[A systematic analysis of neurobiological roles of lithium]. / Neirobiologicheskaya rol' solei litiya.

Lithium salts have been the mainstay of treatment for bipolar disorder for more than 50 years, since the FDA approved the treatment in 1970. Molecular mechanisms of lithium's action include inhibition of glycogen synthase kinase 3 beta and inositol monophosphatase, resulting in induction of brain-derived neurotrophic factor, antiapoptotic proteins, deprivation of calcium-induced apoptosis. Recent findings suggest autophagy regulation as a possible mechanism of lithium neuroprotective action. Moreover, lithium treatment has been reported to decrease accumulation of various pathological proteins including phosphorylated tau and amyloid-B. Also, telomeres length and telomerase activity are suggested to be upregulated by lithium. Clinical applications of lithium treatment include various neurodegenerative diseases, primarily Alzheimer disease, with increasing importance given to the use of lithium microdoses. Chemoreactome screening is used to find more safe and effective lithium compounds.

[Molecular and clinical aspects of the effect of cytidyndiphosphocholine on cognitive functions]. / Molekulyarnye i klinicheskie aspekty deistviya tsitidindifosfokholina na kognitivnye funktsii.

OBJECTIVE: Systematization of the array of publications on cytidyldiphosphocholine (CDP-choline). MATERIAL AND METHODS: Systematic computer analysis of all currently available publications on CDP-choline (1750 publications in PUBMED) using the topological theory of big data analysis. RESULTS: CDP-choline is essential for acetylcholine biosynthesis, phospholipid metabolism, and DNA methylation. The article describes the effects of CDP-choline on acetylcholinergic and other types of neurotransmission, anti-inflammatory, neuroprotective and neurotrophic effects of CDP-choline. Also, the paper presents the effects of the molecule on lipid metabolism and gene expression within the post-genomic paradigm (in particular, an increase in the expression of nicotinic and muscarinic acetylcholine receptors). The results of fundamental and clinical studies of CDP-choline in the treatment of cognitive impairments associated with cerebral ischemia and neurodegeneration are presented. CONCLUSION: The pharmacological effects of CDP-choline are mediated through multiple molecular mechanisms that contribute to the nootropic action of this molecule.

[Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia].

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (Mg BP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (Mg D) (185±90 mg/day). RESULTS: Mg supply was adequate (Mg BP >0.80 mmol/L, Mg D >300 mg/day) in not more than 6 % of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95 % confidence interval [CI] 10-25, р=0.0006). Mg deficit (Mg BP.

Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia.

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (MgBP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (MgD) (185±90 mg/day). RESULTS: Mg supply was adequate (MgBP >0.80 mmol/L, MgD >300 mg/day) in not more than 6% of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95% confidence interval [CI] 10-25, р=0.0006). Mg deficit (MgBP.

[An experimental study of anticonvulsant effects of myo-inositol and folic acid]. / Protivosudorozhnye effekty mio-inozitola v sochetanii s folievoi kislotoi v eksperimente.

AIM: To study the micronutrients that potentiate the action of anticonvulsant drugs, and in particular, of myo-inositol (vitamin B8). MATERIAL AND METHODS: An experimental study of neurotrophic and anticonvulsant effects of a preparation based on myo-inositol (inofert) on thiosemicarbazide models of seizures was carried out. RESULTS: Inofert significantly increased the latent time before the first convulsive seizure, reduced the severity of seizures (p<0.05) and reduced mortality in the models of thiosemicarbazide seizures. Myo-inositol enhanced anticonvulsant action of gabapentin and sodium valproate; neuroprotective effect of myo-inositol was also confirmed. CONCLUSION: The Inofert preparation, containing myo-inositol and folic acid, modulates the effects of drugs with both convulsive and anticonvulsive action, reduces the severity and duration of seizures caused by thiosemicarbazide and increases the survival rate of animals.

[Neurotrophic peptides of сerebrolysin as a basis for anticonvulsant effect of the drug]. / Neirotroficheskie peptidy tserebrolizina kak osnova protivosudorozhnogo potentsiala preparata.

AIM: To study an effect of cerebrolysin on the expression and severity of primary-generalized seizures caused by thiosemicarbazide and to analyze the corresponding molecular mechanisms. MATERIAL AND METHODS: The effects of cerebrolysin were studied on the thiosemicarbazide model of convulsions in 144 male rats. Cerebrolysin was introduced intraperitoneally in the dose of 2.5 ml/kg of body mass 5 days a week during 18 days. RESULTS AND CONCLUSION: Cerebrolysin reduces the severity and duration of seizures caused by thiosemicarbazide and increases the survival rate of animals. Cerebrolysin potentiates the anticonvulsant action of gabapentin and sodium valproate. Neurohistological analysis has shown that the thiosemicarbazide model results in the ischemic brain damage. Cerebrolysin substantially minimizes the ischemic injury of neurocytes induced by thiosemicarbazide and contributes to the restoration of brain tissue morphology.

[Evaluation of the antitumor potential of cerebrolysin]. / Otsenka protivoopukholevogo potentsiala tserebrolizina.

AIM: To investigate the effect of cerebrolysin on the growth and metastasis of malignant tumors in mice (a model of lung carcinoma Lewis). MATERIAL AND METHODS: The study was performed on 60 male mice, hybrids F1 (the age of 2-2.5 months, body weight 19-22g.). Transplantable epidermoid Lewis lung carcinoma (LLC) was used as a standard experimental model to evaluate the properties of the potential antitumor agents. Experimental animals were administered a single intraperitoneal injection of cerebrolysin in doses of 524 mg/kg (n=20) and 1800 mg/kg (n=20) daily from 2 to 16 days after tumor transplantation. RESULTS AND CONCLUSION: Compared with the control group (n=20), cerebrolysin induced growth inhibition of LLC during the treatment (7 to 16 days). An impact of the drug was accompanied by the inhibition of the tumor growth rate by 10-15% (p<0.05). Cerebrolysin demonstrated a dose-dependent effect of reducing the large number of metastases: a number of large metastases significantly decreased by 30-50% with the increase of cerebrolysin dose (p=0.01). Cerebrolysin can significantly suppress the growth rate of Lewis lung carcinoma.

[On Synergism of Potassium and Magnesium in Maintenance of Myocardial Function].

AIM: systematization of studies of synergistic effect of potassium and magnesium on myocardial function. MATERIAL AND METHODS: Analysis of an array of literature using methods of computer learning. RESULTS: Synergism of potassium and magnesium is driven by common causes of deficit (low content in diet, abnormal renal function, iatrogenic causes), by potassium sparing effects of magnesium, and by regulatory properties of magnesium in processes affecting potassium binding proteins (first of all potassium rectifier channels). Magnesium and potassium exert substantial synergism in maintenance of cardiac rhythm (in particular preventing QT prolongation) and in cardioprotection. Combination administration of organic potassium and magnesium salts was shown to be effective for urgent therapy and long term prevention both as intravenous and oral formulations.

[Very low magnesium levels in red blood cells as a significant factor in the etiopathogenesis of borderline disorders].

AIM: Basic studies indicate magnesium deficiency as one of the important, but often neglected, risk factors aggravating the course of borderline disorders (BD). A clinical verification of this notion has been conducted. MATERIAL AND METHODS: Authors studied 62 patients with BD, aged 25-65 years, of inpatient and outpatient settings. Contents of magnesium and other blood electrolytes were determined. RESULTS: Authors found an extremely high prevalence of very low levels of magnesium (Mg) in erythrocytes (<0.3 mmol/l) in patients with BD compared to controls (patients without BD, Mg (er.) 1.62±0.48 mmol/l). It has been shown that low Mg levels in the plasma and red blood cells are associated with a significantly increased risk of the following diagnoses: F07 «Personality and behavioral disorder due to brain disease, damage and dysfunction¼ (p<0.0016), F21 «Schizotypal disorder¼ (p<0.0005) and F34 «Persistent mood [affective] disorders¼ (p<0.0001). The use of Magne B6 Forte (4 tablets/day, 30 days, then 2 tablets/day for 1 year) resulted in a significant increase in the Mg levels in the plasma and erythrocytes, the compensation of anxiety and depressive symptoms, improvement of sleep and general health of the patients, reduced consumption of antidepressants (by 30%). CONCLUSION: Administration of the drugs based on organic salts of magnesium per os improves the condition of patients and reduces their need in pharmacotherapy.

[Magnesium deficiency and dysregulation of vascular tone].

Magnesium deficiency is associated with impaired vascular tone bidirectionally and can lead to both an abnormal increase and abnormal lowering of blood pressure. This article analyzes studies on the relationship between blood pressure parameters and the level of magnesium in the blood. Evidence base for the use of magnesium for correction of vascular tone is presented.

[Diagnostics of magnesium deficiency and measurements of magnesium concentrations in biosubstrates in norm and in various pathologies].

In accordance with the evidence from large-scale studies magnesium deficiency has a significant negative impact on the cardiovascular system, carbohydrate and fat metabolism. Diagnosis of magnesium deficiency should be based on clinical symptoms of magnesium deficit and confirmed by additional diagnostic methods--ECG myography, bone densitometry, and quantitative determination of magnesium in various biosubstrates (whole blood, red blood cells, plasma, serum, saliva, urine, nails, hair). It is also desirable to estimate dietary intake of magnesium according to food frequency questionnaires verified by measurements of magnesium in blood. Analysis of magnesium content in blood and other biosubstrates allows to establish those perturbations of compartmentalization of magnesium in tissues that are typical for a particular pathology. It is important to emphasize that one should not confuse values of magnesium levels measured in serum and in plasma as it leads to serious errors in the diagnosis of magnesium deficiency and results in underdiagnosis of magnesium deficiency (code E61.2 of ICD-10).

[System analysis of the relationship between the metabolism of vitamins by micro-biota and the survival of the positive microflora of the digestive tract].

A perspective direction of the treatment of dysbacteriosis is the use of so-called metabolic prebiotics--products of metabolism of positive flora (for example, water substrate of the products of metabolism of E. coli, S. faecalis, L. acidophilus, L. helveticus (strains of DSM), out of which, as known, drug Hylak Forte is made. Our earlier systematic analysis of metabolomics, representatives of positive microflora, pointed to the fact that the latter contain specific biochemical mechanisms for biosynthesis and processing of a number of vitamins. In the present paper the results of a systematic analysis of the effects of vitamins B2, B6 and K on the survival of the representatives of the positive microflora on the basis of the substrate of metabolic products of positive flora have been presented. The results of the analysis allow us clarify the molecular mechanisms of the therapeutic effects of this drug with a very complex structure and confirm the available clinical data and are an important foundation for subsequent microbiological research. Metabolites in the preparation composition contribute to the normalization of metabolism of pyridoxalphosphate (vitamin B6), flavin adenin dinucleotide (FAD, a derivative of vitamin B2) and nicotinamide dinucleotide (NAD, a derivative of vitamin B3)--cofactors of enzymes that have a significant impact on the survival of microbiota. The proposed molecular mechanisms also indicate on a possible synergies between certain vitamins and micro elements, on the one hand, and molecular components of the preparations on the basis of waste products of microbiota on the other.

[Potassium-preserving properties of magnesium].

Current fundamental research indicates importance of conducting clinical studies of the influence of magnesium content of the body on the potassium homeostasis. In this work we systematically analyze molecular mechanisms through which magnesium regulates potassium homeostasis: ATP-sensitive inward rectifier K-channels, Na+/K(+)-ATPases and their regulatory protein SIK1, transporter SLC12A3 and WNK-kinases. Hyperkalemia as well as hypokalemia require safe and effective prevention and therapy, including restoration of magnesium homeostasis.

[The effect of the table salt substitute sanasol on arterial pressure, water-salt metabolism and kidney functions in experimental pathology of circulatory homeostasis]. / Vliianie zamenitelia povarennoi soli sanasola na arterial'noe davlenie, vodno-solevoi obmen i funktsii pochek pri patologii tsirkuliatornogo gomeostaza v éksperimente.

The potassium-containing salt substitute sanasol was examined for its effects on blood pressure and renal function in normo- and hypertensive rats, as well as on the edematous syndrome in circulatory insufficiency. The antihypertensive and occasional antiedematous effects of sanasol resulted in unfavorable changes in electrolyte balance. Sanasol was found to be ineffective in experimental renal failure.