Increased in vivo and in vitro platelet function in type II- and type IV-hyperlipoproteinemia.
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Biomedical subjects
Publications and source records attributed to R K Baker.
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Recently, evidence has been reported to suggest that human platelets like several other circulating blood cells may bind insulin. To examine whether human platelets contain specific insulin receptors, washed human platelets suspended in Hepes buffer were incubated at 24 degrees C with 125I-insulin in the presence and absence of unlabeled insulin and specific insulin binding was determined. Insulin binding by platelets increased progressively with time of incubation to reach a maximum at 3 h and was proportional to the number of platelets in the incubation mixture. Maximum insulin binding was observed at pH 8. Insulin degradation by platelets as assessed by TCA precipitability and reincubation studies was minimal. Scatchard analysis of the binding data and dissociation studies revealed evidence of negative cooperativity of the platelet insulin receptor. A high affinity dissociation constant of approximately equal to 3 X 10(9) M-1 was determined and the concentration of platelet insulin receptors was estimated as 25 binding sites/micron2 platelet surface area. Binding of 125I-insulin by platelets was inhibited by unlabeled porcine insulin and to a lesser extent by catfish insulin and porcine proinsulin but not by glucagon, prolactin, growth hormone, and thrombin. The findings indicate that human platelets contain specific insulin receptors. The significance of the platelet insulin receptor, particularly with respect to altered platelet function in diabetes mellitus, remains to be determined.
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Halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) is a safe, clinically useful inhalation anesthetic. Rare, unpredictable cases of liver necrosis have been reported following its use. Although the mechanism of this reaction in man is unknown the most plausible is biotransformation to reactive intermediates compounds. The oxidative metabolism of halothane appears to be benign. There is early evidence that reductive (nonoxygen dependent) may be harmful. Since the bromine atom of halothane appears to possess weak bond energy, the reduced, debrominated derivative of halothane, 1,1,1-trifluoro-2-chloroethane, was synthesized and tested for hepatotoxicity in the rat. The derivative is unstable and thus was prepared anaerobically and trapped in propylene glycol solvent. Injection of small amounts of this compound into the portal vein of rats produces extensive liver necrosis. It is postulated that biotransformation of halothane via a reductive pathway could produce this reactive intermediate metabolite.
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The clinical and metabolic effects of porcine calcitonin were assessed in six patients with Paget's disease and two patients with osteoporosis under metabolic balance conditions. The administration of calcitonin for 4-17 wk resulted in an amelioration of the clinical phenomena associated with Paget's disease, including bone pain, increased skeletal vascularity, congestive heart failure, and neurologic deficits secondary to skeletal impingement. The major metabolic effects of calcitonin in Paget's disease included the induction of positive calcium balance of +50 to +240 mg/day, reduction in hyperphosphatasia and hydroxyprolinuria of 15 to 60%, and a deceleration of radiocalcium turnover by 12 to 46%. Natriuresis, phosphaturia, and reduced urinary calcium excretion were observed, whereas sustained hypocalcemia and hypophosphatemia did not occur. The administration of porcine calcitonin was not associated with adverse objective or subjective reactions, toxic effects, or allergic phenomena. There was no evidence of antibody formation or loss of therapeutic potency. Although the response of individual patients with Paget's disease varied widely, the data indicate that calcitonin, presumably through its skeletal anti-resorptive action, is able to reduce skeletal turnover and volume in Paget's disease, and thereby improve the associated clinical and metabolic abnormalities. Long term therapeutic studies in progress suggest that prolonged periods of control of the generalized condition may be feasible. In osteoporosis, neither clinical improvement nor consistent metabolic changes indicative of amelioration of the skeletal disease were observed.
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