RESUMEN
A síndrome de fadiga crônica (SFC) é uma condição clínica que, apesar de muito prevalente, tem tratamento controverso. A suplementação com substratos como glutamina e vitaminas pode atuar como adjuvante terapêutico. Os autores descrevem um medicamento que pode atender essa finalidade, composto por glutamina 200mg, glutamato de cálcio 250mg, cloridrato de piridoxina 20mg e fosfato de ditetraetilamônio 6mg. São descritas também as ações de cada um dos componentes, e como podem auxiliar na terapêutica da SFC e em períodos de convalescença em diversas condições.
The chronic fatigue syndrome (CFS) is a clinical condition which, although highly prevalent, treatment is controversial and supplementation of substrates such as glutamine and vitamins can act as therapeutic adjuvant. A drug composition that can serve this purpose, the composition is glutamine 200mg, 250mg calcium glutamate, 20mg pyridoxine hydrochloride and phosphate ditetraetilammonium 6mg is described. Also described the actions of each component and how they can assist in the treatment of CFS and in periods of convalescence from various other conditions described.
Asunto(s)
Humanos , Masculino , Femenino , Síndrome de Fatiga Crónica/dietoterapia , Síndrome de Fatiga Crónica/terapia , Convalecencia , Vitaminas en la Dieta , Glutamatos/uso terapéutico , Glutamina/uso terapéutico , Minerales/uso terapéutico , Piridoxina/uso terapéutico , Suplementos Dietéticos , Tetraetilamonio/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: There is increasing evidence that potassium channels are involved in the cardiovascular dysfunction of sepsis. This evidence was obtained after the systemic inflammation, cardiovascular dysfunction and organ damage had developed. Here we have studied the consequences of early interference with potassium channels on development of sepsis. EXPERIMENTAL APPROACH: Sepsis was induced by caecal ligation and puncture (CLP) or sham surgery in Wistar rats. Four hours after surgery, animals received tetraethylammonium (TEA; a non-selective potassium channel blocker) or glibenclamide (a selective ATP-sensitive potassium channel blocker). Twenty-four hours after surgery, inflammatory, biochemical, haemodynamic parameters and survival were evaluated. KEY RESULTS: Sepsis significantly increased plasma NO(x) levels, expression of inducible nitric oxide synthase (NOS-2) protein in lung and thigh skeletal muscle, lung myeloperoxidase, urea, creatinine and lactate levels, TNF-α and IL-1ß, hypotension and hyporesponsiveness to phenylephrine and hyperglycemia followed by hypoglycemia. TEA injected 4 h after surgery attenuated the increased NOS-2 expression, reduced plasma NO(x) , lung myeloperoxidase activity, levels of TNF-α and IL-1ß, urea, creatinine and lactate levels, prevented development of hypotension and hyporesponsiveness to phenylephrine, the alterations in plasma glucose and reduced late mortality by 50%. Glibenclamide did not improve any of the measured parameters and increased mortality rate, probably due to worsening the hypoglycemic phase of sepsis. CONCLUSIONS AND IMPLICATIONS: Early blockade of TEA-sensitive (but not the ATP-sensitive subtype) potassium channels reduced organ damage and mortality in experimental sepsis. This beneficial effect seems to be, at least in part, due to reduction in NOS-2 expression.
Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Gliburida/uso terapéutico , Bloqueadores de los Canales de Potasio/uso terapéutico , Sepsis/complicaciones , Tetraetilamonio/uso terapéutico , Animales , Presión Sanguínea , Femenino , Regulación Enzimológica de la Expresión Génica , Frecuencia Cardíaca , Longevidad , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Wistar , Vasoconstrictores/farmacologíaRESUMEN
Intestinal ischemia and reperfusion injury is dependent on the recruitment and activation of neutrophils. Glibenclamide, an ATP-sensitive potassium channel (K(ATP)) blocker, has been shown to suppress neutrophil migration and chemotaxis during acute inflammatory responses by a mechanism dependent on its K(ATP) channel blocking activity. In the present study, we evaluated whether the treatment with glibenclamide prevented local, remote and systemic injury following reperfusion of the ischemic superior mesenteric artery in rats. The artery was made ischemic for a period of 30 or 120 min followed by 30 (mild I/R) or 120 (severe I/R) min of reperfusion, respectively. Glibenclamide (0.8 to 20 mg/kg) or vehicle was administered subcutaneously 40 min prior to the reperfusion. Glibenclamide dose-dependently inhibited the reperfusion-associated increase in vascular permeability and neutrophil accumulation in mild I/R. In the severe injury model, glibenclamide inhibited inflammatory parameters, as assessed by Evans blue extravasation, neutrophil influx and haemoglobin content, and the increase in TNF-alpha (tumor necrose factor-alpha) and IL (interleukin)-6 levels in the intestine and lung. The drug did not affect the increase in IL-1beta and IL-10 levels. TEA, a nonselective potassium channel blocker, also inhibited reperfusion injury in both intestine and lungs of animals submitted to mild and severe I/R. Our experiments suggest a role for K(ATP) channels in mediating neutrophil influx and consequent reperfusion-associated injury in rats. The lack of effect of these drugs on the reperfusion-associated hypotension and lethality may limit their usefulness after severe reperfusion injury.