Determination of mycotoxins by gradient high-performance liquid chromatography using an alkylphenone retention index system.
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Biomedical subjects
Publications and source records attributed to K W Miller.
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Cimetidine dynamics were studied in six multiple-trauma patients receiving 300 to 600 mg every 6 hr for prevention of stress ulceration. Patients received cimetidine intravenously for a mean duration of 7.8 days. There was a positive correlation between cimetidine serum concentration and gastric pH; the correlation between intragastric cimetidine concentration and gastric pH was stronger. The association between therapeutic efficacy (pH greater than 4) and serum concentration over 1 mcg/ml was significant. The association with gastric cimetidine concentration above 2 mcg/ml was significant.
Octanol increases the binding of [3H]-acetylcholine to the desensitized state of the nicotinic receptor in postsynaptic membranes prepared from Torpedo californica. This increase in binding results from an increase in the affinity of [3H]-acetylcholine for its receptor without any change in the number of sites or the shape of the acetylcholine binding curve. High pressures of helium (300 atm) decrease [3H]-acetylcholine binding by a mechanism that changes only the affinity of acetylcholine binding. Helium pressure reverses the effect of octanol on the affinity of [3H]-acetylcholine for its receptor. This pressure reversal of the action of octanol at a postsynaptic membrane is consistent either with pressure counteracting an octanol-induced membrane expansion or with independent mechanisms for the actions of octanol and pressure. The data do not conform with a mechanism in which pressure displaces octanol from a binding site on the receptor protein.
Sugar beets grown on municipal sludge-amended soil were fed to growing lambs for 66 days. The relative hemoglobin content was significantly lower (P less than 0.05) in the lambs fed the sludge-grown sugar beets. The concentration of direct-acting mutagens was significantly higher (P less than 0.05) than controls in blood and urine of the lambs fed the sludge-grown beets. Cadmium concentration was higher, but not significantly (P greater than 0.05) in the livers and kidneys of the lambs fed the sludge-grown beets as compared with controls. Significant differences between treatment groups were not observed in active or passive K+ influxes in RBC; in the activity of hepatic microsomal aniline hydroxylase in p-nitroanisole-O-demethylase, aminopyrene-N-demethylase, or arylhydrocarbon hydroxylase; in tissue ultrastructure of kidney, liver, or muscle as examined by electron microscopy; or in carcass weight, dressing percentage, quality, or yield grade.
Biochemical analyses were conducted to evaluate the nutritional status of a high esophageal cancer risk population in Linxian, People's Republic of China. A study was conducted in September 1980 in which plasma levels of vitamins A, B2, and C were analyzed. In a second study in 1983, the plasma fat-soluble vitamins were analyzed with a newly developed high-performance liquid chromatography method that allowed the simultaneous determination of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, and lycopene in 0.1 ml of plasma sample. The average plasma retinol levels ranged from 24 to 27 micrograms/dl among the population groups, with 20-35% of the individuals having levels under 20 micrograms/dl. Low plasma beta-carotene levels averaging 8-12 micrograms/dl were observed among the population groups. Low plasma alpha-tocopherol levels with average values around 700 micrograms/dl were also observed; about half the individuals were either low or deficient in vitamin E. After 4 months of supplementation with daily multivitamin tablets, the plasma contents of retinol and alpha-tocopherol were significantly increased. The plasma alpha-carotene and beta-carotene were also increased, possibly as a reflection of seasonal changes in the diet or a sparing effect of vitamins A and E on these carotenes. Low plasma ascorbate levels with an average of 567 micrograms/dl were observed, and about 23% of the individuals had values under 200 micrograms/dl. Riboflavin deficiency was prevalent, with about 90% of the subjects having an erythrocyte glutathione activation coefficient over 1.2. The study establishes the low nutritional status in vitamins of the population in Linxian and provides the background for further studies on the effects of nutritional deficiency on carcinogenesis.
The phase equilibria of human very low density lipoprotein (VLDL) and monkey chylomicron lipids was examined. Triglyceride (TG), cholesterol ester (CE), and cholesterol (C) partitioned into both surface monolayer and oil "core" phases of emulsions of lipoprotein lipids, whereas phospholipid was found exclusively in the surface. In addition to phospholipid, the surface lipids consisted of 2-4% (by weight) TG, less than 1% CE, and 22% C (VLDL), 5-8% C (chylomicrons). The oil lipids consisted mainly of TG, but also 13-16% CE (VLDL), 3% CE (chylomicrons), and 1-2% C (VLDL), 0.3-0.4% C (chylomicrons). The equilibrium state of lipids within size subfractions of native lipoproteins was defined using phase diagram analysis. Subfractions were in equilibrium with respect to surface-to-core and interparticle distributions of C molecules. In contrast, subfracitions were not in a state of interparticle TG and CE equilibrium. By using the phase diagrams, the percentages of the total particle lipids carried in the phases of lipoproteins of varying size were calculated. For Sf greater than 400 particles, greater than or equal to 30% of the total particle C molecules are carried in the core, and less than 3% of the TG and CE molecules are located in the surface. Nascent, plasma, remnant, and beta-migrating TG-rich lipoprotein compositions taken from the literature were compared using phase diagrams. Although the total compositions of nascent liver VLDL and lymph chylomicrons vary substantially, they have identical concentrations of C in their respective phases. Upon equilibration with plasma, the surface and core of nascent TG-rich lipoproteins become enriched (2-4-fold) with C. Remnants and beta-VLDL have the most C-rich phases of the TG-rich lipoproteins examined. The analysis indicates that the C concentrations of the phases of a lipoprotein are related to its metabolic status.
The incorporation of cholesteryl oleate and triolein into phospholipid vesicles was studied in cosonicated mixtures of 94 weight % egg phosphatidylcholine and 6 weight % neutral lipid (0-6% triolein and 6-0% cholesteryl oleate). 13C NMR spectroscopy was used to quantitate both neutral lipids in vesicles containing 90% isotopically substituted [carbonyl-13C]cholesteryl oleate and [carbonyl-13C]triolein. Vesicles were also prepared with radiolabeled cholesteryl oleate and triolein and the composition of ultracentrifugal subfractions determined by chemical and radioisotopic methods. For a given starting composition, the incorporation of neutral lipids into vesicles was similar for vesicles prepared and analyzed by the two methodologies. The maximum solubility in vesicles prepared at 55 degrees C with a single neutral lipid was 3.1 weight % triolein (2.8 mol %) and 2.3 weight % cholesteryl oleate (2.8 mol %). In sonication mixtures with both triolein and cholesteryl oleate, the incorporation of each lipid into vesicles was proportional to the starting concentration; the total incorporation of neutral lipid was less than or equal to 4.0% (weight or mole per cent). The solubility limits were intermediate between the theoretical cases of complete additivity and complete competition. The [13C]carbonyl chemical shifts showed that the carbonyl groups of the vesicle-solubilized neutral lipids were close to the vesicle surface and that excess triolein and cholesteryl oleate partitioned into an oil phase containing both triolein and cholesteryl oleate.
The organization of lipids within emulsions composed of triolein (TO), cholesteryl oleate (CO), cholesterol (C), and egg yolk phosphatidylcholine (L) was examined. CO was substituted for TO in a series of emulsions to obtain TO:CO ratios comparable to the triglyceride:cholesterol ester ratios observed in subfractions of triglyceride-rich lipoproteins. The weight fraction of TO in the surface phase (0.02-0.05) was independent of the TO content of the emulsions. However, the weight fraction of CO in the surface phase depended upon the percentage of CO in the emulsions and was less than 0.004 even when 13.7% CO was present in the emulsion. When CO was substituted for TO, the percent of the total particle C which was carried in the droplet oil phase was increased. The interparticle equilibration of lipids was studied in subfractions of sonicated emulsions with particle sizes comparable to triglyceride-rich lipoproteins. The TO:CO ratios of the subfractions of a given emulsion were constant and independent of size, but the C:L ratio decreased in particles of smaller diameter. However, the surface C:L ratio was the same in all particles from a given emulsion. The size dependence of the C:L ratios was attributed to the partitioning of C into the oil cores of the emulsions. Because large droplets have the greatest core:surface mass ratios, more of their total particle C is carried in the core.
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Weanling male Fischer (F), Long-Evans (LE), and Sprague-Dawley (SD) rats were fed a semi-purified basal diet or a 20% cabbage diet for 3 and 4 weeks. Hepatic polysubstrate monooxygenase (PSM) activity was measured. Significant strain differences were found in aniline hydroxylase and p-nitrophenol O-demethylase activities. Aniline hydroxylase and NADPH cytochrome c reductase activities were significantly decreased in all strains after 4 weeks of cabbage dietary treatment. F and LE rats consuming the cabbage diets also had significantly reduced O-demethylase activity after 4 weeks. Except in LE, aminopyrine N-demethylase activity tended to be elevated in the strains consuming the cabbage diets. Cabbage diets increased testes weight in SD and thyroid weights in LE rats. All strains showed decreased thymus weights in the cabbage dietary treatments. This study with rats shows that hepatic PSM activities, as well as some organ changes due to dietary cabbage are strain dependent.
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Cholesterol is commonly supposed to form a micelle in aqueous solution. We have reassessed this finding using a variety of techniques. Centrifugation sedimented cholesterol at all concentrations above 10(-8) M. Density gradient analysis of more concentrated solutions revealed two bands whose densities corresponded to crystalline anhydrous cholesterol and crystalline cholesterol monohydrate. The monohydrate was characterized by light microscopy and phase transition. This band is also claimed to contain micelles, but no enhancement of perylene or diphenylhexatriene fluorescence could be detected. Some crystals of monohydrate could pass through 0.7-microns filters but not through 1.5-nm filters. Crystals of monohydrate were detected on the latter filters when solutions with cholesterol concentrations as low as 2.6 X 10(-8) M were filtered. Thus, under all conditions where micelles might be expected, we have detected micro-crystals of cholesterol monohydrate and we can find no independent evidence to support the existence of a cholesterol micelle.
The pharmacokinetics of gentamicin, including half-life, apparent volume of distribution, total body clearance, and fraction of drug absorbed from IM injection sites, were determined in 3 species of birds of prey (red-tailed hawks, great horned owls, and golden eagles). Significant differences (P less than 0.05) between species were found for the half-life and total body clearance values for this broad-spectrum antibiotic. The values for apparent volume of distribution and fraction absorbed did not differ among species and were similar to those reported in mammals. Rapid and relatively complete absorption from IM injection sites resulted in high bioavailability. After IV administration of 10 mg of gentamicin/kg of body weight, serum concentrations greater than 12 micrograms/ml were present for at least 2 hours and greater than 2 micrograms/ml for 4 to 6 hours. On the basis of the various determinations, an IM dose of 2.5 mg of gentamicin/kg given every 8 hours should provide therapeutic serum concentrations of gentamicin in the 3 species.
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The partial molar volumes of 1-heptanol and 1-octanol in red cell ghosts, in egg phosphatidylcholine bilayers, and in water and phosphate buffer have been measured to a precision of better than 4% by using a density meter. In every case, the partial molar volume was independent of concentration in the range studied. In both membranes, the partial molar volume of each alcohol was close to its molar volume whereas in aqueous solution it was considerably less. Comparison of the two membranes suggests that the major contribution to the partial molar volume arises from alcohol-lipid interactions of each case. Further comparison with partial molar volumes in bulk solvents suggests that on average the alcohols retain a hydrogen bond in the lipid bilayer. The magnitude of the volume change in ghosts is some 5 times less than the corresponding area changes previously reported by others [Roth, S. H., & Seeman, P. (1972) Biochim. Biophys. Acta 255, 190-198]. These two observations can only be resolved by assuming either that the bilayer expands anisotropically, experiencing a decrease in thickness with increasing volume, or that conformational changes in membrane-associated proteins can occur at constant volume to increase membrane area. Finally, these data are used to test the critical volume hypothesis of general anesthetic action. A volume change of 0.15% in red cell ghost membranes is found to be associated with anesthesia, which compares with a value of 0.2% predicted previously from pressure reversal of anesthesia studies. In egg phosphatidylcholine bilayers, a volume change of 0.36% is associated with anesthesia. The larger change in the lipid bilayer compared to the biomembrane originates solely in their different membrane/buffer partition coefficients.
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Cimetidine dynamics were studied in nine multiple-trauma patients. Mean elimination half-life was 2.27 hr, mean volume of the central compartment was 0.29 l/kg, mean volume at steady state averaged 0.90 l/kg, and mean total body clearance was 9.02 ml/min/kg. After intravenous cimetidine, drug concentrated in gastric fluid reached a peak concentration in 3 hr. Gastric plasma cimetidine ratios after equilibration ranged between 3.0 and 4.3. There was a correlation between cimetidine gastric juice concentration and gastric pH (r = 0.50), but no correlation was found between plasma cimetidine concentration and pH (r = 0.13).
This review of available literature attempts to interpret net effects of metabolically inert light gases (He, H2, and Ne) as the resultant of hydrostatic pressure and intrinsic pharmacological effects associated with exposure to these gases, and to assess the relative importance of each component with respect to a number of biological responses. A common pattern is recognizable for pressure reversal of anesthesia, high pressure convulsions, high pressure bradycardia, and certain characteristics of liposome model systems. Using the method of analysis proposed, these lightest gases can be shown to conform to the pattern of relation of potency to physical properties characteristic of more potent gaseous anesthetics, including N2, N2O, and Xe. The relations between effect produced and partial pressure of the acting gas are approximately linear to total pressures of 100 ATA for anesthesia or pressure reversal of anesthesia and (or to a much smaller extent) for the liposome model systems, but not for high pressure convulsions. As a result of these general factors no single gas can be expected to neutralize the effects of hydrostatic pressure with regard to all of the biological responses tested over any significant pressure range. A series of experiments with single cells and tissue cultures have revealed interactions between high pressure and inert gas that do not conform to the pattern set by the responses mentioned so far. These responses cannot yet be shown to constitute a homogeneous group and may represent at least two subgroups. Responses falling into this second heterogeneous category include cell motility, development of cell abnormalities and lysis, and cell and perhaps virus replication or multiplication. The implication of these results for the formulation of biophysical hypotheses to explain interactions between inert gas and high pressure, for considerations of high pressure effects as a safety hazard, and for the problem of experimental approaches to the study of pressure acclimation are discussed briefly.