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

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

PLoS One

Quantitative analysis of the vascular network anatomy is critical for the understanding of the vasculature structure and function. In this study, we have combined microcomputed tomography (microCT) and computational analysis to provide quantitative three-dimensional geometrical and topological characterization of the normal kidney vasculature, and to investigate how 2 core genes of the Wnt/planar cell polarity, Frizzled4 and Frizzled6, affect vascular network morphogenesis. Experiments were performed on frizzled4 (Fzd4-/-) and frizzled6 (Fzd6-/-) deleted mice and littermate controls (WT) perfused with a contrast medium after euthanasia and exsanguination. The kidneys were scanned with a high-resolution (16 μm) microCT imaging system, followed by 3D reconstruction of the arterial vasculature. Computational treatment includes decomposition of 3D networks based on Diameter-Defined Strahler Order (DDSO). We have calculated quantitative (i) Global scale parameters, such as the volume of the vasculature and its fractal dimension (ii) Structural parameters depending on the DDSO hierarchical levels such as hierarchical ordering, diameter, length and branching angles of the vessel segments, and (iii) Functional parameters such as estimated resistance to blood flow alongside the vascular tree and average density of terminal arterioles. In normal kidneys, fractal dimension was 2.07±0.11 (n = 7), and was significantly lower in Fzd4-/- (1.71±0.04; n = 4), and Fzd6-/- (1.54±0.09; n = 3) kidneys. The DDSO number was 5 in WT and Fzd4-/-, and only 4 in Fzd6-/-. Scaling characteristics such as diameter and length of vessel segments were altered in mutants, whereas bifurcation angles were not different from WT. Fzd4 and Fzd6 deletion increased vessel resistance, calculated using the Hagen-Poiseuille equation, for each DDSO, and decreased the density and the homogeneity of the distal vessel segments. Our results show that our methodology is suitable for 3D quantitative characterization of vascular networks, and that Fzd4 and Fzd6 genes have a deep patterning effect on arterial vessel morphogenesis that may determine its functional efficiency

Thermotectonic evolution of an extensional dome : the cenozoic Osogovo-Lisets core complex (Kraishte zone, western Bulgaria)

The Kraishte region of Bulgaria is located at the junction of the Balkanides and Hellenides-Dinarides tectonic belts. Fission-track analysis on both apatites and zircons documents the Cenozoic exhumation of a Precambrian basement bounded by low-angle detachments. Late Eocene - Oligocene extension began prior to 47 Ma and was dominantly in a top-to-the-southwest direction, confirmed by the sense of younging of apatite and zircon ages. This crustal extension controlled the formation of half-graben sedimentary basins on the hanging walls of the detachments. Thermal modelling of these hanging wall units provides evidence for heat transfer across the detachments from a relatively warm rising footwall. From 32 to 29 Ma, pervasive magmatic activity resulted in the emplacement of rhyolitic to dacitic subvolcanic bodies and dykes, along with intrusion of the Osogovo granite. The results give evidence for extension in the southern Balkan older than, and separated from, the Miocene to Quaternary Aegean extension. This might reflect transtension during northeastward extrusion and rotation of continental fragments around the western boundary of Moesia. Eocene - Oligocene extension seems to have been controlled by the distribution of earlier thickening all around the Carpatho-Balkanic orocline, which is reflected by the Cretaceous emplacement of the Morava Nappe in the Kraishte

Formulation And Performance Evaluation Of Betahistine Dihydrochloride Microspheres As Sustained Release Systems

Бетагистин дигидрохлорид представляет собой гистаминовый аналог, широко применяемый для облегчения симптомов, сопутствующих синдром Мениера. По данным фармакокинетических исследований бетагистамин имеет краткую плазменную полужизнь - 3.4 ч. В таких случаях, чтобы поддерживать концентрацию плазмы во время терапевтического „окна”, приходится вводить лекарственное вещество часто, через небольшие интервалы. Это может привести к отсутствию содействия при проведении лечения со стороны пациента, как и к ухудшению его комфорта. Современный подход достижения удлиненного освобождения лекарства заключается в его включении в частицы-носители. ЦЕЛЬ: Разработать лекарство-доставляющую систему с удлиненным освобождением бетагистина, что способствовало бы уменьшению частоты приема и снижению риска появления нежелательных лекарственных реакций. МАТЕРИАЛЫ И МЕТОДЫ: Микросферы получены через W/О эмульсионную технику с испарением растворителя и охарактеризованы по отношению к их размеру, оличественному содержанию бетагистина и эффективности нагрузки. Освобождение с бетагистином, приготовленные через эмульсионную технику с испарением растворителя, показывают склонность к удлиненному освобождению и имеют потенциал лекарствено-освобождающих систем при лечении синдрома Мениер

In Vitro Study of Temperature Changes in Pulp Chamber During Root Planing Procedure Using Er:YAG Laser

Aim: To assess temperature changes at specified time intervals during Er:YAG laser scaling and root planing of surfaces with dental calculus

Effects of Low Level Laser Therapy on Erosive-atrophic Oral Lichen Planus

Background: The erosive-atrophic form of oral lichen planus (OLP) is associated with severe pain and burning sensation and is often unresponsive to treatment. Topical corticosteroids are considered as a medication of first choice but they can produce adverse effects. Therefore, new therapeutic approaches are required

Genomic and Epigenomic Mechanisms of the Interaction between Parasitic and Host Plants

Parasitic plants extract nutrients from the other plants to finish their life cycle and reproduce. The control of parasitic weeds is notoriously difficult due to their tight physical association and their close biological relationship to their hosts. Parasitic plants differ in their susceptible host ranges, and the host species differ in their susceptibility to parasitic plants. Current data show that adaptations of parasitic plants to various hosts are largely genetically determined. However, multiple cases of rapid adaptation in genetically homogenous parasitic weed populations to new hosts strongly suggest the involvement of epigenetic mechanisms. Recent progress in genome-wide analyses of gene expression and epigenetic features revealed many new molecular details of the parasitic plants’ interactions with their host plants. The experimental data obtained in the last several years show that multiple common features have independently evolved in different lines of the parasitic plants. In this review we discuss the most interesting new details in the interaction between parasitic and host plants

Middle Triassic palaeomagnetic data from northern Bulgaria: constraints on Tethyan magnetostratigraphy and palaeogeography

Magnetostratigraphic and biostratigraphic data are presented from the Anisian (Middle Triassic) Peri-Tethyan Edivetur section of northwestern Bulgaria. A dual-polarity component of magnetization carried by magnetite delineates a magnetic stratigraphy of mainly reversed polarity. Magnetozones are dated by means of foraminifer and conodont biostratigraphy. Data from Edivetur are compared with data from Middle Triassic Tethyan limestone sections with the aim of contributing to the completion of the Middle Triassic magnetic polarity time scale. We also propose that paleomagnetic data from Edivetur can be used as proxy data for the paleogeographic position of the Moesian platform. The Moesian platform was located at 21-24\ub0N along the southern margin of Europe. It was probably marginally separated, but not detached or rotated away from Europe by the North Dobrugea transtensional trough, which is interpreted as a back-arc basin resulting from the northward subduction of the Neo-Tethys (Vardar) or Paleo-Tethys ocean. Paleomagnetic data from this study and other minor tectonic elements are used to generate a paleogeographic sketch map of the Pangea-bounded western Tethys and Peri-Tethys at Middle/early Late Triassic time. (C) 2000 Elsevier Science B.V