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Physiological Research Sep 2016Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of...
Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial K(ATP) opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated.
Topics: Animals; Diabetes Mellitus, Experimental; Diazoxide; Heart Diseases; Male; Membrane Fluidity; Mitochondrial Membranes; Mitochondrial Proton-Translocating ATPases; Rats, Wistar; Succinate Dehydrogenase
PubMed: 27643934
DOI: 10.33549/physiolres.933411 -
British Heart Journal May 1978Three patients with primary pulmonary hypertension and one man with suspected thromboembolic pulmonary hypertension were given up to 300 mg diazoxide by injection into...
Three patients with primary pulmonary hypertension and one man with suspected thromboembolic pulmonary hypertension were given up to 300 mg diazoxide by injection into the pulmonary artery. The three patients with primary pulmonary hypertension responded with a fall in total pulmonary resistance and a rise in cardiac output. The patient with suspected thromboembolic pulmonary hypertension did not respond. Haemodynamic and clinical improvement was maintained by oral diazoxide in two of the responders, and in one the prognosis appeared to be greatly improved.
Topics: Adult; Cardiac Output; Diazoxide; Female; Humans; Hypertension, Pulmonary; Injections, Intra-Arterial; Male; Middle Aged; Pulmonary Artery; Vascular Resistance
PubMed: 656227
DOI: 10.1136/hrt.40.5.572 -
Archives of Disease in Childhood Oct 1989Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration...
Seven infants with persistent neonatal hyperinsulinism were treated in Dhahran Health Centre from 1983 to 1986. The insulin:glucose ratio (serum insulin concentration pmol/l) divided by the blood glucose concentration (mmol/l) ranged from 12 to 636, mean (SD) 177 (201). To control hypoglycaemia, diazoxide (12-24 mg/kg/day) was given in a continuous intravenous glucose infusion (12-22 mg/kg/min) on 11 separate occasions, four infants twice each and three infants once each. An increase of more than one standard deviation in the heart and respiratory rates, together with other symptoms of heart failure, was considered to be evidence of diazoxide toxicity. Cardiorespiratory failure (toxicity) occurred on eight of the 11 occasions (73%) in seven infants. The average daily fluid intake, weight change, respiratory rate and heart rate before treatment were similar whether or not the infant developed toxicity. A diazoxide toxicity index was obtained by multiplying the dose of diazoxide by the insulin:glucose ratio to relate the diazoxide dose to the severity of the disease. In all instances when the toxicity index was more than 1533 (mean (SD) 3732 (2741) cardiac toxicity developed. In contrast, infants with a toxicity index of less than 675 (mean (SD) 364 (270), had no symptoms of toxicity. Symptoms were significantly related to the severity of the disease and the diazoxide dose. It is possible to use the toxicity index to predict the risk of toxicity and to calculate a safe dose of diazoxide in infants with persistent neonatal hyperinsulinism.
Topics: Blood Glucose; Diazoxide; Female; Heart Failure; Humans; Hyperinsulinism; Hypoglycemia; Infant; Insulin; Male; Respiratory Insufficiency
PubMed: 2684032
DOI: 10.1136/adc.64.10.1496 -
American Family Physician May 1975Diazoxide is a potent and safe antipressor agent for parenteral administration in hypertensive emergencies. Its rapidity of effect provides distinct advantages. Drug...
Diazoxide is a potent and safe antipressor agent for parenteral administration in hypertensive emergencies. Its rapidity of effect provides distinct advantages. Drug resistance does not develop in responsive patients and adverse effects are mild and infrequent. The minor changes in blood urea concentration, despite a marked reduction in blood pressure, enhance the usefulness of diazoxide in azotemic hypertensive patients.
Topics: Adolescent; Cardiac Output; Diazoxide; Glomerular Filtration Rate; Half-Life; Heart Rate; Humans; Hypertension; Hypertension, Malignant; Hypotension; Injections, Intravenous; Male; Nausea; Vascular Resistance; Vomiting
PubMed: 1130248
DOI: No ID Found -
JAMA Jun 1973
Topics: Administration, Oral; Age Factors; Blood Pressure; Cardiac Output; Child; Diazoxide; Emergencies; Evaluation Studies as Topic; Heart Rate; Humans; Hypertension; Hypoglycemia; Injections, Intravenous; Potassium; Sodium; Vasodilator Agents
PubMed: 4739994
DOI: No ID Found -
British Heart Journal Sep 1979
Topics: Adult; Diazoxide; Female; Humans; Hypertension, Pulmonary; Injections, Intra-Arterial; Pulmonary Artery
PubMed: 508461
DOI: 10.1136/hrt.42.3.362 -
Problemy Endokrinologii Sep 2020Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and...
Congenital hyperinsulinusm is rare disease characterized high secretion of insulin by pancreatic beta cells leading to the development of hypoglycemia. Persistent and transient forms of hyperinsulinism are distinguished. Transient hyperinsulinism are the most common cause of severe hypoglycemia in newborns. The etiology of this disease is not known. There are risk factors for the development of transient hyperinsulinism: asphyxia at birth, prematurity, maternal diabetes, low or large weight by gestation. Hypoglycemia with hyperinsulinism is severe. Therefore, early diagnosis and therapy especially during the neonatal period, are necessary.The article describes 3 clinical cases of transient hyperinsulinism in children with different gestational age and concomitant pathology. All children recevied insulinostatic therapy with diazoxide with a positive effect: euglycemia without glucose requirement . In all children, therapy was completed subsequently. At the time of publication of the article, the physical and psychomotor development of children is normal.
Topics: Diazoxide; Glucose; Humans; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Insulin
PubMed: 33351360
DOI: 10.14341/probl12572 -
Proceedings of the Royal Society of... Sep 1966
Topics: Blood Glucose; Child, Preschool; Diazoxide; Glucose Tolerance Test; Humans; Hypoglycemia; Infant; Male; Middle Aged
PubMed: 5921562
DOI: No ID Found -
The New England Journal of Medicine Jan 1980
Topics: Child; Diazoxide; Female; Hemodynamics; Humans; Hydralazine; Hypertension, Pulmonary; Pregnancy; Time Factors; Vasodilator Agents
PubMed: 7350416
DOI: 10.1056/NEJM198001103020210 -
The Medical Journal of Australia Apr 1979
Topics: Animals; Diazoxide; Hypertension; Injections, Intravenous; Rats
PubMed: 449797
DOI: 10.5694/j.1326-5377.1979.tb112102.x