Evidence for nitric oxide participation in down-regulation of CYP2B1/2 gene expression at the pretranslational level

Septic or inflammatory stimuli suppress drug metabolism by cytochrome P-450 in the liver, presumably at the pretranslational level. We have shown previously that nitric oxide is responsible at least in part for the inhibition by bacterial lipopolysaccharide of phenobarbital-induced CYP2B1/2 activity in vivo. This was attributed to the interaction of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report of nitric oxide with heme in the active-center of cytochrome P450, leading to enzyme inactivation. Here, we report that endogeneous nitric oxide also contributes to LPS-induced suppression of CYP2B1/2 in vivo by down-regulating the expression of CYP2B1/2 protein and mRNA.     

Meniscal transplantation using fresh and cryopreserved allografts. An experimental study in goats.

A comparative study of three subgroups of meniscal transplants was undertaken in the goat model: Group 1 (autograft) involved removal and immediate reimplantation of the meniscus; Group 2, fresh meniscal allografts; and Group 3, cryopreserved (30 days) meniscal allografts. Six months after surgery, tissues were evaluated for gross degenerative changes, proteoglycan concentration (as assessed by uronic acid), water content, vascularity, histology, and cell viability. The contralateral knee served as control for all comparisons. There was no statistical difference in the amount of arthritis present and all transplants demonstrated an essentially normal peripheral vascularity compared to controls. Sections revealed reduced numbers of cells in the central portions of the transplanted menisci and these viable cells demonstrated different behavior in multiplication in tissue culture compared to contralateral controls. Grossly and microscopically, the implanted menisci differed little from the controls. The measurement of proteoglycan concentration and water content of the transplanted meniscal cartilage suggest alterations that may affect the long-term mechanical properties. The autograft specimens showed the water content was very slightly increased (3% to 6%), while the proteoglycan concentration was increased (42% in terms of uronic acid). In contrast, the water content of the fresh allograft group and the cryopreserved group was increased 12% to 24%. Proteoglycan concentration in these groups was decreased up to 56% in portions of some menisci compared to controls. Fresh and cryopreserved meniscal allografts showed peripheral healing, revascularization, cellularity, and incorporation, and grossly appeared good at 6 months in the goat model. The biochemical changes in the extracellular matrix at 6 months raises questions on the long-term function of these transplanted menisci.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.     

Large volume injection and infiltration system

Summary A system which can be used for injection or infiltration of large volumes of fluid is described. This consists of a syringe which fills automatically from a reservoir through an inlet/outlet valve.