Picrates/administration & dosage , Picrates/pharmacokinetics , Rats , Rats, Inbred F344 , Tissue DistributionABSTRACT
Indan, a component of fuels, solvents, and varnishes, is metabolized in male Fischer 344 rats to 1-indanol, 2-indanol, 5-indanol, 1-indanone, 2-indanone, 2-hydroxy-1-indanone, cis-1,2-indandiol, and trans-1,2-indandiol. The metabolites were identified using the techniques of gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The rats treated with indan demonstrated the classic lesions of hydrocarbon-induced nephropathy. The kidney damage produced was less than that found for tetralin and other branched-chain acyclic hydrocarbons.
Subject(s)
Indans/toxicity , Indenes/toxicity , Kidney/drug effects , Administration, Oral , Animals , Gas Chromatography-Mass Spectrometry , Indans/metabolism , Indans/urine , Kidney/metabolism , Male , Rats , Rats, Inbred F344ABSTRACT
Tetralin, a component of fuels, solvents, and varnishes, is metabolized in male Fischer 344 rats to 1-tetralol, 2-tetralol, 2-hydroxyl-1-tetralone, 4-hydroxyl-1-tetralone, 1,2-tetralindiol, and 1,4-tetralindiol. Rats treated with tetralin demonstrated the classic lesions of hydrocarbon-induced nephropathy.
Subject(s)
Kidney Diseases/urine , Naphthalenes/metabolism , Tetrahydronaphthalenes/metabolism , Animals , Chromatography, Gas , Environmental Exposure , Humans , Kidney Diseases/chemically induced , Male , Paint/adverse effects , Rats , Rats, Inbred F344 , Solvents/adverse effects , Tetrahydronaphthalenes/adverse effects , Tetrahydronaphthalenes/toxicityABSTRACT
The metabolism of isopropylcyclohexane and associated renal pathology were evaluated in male Fischer 344 rats exposed by oral gavage. The rats experienced moderate proximal tubular damage similar to that produced by acyclic, branched-chain hydrocarbons. The urinary metabolites of isopropylcyclohexane included cis-4-isopropylcyclohexanol, trans-4-isopropylcyclohexanol, 2-cyclohexylpropanoic acid, 2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-isopropylcyclohexanol, 2c-hydroxy-4c-isopropyl-cyclohexanol, and 2c-hydroxy-4t-isopropylcyclohexanol. The extent and preferred sites of oxidative metabolism of nephrotoxic hydrocarbons could potentially prove useful in elucidating the pathogenic mechanisms.
Subject(s)
Cyclohexanes/metabolism , Kidney Tubules/metabolism , Administration, Oral , Animals , Chromatography, Gas , Cyclohexanes/toxicity , Cyclohexanes/urine , Kidney Tubules/drug effects , Male , Rats , Rats, Inbred F344ABSTRACT
The molecule t-butylcyclohexane is one of the first examples of a branched alkyl group attached to a hydrocarbon ring shown to be capable of producing renal damage at the corticomedullary junction of male rats. A metabolic study of t-butylcyclohexane yielded the following urinary metabolites: trans-4-t-butylcyclohexanol, 2c-hydroxy-4t-t-butylcyclohexanol, 2-methyl-2-cyclohexylpropanoic acid, 2c-hydroxy-4c-t-butylcyclohexanol, 2-methyl-2-cyclohexyl-1,3-propanediol, 2t-hydroxy-4t-t-butylcyclohexanol, and cis -4-t-butylcyclohexanol. As with other hydrocarbons of similar molecular weight that induce nephropathy in male rats, preferential sites of oxidative metabolism were observed that could potentially be related to the pathogenesis.
Subject(s)
Cyclohexanes/metabolism , Kidney Diseases/chemically induced , Animals , Male , Molecular Conformation , Rats , Rats, Inbred F344 , Structure-Activity RelationshipABSTRACT
Branched-chain hydrocarbon-induced nephropathy in male rats was examined using 2,3,4-trimethylpentane. Lesions are elected only in male rats, not in females or in controls. Mechanisms of nephropathy may be the interaction of metabolites with the male rat-specific protein alpha 2u globulin. The identified urinary metabolites of 2,3,4-trimethylpentane in male rats given the hydrocarbon by gavage are 2,3,4-trimethyl-1-pentanol, 2,3,4-trimethyl-2-pentanol and 2,3,4-trimethyl-1-pentanoic acid. Of the C8-isomers, 2,3,4-trimethylpentane dosing leads to the highest incidence of kidney damage in male rats.
Subject(s)
Pentanes/urine , Animals , Chromatography, Gas/methods , Gas Chromatography-Mass Spectrometry/methods , Indicators and Reagents , Kidney/drug effects , Kidney/pathology , Male , Pentanes/toxicity , Rats , Rats, Inbred F344ABSTRACT
The identified urinary metabolites of male rats exposed to indan are: 1- and 2-indanone; 1-, 2- and 5-indanol; 2- and 3-hydroxyl-1-indanone; and cis- and trans-indan-1,2-diol. Indan causes kidney damage in male rats in a manner similar to the cyclic hydrocarbons cis- and trans-decalin and JP-10. Lesions produced by indan occur only in male rats and not in female or control rats.
Subject(s)
Indans/urine , Indenes/urine , Administration, Oral , Animals , Gas Chromatography-Mass Spectrometry/methods , Indans/administration & dosage , Male , RatsABSTRACT
The urinary metabolites of the potent nephrotoxic hydrocarbon 2,3,4-trimethylpentane (2,3,4-TMP) given Fischer-344 male rats by gavage included 1-hydroxy-2,3,4-trimethylpentane, 2,3,4-trimethyl-1-pentanoic acid and 2,3,4-trimethyl-5-hydroxy-1-pentanoic acid. Analyses were performed by gas-liquid chromatography (GC) and gas-liquid chromatography/mass spectrometry (GC/MS). A comparison of the urinary metabolites of 2,3,4-TMP with those of 2,2,4-trimethylpentane (2,2,4-TMP) showed that more monocarboxylic acid was produced with 2,3,4-TMP.
Subject(s)
Pentanes/urine , Animals , Biotransformation , Chromatography, Gas , Gas Chromatography-Mass Spectrometry , Male , Octanes/urine , Rats , Rats, Inbred F344ABSTRACT
The urinary metabolites of n-octane in Fischer 344 rats given the hydrocarbon by gavage included 2-octanol, 3-octanol, 5-oxohexanoic acid, and 6-oxoheptanoic acid. The sex of the animals influenced the relative amounts of metabolites formed. Analyses were performed by gas-liquid chromatography (GC) and gas-liquid chromatography/mass spectrometry (GC/MS). This is the first reported finding of keto acids in hydrocarbon oxidative metabolism. No kidney damage was found as a result of n-octane dosing although the 2,2,4-trimethylpentane (iso-octane) isomer does cause kidney lesions in male rats.
Subject(s)
Octanes/metabolism , Octanols/urine , Administration, Oral , Animals , Chromatography, Gas , Female , Gas Chromatography-Mass Spectrometry , Kidney/drug effects , Kidney/metabolism , Male , Octanes/toxicity , Rats , Rats, Inbred F344 , Sex FactorsABSTRACT
The cis- and trans-decalin stereoisomers have found many uses as solvents and fuel components. The metabolism of the decalin isomers in male and female Fischer-344 rats and the effects of the decalins on renal damage were evaluated. Only male rats had kidney damage. Metabolism of cis-decalin yielded cis,trans-1-decalol and cis,cis-2-decalol in the urine of both sexes, with the male also producing cis,cis-1-decalol. The urinary metabolites of trans-decalin included trans,cis-2-decalol in both male and female rats and trans,trans-1-decalol in males. Extracts of kidney homogenates from male rats, but not from females, dosed with cis- and trans-decalin yielded cis-2-decalone and trans-2-decalone, respectively. A single male rat treated with trans-decalin produced no 2-decalone in the kidney extract and also showed no renal damage.
Subject(s)
Kidney/drug effects , Naphthalenes/metabolism , Animals , Female , Kidney/metabolism , Kidney/pathology , Male , Naphthalenes/toxicity , Rats , Rats, Inbred F344 , Sex Factors , StereoisomerismABSTRACT
The compound 2,2,4-trimethylpentane (2,2,4 TMP) is reported to be especially potent in inducing kidney lesions in male rats (1,2). Although the pathology produced by 2,2,4 TMP has been examined (1), there are no reports concerning the metabolism of 2,2,4 TMP by the male rat. The eight principal urinary metabolites of 2,2,4 TMP found in the urine of Fischer 344 male rats are: 2,2,4-trimethyl-1-pentanol, 2,4,4-trimethyl-1-pentanol, 2,4,4-trimethyl-2-pentanol, 2,2,4-trimethyl-1-pentanoic acid, 2,4,4-trimethyl-1-pentanoic acid, 2,4,4-trimethyl-2-hydroxy-1-pentanoic acid, 2,2,4-trimethyl-5-hydroxy-1-pentanoic acid and 2,4,4-trimethyl-5-hydroxy-1-pentanoic acid.
Subject(s)
Kidney/drug effects , Octanes/metabolism , Animals , Caprylates/urine , Hydroxy Acids/urine , Male , Octanes/toxicity , Octanols/urine , Rats , Rats, Inbred F344ABSTRACT
The identification of the metabolites of the Air Force missile fuel JP-10 was accomplished. 5-Hydroxy-JP-10 was identified as the urinary metabolite of rats, mice and hamsters exposed to JP-10. 5-Keto-JP-10 was a major metabolite found in kidney extracts of male rats exposed to JP-10 but not found in kidney extracts from female rats or from other species. Sex-related differences in the formation of 5-keto-JP-10 in rats were studied.
Subject(s)
Indans/urine , Indenes/urine , Animals , Cricetinae , Environmental Exposure , Female , Gas Chromatography-Mass Spectrometry , Male , Mice , Rats , Rats, Inbred F344ABSTRACT
Theoretical reactivity indices have been used to examine the metabolic reactions presumed, on the basis of recent biochemical evidence, to be responsible for the transformation of polycyclic aromatic hydrocarbon precarcinogens to ultimate carcinogens. Of a large number of indices examined, several show strong correlations with carcinogenic activity in a set of 25 representative compounds. The results support the belief that specific transformations involving dihydrodiol, "bay-region" epoxide, and carbonium ion intermediates are responsible for the carcinogenic activity of these compounds. Additional implications of the results are discussed, including the suggestion that this type of analysis might provide a rapid and simple means for prescreening compounds for potential carcinogens.