The enzyme is then purified for administration. The results show that the biopharmaceutical is safe and many of the parameters of CESD, e.g., elevated transaminases, ferritins, and serum cholesterol levels, respond rapidly, and upon withdrawal of LAL they partially return to pretreatment levels. Although liver biopsies were not a part of this study, several patients had evidence of cholesterol mobilization with transient increases in serum cholesterol

following LAL administration. This result varied between patients and may be related to the degree of liver ��-catenin signaling involvement, e.g., fibrosis. The exact mechanism of this effect is unknown, but likely relates to the delivery of LAL to lysosomes in hepatocytes and Kupffer cells since in rodents this is where most of the enzyme localizes. In future studies, the relationships between the serum cholesterol levels and hepatic histology could be important, as the peak of the cholesterol elevation following LAL administration might serve as a biomarker of excess cholesteryl esters

in the hepatocytes and other cell types. Similarly, the extent of reversibility of tissue lesions and residual damage will need to be assessed. Although not part of this safety study, a role PLX3397 purchase of LAL therapy in WD appears clear since, except for one case, the effects of HSCT have been uniformly poor. However, the lethality of WD will make early and rapid diagnosis essential. The degree of recovery in WD, or CESD, is not known, but based on other rapidly progressive lysosomal storage diseases, e.g., Infantile Pompe disease, earlier therapy leads to better outcomes. As with the other lysosomal storage diseases for which enzyme replacement therapies are available, there remain many questions and issues to address as this therapy for

LAL deficiency states moves forward: how soon to treat, how to predict the disease severity, how much is reversible, what are the long-term effects, are all tissues treated equally, and the list goes on. Importantly, next there are and will be many basic and applied issues that arise from this promising treatment. As with the other lysosomal storage diseases, LAL therapy should stimulate much basic and clinical research into these neglected diseases that will lead to enhanced overall care and improved health of afflicted patients. Gregory Grabowski, M.D. “
“Sexually transmitted infections continue to be a significant medical problem in men who have sex with men. Some of these patients will be seen in gastroenterology and hepatology clinics while others will attend clinics for sexually transmitted disorders. Although the recognition of acquired immunodeficiency syndrome (AIDS) was followed by the use of safer sex practices in the 1980s, epidemiologic studies now indicate increasing rates for at least some infections such as anorectal gonorrhea and syphilis. The common anorectal infections in homosexual men are herpes simplex virus, Neisseria gonorrhoeae, syphilis and Chlamydia trachomatis.