Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin-induced oxidative stress is investigated in rats by measuring changes in plasma and lung tissue levels of glutathione disulfide (GSSG) using a modified enzymatic assay that allows simultaneous measurement of up to 80 samples. Salmonella enteritidis endotoxin (2 and 20 mg/kg) acutely increased both plasma reduced glutathione and GSSG with a rise in the ratio of GSSG to total glutathione. This increase in GSSG was enhanced by pretreatment with 1,3-bis(2-chloroethyl)1-nitrosourea (BCNU), an inhibitor of the glutathione reductase enzyme. However, there was no significant arteriovenous difference in plasma GSSG across the lung, and lung tissue GSSG did not increase after endotoxin treatment. The increase in plasma GSSG was not blocked by vinblastine-induced neutropenia and could not be reproduced by incubating rat blood in vitro with endotoxin. Receptor antagonists of platelet-activating factor (PAF), at a dose that previously inhibited endotoxin-induced lung injury, attenuated the endotoxin-induced increase in plasma GSSG. We conclude that endotoxin causes neutrophil-independent oxidative stress in rats, which may be enhanced by the action of platelet-activating factor.
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PMID:Endotoxin causes neutrophil-independent oxidative stress in rats. 304 43

Indisulam (E7070) is an anticancer agent that is currently being evaluated in phase II clinical studies. A significant reduction in glutathione synthetase and glutathione reductase transcripts by indisulam provided a molecular basis for its combination with platinum agents. Indisulam demonstrated high anti-tumour activity in various preclinical cancer models. The objectives of this study were (1) to determine the recommended dose of indisulam in combination with carboplatin in patients with solid tumours and (2) to evaluate the pharmacokinetics of the combination. Patients with solid tumours were treated with indisulam in combination with carboplatin. Indisulam (350, 500, or 600 mg m(-2)) was given as a 1-hour intravenous infusion on day 1 and carboplatin (5 or 6 mg min ml(-1)) as an intravenous infusion over 30 min on day 2 of a three-weekly cycle. Sixteen patients received study treatment and were eligible. Thrombocytopenia was the major dose limiting toxicity followed by neutropenia. Both drugs contributed to the myelosuppressive effect of the combination. Indisulam 500 mg m(-2) in combination with carboplatin 6 mg min ml(-1) was identified not to cause dose limiting toxicity, but a delay of re-treatment by 1 week was required regularly to allow recovery from myelosuppression. The recommended dose and schedule for an envisaged phase II study in patients with non-small cell lung cancer is indisulam 500 mg m(-2) in combination with carboplatin 6 mg min ml(-1) repeated four-weekly. Patients who do not experience severe thrombocytopenia at cycle 1 will be permitted to receive an escalated dose of indisulam of 600 mg m(-2) from cycle 2 onwards.
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PMID:A phase I and pharmacokinetic study of indisulam in combination with carboplatin. 1728 28