Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

Background: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1).

Toxicity of industrially relevant chlorinated organic solvents in vitro.

The cytotoxic effects of 4 industrially important chlorinated organic solvents, dichloromethane (DCM), 1,2-dichloroethane (DCE), trichloroethylene (TCE), and tetrachloroethylene (PERC) in vitro, were investigated. Jurkat T cells were exposed to the solvents individually for 72 hours and changes in reactive oxygen species (ROS) formation, cell proliferation, intracellular free calcium concentration ([Ca(2+)]), and caspase-3 activity were measured. There was a concentration-dependent increase in the ROS formation and intracellular free [Ca(2+)] following exposure to each of the solvents.

n-Hexane toxicity in Jurkat T-cells is mediated by reactive oxygen species.

Here we assess the role of reactive oxygen species (ROS) formation in the manifestation of n-hexane toxicity in Jurkat T-cells and the chemo-protective potential of the antioxidants epigallocatechin-3-gallate (EGCG) and thymoquinone (TQ) against n-hexane toxicity in vitro. n-Hexane is an important industrial solvent and ambient air pollutant. Subchronic exposure to n-hexane results in a concentration-dependent increase in ROS formation with a corresponding decrease in Jurkat T-cell proliferation.

In vitro exposure of jurkat T-cells to industrially important organic solvents in binary combination: interaction analysis.

Humans are frequently exposed to mixtures of environmental pollutants at low levels over prolonged periods of time yet most toxicity studies deal with acute exposure to high concentrations of single chemicals. Investigation of the biological effects and possible toxic interactions during long-term exposure to such mixtures is warranted. Here Jurkat T-cells were exposed to toluene, n-hexane and methyl ethyl ketone in binary combination.

Sub-chronic toxicity of low concentrations of industrial volatile organic pollutants in vitro.

Organic solvents form an important class of pollutants in the ambient air and have been associated with neurotoxicity and immunotoxicity in humans. Here we investigated the biological effects of sub-chronic exposure to industrially important volatile organic solvents in vitro. Jurkat T cells were exposed to toluene, n-hexane and methyl ethyl ketone (MEK) individually for 5 days and solvent exposure levels were confirmed by headspace gas chromatography.

Validation of a method for acute and subchronic exposure of cells in vitro to volatile organic solvents.

In vitro assessment of organic solvents can be problematic as the volatile nature of these compounds makes maintaining a constant exposure level difficult. However, a stable exposure level must be maintained if reliable dose response data are to be obtained. Here we describe a gas-tight glass exposure system which allows prolonged exposure of cultured cells to constant concentrations of volatile organic solvents.

3,4-Methylenedioxymethamphetamine (ecstasy) activates skeletal muscle nicotinic acetylcholine receptors.

Adverse 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) effects are usually ascribed to neurotransmitter release in the central nervous system. Since clinical features such as fasciculations, muscle cramps, rapidly progressing hyperthermia, hyperkalemia, and rhabdomyolysis point to the skeletal muscle as additional target, we studied the effects of MDMA on native and cultured skeletal muscle. We addressed the question whether malignant hyperthermia (MH)-susceptible (MHS) muscle is predisposed to adverse MDMA reactions.

The effects of propofol on lipid peroxidation and inflammatory response in elective coronary artery bypass grafting.

Objective: To determine whether the antioxidant and anti-inflammatory properties of propofol confer benefit in adult patients undergoing elective coronary artery bypass grafting.

Design: Prospective, blinded, randomized, controlled clinical investigation.

Setting: Single-center, university teaching hospital and academic research laboratory.

Increased sensitivity of the ryanodine receptor to halothane-induced oligomerization in malignant hyperthermia-susceptible human skeletal muscle.

Mutations in the skeletal muscle RyR1 isoform of the ryanodine receptor (RyR) Ca2+-release channel confer susceptibility to malignant hyperthermia, which may be triggered by inhalational anesthetics such as halothane. Using immunoblotting, we show here that the ryanodine receptor, calmodulin, junctin, calsequestrin, sarcalumenin, calreticulin, annexin-VI, sarco(endo)plasmic reticulum Ca2+-ATPase, and the dihydropyridine receptor exhibit no major changes in their expression level between normal human skeletal muscle and biopsies from individuals susceptible to malignant hyperthermia. In contrast, protein gel-shift studies with halothane-treated sarcoplasmic reticulum vesicles from normal and susceptible specimens showed a clear difference.