Ranking Self-reported Gastrointestinal Side Effects of Pharmacotherapy in Sarcoidosis.

BACKGROUND: Clinical manifestations of sarcoidosis vary widely, depending on the intensity of the inflammation and the organ systems affected. So far, no curative treatment exists; the disease can only be suppressed. All treatment options cause side effects affecting quality of life. The aim of this study was to establish and rank the prevalence of self-reported gastrointestinal side effects of drugs used in the treatment of sarcoidosis. METHODS: A cross-sectional web-based anonymous survey about complaints and side effects was conducted among sarcoidosis patients in the Netherlands, United Kingdom, and United States of America. RESULTS: Of the participants, 70% were being treated with one or more drugs. The most important reported side effect was weight gain, associated with increased appetite among prednisone users (as monotherapy as well as in combination with other drugs). Methotrexate (MTX) users especially experienced nausea, with monotherapy as well as combination therapy. Vomiting and weight loss were most prominent among azathioprine and mycophenolate mofetil (MMF) users, whereas diarrhoea was frequently mentioned by MMF and MTX users. The reported side effects of hydroxychloroquine were generally rather mild. CONCLUSION: The current study ranked the gastrointestinal side effects associated with pharmacotherapy in sarcoidosis patients. Pharmacotherapy does have multiple gastrointestinal side effects. The strongest association between a reported side effect and drug use was that of weight gain associated with increased appetite among prednisone users. It would therefore be useful for future research to look further into dietary interventions to counter these side effects and reduce their burden.

[Cachexia and sarcopenia in chronic heart failure : Change in muscle strength and muscle structure]. / Kachexie und Sarkopenie bei chronischer Herzinsuffizienz : Veränderung von Muskelkraft und Muskelaufbau.

Alterations to the body composition, i.e. the makeup of skeletal muscle, fat and bone density, are frequent in heart insufficiency. Their prevalence and clinical consequences are often underestimated. Cachexia is recognized as a complex multifactorial syndrome in chronic diseases that leads to weight loss. This point constitutes the essential differential criterion from sarcopenia. Cachexia is defined as a non-edematous weight loss of more than 5% within 12 months or less. Cachexia means weight loss, while sarcopenia means loss of muscle mass without weight loss because the functional muscle can be replaced by adipocytes. Sarcopenia is defined as a skeletal muscle mass index (SMMI) of at least 2 standard deviations below the mean value of a healthy young reference group between 20 and 30 years of the same sex and ethnic background. At the same time the walking speed is reduced to 1 m/s or the distance covered in a 6-min walk is <400m. The determination of loss of muscle mass should be carried out by whole body scanning, ideally with dual-energy x­ray absorptiometry. A reliable and simple method for measurement of performance capability is the short physical performance battery (SPPB) test. The treatment of sarcopenia and cardiac cachexia in patients with heart insufficiency is still a great challenge. Power and endurance training, nutritional supplementation and drug therapy are possible therapeutic approaches; however, the study situation is unsatisfactory.

Mechanism-based inactivation of N-arylhydroxamic acid N,O-acyltransferase by 7-substituted-N-hydroxy-2-acetamidofluorenes.

N-Arylhydroxamic acid N,O-acyltransferase (AHAT) catalyzes the transfer of the N-acetyl group from N-arylhydroxamic acids to arylamines. In the absence of an arylamine acceptor, AHAT catalyzes the conversion of N-arylhydroxamic acids to reactive electrophilic intermediates that become irreversibly bound to cellular nucleophiles, including those present on AHAT itself. As part of an investigation of the AHAT-catalyzed bioactivation process, a series of 7-substituted analogues of N-hydroxy-2-acetamidofluorene (1) was synthesized and evaluated in vitro as substrates and inactivators of a partially purified hamster hepatic AHAT preparation. All of the compounds functioned as acetyl donors in the AHAT-catalyzed transacetylation of 4-aminoazobenzene (AAB) and all of them were inactivators of AHAT. The inactivation process exhibited apparent first-order kinetics, and the 7-methoxy compound exhibited the largest inactivation rate constant. Quantitative structure-activity analysis provided support for the concept that positively charged species are involved in the inactivation of AHAT by this series of compounds. Results of experiments in which nucleophilic trapping agents such as glutathione, cysteine, methionine, guanosine phosphate, and tRNA were included in incubation mixtures with AHAT and the N-arylhydroxamic acids indicated that electrophiles which diffuse away from the enzyme active site participate in the inactivation process.