Endothelin 3 induces skin pigmentation in a keratin-driven inducible mouse model.

Endothelin 3 (Edn3) encodes a ligand important to developing neural crest cells and is allelic to the spontaneous mouse mutation occurring at the lethal spotting (ls) locus. Edn3(ls/ls) mutants exhibit a spotted phenotype due to reduced numbers of neural crest-derived melanocyte precursors in the skin. In this study, we show that when Edn3 is driven by the keratin 5 promoter and thereby placed proximal to melanocyte lineage cells, adult mice manifest pigmented skin harboring dermal melanocytes. Using a tetracycline inducible system, we show that the postnatal expression of Edn3 is required to maintain these dermal melanocytes, and that early expression of the Edn3 transgene is important to the onset of the hyperpigmentation phenotype. Crosses into Edn3(ls/ls) mutants demonstrate that the Edn3 transgene expression does not fully compensate for the endogenous expression pattern. Crosses into tyrosine kinase receptor Kit(Wv) mutants indicate that Edn3 can partially compensate for Kit's role in early development. Crosses into A(y) mutant mice considerably darkened their yellow coat color suggesting a previously unreported role for endothelin signaling in pigment switching. These results demonstrate that exogenous Edn3 affects both precursors and differentiated melanocytes, leading to a phenotype with characteristics similar to the human skin condition dermal melanocytosis.

[Polymyositis and cerebral metastasis as the initial manifestation of a carcinoma of unknown origin. Apropos of a case]. / Polimiositis y metástasis cerebrales como manifestación inicial de carcinoma de origen desconocido. A propósito de un caso.

Polymyositis is an acute or chronic inflammatory myopathy, being its association with malignancy object of controversy. We report a case of a young male patient, in whom the presence of brain metastases and polymyositis were the initial manifestation of a neoplasm of unknown origin, fact rarely described in literature.

[Rhabdomyolysis and cocaine consumption: presentation of 13 cases]. / Rabdomiolisis y consumo de cocaína: presentación de 13 casos.

We present 13 cases taken care at the Emergency Service, whose diagnosis was acute rhabdomyolysis related to consumption of illicit drugs. In all cases, the presence of cocaine in the urine was detected. Clinical features, other associated factors and complications are described, stressing the etiopathogenic mechanism of presentation of cocaine-related rhabdomyolysis.

[Intraparenchymal cerebral hemorrhage and cocaine]. / Hemorragia intraparenquimatosa cerebral y cocaína.

Medical problems related to cocaine consumption are not rare in our environment; however, to this respect, descriptions in the spanish literature are scarce. We present three cases of intracerebral hemorrhage which occurred after cocaine consumption (intranasal route in two cases and intravenous route in one case). In the three cases, another associated risk factor was observed (alcohol in one case, hypertension in other case, arteriovenous malformation in the third case). We comment on the pathophysiological theories of the cause of bleeding, high-lighting the routine search of this association.

[The Budd-Chiari syndrome as the first manifestation of polycythemia vera]. / Síndrome de Budd-Chiari como primera manifestación de policitemia vera.

The case of a 57-year-old male diagnosed as having Budd-Chiari syndrome secondary to a polycythemia vera, which produced a thrombosis of the suprahepatic veins as a first manifestation, is presented. The rarity of this clinical case and the rapidly lethal evolution of the patient, confirms the bad prognosis of this association.

[Thrombotic thrombocytopenic purpura: the need of an early treatment]. / Púpura trombocitopénica trombótica: necesidad de un tratamiento precoz.

Two patients affected by thrombotic thrombocytopenic purpura (TTP) are treated with plasmapheresis, fresh frozen plasma infusion, steroid and inhibitors of platelet aggregation with an impaired final stage: the first patient died during a plasmapheresis session and the other had a good evolution, obtaining complete recovery, maintained a year later. We discuss the clinical features and highlight the needs for early treatment with all the latest therapies.