PubMed Health⌕ Search

Biomedical subjects

M Cassetta

Publications and source records attributed to M Cassetta.

5 recordsLinked to original sources
PubMed1998

Inhibition of the cardiac sarcoplasmic reticulum Ca2+-ATPase by glucose 6-phosphate is Ca2+ dependent.

Defects in the structure or function of the cardiac sarcoplasmic reticulum (CSR) Ca2+-ATPase presumably contribute to the Ca2+ imbalance in the diabetic myocardium. The susceptibility to nonenzymatic protein glycation by glucose metabolites is suggested due to the relatively high percent of target lysines and arginines (approaching 15 mol%) at the ATP binding and phosphorylation domains. Brief incubations (15 min) of CSR microsomes at 24 degrees C in the presence of 5.0 mM glucose 6-phosphate (Glc6P) inhibited Ca2+-dependent ATPase maximal activity relative to controls. Inhibition was only observed when incubations contained 0.1 mM CaCl2 (1.86 micromol ATP hydrolyzed x mg-1 x min-1, +Glc6P versus 2.78, control). Nonconvergent regression lines drawn from maximal velocities as a function of CSR microsome concentration indicate an irreversible mechanism of inhibition which is supported by an observed depletion in CSR amine content (2.98 micromol -NH2 groups/mg microsomal protein, +Glc6P versus 3.34, control). Glucose 6-phosphate (5.0 mM) in Ca2+-free incubations (plus 0.1 mM EGTA) had no affect on either enzyme activity or total amine content. These data suggest that the E1 but not the E2 conformation of the CSR Ca2+-ATPase is susceptible to Glc6P-mediated modification resulting in diminished maximal Ca2+-dependent ATPase activity.

Animals↗
PubMed1978

Peritoneal dialysis in rabbits. A study of transperitoneal theophylline flux and peritoneal permeability.

Since vasodilators can restore toward normal the decreased peritoneal clearances associated with vascular disease, the influence of aminophylline on peritoneal solute transport was studied in unanesthetized rabbits. Mean control creatinine clearance was 0.56 ml/kg/min and urea clearance 0.80 ml/kg/min. Neither intraperitoneal nor intravenous aminophylline increased peritoneal clearances, nor did the ratio creatinine clearance/urea clearance change from the control value, 0.70. Bidirectional flux of theophylline occurred at clearances of 0.70 ml/kg/min efflux and 0.64 ml/min influx. The removal rate of theophylline was 0.05% min, allowing therapeutic removal of excess aminophylline and warranting supplemental therapy during dialysis if therapeutic theophylline concentrations are required. As the intraperitoneal aminophylline was well tolerated, this route can be considered for therapeutic administration.

Aminophylline↗
PubMed1977

Isoproterenol enhancement of peritoneal permeability.

As peritoneal dialysis is inefficient enouth to be time-consuming and sometimes clinically ineffective, we have evaluated pharmacologic enhancement of peritoneal permeability. Peritoneal dialyses were performed in New Zealand white rabbits by instillation of 50 ml/Kg of isotonic dialysis solution of standard composition. Mean peritoneal clearance of creatinine was 0.60 ml/Kg/min and urea was 0.80 ml/Kg/min, each decreasing as intraperitoneal dwell was prolonged (by .011 ml/Kg/min or less). With 0.04 micrometer/Kg of isoproterenol administered intraperitoneally, clearances increased to 0.91 and 1.30 ml/Kg/min (p less than 0.01). When isoproterenol was added to the dialysis solution one hour or more before instillation, the increment in clearances was less. Instillation of dialysis solution 24 hours after addition of a higher dose of isoproterenol (0.2 micrometer/Kg) did not increase clearances above control. No effect of isoproterenol on bulk flow of water, associated with the osmotic effect of dextrose, was demonstrated. As peritoneal clearances increased, the ratio creatinine clearance: urea clearance did not decrease, consistent with increased peritoneal permeability as well as blood flow.

Animals↗
PubMed1977

Effect of intraperitoneal diuretics on solute transport during hypertonic dialysis.

Hypertonic periotoneal dialysis in New Zealand white rabbits results in increased dialyzate volume, but the sodium content of net ultrafiltrate is 109.5 MEq/l, less than extracellular fluid sodium concentration. With intraperitoneal furosemide, mean net ultrafilrate sodium concentration increased significantly to 121.2 mE1/l while ethacrynic acid had no such effect and both drugs affected dialyzate volume very slightly. Hypertonic peritoneal dialysis increased urea clearance significantly above isotonic dialysis and the addition of ethacrynic acid increased clearances further (P LESS THAN.02). Added furosemide decreased urea clearances suggesting that the effect on sodium transport is not an overall permeability change. During isotonic peritoneal dialysis, furosemide increased peritoneal permeability, i.e. urea and creatinine clearances, but a significantly higher urea clearance resulted from intraperitoneal ethacrynic acid. Furosemide influx clearance average 0.31 ml/kg/min, a mean of 27 percent of the urea clearance. The data suggest that furosemide may be useful to prevent the hypernatremia that may complicate hypertonic peritoneal dialysis, but is not as efficacious as other vasoactive drugs in enhancing peritoneal permeability.

Animals↗