Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is thought to be a genetic defect within the calcium release channel of the sarcoplasmic reticulum in malignant hyperthermia (MH). This primary alteration is hypothesized to influence the function and/or structure of various muscle membrane systems; e.g., to have a direct effect on the composition of the lipid matrix. Therefore, in striated muscle samples, we determined the quantity and fatty acid composition of the various types of membrane phospholipids. German Landrace pigs were classified as normal or susceptible to MH. Total lipid content from longissimus dorsi, semi-membranosus muscle, and heart left ventricular (HLV) samples were extracted with chloroform/methanol and subsequently separated by high performance liquid chromatography. The single phospholipid fractions were collected and, following derivatization, the quantities of individual fatty acids were determined using a capillary gas chromatographic method. In general, samples from the susceptible pigs contained lower absolute amounts of individual phospholipids. The most notable differences occurred in the HLV, where phosphatidylinositol, phosphatidylserine, phosphatidylethanolamine and sphingomyelin were all significantly less (P less than or equal to 0.05). The muscle from the susceptible animals also contained decreased amounts of the polyunsaturated phospholipid-bound fatty acids (P less than or equal to 0.05). These differences in phospholipid and fatty acid concentrations of membranes isolated from swine susceptible to MH may relate to their apparently increased sensitivities to halothane (e.g., fluidizing effects) or elevated temperature.
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PMID:Malignant hyperthermia: an altered phospholipid and fatty acid composition in muscle membranes. 188 38

This paper proposed a multiple headspace single-drop microextraction (MHS-SDME) method coupled to gas chromatography with flame-ionization detection (GC-FID) for direct determination of residual solvents in solid drug product. The MHS-SDME technique is based on extrapolation to an exhaustive extraction of consecutive extractions from the same sample which eliminates the matrix effect on the quantitative analysis of solid samples. The total peak area of analyte is calculated with a beta constant which can be obtained from the slope of the linear regression that related to the peak area of each extraction and the number of extraction times. In this work, a model drug powder was chosen and the amounts of residues of two solvents, methanol and ethanol, were investigated. The factors influencing the extraction process including extraction solvent, microdrop volume, extraction time, sample amount, thermostatting temperature and incubation time were studied. 10mg of drug powder was incubated for 3 h at 140 degrees C prior to the first extraction and thermostatted for 15 min at 140 degrees C between each extraction. Extraction was carried out with 2 microL of dimethyl sulfoxide (DMSO) as the microdrop for 5 min. The features of the method were established using standard solutions. Validation of the proposed method showed good agreement with the traditional dissolution method for analysis of residual solvents in drug product. The results indicated that MHS-SDME has a great potential for the quantitative determination of residual solvents directly from the solid drug products due to its low cost, ease of operation, sensitivity, reliability and environmental protection.
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PMID:Multiple headspace single-drop microextraction coupled with gas chromatography for direct determination of residual solvents in solid drug product. 2059 2