[Efficacy and safety of choline alfoscerate in the preventive therapy of dementia in elderly patients with Mild Cognitive Impairment: a three-year prospective comparative study]. / Effektivnost' i bezopasnost' kholina al'fostserata v preventivnoi terapii dementsii u pozhilykh patsientov s sindromom myagkogo kognitivnogo snizheniya: rezul'taty trekhletnego prospektivnogo sravnitel'nogo issledovaniya.

OBJECTIVE: To study the efficacy and safety of the use of annual course therapy of choline alfoscerate (CA) as a drug potentially capable of slowing or preventing the transition of amnesic type mild cognitive impairment (aMCI) into clinically pronounced dementia in a three-year open comparative study, as well as to explore the possibility of predicting the preventive effect of such therapy based on a number of clinical and biological parameters. MATERIAL AND METHODS: The study included 100 patients with aMCI, randomly divided into 2 groups: the therapeutic group consisted of 50 patients who received CA course therapy once a year for 3 years (20 intravenous infusions of 1000 mg (4 ml) in 100 ml of saline solution for 4 weeks) and a comparison group of 50 patients who underwent an annual examination at the center and did not receive therapy. Clinical and psychopathological, psychometric, immunological, follow-up, and statistical methods were used. RESULTS: A comparative three-year prospective study conducted in a group of aMCI patients treated with annual course therapy of CA for 3 years and aMCI patients who did not receive therapy with similar initial demographic, diagnostic, psychometric and immunological characteristics showed a lower progression of cognitive deficits (12.2% and 39.1%, respectively) and a lower conversion rate (8.2% and 26.1%, respectively) to dementia in the therapeutic group compared with the comparison group. The differences between the initial and final (after 1, 2 and 3 years of follow-up) cognitive functioning indicators in the therapeutic group and the comparison group were significant (p<0.05) on all scales and tests in favor of the therapeutic group throughout the entire follow-up period. CONCLUSION: The results allow us to consider CA as a possible model of preventive dementia therapy aimed at preventing the progression of cognitive deficits and the development of dementia in people at high risk of developing AD - patients with aMCI.

Effect of Oral Choline Alfoscerate on Patients with Keratoconjunctivitis Sicca.

Keratoconjunctivitis sicca (KCS) or dry eye is a disease characterized by ocular surface symptoms. This study aimed to investigate the effectiveness of oral choline alfoscerate (CA) administration as a treatment for KCS. The medical records of dry eye patients who were refractory to topical eyedrops and then took oral CA were reviewed. Results of tear break-up time (TBUT), fluorescein ocular surface staining score (FSS), and tear secretion by the Schirmer test (STT) were analyzed. The results of the ocular surface disease index (OSDI), visual analog pain score (VAS), reporting of the severity and frequency of symptoms, and the modified Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire were also analyzed. The records of 47 patients were analyzed for this study. The mean age was 62.8 ± 9.3 years, and the patients included 9 males and 38 females. TBUT, OSDI, and VAS significantly improved after CA administration compared to before (p < 0.05, paired t-test). After CA administration, symptom frequency and impact on life improved (p < 0.05, paired t-test). No significant change in photophobia or FSS was identified. In conclusion, oral CA administration was effective in improving tear stability and alleviating symptoms of KCS.

Association of nimodipine and choline alphoscerate in the treatment of cognitive impairment in patients with cerebral small vessel disease: study protocol for a randomized placebo-controlled trial-the CONIVaD trial.

BACKGROUND: Vascular cognitive impairment (VCI) is an extremely disabling condition that includes post-stroke dementia and VCI caused by cerebral small vessel disease (SVD). Currently, there is no approved treatment for this condition. Drugs active on the cholinergic pathway have been tested in VCI patients showing positive but limited efficacy. The calcium-antagonist nimodipine also showed some moderate positive effects in VCI patients. AIMS: CONIVaD (choline alphoscerate and nimodipine in vascular dementia) is a pilot, single-center, double-blinded, randomized trial aimed to assess whether the association of choline alphoscerate and nimodipine is more effective than nimodipine alone in reducing cognitive decline in patients with SVD and mild-to-moderate cognitive impairment. METHODS: All patients are evaluated at baseline and after 12 months with: (1) clinical, daily functions, quality of life, and mood assessment and (2) extensive neuropsychological evaluation. After the baseline evaluation, patients are randomly assigned to one of the two arms of treatment: (1) nimodipine 90 mg/die t.i.d plus placebo b.i.d and (2) nimodipine 90 mg t.i.d plus choline alphoscerate 1200 mg/die b.i.d. for a total of 12 months. The primary endpoint is cognitive decline, expressed as the loss of at least two points on the Montreal Cognitive Assessment at 12 months. Secondary endpoints include safety and tolerability, functional, quality of life, and neuropsychological measures. DISCUSSION: CONIVaD study is the first randomized controlled trial to examine the cognitive efficacy of combined choline alphoscerate-nimodipine treatment in VCI patients. Results of this pilot study will serve as a methodological basis for other clinical controlled, multicentric, double-blinded, and randomized trials. TRIAL REGISTRATION: Clinical Trial NCT03228498. Registered 25 July 2017.

L-Alpha-glycerylphosphorylcholine can be cytoprotective or cytotoxic in neonatal rat cardiac myocytes: a double-edged sword phenomenon.

L-Alpha-glycerylphosphorylcholine (GPC) is a widely used food supplement. GPC has been shown to exert beneficial effects in several organs; however, the cardiac effects of GPC have yet to be investigated. The aim of the present study was therefore to map out the effects of GPC on cardiac myocytes, with or without ischemia-reperfusion insult. Neonatal rat cardiac myocytes were treated with GPC at 1, 10, 80, and 100 µM concentrations for 15 min, 3 h, or 24 h, respectively. Cell viability by calcein assay and the degree of oxidative stress by DHE (superoxide level) and H2DCF (total ROS accumulation) staining were measured. In separate experiments, cardiomyocytes were pre-treated with the optimal concentration of GPC for 3 h and then cells were exposed to 4 h of simulated ischemia followed by 2 h of reperfusion (SI/R). Cell viability was measured at the end of the SI/R protocol. In normoxic conditions, the 15-min and the 3-h GPC treatment did not affect cell viability, total ROS, and superoxide levels. Under SI/R conditions, the 3-h GPC treatment protected the cardiac myocytes from SI/R-induced cell death and did not alter the level of oxidative stress. The 24-h GPC treatment in normoxic conditions resulted in significant cell death and increased oxidative stress at each concentration. Here we provide the first evidence for the cytoprotective effect of short-term GPC treatment. However, long-term administration of GPC may exert cytotoxicity in a wide concentration range in cardiac myocytes. These results may draw attention to a comprehensive cardiac safety protocol for the testing of GPC.

Formulation and bioequivalence studies of choline alfoscerate tablet comparing with soft gelatin capsule in healthy male volunteers.

PURPOSE: The aim of this study was to develop a tablet formulation of choline alfoscerate and to assess its bioequivalence by comparing its pharmacokinetic parameters with those of a commercially available soft gelatin capsule (Gliatilin®) in healthy Korean male volunteers. MATERIALS AND METHODS: Film-coated tablet formulation was optimized to control the hygroscopicity of choline alfoscerate. Bioequivalence study was performed under fasted condition with a randomized, single-dose, two-period crossover design. Subjects were orally treated with 1,200 mg of test or reference choline alfoscerate (400 mg × three doses) formulation. Blood samples were collected up to 12 hours the day before dosing to correct the baseline level of choline and 12 hours after dosing to obtain drug absorption profile. Pharmacokinetic parameters were determined after analyzing plasma concentration of choline by using LC-MS/MS. RESULTS: Hygroscopicity of choline alfoscerate was successfully controlled by adding suitable amount of Neusilin® (magnesium aluminometasilicate) in the film-coated tablet. Stability of the tablet formulation was also confirmed under the accelerated condition for 3 months. Bioequivalence study showed that the mean area under the plasma concentration-time curve from time 0 to infinity of test tablet and reference soft capsule was 3.428±2.170 and 3.305±1.803 µg⋅h/mL, respectively; the mean Cmax was 0.365±0.158 and 0.380±0.108 µg/mL, respectively; and the mean Tmax was 3.51±2.57 and 3.85±3.19 hours, respectively. The 90% CIs for geometric mean ratios of test to reference formulation for AUC0-t and Cmax were 84.51%-111.98% and 83.31%-104.10%, respectively, and satisfied the EMA regulatory criteria for bioequivalence. CONCLUSION: Pharmacokinetic parameters including the Cmax and AUC0-t determined after oral administration of the two formulations in healthy Korean male volunteers showed that the differences between the formulations (tablet vs soft capsule) were not significant for bioequivalence. Both formulations were well tolerated, with no serious adverse events reported.

Comparative analyses of DHA-Phosphatidylcholine and recombination of DHA-Triglyceride with Egg-Phosphatidylcholine or Glycerylphosphorylcholine on DHA repletion in n-3 deficient mice.

BACKGROUND: Docosahexaenoic acid (DHA) is important for optimal neurodevelopment and brain function during the childhood when the brain is still under development. METHODS: The effects of DHA-Phosphatidylcholine (DHA-PC) and the recombination of DHA-Triglyceride with egg PC (DHA-TG + PC) or α-Glycerylphosphorylcholine (DHA-TG + α-GPC) were comparatively analyzed on DHA recovery and the DHA accumulation kinetics in tissues including cerebral cortex, erythrocyte, liver, and testis were evaluated in the weaning n-3 deficient mice. RESULTS: The concentration of DHA in weaning n-3 deficient mice could be recovered rapidly by dietary DHA supplementation, in which DHA-PC exhibited the better efficacy than the recombination of DHA-Triglyceride with egg PC or α-GPC. Interestingly, DHA-TG + α-GPC exhibited the greater effect on DHA accumulation than DHA-TG + PC in cerebral cortex and erythrocyte (p < 0.05), which was similar to DHA-PC. Meanwhile, DHA-TG + PC showed a similar effect to DHA-PC on DHA repletion in testis, which was better than that of DHA-TG + α-GPC (p < 0.05). CONCLUSION: We concluded that different forms of DHA supplements could be applied targetedly based on the DHA recovery in different tissues, although the supplemental effects of the recombination of DHA-Triglyceride with egg PC or α-GPC were not completely equivalent to that of DHA-PC, which could provide some references to develop functional foods to support brain development and function.

Evaluation of the effects of two doses of alpha glycerylphosphorylcholine on physical and psychomotor performance.

BACKGROUND: Recent studies have suggested that alpha glycerylphosphorylcholine (A-GPC) may be an effective ergogenic aid. The present study was designed to assess the efficacy of two doses of A-GPC in comparison to placebo and caffeine for increasing countermovement jump performance, isometric strength, and psychomotor function. METHODS: Forty-eight healthy, college aged males volunteered for the present study and underwent baseline assessment of countermovement jump (CMJ), isometric mid thigh pull (IMTP), upper body isometric strength test (UBIST), and psychomotor vigilance (PVT). Following this assessment participants were randomly assigned to groups consisting of 500 mg A-GPC, 250 mg A-GPC, 200 mg Caffeine or Placebo taken daily. Blood samples were collected 1 h and 2 h post initial dose to quantify serum free choline and thyroid stimulating hormone then subjects returned after 7 days of supplementation to repeat CMJ, IMTP, UBIST and PVT. RESULTS: No differences were noted between groups for IMTP, UBIST or PVT performance. Serum free choline was found to be elevated in the two A-GPC groups as compared to placebo (132% and 59% respectively). Serum TSH was found to be significantly depressed in the 500 mg A-GPC group compared to other treatments (p < 0.04). Group differences were noted for maximum velocity and maximum mechanical power on the CMJ (p < 0.05) with the 250 mg A-GPC group demonstrating the greatest improvements in result. CONCLUSIONS: Based upon this evidence, and previous evidence regarding A-GPC, it should be considered as an emerging ergogenic supplement.

Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain.

Choline is involved in relevant neurochemical processes. In particular, it is the precursor and metabolite of acetylcholine (ACh). Choline is an essential component of different membrane phospholipids that are involved in intraneuronal signal transduction. On the other hand, cholinergic precursors are involved in ACh release and carry out a neuroprotective effect based on an anti-inflammatory action. Based on these findings, the present study was designed to evaluate the effects of choline and choline precursor (Choline alphoscerate, GPC) in the modulation of inflammatory processes in the rat brain. Male Wistar rats were intraperitoneally treated with 87 mg of choline chloride/kg/day (65 mg/kg/day of choline), and at choline-equivalent doses of GPC (150 mg/kg/day) and vehicle for two weeks. The brains were dissected and used for immunochemical and immunohistochemical analysis. Inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6 , IL-6 and Tumor Necrosis Factor-α, TNF-α) and endothelial adhesion molecules (Intercellular Adhesion Molecule, ICAM-1 and Vascular cell Adhesion Molecule, VCAM-1) were studied in the frontal cortex, hippocampus, and cerebellum. The results clearly demonstrated that treatment with choline or GPC did not affect the expression of the inflammatory markers in the different cerebral areas evaluated. Therefore, choline and GPC did not stimulate the inflammatory processes that we assessed in this study.

Late treatment with choline alfoscerate (l-alpha glycerylphosphorylcholine, α-GPC) increases hippocampal neurogenesis and provides protection against seizure-induced neuronal death and cognitive impairment.

Choline alfoscerate (α-GPC) is a common choline compound and acetylcholine precursor in the brain, which has been shown to be effective in the treatment of Alzheimer's disease and dementia. α-GPC has been shown to enhance memory and cognitive function in stroke and Alzheimer's patients but currently remains untested in patients suffering from epilepsy. This study aimed to evaluate whether α-GPC treatment after seizure can ameliorate seizure-induced cognitive impairment and neuronal injury. The potential therapeutic effects of α-GPC on seizure-induced cognitive impairment were tested in an animal model of pilocarpine-induced seizure. Seizures were induced by intraperitoneal injection of pilocarpine (25mg/kg) in male rats. α-GPC (250mg/kg) was injected into the intramuscular space once daily for one or three weeks from immediately after seizure, or from 3 weeks after the seizure onset for 3 weeks. Here we found that immediate 1-week treatment of α-GPC showed no neuroprotective effects and neurogenesis. Immediate 3-week treatment of α-GPC showed neuroprotective effect but no effect on neurogenesis. To evaluate the effect of late treatment of α-GPC on cognitive impairment following seizure, rats were injected α-GPC from 3 weeks after seizure for 3 weeks and subjected to a water maze test. In the present study, we found that administration of α-GPC starting at 3 weeks after seizure improved cognitive function through reduced neuronal death and BBB disruption, and increased neurogenesis. Therefore, α-GPC injection may serve as a beneficial treatment for improvement of cognitive function in epilepsy patients.

[Centrally acting cholinomimetics in the complex therapy of progressive glaucomatous optic neuropathy].

UNLABELLED: Many factors exist that are associated with higher risk of glaucoma progression. Arterial hypotension, low perfusion pressure, vasospastic syndrome, diabetes mellitus, myopia, etc. increase the need for neuroprotective therapy, which is aimed at stabilizing the pathological process and creating favorable conditions for maintaining visual functions. The aim of this study was to assess the therapeutic efficacy of Gliatilin as part of the complex treatment of progressive glaucomatous optic neuropathy. MATERIAL AND METHODS: A total of 240 patients were randomly selected and divided into 2 groups, 120 patients each. Both groups were matched for age, somatic comorbidity, and the gravity of the glaucomatous process. Patient age averaged 71.3±1.6 years. Advanced glaucoma prevailed in both groups: 70.0 and 76.6% correspondingly. Neuroprotective therapy included drugs from different pharmacological classes so that different aspects of pathogenesis were addressed. Apart from that, patients from Group I first received intravenous Gliatilin (1000 mg/4ml, 12--15 doses) and then switched to oral (1 capsule b.i.d. for 4 months). All patients underwent standard ophthalmic examination and static perimetry. RESULTS: No adverse effects were observed over the first two weeks of Gliatilin course, during which the patients stayed in the hospital. IOP level was normal and stable. Although neuroprotective therapy does not directly affect IOP, stability of the latter describes the dynamics of the glaucomatous process. When assessing changes in visual functions, particular attention was paid to the central visual field, foveolar and total light sensitivity, peripheral visual field, and MD and PSD indices. All mean values showed a tendency toward improvement, more pronounced in the Gliatilin group. CONCLUSION: A complex therapy cannot be limited to a single drug only, and to make better decisions, one should consider not only ocular, but also general condition of the patient. Adjuvant Gliatilin in the complex therapy of progressive glaucoma is appropriate and efficient, especially in case of systemic atherosclerosis and cerebrovascular insufficiency. The frequency of stabilization therapy depends on the efficacy of the latest course and clinical manifestations of the glaucomatous process.

[Analysis of choline alfoscerate effectiveness in chronic ocular ischemic syndrome].

AIM: To investigate the effectiveness of choline alphoscerate in patients with chronic ocular ischemic syndrome (OIS) and coexisting cerebrovascular disease. MATERIAL AND METHODS: We performed a comprehensive examination of 51 patients aged 46--72 years (57.8±6.82 years on average) and diagnosed with OIS. Patients were divided into two groups. In group 1 (main group, 26 patients) the standard therapy was supplemented with choline alphoscerate. Group 2 (controls, 25 patients) received the standard therapy only. RESULTS: Clinical and functional examinations revealed a more rapid and stable improvement of visual acuity in the choline alphoscerate group. CONCLUSION: Development and application of an adequate combination therapy for patients with ocular ischemic syndrome has yielded an increase in visual acuity, visual fields, and the mean light sensitivity of the retina as well as an improvement of ocular hemodynamics.

[PHARMACOLOGICAL CORRECTION OF RED BLOOD CELL MEMBRANE LIPID SPECTRUM IN PATIENTS WITH CHRONIC CEREBRAL ISCHEMIA ON THE BACKGROUND OF HYPERTENSIVE DISEASE.]

In patients with chronic cerebral ischemia on the background of hypertension grade 2, stage 2, our investigation revealed a significant decrease (by 30.1%) in the level of phospholipids in the erythrocyte membrane and cholesterol esters (by 44.2%), increase in lizofosfa-tidilholina, free cholesterol, triacylglycerides, and free fatty acids (by 23.2 - 46.2%), and change in the ratio of lipid fractions responsible for the structure formation and stabilization of erythrocyte membranes. It was found that the most effective correction of lipid profile in erythrocyte membranes was produced by 10-day injection of a combination of actovegin (200 mg intravenous bolus) and cereton (1000 mg choline alfoscerate intravenous drip in 200.0 mL of 0.9% sodium chloride solution), while the minimum ef- fect was produced by a combination of cerebrolysin (2152 mg concentrated complex of peptides from pig brain, intravenous drip in 100.0 mL of 0.9% sodium chloride solution) and mexidol (250 mg of 2-ethyl-6-methyl-3-hydroxypyridine succinate intravenous bolus). The combination of emoxypine (40 mg of 3-hydroxy-6-methyl-2-ethylpyridine, intramuscularly) and piracetam (1000 mg of 2-oxo-I-pyrrolidine-acetamide intravenous bolus) gave intermediate results.

Apathy Treatment in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.

BACKGROUND: Apathy is a common symptom in Alzheimer's disease (AD), but no treatment has proven to be effective, although administration of cholinesterase inhibitors has been associated with moderate improvements in the short term. OBJECTIVE: This study has compared apathy scores of patients included in "ASCOMALVA" trial treated for two years with donepezil plus a cholinergic precursor (choline alphoscerate), to those of patients receiving donepezil alone with the purpose of assessing if the availability of a higher amount of acetylcholine by combining precursor loading and inhibition of neurotransmitter breakdown would counter apathy in AD. METHODS: Apathy was measured at baseline and 3, 6, 9, 12, 18, and 24 months using the apathy subtest of the Neuropsychiatric Inventory in 113 mild-moderate AD patients. Two matched groups were compared: group 1 (56 subjects) treated with donepezil plus choline alphoscerate and group 2 (57 subjects) treated with donepezil alone. Frontal functions were explored by the Frontal Assessment Battery (FAB) at baseline. RESULTS: Group 1 subjects showed, as a whole, a lower apathy score after 12 to 24 months. The caregiver distress was descreased after 6 to 24 months. Results were unrelated with cognitive scores measured by the MMSE and ADAS-cog test. Subjects with FAB in the normal range had significantly lower scores. CONCLUSIONS: The combination of donepezil with choline alphoscerate is more effective than donepezil alone in countering symptoms of apathy in AD. This suggests that the availability in brain of a higher amount of acetylcholine could affect apathy in AD subjects with spared executive functions.

Protective effects of L-alpha-glycerylphosphorylcholine on ischaemia-reperfusion-induced inflammatory reactions.

PURPOSE: Choline-containing dietary phospholipids, including phosphatidylcholine (PC), may function as anti-inflammatory substances, but the mechanism remains largely unknown. We investigated the effects of L-alpha-glycerylphosphorylcholine (GPC), a deacylated PC derivative, in a rodent model of small intestinal ischaemia-reperfusion (IR) injury. METHODS: Anaesthetized Sprague-Dawley rats were divided into control, mesenteric IR (45 min mesenteric artery occlusion, followed by 180 min reperfusion), IR with GPC pretreatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to ischaemia) or IR with GPC post-treatment (16.56 mg kg⁻¹ GPC i.v., 5 min prior to reperfusion) groups. Macrohaemodynamics and microhaemodynamic parameters were measured; intestinal inflammatory markers (xanthine oxidoreductase activity, superoxide and nitrotyrosine levels) and liver ATP contents were determined. RESULTS: The IR challenge reduced the intestinal intramural red blood cell velocity, increased the mesenteric vascular resistance, the tissue xanthine oxidoreductase activity, the superoxide production, and the nitrotyrosine levels, and the ATP content of the liver was decreased. Exogenous GPC attenuated the macro- and microcirculatory dysfunction and provided significant protection against the radical production resulting from the IR stress. The GPC pretreatment alleviated the hepatic ATP depletion, the reductions in the mean arterial pressure and superior mesenteric artery flow, and similarly to the post-treatments with GPC, also decreased the xanthine oxidoreductase activity, the intestinal superoxide production, the nitrotyrosine level, and normalized the microcirculatory dysfunction. CONCLUSIONS: These data demonstrate the effectiveness of GPC therapies and provide indirect evidence that the anti-inflammatory effects of PC could be linked to a reaction involving the polar part of the molecule.

[The use of cereton in patients with chronic brain ischemia and moderate cognitive impairment].

OBJECTIVE: To study the efficacy and safety of cereton in the treatment of patients with chronic brain ischemia and moderate cognitive impairment. MATERIAL AND METHODS: The study included 25 patients, 16 women and 9 men, mean age 53,8 ± 1,3 years. Moderate cognitive impairment measured with MMSE and HADS was found in all patients. Quality of life was assessed with SF-36. Somatic and neurological studies as well as brain MRI were carried out. Inpatients received cereton in dose 1000 mg in 200 ml of physiological solution during 15 days, after the discharge from the hospital patients received 1 capsule three times a day during 3 months. RESULTS AND СONCLUSION: Cereton had a significant positive effect on patient's condition including cognitive function. Subjective effect was recorded after 5-6 days of treatment, more evident and stable effect was seen from the 15th day. In the end of treatment, clinicians recorded "moderate" effect in 11 patients and "marked" effect in 8 patients (according to patients' reports, those effects were noted in 9 and 12 cases, respectively). The drug was well-tolerated and had a positive effect on quality of life of the patients.

Peripheral inflammatory activation after hippocampus irradiation in the rat.

PURPOSE: To detect the possible biochemical signs of inflammatory activation in the peripheral circulation in a rodent model of hippocampus irradiation, and to examine the effects of L-alpha-glycerylphosphorylcholine (GPC) in this experimental protocol. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats were subjected to 40 Gy cobalt irradiation of both hemispheres of the hippocampus, with or without GPC treatment (50 mg/kg intravenously (i.v.), 5 min before the irradiation, n = 6, each). A third group (n = 6) served as saline-treated control. Blood samples were obtained 3 h after the end of irradiation in order to examine the changes in plasma histamine, tumor necrosis factor-alpha (TNF-α), interleukin 1-beta, interleukin 6 (IL-6) and interleukin 10 (IL-10); liver tissue samples were taken to determine adenosine triphosphate (ATP) concentrations. RESULTS: The hepatic ATP levels were significantly declined, while plasma concentrations of circulating TNF-α, IL-6, IL-10 and histamine were significantly increased after hippocampus irradiation. GPC treatment significantly reduced the irradiation-induced release of cytokines and histamine, and the liver ATP level was maintained at the control value. CONCLUSIONS: Targeted brain irradiation produced measurable pro- and anti-inflammatory cytokine changes in the systemic circulation. GPC supplementation provides significant protection against irradiation-induced peripheral pro-inflammatory activation and ATP depletion.

[The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease].

The main aim of the study was the evaluation of the efficacy and drug safety of cerepro (choline alfoscerate) used for treating outpatients with cerebrovascular disease. Ninety patients with cerebrovascular disease, who had motor, coordination, emotional and cognitive disturbances were enrolled in the study. Sixty patients of the group 1 had stroke, 30 patients (group 2) had chronic ischemic brain disease. All patients received basic therapy (antihypertensive, antiaggregant or anticoagulant, cholesterol-lowering drugs). Cerepro was administrated in combined therapy according to the scheme: 1000 mg cerepro (in 200 ml of the 0.9% NaCl solution) once a day intravenously in drops during 10 days; then 1200 mg daily per os during 6 weeks. We assessed the dynamic of neurological symptoms and restoration of lost functions (MMSE, Feeling-activity-mood test, HDRS, GCI). The results indicate the efficacy of cerepro in outpatients with chronic cerebrovascular disease and stroke. It was demonstrated that cerepro led to improvement of coordination neurological symptoms, cognitive and emotional functions, activity and mood in patients of both groups. Clinical effect was higher in patients after stroke. Cerepro was well tolerated.

Modified phospholipids as anti-inflammatory compounds.

PURPOSE OF REVIEW: Oxidized phospholipids (OxPLs) are abundantly found at sites of inflammation and are considered to play an active role in the modulation of the immune response. Whereas most studies attributed a proinflammatory role to OxPLs, recent studies demonstrate that some products of phospholipid oxidation may in fact exhibit anti-inflammatory properties. This study summarizes the proinflammatory and anti-inflammatory properties of OxPLs and sheds light on the therapeutic potential of OxPL derivatives or analogs for treatment of chronic inflammatory disorders. RECENT FINDINGS: OxPLs may inhibit activation of several Toll-like receptors and can epigenetically reduce the capacity of dendritic cells to function as mature, fully functional immunostimulatory cells. These data demonstrate that OxPLs can induce anti-inflammatory effects. Moreover, VB-201, an orally available synthetic phospholipid analog of the Lecinoxoid family, was found to attenuate inflammation in various preclinical animal models and is currently employed in a phase II clinical trial in psoriasis. SUMMARY: Chemical or biological modifications of phospholipids yield various products, some of which may exhibit anti-inflammatory properties. Identification of such species and generation of more stable/potent anti-inflammatory OxPL variants may represent a novel approach for the treatment of immune-mediated diseases such as psoriasis, atherosclerosis, multiple sclerosis and rheumatoid arthritis.

[Efficacy and tolerability of choline alphoscerate (cereton) in patients with Parkinson's disease with cognitive disorders].

An open 10-day study of treatment effect of cereton in comparison to piracetam has been conducted. Cereton was used in 40 patients (main group) in dosage 1000 mg, piracetam - in 20 patients (control group) in dosage 2000 mg. Both drugs were used intravenous in drops in 200 ml of physiologic saline along with antiparkinsonian medications. Patient's state was assessed with a battery of psychometric scales and neuropsychological tests as well as with instruments for measuring intensity of parkinsonian symptoms, side-effects and quality of life. Marked and moderate improvement of cognitive functions was found in patients of the main group compared to the control one (40% and 25%, respectively, p<0,05). Deterioration of cognitive functions was seen less often in the main group than in the control group (5% and 15%, respectively, p<0,05). Cereton was well-tolerated by patients. Side effects (brief and short-term) were found only in 6 (15%) patients.

[The use of cereton in the rehabilitation of patients with hemorrhagic stroke].

Forty patients were included in the study: 20 patients of main group received cereton in dosage 1000 mg intramuscular during 15 days and 20 patients of control group received placebo. Patient's state was assessed with MMSE, Hodkinson test, "learning of 10 words", Spielberg's trait-state anxiety inventory (a modification of Khanin), Beck depression scale. Brain blood supply was analyzed with rheoencephalography, balance in the vertical position--with stabilometry. The rehabilitation of disturbed cognitive functions measured with MMSE and "learning of 10 words" test was significantly better in the main group of patients (p < 0.05). Reoencephalographic data showed the significant increase of blood supply, mainly in the left brain hemisphere, compared with baseline values (p = 0.05) as well as with the control group (p = 0.03). There was a trend towards the higher rate of blood supply that reflected the decrease of baseline tonus of resistance arteries in both hemispheres, predominantly in the left side, with the positive dynamics as compared to the same values in the controls (p < 0.041). The results of stabilometric study revealed a trend toward the decrease of initially increased deviations of center of pressure on both axes, mostly in the frontal plane, in the main group (p < 0.001). Almost all patients reported a good tolerability of the drug. In conclusion, the course treatment with cereton in the late rehabilitation and residual periods of hemorrhagic stroke leads to the significant improvement of cognitive functions and brain blood supply, in particular brain hemispheric regions, due to the decrease of baseline tonus of resistance arteries and promotes the improvement of balance function.