ABSTRACT
Targeted inhibition of Rho-associated kinase (ROCK)2 downregulates the proinflammatory T cell response while increasing the regulatory arm of the immune response in animals models of autoimmunity and Th17-skewing human cell culture in vitro. In this study, we report that oral administration of a selective ROCK2 inhibitor, KD025, reduces psoriasis area and severity index scores by 50% from baseline in 46% of patients with psoriasis vulgaris, and it decreases epidermal thickness as well as T cell infiltration in the skin. We observed significant reductions of IL-17 and IL-23, but not IL-6 and TNF-α, whereas IL-10 levels were increased in peripheral blood of clinical responders after 12 wk of treatment with KD025. Collectively, these data demonstrate that an orally available selective ROCK2 inhibitor downregulates the Th17-driven autoimmune response and improved clinical symptoms in psoriatic patients via a defined molecular mechanism that involves concurrent modulation of cytokines without deleterious impact on the rest of the immune system.
Subject(s)
Heterocyclic Compounds, 4 or More Rings/pharmacology , Interleukin-10/blood , Interleukin-17/blood , Psoriasis/drug therapy , Skin/drug effects , Skin/immunology , rho-Associated Kinases/antagonists & inhibitors , Administration, Oral , Adolescent , Adult , Aged , Autoimmunity/drug effects , Cytokines/biosynthesis , Cytokines/genetics , Cytokines/immunology , Down-Regulation , Female , Gene Expression Regulation , Heterocyclic Compounds, 4 or More Rings/administration & dosage , Humans , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-17/genetics , Interleukin-17/immunology , Keratinocytes/immunology , Male , Middle Aged , Psoriasis/immunology , Psoriasis/pathology , Severity of Illness Index , Skin/pathology , Th17 Cells/immunology , Young AdultABSTRACT
Se presenta un paciente de 30 años de edad, de la raza blanca, el cual llega al cuerpo de guardia del hospital con signos de anemia aguda y hemorragia abundante del miembro superior derecho, ausencia de pulso radial y cubital, frío, sudoroso obnubilado. Se envió al salón de operaciones. Se realizó anastomosis término terminal de la arteria axilar, se recuperó hemodinámicamente. Es dado de alta a los 17 días con una evolución satisfactoria
Subject(s)
INFORME DE CASO , Wounds and InjuriesABSTRACT
Se expone una actualización del sindrome de la lesión aguda de la mucosa gastroduodenal; se señalan el concepto y los aspectos más importantes de la etiopatogenia y la anatomía patológica. Se hace énfasis en el diagnóstico y tratamiento(AU)
