[Substantiation of the drug «Cytoflavin¼ application and cognitive-behavioral therapy in complex treatment of deforming coxarthrosis in elderly patients.]

The article presents the results of a study of the effectiveness of the addition of a standard course of conservative therapy to 104 patients of the older age group with coxarthrosis deforming the drug «Cytoflavin¼ and cognitive-behavioral therapy courses. It was found that such scheme increases the effectiveness of therapeutic interventions, which manifests itself as the improvement of the mental and physical components of quality of life by reducing pain and increasing the functionality of some of the affected hip. At the heart of positive clinical effect is a decrease in processes of inflammation and reduction of tension of regulatory processes in the organism.

[The effect of antipsychotic drug on monoamine receptors in peripheral blood mononuclear cells: affinity linked mechanism]. / Vliianie antipsikhoticheskikh preparatov na retseptory monoaminov mononuklearnykh kletok perifericheskoi krovi: affinitet-stseplennyi mekhanizm.

Schizophrenia is one of the most serious and common mental disorders, which is characterized by high levels of pathogenic heterogeneity as well as neuroimmune abnormalities, which require treatment with antipsychotic drugs. Monoamines are one of the key neurotransmitters which play an important role in neuroimmune interactions of the human organism. We suggest that the quantity of the monoamine receptors on mononuclear cells of the peripheral blood (PBMCs) can be associated with the cytokine profile of patients. With this quantity being a key component of the mental status correction mechanism in antipsychotic therapy. In this study we measured cytokine levels (IL-6, IL-1b and TGF-b) in blood serum, the protein expression status of the serotonin receptor 5HTR2A and the dopamine receptors D1 (DRD1), DRD2, DRD3 in PBMCs of drug-naive, first episode schizophrenia patients before and after the treatment with olanzapine and haloperidol. This study has shown for the first time that the antipsychotic therapy leads to a decrease in protein levels of monoamine receptors in PBMCs associated with the affinity of the drug used. Blood cytokine levels were significantly higher in serum from studied patients as compared with the reference values. The antipsychotic-linked change of the TGF-b production caused by the therapy is probably associated with the reduction of various monoamine receptors. The relationship between the psychopathological status and the protein level of 5THR2A suggests that the amount of 5HTR2A may serve as a potential biomarker for the personalized appointment of the antipsychotic therapy.

Potential diagnostic markers of olanzapine efficiency for acute psychosis: a focus on peripheral biogenic amines.

BACKGROUND: Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients. METHODS: This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment. RESULTS: The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group. CONCLUSIONS: The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

EVACUATION OF PATIENTS WITH RESPIRATORY FAILURE ON EXTRACORPOREAL MEMBRANE OXYGENATION.

Realising for thefirst time in Russia the transportation of a patient with critical respiratory failure in conditions of EC-MO-therapy, the authors have accumulated great experience of its application at the stage of inter-hospital evacuation. This category ofpatients previously considered non-transportable by the severity of their condition. Having conducted a retrospective analysis of clinical experience in the use of high-tech medical care method, the authors received a zero mortality and questioned the possible new criteria and recommendations in assessing risk of death in patients with life-threatening conditions at the stage of inter-hospital transportation.

[HOLDING OBJECTIVE STRUCTURED CLINICAL EXAMINATIONS FOR ANESTHESIOLOGY AND INTENSIVE CARE CLINICAL RESIDENCY IN STATE GRADUATES CERTIFICATION].

The modern system of medical education requires objective methods to assess clinical competence of medical specialists. Application of objective structured clinical examination (OSCE) during the final certification of graduates of clinical residency allows to evaluate the theoretical knowledge, manual skills. Enabling simulation scenarios in the program makes it possible to objectively evaluate the important non-technical skills of anesthesiologists, identify gaps in the system of training and modify it. The experience of the objective structured clinical examination as part of the state certification of graduates of clinical residency of the Department ofAnesthesiology and Intensive Care, Military MedicalAcademy after C M Kirov allows us to consider this technique in an objective way a comprehensive assessment of the competence of health professionals. Students confirmed its highly realistic, they have revealed the presence of emotional stress during the simulation sessions, the majority agreed that the simulation session increased the level of their readiness to address these situations in clinical practice. Staff of the department is planning to testing and introduction rating scales into a system of assessment, to improved exam program, increasing the number of clinical scenarios for simulation sessions.

[The effectiveness of the combined use of energomonitor antioxidant and cognitive psychotherapy in the treatment of generalized periodontitis in elderly patients].

The aim of the study was to evaluate the effect of combined use of Cytoflavin and cognitive therapy on the dynamics of psychosomatic status and effectiveness of the treatment of generalized periodontitis in elderly patients. The results of treatment of 103 patients aged 60 and older were analyzed. All patients received standard therapy for 10-14 days depending on the severity of the process. In addition, the patients of the main group (51 patients) received Cytoflavin: 2 tabs. 2 times a day with an interval between doses of 8-10 hours for 25 days, and cognitive therapy aimed at training alternative realistic way of life perception. Treatment results were monitored by PMA, Russell periodontal index (PI), Green-Vermillion hygienic index. Psychosomatic dynamics was assessed by means of Spielberger anxiety scale and SUN" methods of before and after a month of treatment. The inclusion in the treatment regimen of Cytoflavin and cognitive therapy had a positive impact: reduction of PMA by 61.8%, PI by 45.3% and Green-Vermillion index by 39.8%. The psychosomatic tests proved anxiety level decrease by 28.7% in terms of "reactive" anxiety and 31.5% in terms of "personal" anxiety, emotional status (21.2%), activity (21.7%) and mood (21.8%) improvement.

[Behavioral psychotherapy and citoftavin in the treatment of deforming coxarthrosis in elderly patients].

The authors studied the efficiency of the expansion of the standard course of conservative therapy of deforming coxarthrosis by appointment Cytoflavin and behavioral therapy. The study was performed on 104 elderly patients. It was found that the addition of the existing scheme increases the effectiveness of therapeutic interventions, which manifests itself as the improvement of the mental and physical components of quality of life by reducing pain and increasing the functionality of some of the affected hip. At the heart of positive clinical effect is a decrease in processes of inflammation and reduction of tension of regulatory processes in the organism. Positive quality extra medical appointments was the absence of significant side effects when taken orally Cytoflavin requiring discontinuation of the drug, as well as the absence of failure patients from further sessions of behavioral therapy.

[Dopamine neurotransmission of peripheral blood lymphocytes is a potential biomarker of psychiatric and neurological disorders].

Current literature on a role of dopamine in the development of mental and neurological disorders suggests that the discovery of endogenous dopamine in peripheral blood lymphocytes gave rise to a new line of research. Dopamine receptors are not only found on cells of the innate immune response (nonspecific), but also on cells of adaptive immune response (specific): T and B lymphocytes. These facts bring a new evidence of interrelationships between the peripheral immune system, neuroinflammation and neurodegeneration and suggest new ways for investigation of the pathogenesis of different mental and neurological disorders, in particular Parkinson's disease, Alzheimer's disease and schizophrenia. There is strong evidence that ligands of dopamine receptors can change the expression of coding genes both in central neurons and in peripheral cells. Thus, peripheral blood lymphocytes may prove a cellular tool to identify dopamine transmission disturbances in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatment.

[Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms].

"Typical" antipsychotics remain the wide-prescribed drugs in modern psychiatry. But these drugs are associated with development of extrapyramidal symptoms (EPS). Preventive methods of EPS are actively developed and they concentrate on personalized approach. The method of taking into account genetic characteristics of patient for prescribing of treatment was proven as effective in cardiology, oncology, HIV-medicine. In this review the modern state of pharmacogenetic research of antipsychotic-induced EPS are considered. There are pharmacokinetic and pharmacodynamic factors which impact on adverse effects. Pharmacokinetic factors are the most well-studied to date, these include genetic polymorphisms of genes of cytochrome P450. However, evidence base while does not allow to do the significant prognosis of development of EPS based on genetic testing of CYP2D6 and CYP7A2 polymorphisms. Genes of pharmacodynamics factors, which realize the EPS during antipsychotic treatment, are the wide field for research. In separate part of review research of such systems as dopaminergic, serotonergic, adrenergic, glutamatergic, GABAergic, BDNF were analyzed. The role of oxidative stress factors in the pathogenesis of antipsychotic-induced EPS was enough detailed considered. The system of those factors may be used for personalized risk assessment of antipsychotics' safety in the future. Although there were numerous studies, the pharmacogenetic-based prevention of EPS before prescribing of antipsychotics was not introduced. However, it is possible to distinguish the most perspectives markers for further research. Furthermore, brief review of new candidate genes provides here, but only preliminary results were published. The main problem of the field is the lack of high- quality studies. Moreover, the several results were not replicated in repeat studies. The pharmacogenetic-based research must be standardized by ethnicity of patients. But there is the ethnical misbalance in world literature. These facts explain why the introduction of pharmacogenetic testing for risk assessment of antipsychotic-induced EPS is so difficult to achieve.

Interaction of fluoroquinolones and certain ionophores in broilers: effect on blood levels and hepatic cytochrome p450 monooxygenase activity.

The concomitant administration to broilers of ionophore coccidiostats and certain chemotherapeutic agents may cause deleterious interactions, with toxicosis and death as possible sequelae. In this study, co-administration of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin. In addition, exposure to lasalocid was not shown to change blood levels of enrofloxacin. However, norfloxacin + lasalocid co-administration induced aminopyrine N-demethylase (AD) activity by day 5 after the last administration of norfloxacin, and induced a rise of norfloxacin levels in the blood. This rise of blood norfloxacin levels after co-administration of norfloxacin + lasalocid implies that lower levels of norfloxacin could be administered in birds also receiving lasalocid.

Interaction of monensin and sulfadimethoxine in broilers, as mediated by hepatic microsomal cytochrome P-450 monooxygenases.

The influence of monensin + sulfadimethoxine on cytochrome P-450 monooxygenase activity in broilers, and the possible consequences of modification of this system, including changes in blood levels of sulfadimethoxine, influence on the duration of xylazine-ketamine anesthesia, total antioxidant status and superoxide dismutase activity were studied. The results indicate that the combination of monensin + sulfadimethoxine gave a short-term inhibition of microsomal cytochrome P-450 monooxygenase activity but apparently did not influence the metabolism of other (exogenic) substances (ketamine, xylazine), and did not change the state of antioxidant systems or the relative liver weight. There was a rise in blood sulfadimethoxine levels.

New treatment regimens in organophosphate (diazinon) and carbamate (methomyl) insecticide-induced toxicosis in fowl.

The objective of this work was to determine optimal treatment regimens for organophosphate (OP) or carbamate insecticide toxicoses in fowl using the antidotes atropine sulfate and pralidoxime chloride (2-PAM). Broiler chicks in treatment groups, each comprising 3 replicates of 6-7 birds/replicate, were gavaged on a body weight (BW) basis with the OP and carbamate insecticides, diazinon and methomyl, respectively, at lethal dosages. Treatment groups were injected with either or both of the antidotes at various dosages as soon as clinical signs appeared. Birds appearing healthy 24 h thereafter were regarded as having been treated successfully. At a dosage of 100 mg/kg BW, atropine was mildly toxic and at 200 mg/kg 2-PAM was severely toxic (but not lethal), whereas at dosages of 50 and 100 mg/kg BW, respectively, the antidotes were at their most effective. With diazinon, atropine alone was only partially effective (12/20 survivors), whereas 2-PAM was extremely efficacious. (20/20 survivors); the combination of the 2 antidotes at 2 dosages was slightly less effective (19/20 survivors) than 2-PAM alone. For methomyl toxicity, atropine was largely successful (18/20 survivors), whereas 2-PAM was mostly unsuccessful (10/20 survivors); the combination at high dosage was less effective (15/20 survivors) than atropine alone, but at a low dosage the combination was the most successful (20/20 survivors). The results indicate that anticholinesterase insecticide toxicoses in fowl should not be treated according to textbook recommendations, and antidotal dosage with atropine should be up to 100 times greater than is commonly recommended. The specific cause of the toxicoses should ideally be determined before treatment is given, but as this is often unknown, a combination of antidotes may be the optimal treatment protocol.

The inhibitory effects of the fluoroquinolone antimicrobials norfloxacin and enrofloxacin on hepatic microsomal cytochrome P-450 monooxygenases in broiler chickens.

The fluoroquinolone antimicrobials norfloxacin and enrofloxacin were found to inhibit hepatic microsomal cytochrome P-450 monooxygenases in the livers of broiler chickens using dosages as given in commercial flocks. Norfloxacin inhibited the process of N-demethylation of aminopyrine to a greater degree, while enrofloxacin more markedly inhibited hydroxylation of aniline.

The effect of feeding dried tomato vines to beef cattle.

Dried Tomato vines (DTV) are used as a feedstuff in some beef cattle in Israel, despite the literature citation that tomato vines contain potentially harmful steroid alkaloids. A small-scale feeding trial over 42 d examined possible deleterious effects of feeding DTV, compared with wheat straw, in beef cows. No differences in hematological values, serum parameters for body weight were seen between the 2 groups. Steroid alkaloid content of the DTV was not examined, but toxic levels of nitrates were found. The main practical hazard in feeding DTV would appear to be from their potentially high nitrate content.

[Estimation of soil fraction of Pu in the formation of irradiation dose of inhabitants of the Bryansk region]. / Znachimost' "pochvennoi fraktsii" Pu v formirovanii doz oblucheniia naseleniia Brianskoi oblasti.

The estimation of plutonium in soils of the contaminated after Chernobyl accident areas of Bryansk Region (Russia) are presented. On the basis of data about Pu concentrations in soils and by means of migration models in "soil-man" system the doses received were assessed. Pu-239, 240 and Pu-238 were determined in samples of autopsy material (lung, liver, bones and tracheobronchial lymph nodes) of residents from Chernobyl-fallout contaminated regions. Effective doses have been obtained by means of data about Pu-concentration in autopsy samples.

The role of microsomal mixed function oxidases in the metabolism and mechanism of action of certain organophosphorus insecticides.

The influence of microsomal mixed function oxidases (MFO) on the biotransformation of pesticides was investigated in experiments with perfusion of isolated rat livers and in whole animals. The pesticides examined were 3 organophosphorus insecticides (OP): S-propyl-O-phenyl-O-ethylthiophosphate (heterophos), a mixture of O,O-dimethyl-O-cyclohexylthionphosphate and O,S-dimethyl-O-cyclohexylthiolphosphate (cyclophos), and dithiophosphonate. The indices of NADPH-dependent hydroxylating systems measured in the microsomal fraction of rat liver homogenates were the activity of aniline hydroxylase, aminopyrine demethylase and the amount of cytochrome P-450. It was shown that not only did the specific chemical structure of the OP and induction or inhibition of MFO determine OP activation and detoxification (and thus its biological action), but also the route and frequency of exposure could influence these parameters.