RESUMEN
Leptospirosis is a zoonosis caused by the spirochete Leptospira interrogans. Most cases of leptospirosis are mild to moderate, and self-limited. The course of disease, however, may be complicated by multiorgan dysfunction such as in Weil's disease. We present a case of Weil's disease with pancreatitis in a young Caucasian man residing in Hawai'i. Although leptospirosis is common in Hawai'i, few patients present with pancreatitis. This report of leptospirosis-induced pancreatitis should help raise awareness of clinicians to assess for pancreatitis when evaluating a patient with leptospirosis and acute abdominal pain.
Asunto(s)
Dolor Abdominal/etiología , Leptospirosis/complicaciones , Pancreatitis/etiología , Adulto , Humanos , Masculino , Enfermedad de Weil/complicaciones , Adulto JovenRESUMEN
The glycosaminoglycan hyaluronan is not merely the simple space filling substance it was long thought to be but is instead being increasingly recognized as a key player in numerous biological processes ranging from embryogenesis to the process of aging. Alterations in hyaluronan syntheses play an important role in ailments associated with aging such as rheumatoid arthritis, atherosclerosis and many forms of cancers, e.g. prostate cancers that mostly affect the elderly. Despite the increasing recognition of hyaluronan as a critical player in many disorders, little is known about the intracellular mechanisms involved in the regulation of the genes encoding hyaluronan synthases (HAS). Herein, evidence is provided that in type-B synoviocytes (TBS) HAS1 is a gene that depends on the transcription factor nuclear factor kappa B (NF-kappaB) for its activation. Stimulating such cells with IL-1beta results in a dose and time dependent activation of HAS1. Pyrrolidine dithiocarbamate (PDTC) blocks IL-1beta induced HAS1 activation entirely. Furthermore, PDTC treatment also prevents the degradation of the IkappaBalpha in TBS as shown by Western blot experiments. EMSA data confirm that PDCT, at concentrations sufficient to completely block IL-1beta induced HAS1 transcription, also entirely blocks IL-1beta induced NF-kappaB translocation. The reported findings stress important differences among the genes encoding hyaluronan and point at a role of HAS1 in inflammatory processes.
Asunto(s)
Glucuronosiltransferasa/metabolismo , Interleucina-1beta/farmacología , FN-kappa B/antagonistas & inhibidores , Pirrolidinas/farmacología , ARN Mensajero/metabolismo , Tiocarbamatos/farmacología , Envejecimiento/metabolismo , Artritis Reumatoide/metabolismo , Artritis Reumatoide/patología , Células Cultivadas , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Glucuronosiltransferasa/genética , Humanos , Hialuronano Sintasas , FN-kappa B/fisiología , ARN Mensajero/genética , Membrana Sinovial/metabolismo , Membrana Sinovial/patología , Transcripción Genética/efectos de los fármacosRESUMEN
Antioxidant protein 2 (AOP2) is a member of a family of thiol-specific antioxidants, recently renamed peroxiredoxins, that evolved as part of an elaborate system to counteract and control detrimental effects of oxygen radicals. AOP2 is found in endothelial cells, erythrocytes, monocytes, T and B cells, but not in granulocytes. AOP2 was found solely in the cytoplasm and was not associated with the nuclear or membrane fractions; neither was it detectable in plasma. Further experiments focused on the function of AOP2 in erythrocytes where it is closely associated with the hemoglobin complex, particularly with the heme. An investigation of the mechanism of this interaction demonstrated that the conserved cysteine-47 in AOP2 seems to play a role in AOP2-heme interactions. Recombinant AOP2 prevented induced as well as noninduced methemoglobin formation in erythrocyte hemolysates, indicating its antioxidant properties. We conclude that AOP2 is part of a sophisticated system developed to protect and support erythrocytes in their many physiological functions.