Clonidine, an alpha 2-adrenoceptor agonist, inhibited the biliary excretion, reduced the plasma clearance and increased the hepatic retention of sulfobromophthalein (BSP) in a dose related fashion in rats. The maximal effects of clonidine on BSP disposition occurred about 4 h after pretreatment. The effects of clonidine on biliary excretion and hepatic retention of BSP were retained following laparotomy (with or without bile duct cannulation); however, the effect of clonidine on plasma disappearance profile was not retained following abdominal surgery. Isobutylmethylxanthine (IBMX) affected BSP disposition in a similar fashion as clonidine, in rats without bile duct cannulation only; no effect of IBMX could be observed in bile duct cannulation rats. Yohimbine, an alpha 2-adrenoceptor antagonist, reversed the effects of clonidine, but not of IBMX, on BSP disposition. It thus seems that clonidine and IBMX exert their effects on BSP disposition by different mechanisms and probably at different sites.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

Interleukin-1-mediated regulation of plasminogen activation in pregnant mare serum gonadotropin-primed rat granulosa cells is independent of prostaglandin production.

OBJECTIVES: This study examines the effects of interleukin-1 (IL-1) on plasminogen activator (PA) activity and prostaglandin (PG) E production in pregnant mare serum gonadotropin (PMSG)-primed granulosa cells and the potential involvement of PGE in the regulation of ovarian plasminogen activation. METHODS: Granulosa cells were obtained from PMSG-primed rat (27-day-old) ovaries and cultured in serum-free conditions for 48 hours in the absence or presence of IL-1 beta (10 ng/mL) with and without transforming growth factor-beta 1 (10 ng/mL). Cellular PA activity was measured through the conversion of plasminogen to plasmin and assay of the plasmin-mediated cleavage of [14C]-labeled globin to acid-soluble products. RESULTS: Exposure of PMSG-primed granulosa cells to IL-1 resulted in a 30% reduction (P < .05) in PA activity. Addition of hCG (1 IU/mL) to the granulosa cell cultures resulted in a 2.3-fold increase in PA activity, an effect significantly attenuated by co-administration of IL-1. The IL-1-mediated inhibition occurred concurrent with a 6.6-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. This latter inhibitory capacity was the result of a significant increase in plasminogen activator inhibitor type 1 (PAI-1), given its abolition by a polyclonal anti-rat PAI-1 immunoglobulin G. The IL-1-mediated effects on PA/PAI-1 were accompanied by a sevenfold increase in PGE content of the spent culture medium. This response was dose dependent. The IL-1 effects on plasminogen activation and PG production were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated responses. Indomethacin, an inhibitor of PG biosynthesis, prevented the IL-1-induced increase in PGE accumulation but failed to affect the response of the PA system. Transforming growth factor-beta 1, a known regulator of IL-1 action, significantly attenuated the IL-1-stimulated PGE production but did not interfere with the ability of IL-1 to affect the PA system. CONCLUSIONS: The present observations suggest a pleiotropic response of PMSG-primed granulosa cells to IL-1, characterized by the induction of PAI-1 concurrent with but independent of PG production. These findings corroborate and extend earlier observations suggesting that IL-1 affects PA activity and PGE production in immature rat ovaries. Moreover, these observations support our contention that IL-1 may play a major regulatory role in the cellular events leading to ovulation and early corpus luteum formation.

Animals↗

PubMedDate not supplied

A two-year crossover therapeutic trial with halofenate and clofibrate.

Twelve patients with Type IV hyperlipoproteinemia were treated with clofibrate and halofenate in a double blind, crossover trial for two years. Drug intake was monitored by determination of the level of the drugs in serum. Halofenate and clofibrate were equally effective in lowering plasma triglycerides and cholesterol levels. Patients who were secretors of ABO blood group antigens in saliva had a greater hypocholesterolemic response to both drugs than those who were nonsecretors. Clofibrate treatment resulted in a significant rise of low density lipoprotein cholesterol. Both drugs lowered serum bilirubin levels and this effect had a significant positive correlation with that on uric acid levels. Halofenate had a greater hypouricemic effect than clofibrate and may be a useful drug for treatment of patients with Type IV hyperlipoproteinemia who have concomitant hyperuricemia.

ABO Blood-Group System↗