Lithium Ascorbate as a Promising Neuroprotector: Fundamental and Experimental Studies of an Organic Lithium Salt.

Given the observable toxicity of lithium carbonate, neuropharmacology requires effective and non-toxic lithium salts. In particular, these salts can be employed as neuroprotective agents since lithium ions demonstrate neuroprotective properties through inhibition of glycogen synthetase kinase-3ß and other target proteins, increasing concentrations of endogenous neurotrofic factors. The results of theoretical and experimental studies of organic lithium salts presented here indicate their potential as neuroprotectors. Chemoreactomic modeling of lithium salts made it possible to select lithium ascorbate as a suitable candidate for further research. A neurocytological study on cerebellar granular neurons in culture under conditions of moderate glutamate stress showed that lithium ascorbate was more effective in supporting neuronal survival than chloride or carbonate, i.e., inorganic lithium salts. Biodistribution studies indicated accumulation of lithium ions in a sort of "depot", potentially consisting of the brain, aorta, and femur. Lithium ascorbate is characterized by extremely low acute and chronic toxicity (LD50 > 5000 mg/kg) and also shows a moderate antitumor effect when used in doses studied (5 or 10 mg/kg). Studies on the model of alcohol intoxication in rats have shown that intake of lithium ascorbate in doses either 5, 10 or 30 mg/kg did not only reduced brain damage due to ischemia, but also improved the preservation of myelin sheaths of neurons.

Encapsulation of vitamin B12 into nanoengineered capsules and soft matter nanosystems for targeted delivery.

Targeted delivery of vitamins to a desirable area is an active branch in a modern pharmacology. The most important and difficult delivery of vitamin B12 is that to bone marrow and nerve cells. Herein we present a first step towards the development of two types of smart carriers, polymer capsules and lyotropic liquid-crystalline nanosystems, for vitamin B12 targeted delivery and induced release. A vitamin B12 encapsulation technique into nanoengineered polymeric capsules produced by layer-by-layer assembling of polymeric shells on CaCO3 templates has been developed. The effectiveness of the process was demonstrated by optical absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM) and small-angle X-ray diffraction. TEM and AFM analyses performed on capsules after their drying, confirmed the presence of the vitamin B12 inside the capsules in the form of crystalline nanoaggregates, 50-300 nm in diameter. Soft lipid nanovectors consisting of amphiphilic phytantriol molecules, which in water excess spontaneously self-assembly in 3D well-ordered inverse bicontinuous cubic bulk phase, were used as alternative carriers for vitamin B12. It was shown that about 30% of the vitamin added in the preparation of the soft lipid system was actually encapsulated in cubosomes and that no structural changes occurred upon loading. The Vitamin stabilizes the lipid system playing the role of its structure-forming element. The biocompatible nature, the stability and the feasibility of these systems make them good candidates as carriers for hydrophilic vitamins.

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.

Effect of alvitili on immunological parameters in often ailing children.

The problem of the rehabilitation of often ailing children is not yet elucidated despite of a substantial amount of research done in this field. It is acknowledged that the impairment of immune reactivity is a pathogenetic foundation of often and prolonged respiratory diseases in children. In this connection, the aim of the study was to evaluate the effect of alvitili on the main immunologic parameters in children who get ill frequently. Alvitili, produced by Solvay Pharma (France), is one of the promising vitamin preparations that contain all necessary water-soluble and oil-soluble vitamins. Thirty children 3-8 years of age were selected for the study: 15 children were included in the group of often ailing children and 15 healthy children made the control group. Immunological examination was carried out using standard methods before and after administration of alvitili at a dose of 5 ml 3 times a day for 3 weeks. Alvitili normalized originally decreased levels of T lymphocytes and T helpers, enhanced expression of early activation markers on the surface of T lymphocytes and T helpers, normalized the number of HLA DR(+) T cells and the level of MIF production. The drug stimulated IgM synthesis, expression of FcgammaRIII on the surface of neutrophils and normalized the IgG level. The study showed that alvitili is an effective remedy in the rehabilitation of ill children, since it compensates a vitamin deficiency that is frequently seen in often-ailing children, and it normalizes various immunological parameters.

Dual effect of cerebrolysin in children with attention deficit syndrome with hyperactivity: neuroprotection and immunomodulation.

Children with attention deficit syndrome with hyperactivity (ADSH) are characterised by attention and motor deficiencies and obvious immune disorders, which manifest as recurrent acute viral respiratory tract infections and changes in immunological parameters. It was established that the structure of deviations in the spectrum of elements in children with ADSH has characteristic features. The atomic emission analysis of cerebrolysin detected an advantageous combination of trace elements with neuroactive and antioxidant properties. The effect of cerebrolysin on immunological parameters was studied in vitro and in vivo. Cerebrolysin was administered in a dose of 1 ml per 10 kg of weight intramuscularly during 1 month. The administration of cerebrolysin resulted in a simultaneous normalization of neurological and immune disorders and in a reduction in the illness rate. In in vitro experiments cerebrolysin enhanced the expression of activation markers (HLA DR, CD25) by CD45(+)CD14(-) lymphocytes, particularly by CD4(+) cells. In vivo it led to the normalization of the numbers of CD4(+), CD19(+), CD16(+) and CD56(+) cells and of the level of serum IgG and IgA. Cerebrolysin normalized the expression of HLA DR molecules on the surface of CD8(+) cells and increased the amount of CD11b(+) lymphocytes. At the same time, it did not affect the level of CD95 molecule expression.

Immunoactive Properties of Cerebrolysin.

In children (aged 3-8 years old) with minimal cerebral dysfunction the immune status was studied before and after cerebrolysin administration in the dosage of 1 ml per 10 kg of child's weight, intramuscularly, within one month. The cerebrolysin administration resulted in an increase in the level of CD19(+) cells with a simultaneous normalization of serum IgG and IgA levels. The count of CD4(+) lymphocytes has risen. Normalization of a relative count of CD16(+) cells (NK) was noted after cerebrolysin therapy. Expression of activation markers (CD25 and HLA DR) in total population of lymphocytes parallelly changed, achieving the parameters of the control group without any changes in expression of CD95 molecule. Under the cerebrolysin influence the activation mainly of T helpers could be observed in vitro.