A novel strategy for the preparation of liposomes: rapid solvent exchange. (1/177)

During the preparation of multi-component model membranes, a primary consideration is that compositional homogeneity should prevail throughout the suspension. Some conventional sample preparation methods pass the lipid mixture through an intermediary, solvent-free state. This is an ordered, solid state and may favor the demixing of membrane components. A new preparative method has been developed which is specifically designed to avoid this intermediary state. This novel strategy is called rapid solvent exchange (RSE) and entails the direct transfer of lipid mixtures between organic solvent and aqueous buffer. RSE liposomes require no more than a minute to prepare and manifest considerable entrapment volumes with a high fraction of external surface area. In phospholipid/cholesterol mixtures of high cholesterol content, suspensions prepared by more conventional methods reveal evidence of artifactual demixing, whereas samples prepared by rapid solvent exchange do not. The principles which may lead to artifactual demixing during conventional sample preparation are discussed.  (+info)

Methylene chloride poisoning in a cabinet worker. (2/177)

More than a million workers are at risk for methylene chloride exposure. Aerosol sprays and paint stripping may also cause significant nonoccupational exposures. After methylene chloride inhalation, significant amounts of carbon monoxide are formed in vivo as a metabolic by-product. Poisoning predominantly affects the central nervous system and results from both carboxyhemoglobin formation and direct solvent-related narcosis. In this report, we describe a case of methylene chloride intoxication probably complicated by exogenous carbon monoxide exposure. The worker's presentation of intermittent headaches was consistent with both methylene chloride intoxication and carbon monoxide poisoning. The exposures and symptoms were corroborated by elevated carboxyhemoglobin saturations and a workplace inspection that documented significant exposures to both methylene chloride and carbon monoxide. When both carbon monoxide and methylene chloride are inhaled, additional carboxyhemoglobin formation is expected. Preventive efforts should include education, air monitoring, and periodic carboxyhemoglobin determinations. Methylene chloride should never be used in enclosed or poorly ventilated areas because of the well-documented dangers of loss of consciousness and death.  (+info)

Fatal case of dichloromethane poisoning. (3/177)

A 47-year-old man was found dead in a factory where dichloromethane (DCM) tanks were stocked. He was making an inventory of the annual stock of DCM contained in several tanks (5- to 8000-L capacity) by transferring the solvent into an additional tank with the help of compressed air. During this operation, one of the tanks overflowed and the man, who was not wearing any protection, was intoxicated. Autopsy showed digestive, suprarenal, and liver bleeding. Blood was also found in the trachea. DCM was identified by headspace gas chromatography-mass spectrometry (GC-MS). A headspace gas chromatography-flame ionization detection technique (GC-HS-FID) optimized for quantitation in biological fluids, organs and viscera was established at autopsy. The following concentrations of DCM were found: blood (150 mg/L), urine (2.0 mg/L), gastric content (5.6 mg/L), brain (122 mg/kg), fat (99 mg/kg), liver (44 mg/kg), lung (20 mg/kg), and kidney (15 mg/kg). A study of the storage stability of DCM was carried out on these samples. Ethanol production was measured in some organs. The results are discussed in light of the rarity of existing literature.  (+info)

Distribution and skewness of occupational exposure sets of measurements in the Norwegian industry. (4/177)

Aggregated occupational sets of exposure measurements from the Norwegian industry registered in the exposure database EXPO at The National Institute of Occupational Health, Oslo were examined with respect to distributions and skewness. Data for lead in blood show a truncated almost normal distribution because of regulations for workers with high lead in blood concentrations. The styrene, dichloromethane and acetone measurements show quasi log-normal distributions possibly because of over-representation of worst-case measurements. The other personal and stationary measurements are relatively good fitted to a log-normal model. The stationary measurements indicate generally lower mean levels than the corresponding personal measurements. The statistical parameter skewness is valuable in connection with an exposure database as a distribution test for raw data and log-transformed data.  (+info)

Dichloromethane as an antisickling agent in sickle cell hemoglobin. (5/177)

Microscopic studies of red cells from homozygous sickle cell patients show that dichloromethane does prevent sickle cell formation in vitro and does cause reversion of sickled cells to normal after exposure to dichloromethane. X-ray structural analysis of human deoxyhemoglobin crystals exposed to dichloromethane shows four unique binding sites. Arguments are presented to suggest that the binding site close to tryptophan 14alpha prevents the formation of helical polymers, i.e., prevent sickling.  (+info)

DNA polymerase I is essential for growth of Methylobacterium dichloromethanicum DM4 with dichloromethane. (6/177)

Methylobacterium dichloromethanicum DM4 grows with dichloromethane as the unique carbon and energy source by virtue of a single enzyme, dichloromethane dehalogenase-glutathione S-transferase. A mutant of the dichloromethane-degrading strain M. dichloromethanicum DM4, strain DM4-1445, was obtained by mini-Tn5 transposon mutagenesis that was no longer able to grow with dichloromethane. Dichloromethane dehalogenase activity in this mutant was comparable to that of the wild-type strain. The site of mini-Tn5 insertion in this mutant was located in the polA gene encoding DNA polymerase I, an enzyme with a well-known role in DNA repair. DNA polymerase activity was not detected in cell extracts of the polA mutant. Conjugation of a plasmid containing the intact DNA polymerase I gene into the polA mutant restored growth with dichloromethane, indicating that the polA gene defect was responsible for the observed lack of growth of this mutant with dichloromethane. Viability of the DM4-1445 mutant was strongly reduced upon exposure to both UV light and dichloromethane. The polA'-lacZ transcriptional fusion resulting from mini-Tn5 insertion was constitutively expressed at high levels and induced about twofold after addition of 10 mM dichloromethane. Taken together, these data indicate that DNA polymerase I is essential for growth of M. dichloromethanicum DM4 with dichloromethane and further suggest an important role of the DNA repair machinery in the degradation of halogenated, DNA-alkylating compounds by bacteria.  (+info)

Growth inhibition of Escherichia coli by dichloromethane in cells expressing dichloromethane dehalogenase/glutathione S-transferase. (7/177)

Dichloromethane (DCM) dehalogenase converts DCM to formaldehyde via the formation of glutathione metabolites and generates 2 mol HCl per mol DCM metabolized. Growth of Escherichia coli expressing DCM dehalogenase was immediately and severely inhibited during conversion of 0.3 mM DCM. Intracellular pH (pH(i)) rapidly decreased and chloride ions were steadily released into the medium. Bacterial growth resumed after completion of DCM conversion and cell viability was unaffected. At 0.6 mM DCM there was no recovery from growth inhibition in liquid culture due to the build-up of inhibitory concentrations of formaldehyde. DCM turnover stimulated potassium efflux from cells, which was suppressed by glucose. The potassium efflux, therefore, did not contribute to growth inhibition. It was concluded that initial growth inhibition results from lowering of the cytoplasmic pH, but severity of growth inhibition was greater than expected for the change in pH(i). Possible contributors to growth inhibition are discussed.  (+info)

Physiologically based pharmacokinetic modeling of inhalation exposure of humans to dichloromethane during moderate to heavy exercise. (8/177)

Dichloromethane (methylene chloride, DCM) is metabolized via two pathways in humans: mixed-function oxidases (MFO) and glutathione-S:-transferase (GST). Most likely, the carcinogenicity for DCM is related to metabolic activation of DCM via the GST pathway. However, as the two pathways are competing, the metabolic capacity for the MFO pathway in vivo is also of interest in risk assessment for DCM. Past estimates of MFO metabolism are based on the in vitro activity of tissue samples. The aim of the present study was to develop a population model for DCM in order to gain more knowledge on the variability of DCM inhalation toxicokinetics in humans, with main emphasis on the MFO metabolic pathway. This was done by merging published in vitro data on DCM metabolism and partitioning with inhalation toxicokinetic data (Astrand et al., 1975, Scand. J. Work.Environ. Health 1, 78-94) from five human volunteers, using the MCMC technique within a population PBPK model. Our results indicate that the metabolic capacity for the MFO pathway in humans is slightly larger than previously estimated from four human liver samples. Furthermore, the interindividual variability of the MFO pathway in vivo is smaller among our five subjects than indicated by the in vitro samples. We also derive a Bayesian estimate of the population distribution of the MFO metabolism (median maximum metabolic rate 28, 95% confidence interval 12-66 micromol/min) that is a compromise between the information from the in vitro data and the toxicokinetic information present in the experimental data.  (+info)