Uremic Sarcopenia.

"Uremic sarcopenia" refers to a progressive decrease in muscle mass, strength, and function despite normal skeletal muscle physiology in patients with chronic kidney disease (CKD). Sarcopenia involves multiple risk factors, comprising immunological changes, hormonal, metabolic acidosis, reduced protein intake, and physical inactivity. All these risk factors, along with complex pathophysiological mechanisms including ubiquitin, insulin/IGF-1, myostatin, and indoxyl sulfate, activate downstream pathways that ultimately increase muscle degradation while reducing muscle regeneration. Uremic sarcopenia not only affects the quality of life but also increases the risk of morbidity and mortality in patients with CKD. Of all the treatment modalities, aerobic and resistance exercise have shown prevention and reduced rate of muscle degeneration. A variety of pharmacological agents have been tried to target different steps in the known pathogenetic pathways, including the use of androgens and anabolic steroids, correction of vitamin D deficiency, use of growth hormone supplementation, and suppression of the ubiquitin pathway. Though some of these techniques have had beneficial results in animal experiments, human trials are still sparse. This review article relates to recent publications that describe the abnormalities in skeletal muscle that primarily leads to muscle wasting and its consequences in patients with CKD.

New Life to an Old Treatment: Pegylated Interferon Beta 1a in the Management of Multiple Sclerosis.

BACKGROUND: In the 1990s, the beta interferons and glatiramer acetate were introduced for treating relapsing-remitting multiple sclerosis. These medications have a demonstrated record of efficacy and safety, although they require frequent administration via injection and are only partially effective. The optimization of treatment in patients who do not respond adequately to this first-line therapy is essential for attaining the best long-term outcomes. Switching to the recently approved emergent therapies is a strategy to consider for treatment of patients with a suboptimal response. OBJECTIVE: This review summarizes the mechanisms of action, clinical benefits, and safety profiles of current multiple sclerosis disease-modifying therapies, including highly efficacious monoclonal antibodies or convenient oral therapies, and with a special focus on the pegylated interferon beta 1a formulation. METHODS: We reviewed the recent literature and human clinical trials on multiple sclerosis therapies by bibliographic search in PubMed and clinicaltrials.gov. RESULTS AND CONCLUSION: Although the first-line interferon beta exhibits a favorable benefit-torisk profile, treatment compliance is compromised potentially due to its known adverse events and frequent injectable administration. Less frequent dosing and improved pharmacological properties have been achieved by reaction of interferon beta with chemically activated polyethylene glycol. Provided that none of the available therapies show better effectiveness for all outcomes and their safety in clinical practice is of a fundamental concern, the pegylated form of interferon beta seems to keep its place as a competitive therapeutic option.