[Developmental dysphasia: assessment of the drug treatment efficacy].

To assess the efficacy of treatment with encephabol, we examined 40 children, aged from 3 to 5 years, with developmental dysphasia. All patients were randomized into two equal groups: group 1 received encephabol (suspension form, daily dosage 200-250 mg, or 12-15 mg/kg) during 2 months; group 2 did not receive this medication. In the first group, there was a significant improvement of expressive and impressive speech and speech attention; the active vocabulary and a number of phrases in colloquial speech increased by a factor of 3 versus 1.5 in the control group. After the treatment with encephabol, the parents reported the decrease in motor disturbances, psychosomatic disorders, the improvement of attention and the emotional state of the children.

[Efficacy of cortexin in the treatment of memory disorders in children].

Children, aged from 7 to 12 years, with memory disorders were treated with cortexin (30 patients) and encephabol (30 patients). The comparative evaluation of efficacy and safety of these drugs was carried out. The higher cortexin efficacy (the improvement in 86.7% of cases) in comparison with encephabol (the improvement in 63.3% of cases) confirmed by the data of neuropsychological and neurophysiological research is established.

[Encephabol in the treatment of cognitive disorders in epilepsy].

Cognitive disorders in patients with epilepsy were studied before and after the 6-week treatment with encephabol. The data on the examination of 24 patients were summarized. Before the treatment, patients with epilepsy demonstrated a larger number of errors, lower speed of reading and worse learning of the content compared to the controls (18 healthy people). Encephabol was prescribed in dosage 600 mg/day to people over 12 years of age and in dosage 300-400 mg/day to people younger than 12 years. The statistically significant improvement of the global self-rating of cognitive functions, speed of reading, decrease of errors as well as learning of the content were seen after the end of treatment. The improvement of cognitive traits was correlated with the improvement of computed EEG parameters (the decrease of delta power in the right temporal and frontal regions). Encephabol did not lead to the increase of epileptiform activity in the EEG. No increase in the number and severity of seizures was noted. In conclusion, encephabol may be used in treatment of cognitive disorders in epilepsy.

Pyritinol for post asphyxial encephalopathy in term babies-- a randomized double-blind controlled trial.

OBJECTIVE: To evaluate the efficacy of pyritinol in improving the neurodevelopmental outcome at one year of age among term babies with post-asphyxial encephalopathy. SETTING: Level II Neonatal Nursery and Child Development Centre, Medical College, Thiruvananthapuram. DESIGN: Randomised placebo controlled double blind trial. PARTICIPANTS: 108 term babies with post-asphyxial encephalopathy, stratified into three grades based on clinical criteria. INTERVENTION: The treatment group (n=54) received pyritinol and the control group (n=54) received placebo, in exactly the same increasing dosage schedule of 1 to 5 mL liquid drug (20-100 mg) from 8th postnatal day until the end of six months. OUTCOME VARIABLES: Mean Mental Development Index (MDI) and mean Psychomotor Development Index (PDI) measured on Bayley Scales of Infant Development at one year of age. RESULTS: No statistically significant difference was observed in MDI or PDI scores at one year between the treatment and control groups. The confidence interval for the differences ranged from -6.3 to 8.7 for MDI and from - 4.1 to 12.7 for PDI. On multiple regression analysis using one year MDI and PDI scores, even after controlling for birthweight, there was no statistically significant difference between the treatment and control groups. CONCLUSION: Pyritinol is not useful in improving the neurodevelopmental status of babies with post-asphyxial encephalopathy at one year of age.

[Efficiency of encefabol use in patients with dyscirculatory encephalopathy]. / Effektivnost' lecheniia éntsefabolom bol'nykh distsirkuliatornoi éntsefalopatiei.

The article presents the findings of the Encefabol treatment of 50 patients aged 56-68 yy with vascular encephalopathy at the I-III stage, caused by atherosclerotic and high blood pressure pathological processes. The individual dose prescription of the medication to patients with vascular encephalopathy was substantiated in the article. The importance of psychodiagnostic tests in assessment of Encefabol treatment efficiency of the disease was shown in the article.

[Cognitive disturbances in patients with tics and Tourette's syndrome and their correction with encephabol]. / Kognitivnye narusheniia u bol'nykh s tikami i sindromom Turetta i ikh korrektsiia éntsefabolom.

Ninety-four patients with tick hyperkinesis (57) and Tourette's syndrome (37) were studied. Neuropsychological examination revealed memory, attention and audio-motor disturbances and symptoms of dysgraphia and dyslexia. Cognitive impairment may develop before ticks appearance and aggravate during hyperkinesis exacerbation. In the patients with Tourette's syndrome, cortical dysfunctions were mostly pronounced. These cognitive disturbances correlated with the indices of spectral analysis of bioelectrical brain activity in frontal and temporal areas. In 83 patients, an efficacy of encephabol treatment combined with basic therapy was studied. Encephabol given in dosage 200-300 mg daily to patients aged 5-7 years and 600 mg--to those aged over 7 years during 6 weeks significantly improved memory, attention and praxis function.

[Current strategies of pathogenetic therapy of Alzheimer's disease]. / Sovremennye strategii patogeneticheskoi terapii bolezni Al'tsgeimera.

This is a review of the data available in the literature and the authors' own findings on pathogenetical rationale for the use and clinical study of current treatments for Alzheimer's disease (AD) (synonym: Alzheimer-type dementia). In the past decade many attempts have been made at targeting different links of the pathogenesis of a neurodegenerative process that underlie AD. Several areas of pathogenetical therapy for AD have been developed on the basis of experimental studies and pilot clinical tests. The most developed areas are as follows: various compensatory (replacement) treatments aimed at overcoming neurotransmitter deficit in different neuronal systems that are damaged in AD to a greater or lesser extent; neuroprotective therapy promoting increased viability (survival) of neurons and their plasticity, and vasoactive therapy. Rather new directions of AD pathogenetic therapy, such as antiinflammatory and hormonal therapy along with antiamyloid therapeutic strategies are still under study.

Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation.

70 patients with probable Alzheimer's disease were randomly allocated to four groups: 17 patients received only social support, 18 cognitive training twice a week, in 17 cognitive training was combined with pyritinol 2 x 600 mg/day and in 18 cognitive training was combined with phosphatidylserine 2 x 200 mg/day. Treatment duration was 6 months. Before and after treatment, the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose. Before treatment the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. Electrophysiological changes were assessed as EEG power, globally and in 4 frequency bands. This 6-month study in four groups of patients with Alzheimer's disease indicated that phosphatidylserine treatment has an effect on different measures of brain function. Since neuropsychological improvements were best documented after 8 and 16 weeks and faded towards the end of the treatment period, it must be concluded that this symptomatic therapy is mainly of short-term benefit and was overcome by the progressive pathological changes at the end of the treatment period.

Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease.

Forty patients with probable Alzheimer's disease (AD) were selected from a pool of 80 patients and assigned to 4 groups. Each received either social support, cognitive training only, or cognitive training in combination with pyritinol or phosphatidylserine. Treatment duration was 6 months. Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography (PET) and 2[18F]-fluoro-2-deoxy-D-glucose (FDG). Before treatment, the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task. They did not differ in scores of a neuropsychological test battery. After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions, and an improvement in cognitive functioning compared to the other groups. The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone.

Comparison of pyritinol and auranofin in the treatment of rheumatoid arthritis. The European Multicentre Study Group.

The efficacy and tolerability of pyritinol (PY) and auranofin (AU) were compared in a multicentre double-blind study. Patients with RA received 600 mg/day PY or 6 mg/day AU for 1 year. Response was rated by a defined improvement in at least four of the following: Ritchie index, joint swelling index, rating scales for pain and general well-being, functional index, morning stiffness, ESR. Of the 139 fully evaluable PY patients 61 (44%) dropped out due to adverse events or response failure compared with 44 (31%) of the 142 AU patients. In patients treated for 1 year efficacy parameters improved more in the PY than in the AU group, with significant differences for the general well-being (P = 0.022), ESR (P = 0.029) and haemoglobin (P = 0.0042). The response rate for PY (61/78 patients, 78%) was significantly superior to AU (58/98 patients, 59% P = 0.009). An intention-to-treat analysis corroborated this result (P = 0.030). Adverse events (AE) occurred in 64% of PY patients and in 58% of AU patients: main AE were mucocutaneous symptoms (PY 36%, AU 23%) and gastrointestinal complaints (PY 30% AU 37%). Single cases of proteinuria, hepatic and haematological abnormalities were noted in both groups.

[Chemotherapy of destructive pulmonary tuberculosis with antioxidants and antihypoxic agents]. / Khimioterapiia destruktivnogo tuberkulëza lëgkikh s primeneniem antioksidantov i antigipoksantov.

The trial included 155 patients with destructive pulmonary tuberculosis: 60 on conventional antibacterial therapy (isoniazid, rifampicin, streptomycin), 95 on intensive chemotherapy (isoniazid, rifampicin, streptomycin, pirazinamid or ethambutol, vitamins for initial 2-3 months). 69 patients from the latter group received adjuvant antioxidants (tocopherol acetate or galascorbin) in combination with one of the antihypoxants (piracetam, calcii pangamas, piriditol). The intensive chemotherapy promoted a decrease in duration of bacterial discharge, destruction discontimation, cavernous healing, reduced incidence rates of side effects. Metabolic processes characterizing lipid peroxidation and redox improved.

Therapeutic efficacy of pyritinol in patients with senile dementia of the Alzheimer type (SDAT) and multi-infarct dementia (MID).

This trial was performed to investigate the efficacy of pyritinol in the treatment of senile dementia. Initially, a total of 183 inpatients were screened for eligibility. Of 164 patients who met the inclusion criteria, 156 completed the trial. Allocation of the patients to the Senile Dementia of the Alzheimer Type group or the Multi-Infarct Dementia group was based on the Hachinski Ischemic Score, computed tomography scans and electroencephalographic (EEG) findings. In a 12-week double-blind treatment phase either 200 mg pyritinol dihydrochloride-monohydrate or placebo was given 3 times daily. Confirmatory statistics included item 2 of the Clinical Global Impression, the total score of the Short Cognitive Performance Test (Syndrom Kurz Test) and the factor 'cognitive disturbances' of the Sandoz Clinical Assessment Geriatric scale. In addition, data on tolerance, of EEG brain mapping and of a responder analysis were evaluated based on descriptive statistics. The therapeutic efficacy of pyritinol was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all 3 target variables. The clinical relevance of the outcome was underlined by the analysis of the descriptive variables and by the convergence found at the different observation levels. The EEG mapping demonstrated significant differences between placebo and pyritinol, with the latter decreasing slow and increasing fast alpha and beta activity, which reflects improvement of vigilance. Based on the results of this trial, it can be accepted that the therapeutic effect of pyritinol is superior to placebo in patients with mild to moderate dementia of both degenerative and vascular etiology.

[Nootropic activity of nicotinamide and its structural analogs]. / Nootropnaia aktivnost' nikotinamida i ego strukturnykh analogov.

It is known that endogenic nicotinamide has a tranquilizing and stress-protective activity. The present investigations show the nootropic effect of this drug and its analogs nicomorpholine and acethylnicotinate on acute models of hypoxia and amnesia. The present results revealed that the observed nootropic activity of nicotinamide and its analogs is more expressed than this of piracetam, pyritinol and meclofenoxate. Having in mind the similarity of pharmacological effects of piracetam and nicotinamide (antihypoxic, antiamnestic and anxiolytic) we try if these drugs have electronic-structure similarities. The analysis revealed some similarity of these drugs' molecules in relation to the composition and distribution of polar centres pi- and p-electronic areas) distance between them, topography of separate molecule parts.

Testing drug effects against hypoxic damage of cultured neurons during long-term recovery.

Cultured neurons of chick cerebral embryo hemispheres were used to study drug effects against neuronal damage caused by hypoxia during long-term recovery. Sodium cyanide (NaCN, 1 mmol/l) induces hypoxia-like conditions by inhibiting oxydative phosphorylation. The sensitivity of the cultured neurons against this type of hypoxia was determined after 3, 4, 5 and 6 days of cultivation followed by 4, 3, 2 days and 1 day of recovery, respectively. The ATP level and the viability of cells as well as the total cell number and the protein content of the cultures were used to characterize the extent of posthypoxic neuronal damage. A hypoxic period of 30 min after 4 days of cultivation followed by 3 days of recovery seemed to be appropriate for determining protective drug effects. The drug effects obtained were comparable to those from in vivo models of cerebral ischemia or hypoxia. The results suggest that cultured neurons exposed to hypoxia and to long-term recovery could be suitable for studying post-hypoxic neuronal damage as well as neuroprotective drug effects.