Yoga vs Physical Therapy in Multiple Sclerosis: Results of Randomized Controlled Trial and the Training Protocol.

Background: Yoga originated in the territory of modern India more than 3,000 years ago uses techniques for working with the musculoskeletal system, cardiorespiratory system, and attention. Currently, the effectiveness and safety of yoga in patients with various neurological disorders, including multiple sclerosis (MS), is of interest to many scientists and clinicians. Purpose: The main aim of this study is to examine the effect of yoga on symptoms and quality of life in patients with MS vs physical therapy (exercise therapy) and no exercise. Methods: The patients were randomly assigned to three groups (yoga, physical therapy (PT), or waiting list). After 12 weeks of regular exercises (or the absence of them), the effect of yoga and PT on the functional status and quality of life of patients were evaluated. The data were collected during the patients' two visits to the study center - before the start of the study and at the end of the 12-week period. The in-person examination included a doctor's assessment of the Expanded Disability Status Scale (EDSS), the SF-36 quality of life questionnaire, the fatigue scale, the Berg balance scale, and the 6-min walking test. Results: A total of 36 patients finished the clinical study: thirty women and six men. There was no statistically significant difference between the groups in terms of improvement in MS symptoms as measured by the balance, walking test, and fatigue scales. However, in the analysis of eight criteria of SF-36 quality-of-life questionnaire by the covariation analysis, statistically significant differences were found in favor of the yoga group in terms of physical functioning (PF) (p = .003), life activity (VT) (p < .001), mental health (MH) (p = 013), and social functioning (SF) (p = .028). Conclusion: Thus, regular yoga classes under the guidance of qualified staff are a promising method of non-drug rehabilitation of patients with MS with motor disorders.

Penicillin acylase-catalyzed synthesis of beta-lactam antibiotics in highly condensed aqueous systems: beneficial impact of kinetic substrate supersaturation.

Advantages of performing penicillin acylase-catalyzed synthesis of new penicillins and cephalosporins by enzymatic acyl transfer to the beta-lactam antibiotic nuclei in the supersaturated solutions of substrates have been demonstrated. It has been shown that the effective nucleophile reactivity of 6-aminopenicillanic (6-APA) and 7-aminodesacetoxycephalosporanic (7-ADCA) acids in their supersaturated solutions continue to grow proportionally to the nucleophile concentration. As a result, synthesis/hydrolysis ratio in the enzymatic synthesis can be significantly (up to three times) increased due to the nucleophile supersaturation. In the antibiotic nuclei conversion to the target antibiotic the remarkable improvement (up to 14%) has been gained. Methods of obtaining relatively stable supersaturated solutions of 6-APA, 7-ADCA, and D-p-hydroxyphenylglycine amide (D-HPGA) have been developed and syntheses of ampicillin, amoxicillin, and cephalexin starting from the supersaturated homogeneous solutions of substrates were performed. Higher synthetic efficiency and increased productivity of these reactions compared to the heterogeneous "aqueous solution-precipitate" systems were observed. The suggested approach seems to be an effective solution for the aqueous synthesis of the most widely requested beta-lactam antibiotics (i.e., amoxicillin, cephalexin, cephadroxil, cephaclor, etc.).

Quantitative characterization of the nucleophile reactivity in penicillin acylase-catalyzed acyl transfer reactions.

Nucleophile reactivity of two most known nuclei of penicillins and cephalosporins, 6-aminopenicillanic (6-APA) and 7-aminodesacetoxycephalosporanic (7-ADCA) acids, was quantitatively characterized. In penicillin acylase (PA)-catalyzed acyl transfer reactions the relative reactivity of the added nucleophile compared to the water (i.e. nucleophile reactivity) is defined by two complex kinetic parameters beta(0) and gamma, and depends on the nucleophile concentration. In turn, parameters beta(0) and gamma were shown to be dependent on the structure of both reactants involved: nucleophile and acyl donor. Analysis of the kinetic scheme revealed that nucleophile reactivity is one of a few key parameters controlling efficiency of PA-catalyzed acyl transfer to the added nucleophile in an aqueous medium. Computation of the maximum nucleophile conversion to the product using determined nucleophile reactivity parameters in the synthesis of three different antibiotics, ampicillin, amoxicillin and cephalexin, showed good correlation with the results of corresponding synthetic experiments. Suggested approach can be extended to the quantitative description and optimization of PA-catalyzed acyl transfer reactions in a wide range of experimental conditions.

Penicillin acylase-catalyzed ampicillin synthesis using a pH gradient: a new approach to optimization.

The penicillin acylase-catalyzed synthesis of ampicillin by acyl transfer from D-(-)-phenylglycine amide (D-PGA) to 6-aminopenicillanic acid (6-APA) becomes more effective when a judiciously chosen pH gradient is applied in the course of the process. This reaction concept is based on two experimental observations: 1) The ratio of the initial synthesis and hydrolysis rates (V(S)/V(H)) is pH-dependent and exhibits a maximum at pH 6.5-7.0 for a saturated solution of 6-APA; 2) at a fixed 6-APA concentration below saturation, V(S)/V(H) increases with decreasing pH. Optimum synthetic efficiency could, therefore, be achieved by starting with a concentrated 6-APA solution at pH 7 and gradually decreasing the pH to 6.3 in the course of 6-APA consumption. A conversion of 96% of 6-APA and 71% of D-PGA into ampicillin was accomplished in an optimized procedure, which significantly exceeds the efficiency of enzymatic synthesis performed at a constant pH of either 7.0 or 6.3.