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The Veterinary Record Aug 1981
Topics: Adenoma, Islet Cell; Administration, Oral; Animals; Blood Glucose; Diazoxide; Dog Diseases; Dogs; Insulinoma; Male; Pancreatic Neoplasms
PubMed: 6275601
DOI: 10.1136/vr.109.9.178 -
Clinics (Sao Paulo, Brazil) Feb 2017We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis.
OBJECTIVE:
We aimed to assess the effects of diazoxide on the mortality, pancreatic injury, and inflammatory response in an experimental model of acute pancreatitis.
METHODS:
Male Wistar rats (200-400 g) were divided randomly into two groups. Fifteen minutes before surgery, animals received physiological (0.9%) saline (3 mL/kg) (control group) or 45 mg/kg diazoxide (treatment group) via the intravenous route. Acute pancreatitis was induced by injection of 2.5% sodium taurocholate via the biliopancreatic duct. Mortality (n=38) was observed for 72 h and analyzed by the Mantel-Cox Log-rank test. To study pancreatic lesions and systemic inflammation, rats (10 from each group) were killed 3 h after acute pancreatitis induction; ascites volume was measured and blood as well as pancreases were collected. Pancreatic injury was assessed according to Schmidt's scale. Cytokine expression in plasma was evaluated by the multiplex method.
RESULTS:
Mortality at 72 h was 33% in the control group and 60% in the treatment group (p=0.07). Ascites volumes and plasma levels of cytokines between groups were similar. No difference was observed in edema or infiltration of inflammatory cells in pancreatic tissues from either group. However, necrosis of acinar cells was lower in the treatment group compared to the control group (3.5 vs. 3.75, p=0.015).
CONCLUSIONS:
Treatment with diazoxide can reduce necrosis of acinar cells in an experimental model of acute pancreatitis, but does not affect the inflammatory response or mortality after 72 h.
Topics: Animals; Cholagogues and Choleretics; Diazoxide; Disease Models, Animal; Male; Pancreatitis, Acute Necrotizing; Random Allocation; Rats; Rats, Wistar; Taurocholic Acid; Vasodilator Agents
PubMed: 28273237
DOI: 10.6061/clinics/2017(02)10 -
Lancet (London, England) Jun 1972
Topics: Acute Kidney Injury; Administration, Oral; Adult; Diabetic Ketoacidosis; Diazoxide; Female; Humans; Hypertension, Malignant; Male; Pancreatitis
PubMed: 4113603
DOI: 10.1016/s0140-6736(72)91132-4 -
Pediatrics International : Official... Dec 2017Diazoxide, an ATP-sensitive potassium channel opener, is the main therapeutic agent for treating hyperinsulinemic hypoglycemia. The aim of this study was to determine...
BACKGROUND
Diazoxide, an ATP-sensitive potassium channel opener, is the main therapeutic agent for treating hyperinsulinemic hypoglycemia. The aim of this study was to determine the in vivo ductus arteriosus (DA)-dilating effects of diazoxide in fetal and neonatal rats.
METHODS
Near-term rat pups delivered via cesarean section were housed at 33°C. After rapid whole-body freezing, the ductus arteriosus (DA) diameter was measured using a microscope and a micrometer. Full-term pregnant rats (gestational day 21) were injected i.p. with diazoxide (10 and 100 mg/kg) 4 h before delivery, and the neonatal DA diameter was measured at 0, 30, or 60 min after birth. The newborn rats were also injected i.p. with diazoxide (10 and 100 mg/kg) at birth or 60 min after birth. DA was measured at 0, 30, or 60 min after injection. In the fetal investigation, the effect of diazoxide was studied via simultaneous application of indomethacin (10 mg/kg) and L-nitroarginine methyl ester (L-NAME) on gestational days 21 and 19.
RESULTS
The control rats had rapid postnatal DA constriction (diameter, 0.80 and 0.08 mm at 0 and 60 min after birth, respectively). Diazoxide had a dose-dependent inhibitory effect on postnatal DA constriction. Prenatal diazoxide (10 mg/kg) inhibited postnatal DA closure (0.20 mm at 60 min after birth). The diazoxide injection (10 mg) at birth inhibited postnatal DA closure (0.14 mm at 60 min after birth). Diazoxide injection in 60-min-old rats dilated the constricted DA at 60 min (0.10 mm vs. 0.02 mm in the controls). In the fetal investigation, diazoxide inhibited the fetal DA constrictive effect of indomethacin and L-NAME.
CONCLUSION
Diazoxide attenuates postnatal DA constriction and dilates a closing DA in fetal and neonatal rats.
Topics: Animals; Animals, Newborn; Diazoxide; Dilatation, Pathologic; Ductus Arteriosus; Female; KATP Channels; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Vasodilator Agents
PubMed: 28901668
DOI: 10.1111/ped.13424 -
Clinical Pharmacology and Therapeutics 1973
Topics: Administration, Oral; Adult; Animals; Chemical Phenomena; Chemistry; Dialysis; Diazoxide; Dogs; Half-Life; Humans; Hypoglycemia; Infant; Infant, Newborn; Infant, Premature; Injections, Intravenous; Kinetics; Male; Protein Binding; Rats; Serum Albumin; Time Factors; Tritium
PubMed: 4683074
DOI: 10.1002/cpt197314173 -
Clinical Endocrinology Feb 2024
Topics: Humans; Diazoxide; Hyperinsulinism; Hypertension, Pulmonary
PubMed: 38059616
DOI: 10.1111/cen.14996 -
Postgraduate Medical Journal Oct 1997A survey of UK patients receiving the drug diazoxide, revealed 40 patients with insulinoma on this treatment. Mean age (+/- SD) was 67 +/- 18 years, and 74% were female....
A survey of UK patients receiving the drug diazoxide, revealed 40 patients with insulinoma on this treatment. Mean age (+/- SD) was 67 +/- 18 years, and 74% were female. Duration of treatment was 7 +/- 6 years (range 1-22). Most (55%) patients were treated with diazoxide because of tumour non-localisation (including failed previous surgery). Metastatic disease (20%) and poor surgical risk (10%) were other indications. Side-effects (notably fluid retention and hirsutism) were common (47%) but not troublesome. Treatment was highly effective--59% were symptom free and 38% had only occasional symptoms. Only one patient had frequent hypoglycaemia despite treatment. We conclude that diazoxide is effective in the management of insulinoma. Side-effects are common but not problematic. Treatment should be considered for all patients not cured by surgery, or unsuitable for surgical treatment.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Diazoxide; Female; Health Care Surveys; Humans; Insulinoma; Kidney Diseases; Male; Middle Aged; Neoplasms, Unknown Primary
PubMed: 9497974
DOI: 10.1136/pgmj.73.864.640 -
The Medical Journal of Australia Oct 1974
Topics: Administration, Oral; Creatinine; Diazoxide; Edema; Furosemide; Humans; Hypertension, Malignant; Hypoglycemia; Parkinson Disease, Secondary; Propranolol
PubMed: 4444609
DOI: 10.5694/j.1326-5377.1974.tb71047.x -
Journal of Clinical Pharmacy and... Dec 2002Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers/activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia.
METHODS
Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study.
RESULTS
Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores.
CONCLUSION
The results of this study present a novel application for potassium channel openers/activators in the neuropsychiatric disorders and diazoxide may be an effective adjuvant agent in the management of schizophrenia.
Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Diazoxide; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Potassium Channels; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome
PubMed: 12472985
DOI: 10.1046/j.1365-2710.2002.00445.x -
The Annals of Thoracic Surgery Jan 2004Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and...
BACKGROUND
Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro.
METHODS
The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation.
RESULTS
Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation.
CONCLUSIONS
This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.
Topics: Cell Hypoxia; Diazoxide; Dose-Response Relationship, Drug; Heart; Humans; In Vitro Techniques; Myocardium
PubMed: 14726066
DOI: 10.1016/s0003-4975(03)01295-5