RESUMEN
We previously reported that statins improve the symptoms of X-linked nephrogenic diabetes insipidus (X-NDI) in animal models. The aim of this study was to verify whether the pleiotropic effect of statins on AQP2 trafficking and kidney-concentrating ability, observed in rodents, was attainable in humans at therapeutic doses. We enrolled 24 naïve hypercholesterolemic patients and measured urine excretion of AQP2 (uAQP2) at baseline and during 12 weeks of treatment with simvastatin 20 mg/day. Simvastatin induced a rapid and significant increase of uAQP2, reduced the 24-hour diuresis, and increased urine osmolality. These effects were also maintained in patients chronically treated with statins for at least 1 year. This study strongly suggests that statins may effectively enhance the efficacy of current pharmacological treatment of patients with urine-concentrating defects caused by defective AQP2 plasma membrane trafficking, like X-NDI.
Asunto(s)
Anticolesterolemiantes/farmacología , Acuaporina 2/orina , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Hipercolesterolemia/tratamiento farmacológico , Simvastatina/farmacología , Adulto , Anciano , Anticolesterolemiantes/uso terapéutico , Diuresis/efectos de los fármacos , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lovastatina/farmacología , Masculino , Persona de Mediana Edad , Concentración Osmolar , Simvastatina/administración & dosificación , Simvastatina/uso terapéutico , Factores de TiempoRESUMEN
PURPOSE: The purpose of this study was to explore the potential role of deranged fecal microRNA (miRNA) pattern as a reliable warning signal of colorectal cancer (CRC), a subset of fecal CRC-related miRNAs was evaluated in CRC patients, before and after surgery, and in healthy controls. METHODS: Twenty CRC patients and 20 age/sex-matched healthy volunteers with negative colonoscopy entered the study. Cancer biopsy, colonic mucosa from the resected specimens, and fecal samples from patients and controls were screened for 13 miRNAs involved in CRC onset and progressions by reverse transcription quantitative PCR (RT-qPCR). Postoperative evaluation of fecal miRNAs was carried out after a median follow-up of 18 months (range 12-30). RESULTS: Two out 13 miRNAs (RNU6B, miR-16-3p) were used as internal controls leaving 11 available for analysis. Cancer tissue contained significantly higher expression of all miRNAs, compared to normal mucosa (p < 0.05). Expression of preoperative levels of five fecal miRNAs, (miR-19-b-3p, miR-20a-5p, miR-21-3p, miR92a-3p, miR141) was significantly higher in CRC patients compared to controls and significantly decreased after curative surgery. Three out of these five miRNAs (miR20a-5p, miR21-3p, and miR141) returned to values comparable to normal controls. CONCLUSIONS: A set of three specific fecal miRNAs is overexpressed before surgery, and return within the normal range after cancer removal could be considered as an appealing opportunity for a new reliable tool for CRC secondary prevention. However, their role needs to be explored in large prospective trials and compared with the existing screening tools.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/cirugía , Cirugía Colorrectal , Heces/química , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Demografía , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Estabilidad del ARN/genética , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
Familial Mediterranean fever (FMF), an inherited autosomal recessive disorder, is characterized by sporadic, paroxysmal attacks of fever and serosal inflammation, lasting 1-3 days. Patients may develop renal amyloidosis, arthritis, serositis, and skin and oral lesions. Diagnosis is based on clinical features, response to treatment with colchicine, and genetic analysis. Colchicine prevents attacks and renal amyloidosis, in addition to reversing proteinuria. Nonresponders may receive novel therapy, including interleukin (IL)-1 receptor antagonists and IL-1 decoy receptor. Recently, new options have been considered.
Asunto(s)
Productos Biológicos/uso terapéutico , Colchicina/uso terapéutico , Descubrimiento de Drogas/tendencias , Fiebre Mediterránea Familiar/tratamiento farmacológico , Animales , Productos Biológicos/química , Colchicina/química , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/genética , Humanos , Proteína Antagonista del Receptor de Interleucina 1/química , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Resultado del TratamientoRESUMEN
We report a case of symptomatic massive liver echinococcosis due to Echinococcus granulosus, unexpectedly found in a 34 year old woman living in Apulia, Italy. Based on size (max diameter 18 cm), clinical presentation, geographical area, and natural history of echinococcosis, we estimate that the initial infection should have occurred 9-20 yrs before. Presenting symptoms were those of typical mass effect with RUQ pain, pruritus, malaise, and recent weight loss. Abdominal ultrasound diagnosis of probable echinococcal cyst was subsequentely confirmed by positive serology and further detailed by radiological imaging. The cyst was massively occupying subdiaphragmatic liver segments and extending to the omentum and the stomach. The characteristics of the lesion were compatible with the WHO 2003 classification type CE2l, indicating a large active fertile cyst with daughter cysts. The cyst was successfully treated with medical therapy followed by surgery. The prevalence, diagnostic workup, management, and costs of echinococcosis are discussed in this case presentation.
Asunto(s)
Equinococosis Hepática/diagnóstico , Hígado , Adulto , Equinococosis Hepática/parasitología , Equinococosis Hepática/patología , Equinococosis Hepática/terapia , Femenino , Interacciones Huésped-Parásitos , Humanos , Hígado/parasitología , Hígado/patología , Hígado/cirugía , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Mitochondrial dysfunction determines the onset and progression of chronic deleterious conditions including liver diseases. The in vivo assessment of mitochondrial function, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific functions and to develop diagnostic, prognostic and therapeutic strategies. The application of breath tests in the clinical setting to evaluate mitochondrial fitness may elegantly and noninvasively overcome the difficulties due to previous complex techniques and may provide clinically relevant information, i.e the effects of drugs presenting mitochondrial liabilities. Substrates meeting this requirement include alpha-ketoisocaproic acid and methionine, both decarboxylated by mitochondria. Long and medium chain fatty acids that are metabolized through the Krebs cycle and benzoic acid, which undergoes glycine conjugation, may also reflect the mitochondrial performance. This review focuses on the utility of breath tests to assess mitochondrial function in humans, thus contributing to unravel potential mechanisms associated with the dysfunction of this organelle network in the pathophysiology of liver diseases.
Asunto(s)
Pruebas Respiratorias , Dióxido de Carbono/metabolismo , Isótopos de Carbono , Hepatopatías/diagnóstico , Pruebas de Función Hepática , Mitocondrias Hepáticas/metabolismo , Enfermedades Mitocondriales/diagnóstico , Biomarcadores/metabolismo , Gases , Humanos , Hepatopatías/metabolismo , Enfermedades Mitocondriales/metabolismo , Valor Predictivo de las PruebasRESUMEN
Mitochondria play a key role in intracellular energy-generating processes, cell life and death, and are heavily involved in several metabolic pathways by integrating signaling networks; thus, a very large number of conditions are characterized by mitochondrial bioenergetic in humans. Often, mitochondrial changes are directly or indirectly dependent on the activation of intracellular stress cascades or death receptor-mediated pathways. Reactive oxygen species (ROS) formation, glutathione (GSH) depletion, protein alkylation and respiratory complex alterations are major events associated with mitochondrial dysfunction and represent critical initiating events in most forms of chronic liver disease. Through creating an analogy with a disrupted electric circuit gone bad, the present review focuses initially on how hepatic mitochondrial bioenergetics is affected in the context of drug and disease-induced liver failure and how targeting mitochondria with several antioxidant agents can be helpful for preventing the disruption of the mitochondrial electric circuit.