Development and in vitro evaluation of mucoadhesive microsphere carriers for intranasal delivery of betahistine dihydrochloride.

The aim of the present work was to formulate and evaluate betahistine-loaded chitosan microspheres intended for nasal delivery with focus on their mucoadhesive properties. Betahistine-loaded chitosan microspheres were obtained via W/O emulsion solvent evaporation technique and were characterized for particle size, surphace morfology and entrapment efficiency. FTIR spectroscopy was carried out to evaluate drug-polymer interaction and powder X-ray diffractometry was applied to investigate crystallinity transformations. Tensile studies were carried out using sheep nasal mucosa to evaluate in vitro mucoadhesion. Drug release into phosphate buffer saline pH 7.4 was performed and dissolution profiles of the formulations were obtained. The results showed that the microspheres were spherical in shape having smooth surface and mean particle size of 3.82 µm to 7.69 µm which is appropriate for optimum deposition in the nasal cavity. The mean particle size increased when chitosan solutions with higher viscosity were used. In vitro mucoadhesion studies indicated that chitosan microspheres had good mucoadhesive properties and could adequately adhere to nasal mucosa. It was observed that polymer concentration enhancement led to increased mucoadhesive strength. Betahistine release studies from the microspheres showed similar and slightly icreasing dissolution profiles. Acording to the obtained results, betahistine-loaded chitosan microspheres prepared by solvent evaporation method proved to be capable of sustained release and could be used via nasal route as an alternative to oral administration

Possible role of 18-kDa translocator protein (TSPO) in etifoxine-induced reduction of direct twitch responses in isolated rat nerve-skeletal muscle preparations

Purpose: To determine the effects of etifoxine on directly-elicited twitch tension of isolated rat nerveskeletal muscle preparations and to propose a possible explanation of the mechanism of the observed effect.Methods: Striated muscles contractile activity was elicited by electrical field stimulation. The effects of etifoxine and nifedipine on direct single twitch response were studied.Results: The results demonstrate that the effect of etifoxine on skeletal muscle depends on the concentrations: low concentrations (10-8 М and 10-7 М) have little effect on twitch tension, whereas higher concentrations (10-6 М and 10-5 М) induced a significant decrease in the direct single twitch response in comparison to controls. The mean IC50 (reduction of directly-elicited twitch tension) of etifoxine was 0.85 x 10-6 M. The selective L-type calcium channel blocker nifedipine (10-5 М) induced a greater decrease in the muscle force than 10-6 М etifoxine. The different abilities of etifoxine and nifedipine to reduce direct single twitch response may be related to their distinct mechanisms of action. The observed effect of etifoxine could be more complex. Probably etifoxine acts as a non-selective agent not only on L-type calcium channels Cav1.1 localized in sarcolemma but also on 18-kDa translocator protein (TSPO) in skeletal muscle.Conclusion: Etifoxine-induced reduction of direct twitch responses could be attributed to an effect on TSPO and Cav1.1. Knowledge of the effects of TSPO ligands on the contraction of skeletal muscle might explain the role of TSPO in muscle contractility.Keywords: Etifoxine, TSPO, Calcium channels, Direct single twitch response, Striated muscl

Possibilities for development of the market management in diagnostic and advisori center St. Ivan Rilski Varna

Публикацията има за цел да представи проучване относно удовлетвореността на пациентите и лекарите - специалисти в диагностично консултативен център (ДКЦ) `Св. Иван Рилски` Варна и възможностите за развитие на маркетинговият мениджмънт в ДКЦ Св.Иван Рилски Варна. Информацията е събрана чрез провеждане на анкетни проучвания сред пациенти и работещи в лечебното заведение (ЛЗ). Преобладава мнението за удовлетвореност и сред двете групи респонденти. Развитието на маркетинговият мениджмънт в ДКЦ `Св.Иван Рилски` ЕООД Варна е свързано с разработване на маркетингова стратеия за предлагане на нови продукти, чиито пазарни позиции бележат висок пазарен ръст и възможности за реинвестиране на финансови средства към тях.The publication aims to represent a research regarding the contentment of patients and physicians - specialists, in Diagnostics and advisory center ‘St. Ivan Rilski` - Varna, as well as the possibilities for development of the market management in the said Diagnostic and advisory center. The information is gathered through an inquiry among patients and employees of the said health institution (HI). Prevailing are satisfactory responses and opinions among both groups. The development of the market management of Diagnostic and advisory center `St. Ivan Rilski` EOOD Varna is connected with the design of a market strategy for the supply of new products with high market growth and possibilities for reinvestment of financial funds in them

Denatonium benzoate decreases the effect of histamine in vitro and in rats

Purpose: To evaluate the effect of denatonium benzoate (DB) in histamine-induced model of inflammation and the effect of the selective H1 receptor agonist (2-(2-Pyridyl) ethylamine) on rat gastric smooth muscle strips pretreated with DB.Methods: The anti-inflammatory effect of DB was evaluated in vivo on histamine-induced rat paw edema. In vitro studies on spontaneous muscle contraction were performed on smooth muscle strips isolated from rat gastric corpus.Results: The results showed a well-defined anti-inflammatory effect of DB (15 mg/kg) during the early stage of rat paw edema at the 15th (p < 0.001), 30th (p < 0.01) and 60th min (p < 0.001) compared to control. In vitro experiments indicated reduced spontaneous contractile activity of smooth muscle strips to H1 receptor agonist in the presence of DB (0.5 μM). The vascular effects of histamine are mediated by H1 receptors. Substances, which reduce the effect of histamine on the H1 receptors could influence the early stage of histamine-induced inflammation.Conclusion: The results show that the anti-inflammatory activity of DB probably is related to its antagonistic activity on histamine H1 receptors. The results would contribute to the search for new antiinflammatory drugs. Keywords: Denatonium benzoate, Inflammation, Histamine, Muscle contractio

Cadomian and post-cadomian tectonics west of the Rhodope Massif – The Frolosh greenstone belt and the Ograzhdenian metamorphic supercomplex

The Frolosh Greenstone Belt (FGB) is traced at a distance of more than 200 km in the territories of Bulgaria, Macedonia and Serbia. It consists of various greenschist-facies rocks (actinolite schists, phyllites, calcareous schists, impure marbles, metasandstones, metadiabases, massive green rocks, etc.) of the Frolosh metamorphic complex with bodies of metabasites (including lherzolites), and inliers (retrogressed mica gneisses and migmatites) from the Ograzhdenian supercomplex. The complex is in­truded by bodies of gabbro (occasionally with ultramafic cumulates), diorites to granites (Struma diorite formation). U-Pb studies on zircons yielded Cadomian ages within the time span between c. 574 and 517 Ma. The Frolosh complex covers the ultrametamorphic (migmatized gneisses and amphibolites; tourma­line-biotite schists; quartzo-feldspathic gneisses; lensoid bodies of metaperidotites to norites) of the Ograzhdenian supercomplex. The Ograzhdenian rocks are intersected by diatectic metagranites over­printed by amphibolite-facies metamorphism. Dominant U-Pb ages vary between 470 and 430 Ma. The contact between the Frolosh complex and the Ograzhdenian supercomplex has been subject of long dis­cussion and controversial interpretations. Now we emphasize on the multistage developments of both complexes as demonstrated both by field evidence and isotopic dating. The Ograzhdenian supercomplex has been subject of Precambrian tectonometamorphism witnessed by Rb-Sr whole-rock isochron data and relict U-Pb zircon data. Ordovician to Silurian anatectites (metatectic migmatization, diatexis) are in­truded by Permo-Triassic granites. The contact between the Ograzhdenian supercomplex and the covering Frolosh complex is regarded as a thick complex zone of multistage tectonometamorphic development rather than a “razor-blade” surface of one-stage origin. As a boundary between suprastructure and infra­structure, it played an important role throughout the Phanerozoic, and acted as a screen with a steep ther­mal gradient during the Ordovician-Silurian anatexis and metamorphism in the Ograzhdenian supercom­plex. For to verify this hypothesis, new detailed structural and isotopic studies are needed