Serological changes following a single intravenous Corynebacterium parvum injection in the rat

Summary Changes in circulating levels of immunoglobulins (IgM and IgG), C3, acute-phase reactants, total protein, albumin, iron, and indicators of hepatic and renal function were monitored for up to 3 weeks after a single IV Corynebacterium parvum (C. parvum) injection. In addition to a marked increase in immunoglobulins, there was also evidence of complement activation and of tissue injury typified by a classic acute phase response in levels of ₂-macroglobulin and fibrinogen.A fall in total protein and albumin levels was observed during the first 2 days after C. parvum administration, and significant decreases in serum iron also occurred within the first 4 days. In contrast, increases in serum transaminase and alkaline phosphatase activity were consistent with hepatic injury. Furthermore, raised levels of urea and creatinine suggested mild impairment of renal function.These results indicate the need for serial, serological monitoring of immunological, hepatic and renal function during systemic immunotherapy with C. parvum.     

Toxicokinetics of a single intravenous dose of rac-propranolol versus optically pure propranolol in the rat

Conscious male Wistar SPF Riv:TOX rats were dosed intravenously with 2.5, 5, or 10 mg/kg rac-propranolol·HCl, or with 5 mg/kg of either (-)-(S)- or (+)-(R)-propranolol·HCl. Disposition of (-)-(S)- and (+)-(R)-propranolol after dosing of rac-propranolol was linear in the dose range examined. Total plasma clearance was not changed in animals dosed with the individual enantiomers compared to the animals that were dosed with rac-propranolol. However, for (-)-(S)-propranolol both volume of distribution and elimination half-life decreased, whereas for (+)-(R)-propranolol increases were observed for these characteristics, in animals dosed with the individual enantiomers. Our observations suggest that the (+)-(R)-enantiomer competes with (-)-(S)-propranolol for plasma protein binding sites, resulting in lower plasma protein binding of the (-)-(S)-enantiomer when the racemate is administered. From recent toxicological experiments, it was concluded that rac-propranolol is more toxic than the individual enantiomers in the rat, when dosed iv at the same total mass. It is concluded that the observed potentiation of toxic effects of propranolol enantiomers when administered as a racemate can at least partly be explained by a pharmacokinetic interaction. © 1995 Wiley-Liss, Inc.     

Permanent sterility in the male rat after a single oral dose of pipecolinomethyl-hydroxyindane

A single oral dose (150 mg/kg) of DL-6-(N-alpha-pipecolinomethyl)-5-hydroxy-indane maleate dissoved in distilled water was administered to Sprague-Dawley male rats living under controlled conditions. After dosage the male rats cohabited with female rats which were replaced weekly. The incidence of pregnancy was determined for 20 weeks. The male rats were then killed and the testes examined histologically. Results showed subnormal fertility at the 3rd and 4th week, sterility at the 5th week. Sterility persisted until Week 20. Histological evidence showed absence of spermatogenic cells in treated rats with no signs of regeneration.