Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Evaluation of amphotericin B-cyclosporine interaction in the rat

Although a significant interaction between cyclosporine and amphotericin-B (AmpB) has been observed clinically, these findings have not been duplicated in animal studies. A total of 64 male albino rats were used in single- and multiple-dose experiments with AmpB and CsA in the absence or presence of systemic Candida infection. No significant differences in glomerular filtration rate were found in rats given single i.v. doses of AmpB 1 mg/kg compared with AmpB and CsA. Furthermore, rats given i.p. AmpB 1 mg/kg and CsA 10 mg/kg daily for 10 days showed no significant differences in GFR compared with animals given CsA alone. Morphology and CsA whole-blood pharmacokinetics were not different between groups administered single-dose CsA, AmpB, or the combination; similarities also existed with multiple-dose studies. In an attempt to mimic the clinical setting, 2 groups of rats were administered i.p. CsA 10 mg/kg/day for 10 days followed by inoculation of Candida albicans. After 48 hr, a single i.v. dose of AmpB 1.0 mg/kg was associated with a 33% decline in GFR compared with those given sterile water (P less than 0.05). Systemic clearance of CsA was markedly reduced in candidiasis rats administered AmpB compared with controls given sterile water. A significant reduction in renal Candida colony-forming units was found in rats given CsA and AmpB compared with those administered CsA alone. These data suggest that the presence of systemic Candida highlights the interaction of CsA and AmpB in the rat model.     

Barium and strontium leaching from aged glass particle/resin matrix dental composites.

OBJECTIVES: This study characterizes the loss of Ba and Sr from glass particle/resin-matrix dental composites during simulated aging. METHODS: X-ray wavelength dispersive spectrometry and secondary ion mass spectrometry were used to analyze the Ba and Sr content from the surfaces of three commercial dental composites after aging for 4 and 8 months in humid air, artificial saliva, water, and 50% ethanol. RESULTS: Aging in artificial saliva caused the greatest leaching of Ba or Sr for all the specimens, compared with either lesser or no leaching for aging in ethanol and water. Differences in leaching were observed between the different composites. Composites aged in artificial saliva also picked up elements in the saliva solution and displayed crystallite formation on the surface. Samples aged in ethanol displayed cracking which was not observed for water or artificial saliva. SIGNIFICANCE: Dental composites display ion leaching from their surfaces over periods of four to eight months. Three mechanisms are proposed to explain differences in leaching for the various composites and aging solutions. Surface mineralization is also proposed to occur as a self-repair mechanism in artificial saliva.     

Occult gunshot injury of the temporal bone.

Increasing firearms violence has produced much public disquiet in recent months and Liverpool has seen a particularly well publicized spate of shootings. This is a case report of an initially occult intracranial injury which illustrates the unpredictable nature of missile trauma and the importance of computerised tomography in all cases of gunshot injury to the head.