Effect of carbamazepine on the structure-function relations in the development of the epileptic structure

The experiments on white outbred male rats with cobalt-induced epileptogenic focus in the left sensomotor cortical region showed that the anticonvulsant effect of carbamazepine (20 mg/kg) depends on the functional state of the epileptic system (ES). In various stages of the ES development, the drug effect is related to the influence upon the determinant focus generating the epileptic activity. In the initial stage, carbamazepine primarily affects epileptic activity of the cortical foci (ipsi- and contralateral hemisphere). In the second (generalization) stage, the drug decreases the epileptic activity in all structures, but to a greater extent, in the dorsal hippocampus and lateral hypothalamus.     

Obtaining diagnostic fluorescent monoclonal immunoglobulins against the V. cholerae 0139-serovar

Below is given a procedure of the obtaining diagnostic fluorescent monoclonal immunoglobulin to detect cholera vibrios of O139 serovar. While obtaining preparations it was managed to determine optimal FTTS-MKA ratio, duration of their conjugation, series of fluorochrome. Test specimens of fluorescent monoclonal immunoglobulin provides intensive glow of V cholerae O139 cells in the working dilution 1:16-1:32. Tests of diagnostic FTTS-MKA on the great number of homologic and heterologic strains showed their strict specificity and high sensibility as to cholera vibrios of O139 serogroup.     

Studies of the immunostimulating properties of lipopolysaccharides and dextran sulfate based on a model of radiogenic immunodepression]

At a model of initial immunoresponse of mice to sheep erythrocytes the immunostimulating activity of lipopolysaccharide (LPS) and dextransulphate (DS) was tested. It was shown, that suppression of the immunosystem after influence of radiation can be compensated successfully by application of lipopolysaccharide and dextransulphate. The prophylactic application of these preparation is more ineffective.     

Genotype-Dependent Changes in Pain Thresholds in Adult Mice after Neonatal Treatment

We studied the effect of neonatal treatment with pharmacological preparations (Semax and buspiron) and solvents (distilled water and physiological saline) on the pain threshold in 3-4-month-old mice of 6 genotypes. Neonatal administration of the solvent (nociceptive stimulation) decreased pain thresholds in DBA/2, 101/HY, and RSB males, but not in female mice and animals of other strains. Neonatal administration of Semax significantly increased pain thresholds in adult DBA/2 and 101/HY males compared to those in animals neonatally treated with the solvent. Injection of buspiron in the neonatal period decreased pain thresholds in RLB males.     

Biodegradable ureteral stents in treating patients with infravesical obstruction

Biodegradable endoprostheses SR-PLGA and SR-PLLA were used in combined treatment of 39 patients with urethral stricture (n = 24), neurogenic urinary bladder (n = 9), benign prostatic hyperplasia (n = 4), prostatic cancer (n = 2). In definition of indications for stent implantation the leading role was assigned to preoperative diagnosis of the state of the urinary bladder, urethra and sphincters using urodynamic tests and dynamic Doppler and three-dimensional echourethrography. Introduction of biodegradable urethral stents provides adequate spontaneous urination and allows avoiding external drainage. This prevents nosocomial infection and lowers the number of inflammatory complications. Palliative usage of stents in inoperable and neurological patients is effective in their medical and social rehabilitation. Analysis of errors and complications in 8 patients demonstrates that implantation of biodegradable stents is not absolute safe and requires some caution.     

The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia

Schizophrenia (Sch) is a severe and widespread mental disorder. Antipsychotics (APs) of the first and new generations as the first-line treatment of Sch are not effective in about a third of cases and are also unable to treat negative symptoms and cognitive deficits of schizophrenics. This explains the search for new therapeutic strategies for a disease-modifying therapy for treatment-resistant Sch (TRS). Biological compounds are of great interest to researchers and clinicians, among which D-Serine (D-Ser) and D-Aspartate (D-Asp) are among the promising ones. The Sch glutamate theory suggests that neurotransmission dysfunction caused by glutamate N-methyl-D-aspartate receptors (NMDARs) may represent a primary deficiency in this mental disorder and play an important role in the development of TRS. D-Ser and D-Asp are direct NMDAR agonists and may be involved in modulating the functional activity of dopaminergic neurons. This narrative review demonstrates both the biological role of D-Ser and D-Asp in the normal functioning of the central nervous system (CNS) and in the pathogenesis of Sch and TRS. Particular attention is paid to D-Ser and D-Asp as promising components of a nutritive disease-modifying therapy for TRS.     

Highly homogenous tri-acylated S-LPS acts as a novel clinically applicable vaccine against Shigella flexneri 2a infection

Shigellosis, a major cause of diarrhea worldwide, exhibits high morbidity and mortality in children. Specificity of Shigella immunity is determined by the structure of the main protective O-antigen polysaccharide component incorporated into the lipopolysaccharide (LPS) molecule. Endotoxicity, however, precludes LPS clinical use. Thus, there is still no vaccine against the most prevalent shigellosis species (serotype S. flexneri 2a), despite ongoing efforts focused on inducing serotype-specific immunity. As LPS is highly heterogenous, we hypothesized that more homogenous pools of LPS might be less toxic. We developed a method to generate a homogenous S. flexneri 2a LPS subfraction, Ac₃-S-LPS, containing long chain O-specific polysaccharide (S-LPS) and mainly tri-acylated lipid A, with no penta- and hexa-acylated, and rare tetra-acylated lipid A. Ac₃-S-LPS had dramatically reduced pyrogenicity and protected guinea pigs from shigellosis. In volunteers, 50?µg of injected Ac₃-S-LPS vaccine was safe, with low pyrogenicity, no severe and few minor adverse events, and did not induce pro-inflammatory cytokines. In spite of the profound lipid A modification, the vaccine induced a prevalence of IgG and IgA antibodies. Thus, we have developed the first safe immunogenic LPS-based vaccine candidate for human administration. Homogenous underacetylated LPSs may also be useful for treating other LPS-driven human diseases.Clinical trial registry: http://grls.rosminzdrav.ru/     

SOFFCO, Montpellier 31 mai–2 juin 2012

Index

SOFFCO, Montpellier 31 mai–2 juin 2012 Index des auteurs     

Behavioral screening of two mouse lines selected for different brain weight.

1. Several behavioral tests were used to compare two lines of mice selected for large (LB) and small brain (SB) weight on the basis of brain/body weight ratio values. 2. An elevated pain sensitivity as well more intense startle response was shown in SB mice in comparison with LB mice. 3. In inescapable situations of slip funnel and tail suspension tests, analogues of the Porsolt swim test, higher immobility scores in SB mice suggest an increased level of fear and/or anxiety the stress situations. 4. The SB mice demonstrated higher levels of locomotion in open field and cross-maze tests. In the latter test, the SB mice also showed increased tendency for stereotyped alternation of two arms during maze exploration. 5. Acute administration of a moderate dose of ethanol (3 g/kg) had opposite effects on the total time of cross-maze exploration: this measure increased in the SB and decreased in the LB line. By contrast, the tendency for stereotypy was similarly increased and the efficacy of maze exploration decreased in both lines.