An Improved Method for the Synthesis of the of Indole[2,3-a]Pyrrolo[3,4-c]Carbazole-5,6-Dione N-Glycosides and their Cytotoxic Activity

Pharmaceutical Chemistry Journal - Use of formylindolylacetic acid as a reagent at the stage of preparing the glycosides of bis(indolyl)furan-2,5-diones and dioxane as solvent increased yields from...     

Non‐classical mechanism of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor channel block by fluoxetine

Antidepressants have many targets in the central nervous system. A growing body of data demonstrates the influence of antidepressants on glutamatergic neurotransmission. In the present work, we studied the inhibition of native Ca²⁺‐permeable and Ca²⁺‐impermeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors in rat brain neurons by fluoxetine. The Ca²⁺‐impermeable AMPA receptors in CA1 hippocampal pyramidal neurons were weakly affected. The IC₅₀ value for the inhibition of Ca²⁺‐permeable AMPA receptors in giant striatal interneurons was 43 ± 7 μm . The inhibition of Ca²⁺‐permeable AMPA receptors was voltage dependent, suggesting deep binding in the pore. However, the use dependence of fluoxetine action differed markedly from that of classical AMPA receptor open‐channel blockers. Moreover, fluoxetine did not compete with other channel blockers. In contrast to fluoxetine, its membrane‐impermeant quaternary analog demonstrated all of the features of channel inhibition typical for open‐channel blockers. It is suggested that fluoxetine reaches the binding site through a hydrophobic access pathway. Such a mechanism of block is described for ligands of sodium and calcium channels, but was never found in AMPA receptors. Molecular modeling suggests binding of fluoxetine in the subunit interface; analogous binding was proposed for local anesthetics in closed sodium channels and for benzothiazepines in calcium channels.     

Genetic variability of wild-type measles viruses, circulating in the Russian Federation during the implementation of the National Measles Elimination Program, 2003–2007

Genetic characterization of wild-type measles viruses (MVs) is an important component of laboratory surveillance of measles. In this study, a phylogenetic analysis was performed of the nucleoprotein gene sequences of 228 MVs isolated in the Russian Federation between 2003 and 2007. Five genotypes, D4, D5, D6, D8, and H1, were detected. From 1999 through the first 6 months of 2003, the most prevalent genotype in the European part of Russia was D4. All genotype D4-type viruses were closely related to each other (with overall sequence diversity of ≤0.9%), suggesting the presence of a single endemic MV strain. After 2003, viruses with closely related sequences within genotype D6 (≤0.9% sequence diversity) were prevalent. During this time, there was a low level of indigenous transmission of genotype D6, and genotype D6 viruses were imported from neighbouring countries, which led to the identification of two lineages of genotype D6, i.e. D6a and D6b. Lineage D6a was closely related to viruses isolated in Turkey, Kazakhstan, and Uzbekistan, whereas lineage D6b was linked to a large outbreak in Ukraine in 2005–2006. Genotypes H1, D5 and D8 were associated with sporadic cases and clusters of transmission linked to importations. Enhanced vaccination interrupted the transmission of the previous endemic lineage D4 in 2003 and of lineage D6a in 2005, although an accumulation of susceptible individuals in the population allowed for prolonged circulation of lineage D6b. These data on MV genotype distribution, in conjunction with the epidemiological data for measles, show considerable progress in measles control and suggest that regional elimination is possible.     

Effect of chronic administration of imipramine on 2A-serotonin receptor mRNA in brain cortex of rats predisposed and resistant to catalepsy

Rats selected by predisposition to catalepsy showed decreased level of 2A-serotonin receptor mRNA in the frontal cortex in comparison with Wistar rats (p<0.05). Chronic administration of tricyclic antidepressant imipramine hydrochloride 2-fold increased the content of receptor mRNA in genetically cataleptic rats (p<0.001) and did not change this parameter in Wistar rats. These results prompted us to revise current notion on the mechanisms of chronic effect of imipramine on 2A-serotonin receptors.     

Clinico-experimental aspects of liposomal therapy of bronchial asthma patients with hydrocortisone therapy

AIM: Clinical and experimental validation of liposomal therapy with hydrocortisone as a perspective treatment of bronchial asthma (BA). MATERIAL AND METHODS: Multistage trials of the liposomal treatment were made on 96 animals and in 137 BA patients. The decision on this treatment was based on the activity of bronchial inflammation and absence of contraindications. Liposomes were introduced endobronchially after a session of jet high-frequency artificial lung ventilation. RESULTS: Clinical endoscopic remission was achieved shortly after the treatment start in most of the patients. External respiration function and gas composition of blood improved, concentration of malonic dialdehyde lowered while catalase and glucose-6-phosphate dehydrogenase activity enhanced, inhalation sympathomimetics requirement reduced. CONCLUSION: Clinicomorphological and laboratory evidence obtained indicate high efficiency of liposomal therapy as an alternative to basic treatment of BA.