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J C Katz

Publications and source records attributed to J C Katz.

5 recordsLinked to original sources
PubMed1986

AIDS hysteria.

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Acquired Immunodeficiency Syndrome↗
PubMed1986

Selective protection against cis-diamminedichloroplatinum(II)-induced toxicity in kidney, gut, and bone marrow by diethyldithiocarbamate.

Diethyldithiocarbamate (DDTC) has been shown to inhibit nephrotoxicity induced by cis-platinum (DDP) without inhibition of tumor response in the rat. We report here that DDTC at doses of 25-300 mg/kg inhibits DDP-induced nephrotoxicity and bone marrow toxicity in C57BL/6 X DBA/2F1 (hereafter called B6D2F1) mice, F344 rats, and beagle dogs and is also antiemetic in the dog. DDTC doses which afford excellent protection do not decrease median survival time following DDP treatment in L1210 and P388 leukemias, B16 melanoma, and Lewis lung and colon 26 carcinomas in B6D2F1 mice when DDTC is given 2 h after DDP. Preliminary experiments indicate that DDTC does not alter median survival time after treatment of P388 leukemia with the platinum analogues diammine(1,1-cyclobutanedicarboxylato)platinum(II) and cis-diisopropylamine-cis-dichloro-trans-dihydroxyplatinum(IV ). Maximum blood urea nitrogen levels after DDP treatment are reduced significantly by DDTC in all species; blood urea nitrogen elevation, total kidney platinum, weight loss, and leukopenia correlate with DDP-DDTC interval in the rat and indicate optimum protection at 2 h, the shortest interval examined. Bone marrow toxicity was assessed by peripheral white blood cell counts in all species and by marrow cellularity in the mouse. White blood cell nadirs were higher and bone marrow recovered more rapidly after DDTC compared with DDP given alone. DDP reduced marrow cellularity 50-60% in the mouse; administration of DDTC 2 h after DDP afforded no protection to the lymphocytes in the marrow but maintained the granulocyte + precursor population near control levels. DDTC plasma pharmacokinetic values have been determined after s.c., i.p., and i.v. administration in the mouse, rat, and dog. Peak plasma levels of 0.3-1.2 mM are observed after a 250-mg/kg dose, with a plasma half-life of 10-20 min. Our data indicate that DDTC may provide protection against most clinically significant toxicities arising from cis-platinum at doses which do not inhibit tumor response.

Animals↗
PubMed1980

Effect of diethyldithiocarbamate rescue on tumor response to cis-platinum in a rat model.

The nephrotoxic effects of cis-dichlorodiamineplatinum(II) (NSC-119875) (DDP) in female F344 rats were effectively inhibited by administration of sodium diethyldithiocarbamate (DDTC) in doses of 750 mg/kg intraperitoneally or 100 mg/kg intravenously 2 hr after administration of DDP. Rats were inoculated with mammary tumor 13762 and treated after 10 days with DDP (2.0 or 8.0 mg/kg) with or without DDTC rescue (750 mg/kg intraperitoneally or 100 mg/kg intravenously). Initial reductions in tumor size were identical with or without rescue in all experiments. High-dose intraperitoneal rescue, however, resulted in earlier relapse and more rapid progressions at both DDP doses than was observed in the absence of rescue. Low-dose intravenous rescue led to a tumor response identical to that observed without rescue. Urinary excretion of free DDTC was increased by prior administration of acetazolamide; however, this combination was more toxic to rats after DDP administration than was DDTC alone. Intravenous administration of DDTC appeared to be the most effective route for delivery of this ligand to the kidney. These results support our earlier mechanistic hypothesis and demonstrate the feasibility of inhibition of cis-platinum toxicity by DDTC without inhibition of the antitumor effect.

Acetazolamide↗