RESUMEN
Platelet-activating factor (PAF) is a potent lipid inflammatory mediator acting on cells through its specific receptor. Plasma PAF-acetylhydrolase (PAF-AH) is the main enzyme that inactivates PAF in blood, participating in its homeostasis. The objective of this study was to investigate the involvement of PAF in the liver fibrotic process using an experimental animal model. Liver fibrosis was induced in adult male Wistar rats by administration of thioacetamide (TAA) in drinking water (300 mg/l) for three months. The animals were sacrificed at time 0 (control group) and after 1, 2, and 3 months. PAF levels in liver and blood and PAF-AH activity in plasma were determined. Liver histopathological examination was also performed. TAA administration resulted in progressively increased liver fibrosis, leading finally to the formation of cirrhotic nodules in the liver. Throughout the experiment PAF levels in liver tissue remained stable. "Total" ("free" plus "bound") PAF levels in blood decreased, reaching statistically significant differences in the first and third months compared with the control group (P < 0.05). "Free" PAF levels in blood were higher at one month (P < 0.05) and decreased gradually thereafter. In all treated groups, "bound" PAF levels in blood decreased whereas plasma PAF-AH activity increased (P < 0.05) compared with the control group. Our data indicated alterations of PAF levels in blood and PAF-AH activity during fibrosis induction, implicating participation of PAF in the liver fibrotic process.
Asunto(s)
Cirrosis Hepática Experimental/metabolismo , Hígado/patología , Factor de Activación Plaquetaria/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Progresión de la Enfermedad , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/patología , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , Tioacetamida/toxicidadRESUMEN
An 80-year-old woman on maintenance hemodialysis therapy developed severe hypercalcemia under vitamin D treatment for secondary hyperparathyroidism. To avoid the toxic calcemic effects, cinacalcet was introduced and the dose of vitamin D was substantially decreased. Cinacalcet targets the calcium-sensing receptor and decreases parathyroid hormone levels without increasing calcium and phosphorus levels. Three days after starting cinacalcet therapy, the patient developed palpable purpura on both upper and lower extremities that resolved after discontinuation of cinacalcet and administration of steroids. Skin biopsy of the initial eruption showed leukocytoclastic vasculitis. According to the Naranjo adverse drug reaction probability scale, leukocytoclastic vasculitis probably was caused by cinacalcet introduction. Drug-induced vasculitis is a poorly defined disorder, and, in most cases, no pathogenetic mechanism can be described. An idiosyncratic reaction to the agent often is proposed. Cinacalcet should be considered a causative agent of cutaneous leukocytoclastic vasculitis, and although this is the result of only a clinical observation, further attention is required in the future because cinacalcet recently has been introduced in the treatment of secondary hyperparathyroidism in patients on long-term hemodialysis therapy.
Asunto(s)
Naftalenos/efectos adversos , Vasculitis Leucocitoclástica Cutánea/inducido químicamente , Anciano de 80 o más Años , Cinacalcet , Femenino , HumanosRESUMEN
Zinc is an essential trace element, exerting important antioxidant, anti-inflammatory, and antiapoptotic effects. It affects growth and development and participates in processes such as aging and cancer induction. The liver is important for the regulation of zinc homeostasis, while zinc is necessary for proper liver function. Decreased zinc levels have been implicated in both acute and chronic liver disease states, and zinc deficiency has been implicated in the pathogenesis of liver diseases. Zinc supplementation offers protection in experimental animal models of acute and chronic liver injury, but these hepatoprotective properties have not been fully elucidated. In the present review, data on zinc homeostasis, its implication in the pathogenesis of liver diseases, and its effect on acute and chronic liver diseases are presented. It is concluded that zinc could protect against liver diseases, although up to now the underlying pathophysiology of zinc and liver interactions have not been defined.
Asunto(s)
Hepatopatías/metabolismo , Hígado/metabolismo , Zinc/metabolismo , Carcinoma Hepatocelular/metabolismo , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Hepatopatías/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Zinc/deficiencia , Zinc/uso terapéuticoRESUMEN
Hydatid disease is endemic in Greece, and has been known from Hippocrates' time to cause cysts in the liver. We report here three very rare cases of primary gallbladder hydatid disease without prior history or evidence of concurrent disease activity in any other location. To our knowledge, only two previous reports exist, each of one patient suffering from primary gallbladder hydatid disease. Unlike the insidious hydatid cysts of the liver, gallbladder hydatidosis in our patients was associated with early diagnosis, due to gallbladder dysfunction symptoms presenting early in its course. Moreover, the size of gallbladder cysts compared to liver cysts at diagnosis was small (maximal diameter, <5 cm), making total cyst excision along with cholecystectomy feasible for all of our patients. During long-term follow up of the patients (up to 10 years), no disease recurrences were noted. We provide supporting evidence that primary gallbladder hydatidosis presents a different pathophysiological and clinical course, having better prognosis, when compared with the usual liver disease.