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American Journal of Diseases of... Apr 1969
Topics: Blood Glucose; Child; Child, Preschool; Diazoxide; Female; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Hypoglycemia; Infant; Insulin; Insulin Secretion; Leucine; Male; Tolbutamide
PubMed: 5773408
DOI: 10.1001/archpedi.1969.02100030413004 -
Archives of Disease in Childhood Aug 1972Four infants were born to women treated with oral diazoxide for the last 19 to 69 days of pregnancy. Maternal plasma levels of diazoxide in the 5 days before delivery...
Four infants were born to women treated with oral diazoxide for the last 19 to 69 days of pregnancy. Maternal plasma levels of diazoxide in the 5 days before delivery were related to the intake of the drug and varied between 11 and 43 μg/ml. At delivery the umbilical plasma diazoxide level was lower than that in the mother and was 6·5 to 25 μg/ml. At the age of 24 hours the plasma diazoxide level in the infants had not altered appreciably. Diazoxide was present in the amniotic fluid and was excreted in the urine in the first week of life. Urinary diazoxide excretion was greatest on days 2 and 3 and had fallen to low or undetectable levels by days 6 and 7. No effect of diazoxide was noted on the blood pressure or blood sugar levels of the infants in the first 24 hours. The glucose tolerance of 2 of the infants was normal at 24 hours, but that of the other 2, whose mothers had diabetes, was impaired. Each of the infants developed alopecia and one had hypertrichosis lanuginosa. Abnormal hair growth was first noted at the age of 1 week and persisted when the infants were last seen at the ages of 5 months to 1 year. The bone age of 3 was normal at a chronological age of 5 to 7 months but the fourth, when aged 1 year, had retarded ossification in the wrist. No abnormalities were detected in blood counts, immunoglobulin levels, or ocular development.
Topics: Abnormalities, Drug-Induced; Adult; Age Determination by Skeleton; Alopecia; Amniotic Fluid; Blood Glucose; Diabetes Complications; Diazoxide; Female; Glucose Tolerance Test; Humans; Hypertrichosis; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy
PubMed: 4340017
DOI: 10.1136/adc.47.254.537 -
Neuroscience Letters Jan 2005Aging and dementia are accompanied by cerebral white matter (WM) injury, which is considered to be of ischemic origin. A causal link between cerebral ischemia and WM... (Comparative Study)
Comparative Study
Aging and dementia are accompanied by cerebral white matter (WM) injury, which is considered to be of ischemic origin. A causal link between cerebral ischemia and WM damage has been demonstrated in rats; however, few attempts appear to have been made to test potential drugs for the alleviation of ischemia-related WM injury. We induced cerebral hypoperfusion via permanent, bilateral occlusion of the common carotid arteries of rats. A mitochondrial ATP-sensitive potassium channel opener diazoxide (5 mg/kg) or its solvent dimethyl sulphoxide (DMSO) was administered i.p. (0.25 ml) on 5 consecutive days after surgery. Sham-operated animals served as control for surgery, and non-treated rats as controls for treatments. Thirteen weeks after surgery, the animals were sacrificed and astrocytes and microglia were labeled immunocytochemically in the internal capsule, the corpus callosum and the optic tract. The astrocytic proliferation was enhanced by cerebral hypoperfusion in the optic tract, and reduced by diazoxide in DMSO, but not by DMSO alone in the corpus callosum. After carotid artery occlusion, microglial activation was enhanced two-fold in the corpus callosum and four-fold in the optic tract. DMSO decreased microglial activation in the optic tract, while diazoxide in DMSO, but not DMSO alone, restored microglial activation to the control level in the corpus callosum. In summary, the rat optic tract appeared to be particularly vulnerable to ischemia, while the effect of diazoxide was restricted to the corpus callosum. We conclude that diazoxide dissolved in DMSO can moderate ischemia-related neuroinflammation by suppressing glial reaction in selective cerebral WM areas.
Topics: Animals; Astrocytes; Brain Ischemia; Corpus Callosum; Diazoxide; Dimethyl Sulfoxide; Male; Rats; Rats, Wistar; Visual Pathways
PubMed: 15619542
DOI: 10.1016/j.neulet.2004.10.007 -
Journal of Analytical Toxicology 1981Three cases of chlorpropamide overdose are reported. Plasma levels of chlorpropamide, diazoxide, glucose, and insulin are presented for each patient during treatment....
Three cases of chlorpropamide overdose are reported. Plasma levels of chlorpropamide, diazoxide, glucose, and insulin are presented for each patient during treatment. The simultaneous analysis of chlorpropamide, hydrochlorothiazide, and diazoxide in plasma by high pressure liquid chromatography (HPLC) is also reported. Although all three cases presented at hospital with potentially lethal plasma levels of chlorpropamide, each was successfully treated with intravenous diazoxide and glucose. Plasma diazoxide concentrations between 50-100 microgram/mL appear to be optimal in achieving therapeutic control of chlorpropamide induced hypoglycemia.
Topics: Adolescent; Adult; Chlorpropamide; Diazoxide; Female; Humans; Hypoglycemia; Male
PubMed: 7339213
DOI: 10.1093/jat/5.6.287 -
Iranian Journal of Allergy, Asthma, and... Oct 2017No Abstract.
No Abstract.
Topics: Child, Preschool; Desensitization, Immunologic; Diazoxide; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Nesidioblastosis; Treatment Failure; Treatment Outcome
PubMed: 29149786
DOI: No ID Found -
The Journal of Clinical Endocrinology... Jun 2018It has been suggested that stimulation of lipolysis by diazoxide (DZX)-mediated insulin suppression may be useful in treating obesity. However, the optimal dose to... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
It has been suggested that stimulation of lipolysis by diazoxide (DZX)-mediated insulin suppression may be useful in treating obesity. However, the optimal dose to promote lipolysis without causing hyperglycemia is unknown.
OBJECTIVE
To assess the effects of DZX in nondiabetic obese men on lipid and glucose metabolism.
DESIGN
Double-blind, placebo (PL)-controlled, 6-month trial in men with a body mass index of 30 to 37.5 kg/m2 treated with a combination of caloric restriction, a standardized exercise program, and DZX or PL dose escalation.
RESULTS
The mean maximal tolerated dose of DZX was 422 ± 44 mg/d (range, 200 to 700 mg/d). Dose-limiting events were edema (n = 11), hyperglycemia (n = 6), and nausea (n = 2). After dose reduction to a level free of clinical side effects, DZX treatment was associated with a markedly greater decrease in fasting insulin levels than PL (-72.3 ± 3.5% vs -23.0 ± 12.6%; P < 0.001) and a significant improvement of blood pressure and plasma lipid levels. The decline in insulin levels occurred at the cost of a small increase in plasma glucose (0.6 ± 0.2 mmol/L vs -0.1 ± 0.1 mmol/L; P = 0.04) and hemoglobin A1C (0.2 ± 0.1% vs 0.0 ± 0.1%; P = 0.17).
CONCLUSION
In nondiabetic obese men, insulin levels can be reduced up to 70% without major metabolic side effects. The marked intersubject variation in maximal tolerated dose indicates that DZX dose titration needs to be individualized.
Topics: Adult; Blood Glucose; Body Mass Index; Caloric Restriction; Diazoxide; Double-Blind Method; Exercise Therapy; Humans; Insulin; Lipid Metabolism; Lipids; Lipolysis; Male; Middle Aged; Obesity; Young Adult
PubMed: 29618011
DOI: 10.1210/jc.2018-00161 -
Brain Research Sep 2004Diazoxide (DIAZ), an opener of mitochondrial ATP-sensitive K(+) channels (mK(ATP)), protects neurons against hypoxic/ischemic stress in vivo, however, direct evidence... (Comparative Study)
Comparative Study
Diazoxide (DIAZ), an opener of mitochondrial ATP-sensitive K(+) channels (mK(ATP)), protects neurons against hypoxic/ischemic stress in vivo, however, direct evidence showing mitochondrial effects of DIAZ in postischemic neurons is lacking. We investigated if DIAZ affects mitochondrial alterations after global ischemia/reperfusion (I/R) in CA1 pyramidal neurons by using oxalate-pyroantimonate electron cytochemistry. Anesthetized piglets were either non-treated, or treated with DIAZ (3 mg/kg, iv), I/R, DIAZ+I/R, or 5-hydroxy-decanoate (5HD)+DIAZ+I/R (n=6, 6, 11, 5, 7, respectively). Ischemia (10 min) was induced by intracranial pressure (ICP) elevation. After 5-30 min of reperfusion, the brains were fixed for ultrastructural studies. Relative volumes of Ca(2+)-containing deposits and mitochondria in CA1 pyramidal cells were determined by point counting on electron micrographs. I/R resulted in maximal increases in mitochondrial volume (from 7.14+/-0.63% to 9.74+/-0.57%*), and Ca(2+) levels (from 5.86+/-1.11% to 11.39+/-1.35%*; mean+/-S.E.M., *p<0.05) at 10-15-min reperfusion time. In this interval, pretreatment with DIAZ virtually abolished mitochondrial swelling (6.88+/-0.49%) and Ca(2+) accumulation (5.15+/-0.82%) evoked by I/R. The protective effect of DIAZ was reduced by 5HD, an inhibitor of mK(ATP), resulting in a calcium accumulation similar to that after IR (10.44+/-1.98%). Thus, DIAZ might preserve mitochondrial integrity in CA1 pyramidal cells after I/R, at least in part mediated by mK(ATP).
Topics: Animals; Animals, Newborn; Brain Ischemia; Calcium; Diazoxide; Female; Male; Mitochondrial Swelling; Pyramidal Cells; Swine
PubMed: 15306243
DOI: 10.1016/j.brainres.2004.05.088 -
Harefuah Jan 1978
Topics: Delivery, Obstetric; Diazoxide; Eclampsia; Female; Humans; Pregnancy; Time Factors
PubMed: 648959
DOI: No ID Found -
The Journal of Pharmacology and... Jan 1974
Topics: Adult; Animals; Bile; Carbon Radioisotopes; Chromatography, Thin Layer; Diazoxide; Dogs; Erythrocytes; Feces; Female; Guinea Pigs; Half-Life; Haplorhini; Humans; In Vitro Techniques; Infant, Newborn; Kidney; Liver; Macaca; Male; Protein Binding; Rabbits; Rats; Serum Albumin; Species Specificity; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Time Factors; Tritium
PubMed: 4203373
DOI: No ID Found -
The American Journal of Cardiology Sep 1977Ninety-one doses of diazoxide were administered intravenously to 41 patients with hypertensive crises. Diastolic blood pressure was reduced from an average of 139 to 98... (Clinical Trial)
Clinical Trial
Ninety-one doses of diazoxide were administered intravenously to 41 patients with hypertensive crises. Diastolic blood pressure was reduced from an average of 139 to 98 mm Hg within 10 minutes. On the basis of a retrospective analysis of the response of diastolic blood pressure, it was possible to determine within 10 minutes of injection whether a second dose would be required. Therapy was judged to be effective in 38 of 41 patients; 35 percent of injections were ineffective. Concomitant administration of furosemide was not shown to have a beneficial antihypertensive effect. Mean blood urea nitrogen was 59.5 mg/100 ml initially and was not significantly different 2 weeks after therapy. None of the patients demonstrated clinical evidence of diazoxide-induced deterioration of coronary circulation. Electrocardiograms obtained 2 weeks after diazoxide therapy failed to show evidence of new ischemic changes. Only 9 percent of patients complained of side effects, and these were transient and relatively innocuous. It is concluded that diazoxide is both safe and efficacious in the management of hypertensive crises.
Topics: Adult; Aged; Blood Glucose; Blood Pressure; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Diazoxide; Drug Evaluation; Electrocardiography; Female; Furosemide; Heart Rate; Humans; Hypertension; Injections, Intravenous; Male; Middle Aged
PubMed: 331925
DOI: 10.1016/0002-9149(77)90164-3