Twenty-four patients undergoing gall bladder surgery and placement of a Kehr T-tube were examined for imipenem pharmacokinetics in plasma and bile fluid following an intravenous short-term infusion (20 min) of 500 mg respectively 1000 mg each of imipenem and cilastatin. In group I (500 mg; 12 patients) a mean peak concentration in bile fluid of 10.5 mg/l (range 1.5 to 16.7 mg/l) was reached just after 10 min. 60 min after the end of infusion the imipenem concentration was between 8 and 9 mg/l. In group I the half-life of imipenem in bile was 0.84 h. In group II (1000 mg; 12 patients) the mean peak level in bile fluid was 1&.5 mg/l (range 3.5 to 51.3 mg/l). The half-life in bile was 1.24 h in this group. The data indicated that 4 h after the administration of either 1000 mg or 500 mg, imipenem serum and bile concentrations were markedly above the MIC values for pathogens expected to be found in infections of the biliary tract.

Aged↗

PubMedDate not supplied

Post-mortem changes in skeletal muscle protease and creatine phosphokinase activity--a possible marker for determination of time of death.

The pattern of change in activity of two enzymes in rat skeletal muscle during body storage after death has been determined. Myofibrillar protease activity was found to increase linearly with time of storage post mortem at room temperature but not at 4 degrees C. In contrast, creatine phosphokinase activity declines linearly with time, and again storage at 4 degrees C prevented the change in enzyme activity. Starvation of animals for 5 days or forced exercise prior to death did not markedly alter the rate of change in activity of the two enzymes, although creatine phosphokinase specific activity at time of death was higher in the starved and exercised rats as compared to control animals. A plot of the logarithm of protease/creatine phosphokinase specific activities ratio versus time post mortem yields a linear curve at room temperature. These observations offer a potential method for estimating time of death.

Animals↗

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

Two channels reduced to one.

Explore the source record for details and available documents.

Aspartic Acid↗