RESUMEN
Retinitis pigmentosa (RP) is a group of inherited diseases that cause blindness due to the progressive death of rod and cone photoreceptors in the retina. There are currently no effective treatments for RP. Inherited mutations in rhodopsin, the light-sensing protein of rod photoreceptor cells, are the most common cause of autosomal-dominant RP. The majority of mutations in rhodopsin, including the common P23H substitution, lead to protein misfolding, which is a feature in many neurodegenerative disorders. Previous studies have shown that upregulating molecular chaperone expression can delay disease progression in models of neurodegeneration. Here, we have explored the potential of the heat-shock protein co-inducer arimoclomol to ameliorate rhodopsin RP. In a cell model of P23H rod opsin RP, arimoclomol reduced P23H rod opsin aggregation and improved viability of mutant rhodopsin-expressing cells. In P23H rhodopsin transgenic rat models, pharmacological potentiation of the stress response with arimoclomol improved electroretinogram responses and prolonged photoreceptor survival, as assessed by measuring outer nuclear layer thickness in the retina. Furthermore, treated animal retinae showed improved photoreceptor outer segment structure and reduced rhodopsin aggregation compared with vehicle-treated controls. The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. Furthermore, the unfolded protein response (UPR), which is induced in P23H transgenic rats, was also enhanced in the retinae of arimoclomol-treated animals, suggesting that arimoclomol can potentiate the UPR as well as the HSR. These data suggest that pharmacological enhancement of cellular stress responses may be a potential treatment for rhodopsin RP and that arimoclomol could benefit diseases where ER stress is a factor.
Asunto(s)
Respuesta al Choque Térmico/efectos de los fármacos , Hidroxilaminas/farmacología , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Degeneración Retiniana/prevención & control , Retinitis Pigmentosa/prevención & control , Rodopsina/deficiencia , Rodopsina/metabolismo , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Citoprotección , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrorretinografía , Humanos , Mutación , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patología , Ratas , Ratas Sprague-Dawley , Ratas Transgénicas , Degeneración Retiniana/genética , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Degeneración Retiniana/fisiopatología , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/metabolismo , Retinitis Pigmentosa/patología , Retinitis Pigmentosa/fisiopatología , Rodopsina/genética , Factores de Tiempo , Transfección , Respuesta de Proteína Desplegada/efectos de los fármacos , Visión Ocular/efectos de los fármacosRESUMEN
Transitional cell carcinoma (TCC) of the renal pelvis was found in two dogs, a 7-year-old male English Setter and a 11-year-old female Shetland shepherd. Affected dogs were presented for clinical examination without any specific symptoms but haematuria in case 1 and occurrence of whitish material in the urine of case 2; neoplastic disorders were discovered with ultrasonographic investigation and fine needle aspiration biopsy. Histopathological examination was carried out after nephrectomy and ureterectomy of the affected kidney of both dogs, and confirmed the diagnosis of non-invasive and low grade TCC in case 1 and of infiltrating TCC in case 2. The clinical, gross, cytological and histopathological features of these rare tumours originating from transitional epithelium of the renal pelvis are reported.
Asunto(s)
Carcinoma de Células Transicionales/veterinaria , Enfermedades de los Perros/patología , Neoplasias Renales/veterinaria , Pelvis Renal , Animales , Biopsia con Aguja Fina/veterinaria , Carcinoma de Células Transicionales/patología , Perros , Femenino , Neoplasias Renales/patología , Pelvis Renal/patología , MasculinoRESUMEN
The diagnostic capacity of a semiquantitative latex test for lipase measurement was compared with the measurement of other pancreatic enzymes in 100 consecutive patients admitted to a general hospital for recent onset of severe abdominal pain. Positive results of the test were found in two patients with acute pancreatitis, and in one out of three chronic pancreatitis relapses. The test yielded false-positive results only in two patients who had no apparent pancreatic involvement. A marginal increase in other pancreatic enzymes was found in a few patients with acute biliary or appendicular problems. In conclusion, the lipase latex test can be suggested in an emergency setting as a quick and reliable alternative to serum amylase to rule out a diagnosis of acute pancreatitis.