Effects of diazoxide in experimental acute necrotizing 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.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

Hipoglucemia por hiperinsulinismo. A propósito de un caso / Hypoglycemia by hyperinsulinism. To purpose of a case

Se presenta un recién nacido con hipoglucemia refractaria al tratamiento, secundario e hiperinsulinismo. Se describen los hallazgos clínicos, de laboratorio, los diagnósticos diferenciales y el tratamiento con el propósito de analizar esta patología infrecuente.

Persistent hyperinsulinemic hypoglycemia of infancy: experience at Siriraj Hospital.

BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is the most common cause of recurrent or persistent hypoglycemia in early childhood. Conventionally, pancreatectomy (Px) has often been recommended to control hypoglycemia. However, PHHI can be managed successfully by intensive medical treatment to avoid pancreatectomy. METHOD: Data from 10 infants (8M, 2F) with PHHI were retrospectively analyzed. RESULTS: Eight patients (80%) developed symptoms within 72 hours after birth (early-onset). Six patients (60%) underwent 85 per cent-95 per cent Px due to failure of medical treatment. Two patients who underwent less than 95 per cent Px required second Px (97% and 99%). One patient developed permanent diabetes mellitus and malabsorption. Hypoglycemia could be successfully managed by medication alone in four patients (40%). Of these, three patients had early-onset neonatal hypoglycemia. Medication could be discontinued in three patients (75%). Three of ten patients (30%) had delayed development. Pancreatectomies and/or the diagnosis of PHHI were made late for these patients. One of these three children also developed epilepsy. CONCLUSIONS: Patients with PHHI frequently require pancreatectomy which commonly results in long-term complications especially diabetes mellitus and malabsorption. Our data suggest that PHHI can be managed successfully with an intensive medical regimen even in patients with early-onset hypoglycemia. Although medical management is very laborious for the family and physician, it should be applied until euglycemia is accomplished. Moreover, the early diagnosis of PHHI and the successful hypoglycemic control are very necessary to prevent permanent neurologic sequelae.

Hiperinsulinismo en un lactante mayor / Hyperinsulinism in major lactant

Se presenta el caso de una lactante mayor de 20 meses de edad, con antecedente de asfixia perinatal, hipoglicemia durante el período neonatal, quien presenta cuadro convulsivo desde los seis meses, consulta en malas condiciones generales, hipoglicémica y con Glasgow de 3/15, ameritando administración de elevados tenores de glucosa EV. La relación glicemia/insulinemia fue menor de 2,6 por lo que se concluye el diagnóstico de hiperinsulinismo. Se instauró tratamiento con Diazóxido evolucionando satisfactoriamente

Crisis hipertensivas / Hypertensive crisis

La cisis hipertensiva, afortunadamente es una complicacion relativamente rara de la hipertension arterial. El cuadro clinico es reconocido por valores de presion arterial elevados y sintomas cardiovasculares, neurologicos y visuales progresivos, y en algunos casos con falla renal y trastornos hematologicos concomitantes. Una vez diagnosticado, el paciente es hospitalizado en una unidad de cuidados intensivos, para el inicio rapido de la terapia hipotensora y las medidas terapeuticas alternas. Una vez controlada la presion arterial y si las condiciones clinicas del paciente lo permiten, se iniciara la medicacion oral. Los resultados obtenidos con las anteriores medidas terapeuticas han sido satisfactorios a medida que se adquiere mas experiencia con el uso de nuevos farmacos y se obtiene un mejor pronostico para estos pacientes. Se quiere resaltar que una vez diagnosticada la crisis hipertensiva se necesita de una atencion rapida y adecuada para un mejor control de la presion arterial

Infusäo lenta de diazóxido associado a furosemida no tratamento da crise hipertensiva / Diaroxide slow infution associated with furosemide in treatment of hypertensive crisis

Selecionou-se, em serviço de urgência, 28 pacientes, idade média de 46 anos, com pressäo arterial distólica > ou = 130 mmHg e sintomas agudos ou fundoscopia com alteraçöes vasculares recentes, dividindo-os em dois grupos. Tratou-se o primeiro grupo, composto de 15 pacientes, com dizóxido (15 mg/minuto); dose máxima (300 mg) ssob a forma de infusäo lenta associado a furosemida (20 mg) venosa e o segundo, composto de 13 pacientes, apenas coccm diazóxido. Ocorreuqueda gradativa da pressäo arterial média (PAM) nos dois grupos, atingindo a variaçäo final da PAM (delta PAM) 24,15 ñ 2,09% no grupo que recebeu diurético e 23,61 ñ 2,91% no outro grupo. A diferença da delta PAM observada entre os dois grupos näo tem significado estatístico. A pressäo arterial diastólica permaneceu > ou = 130 mmHg após o término da infusäo em quatro pacientes (14,28%) com PAM incial > 180 mmHg sendo um (6,66%) do primeiro grupo e três (23%) do segundo grupo. Estes pacientes foram submetidos a nova infusäo sem diurético, obtendo-se uma delta PAM de 21,25%. Suspendeu-se a infusäo em dois pacientes (15,38%) do segundo grupo com PAM inicial de 160 e 156,6 mmHg respectivamente, que apresentaram queda rápida da pressäo arterial diastólica abaixo de 110 mmHg. Concluiu-se que a infusäo lenta de diazóxido é uma alternativa segura e eficaz no tratamento da crise hipertensiva, näo se necessitando associaçäo rotineira com furosemida, exceto talvez quando a PAM inicial estiver acima de 180mmHg