Selective synthesis of A-ring Е-arylidene derivatives from ß-sitosterol and their activity.

A series of 24-ethylcholest-4-ene-3,6-dione 2E-arylidene-derivatives has been synthesized by a Claisen-Schmidt reaction from a natural phytosterol ß-sitosterol with yields of 80-85%. The structure of the obtained compounds was confirmed by NMR spectroscopy, including two-dimensional correlation experiments. The synthesized compounds were evaluated for their in vitro cytotoxicity and α-glucosidase inhibitory activity. It was established that compound 3 with pyridin-3-ylmethylene moiety exhibited a selective cytotoxic effect against the U251 cancer cell line with 99.31% inhibition of cancer cell growth. Compounds with pyridin-4-ylmethylene 4 and furan-2-ylmethylene-5 fragments were the most active inhibitors of α-glucosidase with IC50 64.00 and 38.95 µM, being 3- and 5-times more active than acarbose. Binding mode to α-glucosidase and ADMET characteristics for the lead molecule 5 were proposed computationally. To sum up, an efficient approach to the derivatives with promising antidiabetic activity based on available natural product ß-sitosterol is suggested.

Synthesis of C17-[5-methyl-1,3]-oxazoles by N-propargylation of triterpenic acids and evaluation of their cytotoxic activity.

A series of unexpected triterpenic C17-[5-methyl-1,3]-oxazoles along with targeted N-propargylamides was synthesized by an interaction of acid chlorides with propargylamine hydrochloride. We proposed that the formation of methyl oxazole passes through an alternative pathway by the participation of the terminal alkyne carbon atom and acid chloride intermediate with following intramolecular rearrangements. The synthesized compounds were evaluated for their cytotoxicity at the U.S. National Cancer Institute. 28-Nor-17-(5-methyloxazol-2-yl)-2-cyano-2,4-seco-3-nor-lup-4(23),20(29)-diene has demonstrated the highest activity with GI50 ranged from 1.03 to 16.4 µM against different cancer cell lines. Molecular docking in Kelch domain of Keap1 protein was performed to study a possible molecular target. Thus, we have shown for the first time that triterpenic C17-[5-methyl-1,3]-oxazoles are alternative products of the interaction of triterpenic acid chlorides with propargylamine hydrochloride and they have an advantage over corresponding N-propargylamides as cytotoxic agents.

[The restoration of the shoulder joint function in the patients presenting with hemiparesis during the acute phase of hemispheric stroke]. / Vosstanovlenie funktsii plechevogo sustava u patsientov s gemiparezom v ostryi period polusharnogo insul'ta.

The impaired function of the shoulder joint resulting from cerebral stroke is a common disorder involving permanent total disability as well as impaired capability of self-care. The functional pathological changes in the shoulder joint and the dynamics of the patients' health status during the acute period of cerebral stroke remain virtually unexplored. AIM: The objective of the present study was to obtain a deeper insight into the process of recovery of the movements in the shoulder joint of the patients presenting with hemiparesis during the acute period of hemispheric stroke based on the results of the analysis of the biomechanical data and the targeted training with biofeedback (BFB). MATERIAL AND METHODS: The study included three groups comprised of 25 subjects each. One (control) group included the subjects having neither neurological nor orthopedic pathology. The second group consisted of the patients receiving the conventional treatment in the combination with therapeutic physical exercises (TPE). Group 3 was composed of the patients given the standard course of conventional and physical (TPE) therapy complemented by biofeedback training (the TPE/BFB group). The study included clinical investigations and biomechanical registration of the movements of the shoulder joints and trunk. RESULTS: The results of the study gave evidence that the patients presenting with hemiparesis during the acute period of hemispheric ischemic stroke including those treated with the application of the active means and methods of rehabilitation, such as BFB training, showed no appreciable dynamics of the parameters being evaluated with the use of the relevant clinical scales. The biomechanical study has demonstrated that the movements in the shoulder joints (in a single plain) of the patients comprising the control group are characterized by the presence of the main component with a maximum amplitude in the plane of this movement and additional components (in other planes with a significantly lower amplitude); they are accompanied by the ancillary movements of the trunk. Functionally, the condition of paresis at the level of the shoulder joint is characterized by a decrease in the amplitude of the primary movement and the increase of one of the additional amplitudes, with the growing amplitude of the auxiliary movements of the trunk. The biomechanical methods for the objective assessment have revealed the following functional changes in the shoulder joints: the 6% improvement of flexion in the group of the patients treated with the use of therapeutic physical exercises and the 10% improvement in those treated with the combination of TPE and BFB. Moreover, abduction in the patients of these two groups improved by 4% and 9% respectively. CONCLUSIONS: The method for the study of kinematics of the movements in the shoulder joints appears to be most sensitive and informative for the purpose of diagnostics of disorders of the motor function and assessment of the process of its restoration in the patients presenting with hemiparesis during the acute period of hemispheric stroke.

[The modern approaches to the restoration of postural balance in the patients suffering from the consequences of an acute cerebrovascular accident (CVA)].

BACKGROUND: the most frequent and severe consequences of an acute cerebrovascular accident (CVA) are locomotor and coordination disorders which significantly increase the risk of falling in a static position and when walking. The methods used for the rehabilitation of the affected patients are designed in the first place to enable the patients to acquire the skills necessary for maintaining the static balance. The modern equipment allows to carry out coordination training in the static position and also during walking. AIM: The objective of the present study was to evaluate, based on the results of our original research, the feasibility and effectiveness of the application of the «Balance tutor¼ system developed for the restoration of static and dynamic balance in the framework of the combined rehabilitation treatment of the patients suffering from impaired postural balance as a consequence of acute cerebrovascular accident (CVA). MATERIALS AND METHODS: A total of 56 patients presenting with impaired postural balance following CVA were available for the examination. All of them underwent functional testing to assess the static and dynamic balance, walking abilities, and the risk of falling down including the study with the use of computer-assisted stabilometry. RESULTS: The study has demonstrated that the inclusion of the «Balance tutor¼ system for the restoration of the static and dynamic balance in the combined rehabilitative treatment of the patients having postural balance disorders after the CVA reduces the risk of fall for a walking patient, improves his (her) static and dynamic balance, increases the patient's ability to move without exterior help. The patients comprising the main study group were found to experience a decrease of statokinesiogram space in the «eyes are open¼ position (p = 0.0576, the Mann-Whitney U test) as well as a reliable decrease of the statokinesiogram space in the «eyes are closed¼ position (p=0.0063, the Mann-Whitney U test). Similar changes occurred in speed of pressure center relocation. By the end of the rehabilitation course, the patients of the main group exhibited a reliable enhancement in the dynamic balance rates estimated with the use of the Berg Balance Scale (p=0.028, Tukey's criterion), an increase in stability based at the Tinneti scale, p=0.0291; Tukey's criterion), and a decrease of the risk of falling during walk assessed with the application of Dynamic Gait Index scale (p = 0.0001, Tukey's criterion). DISCUSSION: The results of the present study with the inclusion of the «Balance tutor¼ system in the program of combined rehabilitation of the patients suffering from the consequences of CVA in the form of the postural balance impairment give evidence of the feasibility and effectiveness of this approach. There is reason to believe that its application is likely to reduce the risk of falling down and to improve characteristics of static and dynamic balance. CONCLUSION: The inclusion of the «Balance tutor¼ system in the program of combined rehabilitation of the patients suffering from the consequences of CVA in the form of the postural balance impairment is both feasible and effective.

[The application of the acupuncture techniques for the combined treatment of neurotic tics in the children]. / Ispol'zovanie metodov refleksoterapii v kompleksnom lechenii nevroticheskikh tikov u detei.

At present, the frequency of neurosis in the children is growing under the influence of the increasingly intensive stressful factors. The neurotic ticks are one of the manifestations of neurosis in the children characterized by involuntary movements; they are often accompanied by hyperactivity, deficit of attention, fatigue, and headaches. AIM: The objective of the present study was to evaluate the effectiveness of acupuncture used for the treatment of neurotic tics in the children. MATERIAL AND METHODS: The study was carried out at the basis of the department of children's rehabilitation of the Moscow city polyclinic #39. All the children were counselled by a neurologist, psychologist, and acupuncturist. An electroencephalogram was obtained from each patient and a questionnaire study involving the patients' parents was conducted. The patients were treated with the application of reflexotherapy and were given recommendations of a psychologist. A total of 30 children at the age from 6 to 12 years were available for the examination. The participants of the study were allocated to two groups depending on the strategy of the outpatient care. Group 1 was comprised of the patients (n=17) who were given 3 courses of reflexotherapy in addition to pharmacotherapy and psychologist's recommendations. The patients included in group 2 served as controls (n=13) and received only medications and psychotherapy without acupuncture. The effectiveness of the treatment was evaluated based on the dynamics of the patients' complaints. RESULTS AND DISCUSSION: The resullts of the study give evidence of the higher effectiveness of the treatment of the children suffering from neurotic ticks with the application of acupuncture therapy compared with the conventional approach. A few courses of reflexotherapy provided in the combination with pharmacotherapy and the compliance with the recommendations of a psychologist resulted in the more efficient elimination of the neurotic tics together with the associated hyperactivity, deficit of attention, fatigue, and headaches than the use of medication therapy and psychotherapy without acupuncture.

[The dynamics of shoulder joint function in patients with hemiparesis in the acute period of carotid stroke]. / Dinamika funktsii myshts plechevogo poiasa u bol'nykh s gemiparezom v ostrom periode karotidnogo insul'ta.

AIM: To evaluate the recovery of shoulder joint function in patients with hemiparesis in the acute period of hemispheric stroke on the basis of the analysis of electromyography (fEMG) of the muscles of this region before and after rehabilitation measures, including targeted training with biofeedback (BFB). MATERIAL AND METHODS: Three groups of 25 people each were studied. Patients of the physical therapy (PT) group received standard treatment and physical therapy; patients of the PT+BFB group received BFB training in addition to PT; the control group consisted of people without neurological and orthopedic symptoms. A clinical study and EMG of the muscles of the shoulder girdle during testing movements was performed. RESULTS: On the side of paresis, the function of muscles was characterized by a decrease in the bioelectric activity (movement amplitude was decreased as well) and later phase of the maximum EMG activity compared to the norm. The time of maximum EMG activity had a trend towards the shift to the normal values during the treatment process, but the difference reached a statistically significant level not for all muscles and all movements. There were variants of the functions of the paretic muscles accompanied by the increased EMG activity. In the early stages (up to 21 days) of stroke, no significant changes in the EMG activity of shoulder girdle muscles were observed. The PT+BFB group showed better results than the PT group not only in the onset of activity, but also in the reduction of the amplitude when performing the same movement that indirectly suggested the more optimal inclusion of muscles in the motor act. In the period of acute hemispheric stroke, there were changes not only in the EMG activity of muscles of the affected side, but also of the contralateral side. CONCLUSION: A fEMG of the muscles is a more sensitive and informative method of the diagnosis of disorders of motor function and assessment of recovery process of the muscles of the shoulder joint in patients with hemiparesis.