RESUMEN
The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting-edge C-H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm-changing activity along with the components that trigger opposite modes of action. The first period-shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.
Asunto(s)
Carbazoles/química , Ritmo Circadiano , Criptocromos/química , Sulfonamidas/química , Factores de Transcripción ARNTL/genética , Sitios de Unión , Carbazoles/síntesis química , Carbazoles/farmacología , Carbono/química , Línea Celular , Ritmo Circadiano/efectos de los fármacos , Criptocromos/metabolismo , Genes Reporteros , Células HEK293 , Humanos , Hidrógeno/química , Mediciones Luminiscentes , Simulación del Acoplamiento Molecular , Estructura Terciaria de Proteína , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/farmacologíaRESUMEN
A 53-year-old woman with systemic lupus erythematosus presented with a 3-day history of fever and coughing. Diagnosis of pneumococcal bronchitis was made based on symptoms and positivity of pneumococcal urinary antigen test. On day 3, severe low back pain acutely occurred. Pneumococcal vertebral osteomyelitis and psoas abscess was diagnosed 17 days later by yield of penicillin-susceptible S. pneumoniae strain in blood cultures and drainage fluid. Although pneumococcal urinary antigen test is a useful tool for the diagnosis of pneumococcal pneumonia, we should consider the possibility of pneumococcal infections other than pneumonia or overwhelming bacteremia in immunosuppressive patients when urinary antigen test is positive.
Asunto(s)
Vértebras Lumbares , Osteomielitis/diagnóstico , Osteomielitis/microbiología , Infecciones Neumocócicas/diagnóstico , Absceso del Psoas/diagnóstico , Enfermedades de la Columna Vertebral/microbiología , Antígenos Bacterianos/orina , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Osteomielitis/complicaciones , Osteomielitis/orina , Infecciones Neumocócicas/complicaciones , Infecciones Neumocócicas/orina , Absceso del Psoas/complicaciones , Absceso del Psoas/orina , Enfermedades de la Columna Vertebral/orina , Streptococcus pneumoniae/inmunologíaRESUMEN
Cryptococcal meningitis is a recognized complication of systemic lupus erythematosus (SLE), with high mortality rates, particularly in those treated with immunosuppressive agents. We describe a patient diagnosed simultaneously with cryptococcal meningoencephalitis and SLE and reviewed four similar cases reported in the literature. In our case, profound low CD4 lymphocyte count and low complement levels were observed. The patient was treated with prednisolone, fluconazole, and 5-flucytosine and evinced good clinical improvement. This case suggests that intrinsic immunological abnormality related to SLE predisposed to opportunistic infections.