Polyamine-Derived Aminoaldehydes and Acrolein: Cytotoxicity, Reactivity and Analysis of the Induced Protein Modifications.

Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases.

Relationship between Patient Preferences, Attitudes to Treatment, Adherence, and Quality of Life in New Users of Teriflunomide.

Background: A poor patient adherence often limits the real-world effectiveness of an oral disease-modifying therapy (DMT) for multiple sclerosis (MS). In the present study, we aimed to map patient preferences, attitudes toward treatment, and quality of life to identify the predictors of non-adherence to teriflunomide. Methods: This was a single-arm, non-interventional, multicenter study (Czech Act 378/2007 Coll.) consisting of three visits: the first at treatment initiation (teriflunomide 14 mg), and then after 3 and 9 months of therapy. We enrolled both DMT-naïve and patients who had undergone a DMT diagnosed with a clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). The functional status and MS activity were estimated using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR); the quality of life via the Multiple Sclerosis Impact Scale (MSIS-29); the medication adherence with the Morisky Medication Adherence Scale (MMAS-8); the confidence in the ability to take medications by the Self-Efficacy for Appropriate Medication Score (SEAMS); and the attitude to the therapy via the Beliefs about Medicines Questionnaire (BMQ). After nine months of therapy, we predicted the adherence to teriflunomide (MMAS-8) by fitting a multivariate ordinal logistic model with EDSS changes, gender, previous DMT, MSIS-29, BMQ, and SEAMS as the explanatory variables. Results: Between 2018 and 2019, 114 patients were enrolled at 10 sites in the Czech Republic. The mean age was 41.2 years, 64.8% were diagnosed with a CIS, 52.4% were DMT-naïve, and 98.1% of patients preferred an oral administration at the baseline. The mean EDSS baseline was 1.97 and remained constant during the 9 months of therapy. The ARR baseline was 0.72 and dropped to 0.19 and 0.15 after 3 and 9 months, respectively. Despite a more than 4-fold higher ARR baseline, the treatment-naïve patients achieved an ARR at 9 months comparable with those previously treated. There were ten non-serious adverse reactions. After nine months of teriflunomide therapy, 63.3%, 21.2%, and 15.4% of patients had a high, medium, and low adherence, respectively, as per the MMAS-8; 100% of patients preferred an oral administration. The SEAMS score (odds ratio (OR) = 0.91; p = 0.013) and previous DMT (OR = 4.28; p = 0.005) were the only significant predictors of non-adherence. The disability, the quality of life, and beliefs about medicines had no measurable effect on adherence. Conclusion: After nine months of teriflunomide therapy, both the disability and quality of life remained stable; the relapse rate significantly decreased, 63.3% of patients had a high adherence, and 100% of patients preferred an oral administration. A low adherence was associated with previous DMT experiences and a low self-efficacy for the appropriate medication (i.e., the confidence in one's ability to take medication correctly).