The in vitro liver microsomal oxidation of eptam (ethyl N,N-dipropylthiocarbamate) in the presence of freshwater and salt water adapted striped bass liver microsomes was investigated. In freshwater hepatic microsomes from striped bass, eptam is S-oxygenated in a process consistent with the involvement of monooxygenase activity. In contrast, both eptam S-oxide and eptam sulfone are formed in microsomes from salt water adapted striped bass microsomes in a process that is independent of monooxygenase activity and consistent with a role of cooxidation by hydroperoxy fatty acids. The mechanism of oxidation of eptam by hydroperoxy fatty acids may involve radical species. Both eptam S-oxide and eptam sulfone are efficient carbamylating agents toward thiol nucleophiles and react with substituted thiophenols to produce thiocarbamates while eptam itself is relatively stable to trans thiocarbamylation. Monooxygenase-catalyzed S-oxygenation of eptam in freshwater striped bass hepatic microsomes may represent a bioactivation route, which may explain the toxicity of thiocarbamate herbicides such as eptam toward freshwater fish.

Animals↗

PubMedDate not supplied

Chronic toxic effects of polyphenyl mixtures.

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Animals↗

PubMedDate not supplied

Accelerator mass spectrometry (AMS): recent experience of its use in a clinical study and the potential future of the technique.

1. The technique of accelerator mass spectrometry (AMS) is outlined. 2. The use of AMS in an initial validation study in animals is outlined. As part of the validation of the technique, samples from the animal study were analysed by both liquid scintillation counting (LSC) and, following dilution, by AMS. The results were similar. 3. The use of AMS in support of a clinical study is described. Six healthy male human volunteers were administered 2.7 mg [14C]-GI1817771 (121 Bq; 3.3nCi) to produce an exposure to ionizing radiation of 0.06 microSv. Mass balance in recovery of administered radioactivity was achieved and information about the presence of systemically circulating metabolites was gained. 4. The future potential of the technique of AMS is discussed.

Administration, Oral↗

PubMedDate not supplied

Giant platelet disorders in African-American children misdiagnosed as idiopathic thrombocytopenic purpura.

A retrospective chart review of six African-American children with a diagnosis of macrothrombocytopenias (MTCP) was performed to evaluate the accuracy of their diagnosis. The following was diagnosed in the six children with MTCP: Fechtner syndrome (two children), Sebastian syndrome (one child), and unnamed MTCP (three children). In five families, chronic idiopathic thrombocytopenic purpura (ITP) was diagnosed in the propositus, which resulted in therapy using steroids, intravenous immunoglobulin (IVIG), and in one case splenectomy. Bleeding symptoms were generally mild. All six patients had thrombocytopenia ranging from 10 to 125 x 10(9)/L with mean platelet volume of 8 to 20 fL. Bleeding times were abnormal in two of three patients, and platelet aggregation was abnormal in three of four patients tested. Bone marrow aspirates were reported as increased megakaryocytes in the three patients on whom the procedure was performed. Ultrastructural morphology of platelets and leukocytes was performed in all six patients demonstrating giant platelets in all six patients and leukocyte inclusions in three patients. Differentiating MTCP from the more common ITP can be difficult but important in avoiding unnecessary diagnostic studies and potentially harmful therapy associated with ITP.

Bernard-Soulier Syndrome↗

PubMedDate not supplied

Dietary modulation of colonic mucosal urokinase activity in rats.

The amount and type of dietary fibre ingested influences colonic luminal characteristics, especially the concentration of carbohydrate fermentation products such as butyrate. This study aimed to assess whether diets supplemented with fibres of differing fermentability (delivering different amounts of butyrate to the colon) influence mucosal activities of urokinase and brush border hydrolases, and epithelial turnover. Groups of five rats were fed one of four diets containing low (2%), highly fermented (guar 10% or oat bran 10%) or slowly fermented fibre (wheat bran 10%) for 4 weeks. Activities of urokinase, alkaline phosphatase, dipeptidyl peptidase IV and maltase were measured in mucosal homogenates of proximal and distal colon and from rectum. Proliferative kinetics were assessed in distal and proximal colon by the metaphase arrest technique. Hydrolase activities were similar across all four dietary groups but a significant difference was found for urokinase (P = 0.014). This was due to a reduction in urokinase activities of > 30% at the three sites in the wheat bran group compared with the other groups. Of proliferative indices, only crypt column height differed across the groups (P = 0.038) and was highest in rats fed wheat bran and lowest in those fed the low fibre diet (P = 0.047). The proportion of mitoses in the top one-fifth of the crypt also differed across groups (P = 0.038) due to the high values in the distal colon of the low fibre group. Thus, addition of a slowly fermented (but not highly fermented) fibre to the diet of rats reduces net urokinase activity in large bowel mucosa and increases the life span of colonic epithelial cells without changing activities of brush border hydrolases.

Alkaline Phosphatase↗