The effect of long-term danazol prophylaxis on liver function in hereditary angioedema-a longitudinal study

Background Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients. Methods Characteristic parameters of liver function (including bilirubin, GOT, GPT, γGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively. Results From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study. Conclusions Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients. © Springer-Verlag 2009

Role of Hsp70 in Multiple Sclerosis: An Overview

For many years heat shock protein 70 (Hsp70) was considered exclusively an intracellular chaperone contributing to protein proteostasis and in apoptotic pathway block. Lately it has been demonstrated that Hsp70 is actively released in the extracellular environment, thereby promoting the activation of the immune system by stimulating innate and adaptive responses through the activation of APCs. Its expression in the nervous system is induced in a variety of pathological conditions. Emerging evidences displayed that Hsp70 is a critical regulator in normal neural cells. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) directed against myelin antigens. In this review, we focus our attention on the possible protective or detrimental Hsp70 role in multiple sclerosis. A better comprehension will be useful to take advantage of its potential as a therapeutic target