Some aspects of treatment for cognitive impairments. Cyticolin: pharmacological characteristics, possible benefits, aspects of use

The paper reviews the data available in the literature on the pharmacokinetic and pharmacodynamic properties of cyticolin and its use in cognitive impairments (CIs).It assesses trials investigating the effect of cyticolin on cognitive functions, including its possible role in increasing Sirtuin 1 (SIRT1) expression. The results of the latest multicenter trials of the drug used to treat dementia syndrome are analyzed in elderly patients with clinical presentations of mental confusion (the VITA trial) and mild vascular CIs (the IDEALE trial).Cyticolin is able to potentiate neuroplasticity and is a natural precursor of phospholipids, mainly phosphotidylcholine that serves as a source of choline in the metabolic pathways of acetylcholine biosynthesis. The VITA and IDEALE have shown that the parenteral and oral administrations of cyticolin are effective and safe in the treatment of moderate vascular CIs and dementia with clinical presentations of mental confusion. Cyticolin therapy is used to reduce the risk of side effects and to delay of loss of the therapeutic effects of levodopa preparations. Cyticolin has been noted to have a positive effect on cognitive functions in patients with Alzheimer’s disease if it is used as an additional therapy

Evaluation of the cognitive-motor training effectiveness in combination with drug therapy among patients with moderate cognitive disorders: the own research results

Introduction. Non-drug methods of therapy for cognitive impairment is one of the topical areas of neurology. Studies have shown that cognitive training may be beneficial for maintaining mental alertness in healthy older adults, while patients with dementia and mild cognitive impairment are more likely to benefit from cognitive-motor training or rehabilitation. It is possible that the severity and type of cognitive disorders, as well as patients’ adherence to training, the correct construction of tasks, may affect the effectiveness of non-drug therapy for cognitive disorders.Аim. The aim of this study was to evaluate the effectiveness of cognitive-motor training developed at Sechenov University in patients with moderate cognitive impairment (MCI).Materials and methods. 41 patients were included in the study, including 8 women and 33 men, the average age of patients was 60.3 ± 8.5 years, the average level of education was 14.2 ± 8.7 years, of which 15 patients met the criteria AD, 26 – VCI criteria. Patients underwent quantitative neuropsychological testing, assessment of emotional disorders, and also assessed such indicators as satisfaction with the quality of life, adherence to therapy. Subsequently, the patients were divided into groups of individual and group cognitive training. Classes with patients were held according to the standard scheme, 30–50 minutes a day, for 40 days. After 3 months, 10 patients were randomly selected from the individual training group and received an additional course of group cognitive-motor training.Results. Тhe study showed that after 1.5 months, patients showed a significant decrease in the severity of cognitive disorders (p < 0.05). The greatest positive dynamics was noted in relation to the level of attention (p < 0.05), memory (including primary modal-nonspecific mnestic impairment, p < 0.05), logical operations (p < 0.05). The patients included in the study also showed a significant decrease in the severity of depression (p < 0.05). The analysis showed that significant positive dynamics was recorded both in patients of the individual CT group and in patients who received group CT (p < 0.05). The positive effect on cognitive functions was maintained during the three months of follow-up. Comparative analysis of study patients after 6 months showed that patients who received additional sessions with a trainer reported an additional improvement in well-being. These differences were statistically significant, despite the small number of patients included in the repeat CT group (p < 0.05).Conclusions. The effectiveness of cognitive-motor training in patients with MCI was noted. The results obtained allow us to recommend this type of cognitive-motor training for use in clinical practice by neurologists, therapists and psychiatrists as an additional effective method for the treatment of cognitive impairment

Nonpharmacological treatment of cognitive impairment: cognitive training guidelines

Important aspects of the treatment of cognitive impairments are their early detection, prevention and timely prescription of drug therapy. The method of non-drug prevention and, at the same time, the treatment of cognitive impairment is cognitive training. There are cognitive training, cognitive stimulation and cognitive rehabilitation. The content of  cognitive training should be determined by the type and severity of the patient’s cognitive impairment; effectiveness depends, among other things, on the duration of the sessions and on the commitment of patients to cognitive training. At the Department of Nervous Diseases and Neurosurgery of Sechenov University, guidelines have been developed that allow cognitive training for patients with mild and moderate cognitive impairments. The effectiveness of methodological recommendations has been confirmed by studies; they were introduced into the work of the neurological and neurosurgical departments of the clinic of nervous diseases of the Sechenov University. Taking into account the development of modern technologies, it seems interesting and important to create methods of cognitive training that will allow the patient to study using a smartphone, tablet or computer, and the doctor to remotely monitor the well-being and track the results of the patient’s therapy. In the fall of 2022, the Health Formula program will be launched on the basis of the My Health app, designed specifically to support patients with cognitive impairments. Health Formula is an online service for remote communication between a doctor and a patient, the purpose of which is to increase patient compliance and the effectiveness of the treatment itself. The application will contain a set of cognitive exercises to complement the prescribed drug therapy. At the initial stage, the course will be a balanced selection of video exercises, which will later be included in the global interactive program for patients with CI

Postoperative cognitive dysfunction: etiology, clinical features, diagnosis

Introduction. The present study analyzed the possibility of using neuropsychological tests to assess postoperative cognitive dysfunction. New data were obtained: in the postoperative period, hippocampal memory impairments predominate in patients, which makes it expedient to use methods for diagnosing primary modal-nonspecific memory disorders in patients who are to undergo neurosurgical intervention on the spinal cord.The aim of the study to evaluate the influence of surgery with anesthesia on the cognitive functions of middle-age patients.Materials and methods. The study included 20 middle-aged patients. All patients had to undergo spinal surgery. Patients received total intravenous anesthesia with propofol induction (4–12 mg/kg/hr). Cognitive functions before and after the operation were made with the use of the MoCA, TMT A and B, FCSRT, state-trait anxiety inventory test (STAI).Results. The development of POCD was noted in 15% of cases. The patients showed a decrease in the FCSRT prompt index (1st day = 87 ± 9.0; 2nd day = 83 ± 15; p = 0,0005), while the overall severity of cognitive impairments (total score of MoCA) did not change significantly (standard deviation according to MoCA: 24.25 ± 2.86 on day 1 and 24 ± 3.24 on the second day, p = 0.61). The RT level decreased by day 2: 44.65 ± 7.4 versus 41.1 ± 8.2 (p = 0.001). Correlation analysis did not show the relationship between the age of patients, education level, comorbidity and development of POCD; however, the duration of anesthesia was associated with a decrease in MoCA scores (Pearson’s correlation coefficient r = –0.44; p = 0.050).Conclusion. Thus, our study shows that the study of hippocampal memory impairments is important in patients with POCD. These data differ from the data of researchers presented earlier, where the most important clinical manifestations of POCD are considered to be a decrease in attention and speed of mental processes. Of course, the small sample size dictates the need for additional research

Противовоспалительный и регенеративный эффект подавления гипоксийного сигналинга на модели хронической обструктивной болезни легких

The aim of this study was to investigate anti-inflammatory and regenerative effects of inhibited activation of hypoxic signaling in COPD model using cyclooxygenase-2 (COX-2)-dependent pro-inflammatory cascade inhibition. Methods. COPD was modelled in rats by nitrogen dioxide (NO2, 30-40 mg×m–3) exposure for 90 days. Celecoxib was used as COX-2 inhibitor. The study group rats were given celecoxib (25 mg×kg–1) through an esophageal probe after 30 days of exposure. Control rats were given saline solution. The group 3 rats were intact. The rats were put out of the experience using cervical dislocation after 60 and 90 days of NO2 exposure. Bronchoalveolar lavage fluid (BALF) cytology was analyzed. COX-2, hypoxia-inducible factor-1α (HIF-1α), interleukin-17 (IL-17), and surfactant protein D (SP-D) were measured in BALF using ELISA method. Histological examination of the lung tissue was also performed. Results. 90-day exposure of NO2 resulted in 7.7-fold increase in BALF neutrophil count compared to that in intact rats. Pro-inflammatory mediators (СOX-2, HIF-1α, and IL-17) significantly increased and SP-D level decreased in BALF. Administration of celecoxib was accompanied by normalization of BALF cytology profile and decrease in COX-2, HIF-1α, and IL-17 levels in BALF; this could indicate a reduction in the hypoxic signaling activity and in inflammation. The growth of SP-D concentration could be considered as a result of the alveolar epithelium restoration. This was confirmed by histological examination of the lung tissue. Conclusion. COX-2 inhibition suppressed HIF-1α-signaling and decreased the lung inflammation. The results confirm a functional and regulatory relationship between HIF-1α and COX-2 signaling cascades that could be a therapeutic target for preventing the progression of inflammation and airway remodeling in COPD.Цель. Оценка противовоспалительного и регенеративного эффекта предотвращения активации гипоксийного сигналинга на модели хронической обструктивной болезни легких (ХОБЛ) путем ингибирования циклооксигеназы-2 (СОХ-2)-зависимого провоспалительного каскада. Материалы и методы. При помощи экспозиций диоксидом азота (NO2, 30–40 мг / м3) в течение 90 дней у крыс создана модель ХОБЛ. В качестве ингибитора СОХ-2 применялся целекоксиб. С 30-го дня крысам 1-й группы через пищеводный зонд вводился целекоксиб (25 мг / кг); животные 2-й группы (контроль) получали 0,9%-ный NaCl. Интактные крысы составили 3-ю группу. Животные выводились из опыта после 60 и 90 дней экспозиции NO2 путем цервикальной дислокации. При этом выполнялась цитография бронхоальвеолярной лаважной жидкости (БАЛЖ), определялось содержание COX-2, гипоксия-индуцибельного фактора-1a (HIF-1a), интерлейкина (IL)-17, сурфактантного протеина D (SP-D) методом ELISA. Выполнено гистологическое исследование легочной ткани. Результаты. Показано, что после 90-дневной экспозиции NO2 в БАЛЖ контрольных особей содержание нейтрофилов в 7,7 раза превышало интактное значение. Достоверно возрастало содержание провоспалительных медиаторов СОХ-2, HIF-1α, IL-17, а уровень SP-D снижался. Применение целекоксиба сопровождалось нормализацией цитологического профиля БАЛЖ и уменьшением содержания СОХ-2, HIF-1α, IL-17, что свидетельствовало о снижении активности гипоксийного сигналинга и воспалительного процесса. Значительно возрастала концентрация SP-D, что можно рассматривать как следствие восстановления морфологической структуры бронхоальвеолярного эпителия, о чем свидетельствовали данные гистологического исследования легочной ткани. Заключение. При ингибировании СОХ-2 отмечен супрессивный эффект на HIF-1α-сигналинг и уменьшение легочного воспаления. Полученные результаты подтверждают функционально-регуляторную связь HIF-1α и СОХ-2-сигнальных каскадов, которая может быть терапевтической мишенью для предотвращения прогрессирования воспаления и ремоделирования дыхательных путей при ХОБЛ

Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers

Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCAI allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Fucans, but Not Fucomannoglucuronans, Determine the Biological Activities of Sulfated Polysaccharides from Laminaria saccharina Brown Seaweed

Sulfated polysaccharides from Laminaria saccharina (new name: Saccharina latissima) brown seaweed show promising activity for the treatment of inflammation, thrombosis, and cancer; yet the molecular mechanisms underlying these properties remain poorly understood. The aim of this work was to characterize, using in vitro and in vivo strategies, the anti-inflammatory, anti-coagulant, anti-angiogenic, and anti-tumor activities of two main sulfated polysaccharide fractions obtained from L. saccharina: a) L.s.-1.0 fraction mainly consisting of O-sulfated mannoglucuronofucans and b) L.s.-1.25 fraction mainly composed of sulfated fucans. Both fractions inhibited leukocyte recruitment in a model of inflammation in rats, although L.s.-1.25 appeared to be more active than L.s.-1.0. Also, these fractions inhibited neutrophil adhesion to platelets under flow. Only fraction L.s.-1.25, but not L.s.-1.0, displayed anticoagulant activity as measured by the activated partial thromboplastin time. Investigation of these fractions in angiogenesis settings revealed that only L.s.-1.25 strongly inhibited fetal bovine serum (FBS) induced in vitro tubulogenesis. This effect correlated with a reduction in plasminogen activator inhibitor-1 (PAI-1) levels in L.s.-1.25-treated endothelial cells. Furthermore, only parent sulfated polysaccharides from L. saccharina (L.s.-P) and its fraction L.s.-1.25 were powerful inhibitors of basic fibroblast growth factor (bFGF) induced pathways. Consistently, the L.s.-1.25 fraction as well as L.s.-P successfully interfered with fibroblast binding to human bFGF. The incorporation of L.s.-P or L.s.-1.25, but not L.s.-1.0 into Matrigel plugs containing melanoma cells induced a significant reduction in hemoglobin content as well in the frequency of tumor-associated blood vessels. Moreover, i.p. administrations of L.s.-1.25, as well as L.s.-P, but not L.s.-1.0, resulted in a significant reduction of tumor growth when inoculated into syngeneic mice. Finally, L.s.-1.25 markedly inhibited breast cancer cell adhesion to human platelet-coated surfaces. Thus, sulfated fucans are mainly responsible for the anti-inflammatory, anticoagulant, antiangiogenic, and antitumor activities of sulfated polysaccharides from L. saccharina brown seaweed

Glucosinolates, myrosinase hydrolysis products, and flavonols found in rocket (Eruca sativa and Diplotaxis tenuifolia)

Rocket species have been shown to have very high concentrations of glucosinolates and flavonols, which have numerous positive health benefits with regular consumption. In this review we highlight how breeders and processors of rocket species can utilize genomic and phytochemical research to improve varieties and enhance the nutritive benefits to consumers. Plant breeders are increasingly looking to new technologies such as HPLC, UPLC, LC-MS and GC-MS to screen populations for their phytochemical content to inform plant selections. Here we collate the research that has been conducted to-date in rocket, and summarise all glucosinolate and flavonol compounds identified in the species. We emphasize the importance of the broad screening of populations for phytochemicals and myrosinase degradation products, as well as unique traits that may be found in underutilized gene bank resources. We also stress that collaboration with industrial partners is becoming essential for long-term plant breeding goals through research

Algorithm for the treatment of sleep disorders in patients with cognitive impairment

Algorithm for the treatment of sleep disorders in patients with cognitive impairmen

Alzheimer’s disease: diagnosis and treatment

The main issues of the epidemiology and the early and late clinical manifestations of Alzheimer’s disease (AD), the most common cause of dementia in the elderly, are discussed. Current data on the pathogenesis of, new treatment strategies for AD, and investigator’s altered views on the course of the disease are given. The fact that AD is a long-term, progressive disease that develops long before the occurrence of the first clinical symptoms is beyond question now. This necessitates the design of new diagnostic criteria and methods that allow the disease to be diagnosed as early as possible. The main aspects of basic symptomatic therapy for AD are discussed in detail. The basic principles of its correct treatment using new dosage forms that permit a complete therapeutic effect to be achieved are given