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131.
The triflates and pivalates of 3 alpha-hydroxymethyl-6-substituted-2,2-dimethylpenam sulfones 3, 5; methyl and benzyl 6-substituted penicillanates 6-9 and 3-exo-methylene-6-substituted-2,2-dimethylpenam sulfone 4 were synthesized. These novel compounds were evaluated as elastase inhibitors using porcine pancreatic elastase. The effects that structural modifications of substituents on C-3 and C-6 in the penam nucleus have on elastase activity were examined and several similarities and distinctions were identified when compared to the reported penicillin esters and amides elastase inhibitors. 相似文献
132.
133.
M Spindler KW Saupe ME Christe HL Sweeney CE Seidman JG Seidman JS Ingwall 《Canadian Metallurgical Quarterly》1998,101(8):1775-1783
An arginine to glutamine missense mutation at position 403 of the beta-cardiac myosin heavy chain causes familial hypertrophic cardiomyopathy. Here we study mice which have this same missense mutation (alphaMHC403/+) using an isolated, isovolumic heart preparation where cardiac performance is measured simultaneously with cardiac energetics using 31P nuclear magnetic resonance spectroscopy. We observed three major alterations in the physiology and bioenergetics of the alphaMHC403/+ mouse hearts. First, while there was no evidence of systolic dysfunction, diastolic function was impaired during inotropic stimulation. Diastolic dysfunction was manifest as both a decreased rate of left ventricular relaxation and an increase in end-diastolic pressure. Second, under baseline conditions alphaMHC403/+ hearts had lower phosphocreatine and increased inorganic phosphate contents resulting in a decrease in the calculated value for the free energy released from ATP hydrolysis. Third, hearts from alphaMHC403/+ hearts that were studied unpaced responded to increased perfusate calcium by decreasing heart rate approximately twice as much as wild types. We conclude that hearts from alphaMHC403/+ mice demonstrate work load-dependent diastolic dysfunction resembling the human form of familial hypertrophic cardiomyopathy. Changes in high-energy phosphate content suggest that an energy-requiring process may contribute to the observed diastolic dysfunction. 相似文献
134.
135.
Eucapnic hypoxia lowers human cold thermoregulatory response thresholds and accelerates core cooling
CE Johnston MD White M Wu GK Bristow GG Giesbrecht 《Canadian Metallurgical Quarterly》1996,80(2):422-429
Hypoxia lowers the basic thermoregulatory responses of animals and humans. In cold-exposed animals, hypoxia increases core temperature (Tco) cooling rate and suppresses shivering thermogenesis. In humans, the experimental effects of hypoxia on thermoregulation are equivocal. Also, the effect of hypoxia has not been separated from that of hypocapnia consequent to hypoxic hyperventilation. To determine the isolated effects of hypoxia on warm and cold thermoregulatory responses and core cooling during mild cold stress, we examined the Tco thresholds for sweating, vasoconstriction, and shivering as well as the core cooling rates of eight subjects immersed in 28 degrees C water under eucapnic conditions. On 2 separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects inspired humidified room air during the control trial. For the eucapnic hypoxia trial, they inspired 12% O2-balance N2 with CO2 added to maintain eucapnia. Eucapnic hypoxia lowered the Tco thresholds for vasoconstriction and shivering by 0.14 and 0.19 degrees C, respectively, and increased core cooling rate by 33% (1.83 vs. 1.38 degrees C/h). These results demonstrate that eucapnic hypoxia enhances the core cooling rate in humans during mild cold stress. This may be attributed in part to a delay in the onset of vasoconstriction and shivering as well as increased respiratory heat loss during hypoxic hyperventilation. 相似文献
136.
MA Mooney DM Vaughn GA Reinhart RD Powers JC Wright CE Hoffman SF Swaim HJ Baker 《Canadian Metallurgical Quarterly》1998,59(7):859-863
OBJECTIVES: To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing. ANIMALS: 30 purpose-bred Beagles. PROCEDURE: Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E, 95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken from 4-day-old wounds of each dog and analyzed by gas chromatography-mass spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n-3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites. RESULTS: Qualitative analysis was carried out on AA, EPA, adrenic acid, docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway. These molecules were further quantified with respect to diet to determine significant differences. By analysis of the AA-to-EPA ratio, diet A was different from diets D and E and diets B and C were different from diet E (P < 0.05). By analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E (P < 0.05). Though biochemical analysis indicated dietary dependence, histopathologic data indicated no significant difference with respect to diet groups. CONCLUSION: The biochemical component of the inflammatory stage of wound healing can be manipulated by diet. CLINICAL RELEVANCE: Omega-3 fatty acid-enriched diets can be used to control inflammation associated with dermatologic conditions. 相似文献
137.
138.
JV Pothuluri JB Sutherland JP Freeman CE Cerniglia 《Canadian Metallurgical Quarterly》1998,64(8):3106-3109
The fungus Cunninghamella elegans was used to biotransform 6-nitrochrysene, a mutagen that is a widespread environmental contaminant. After 6 days, 74% of the 3H-labeled 6-nitrochrysene added had been metabolized to two isomeric sulfate conjugates. These conjugates were separated by high-performance liquid chromatography and identified by UV-visible, 1H nuclear magnetic resonance, and mass spectral techniques as 6-nitrochrysene 1-sulfate and 6-nitrochrysene 2-sulfate. 相似文献
139.
AS Cohen T Beaconsfield A al-Kutoubi CE Handler BE Glenville 《Canadian Metallurgical Quarterly》1996,61(4):1257-1259
A 35-year-old woman underwent reconstruction of her right pulmonary artery for treatment of acquired right pulmonary artery stenosis. The stenosis was secondary to tuberculosis causing both an extrinsic and an intrinsic obstructive component. After her reconstruction, the patient made an uneventful recovery, and perfusion to the right lung was subsequently restored. 相似文献
140.
Under in vitro conditions N-alpha-tosyl L-arginine methyl ester (TAME) induced a concentration dependent contractile response on ileal strips with EC50 of 4.3 x 10(-5) M as compared to acetylcholine which induced sustainable contractions with EC50 of 3.2 x 10(-6) M. The present study is the first to demonstrate that TAME is a potent constrictor of non-airway smooth muscle. 相似文献