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

FLORA, MYCOTA AND VEGETATION OF KUPENA RESERVE (RODOPI MOUNTAINS, BULGARIA)

The paper represents results from recent complex studies of flora, mycota and vegetation within the Kupena Reserve (Rodopi Mts, Bulgaria). Twenty three species, referred to 2 divisions, 4 classes and 16 families are recorded for the bryoflora. The vascular flora is presented by 368 species from 57 families, 121 of which are considered as medicinal plants. Eighty seven species of larger ascomycetes and basidiomycetes are found and reported for first time in the reserve. Four of them are of a high conservation value. The vegetation cover is consisted of mixed and monodominant deciduous and coniferous forests, as well as of mire, riverbank and mesic grasslands. Thirteen types of habitats according to the Habitats Directive classification have been recorded within the reserve

Amorpha fruticosa invasibility of different habitats in lower Danube

Abstract. Danube River plays a role of major corridor for plant invasions. Downstream is expected to be more strongly affected by such invasions. There were scarce data about alien plants dispersion by habitats in Bulgarian part of Danube. Sampling sites were selected on the river banks and on several islands and Amorpha fruticosa cover together with number of alien plants were sampled. Four habitat types were recognized. Most affected by indigo bush were poplar plantations while natural forests due to their closed structure and biodiversity remain less influenced

Carbopol hydrogel/sorbitan monostearate-almond oil based organogel biphasic formulations: Preparation and characterization of the bigels

Purpose: To obtain and evaluate carbopol hydrogel/sorbitan monostearate-almond oil-based organogel biphasic formulations (bigels) as a semi-solid vehicle for medicated topical applications.Methods: Bigel formulations were obtained under mild conditions at a hydrogel/organogel ratio of 80/20, 70/30, and 60/40 (w/w). Their stability, viscosity, spreadability, microarchitecture, and acute skin toxicity were evaluated.Results: Two formulations, prepared at ratios of 80/20 and 70/30, were stable based on intermediate stability testing, and had a similar viscosity and spreadability (38.0 ± 1.0 mm and 37.3 ± 0.6 mm, p > 0.05, respectively). Both of these formulations had a bimodal droplet size distribution and very similar values for the droplet mean diameter (0.33 ± 0.05 μm and 2.35 ± 0.44; and 0.34 ± 0.04 μm and 2.59 ± 0.21 μm). The formulation obtained at a ratio of 60/40 was unstable during storage. The in vivo results did not reveal any signs of skin toxicity.Conclusion: Considering their beneficial properties, the developed bigels are a potential semi-solid vehicle for topical application and exhibit a moisturizing effect.Keywords: Almond oil, Bigels, Carbopol hydrogel, Moisturizing effect, Organogel, Sorbitan monostearat

The Role of the Striatum in Learning to Orthogonalize CD Action and Valence: A Combined PET and 7 T MRI Aging Study

Pavlovian biases influence instrumental learning by coupling reward seeking with action invigoration and punishment avoidance with action suppression. Using a probabilistic go/no-go task designed to orthogonalize action (go/no-go) and valence (reward/punishment), recent studies have shown that the interaction between the two is dependent on the striatum and its key neuromodulator dopamine. Using this task, we sought to identify how structural and neuromodulatory age-related differences in the striatum may influence Pavlovian biases and instrumental learning in 25 young and 31 older adults. Computational modeling revealed a significant age-related reduction in reward and punishment sensitivity and marked (albeit not significant) reduction in learning rate and lapse rate (irreducible noise). Voxel-based morphometry analysis using 7 Tesla MRI images showed that individual differences in learning rate in older adults were related to the volume of the caudate nucleus. In contrast, dopamine synthesis capacity in the dorsal striatum, assessed using [18F]-DOPA positron emission tomography in 22 of these older adults, was not associated with learning performance and did not moderate the relationship between caudate volume and learning rate. This multiparametric approach suggests that age-related differences in striatal volume may influence learning proficiency in old age

Scale-dependent plant diversity in Palaearctic grasslands: a comparative overview

Here we present an extensive overview of plant diversity values in Palaearctic grasslands for seven standard grain sizes from 0.0001 to 100 m². The data originate from 20 studies, including the Field Workshops of the Eurasian Dry Grassland Group (EDGG), ranging geographically from Spain in the west to Siberia in the east, from Sicily in the south to Estonia in the north and from the sea coast up to 3100 m a.s.l. The majority of data is from dry grasslands (Festuco-Brometea, Koelerio-Corynephoretea, Cleistogenetea squarrosae), but there are also some mesic, wet, saline, acidic, alpine and Mediterranean grasslands included. Among others, we compiled data from 1795 1-m², 1109 10-m² and 338 100-m² plots. In all cases we present mean, minimum and maximum richness for the seven grain sizes, plus, in cases where also terricolous bryophytes and lichens had been recorded, the same values for total “plant” species richness, non-vascular plant species richness and fraction of non-vascular plants. The maximum richness values were 82, 101 and 134 for all “plants”, and 79, 98 and 127 vascular plants at grain sizes of 1 m², 10 m² and 100 m², respectively (all in Transylvania, Romania). Our overview comprises new, hitherto unpublished world records of vascular plant species richness at the scales of 0.0001 m² (9) and 0.001 m² (19, both shoot presence), from meso-xeric, basiphilous grasslands in Navarre, Spain, which is much higher than the previously known maxima. The highest values of non-vascular plant richness at 1 m², 10 m² and 100 m², respectively, were 49, 64 and 64, respectively (all in Sedo-Scleranthenea communities of Öland, Sweden, and Saaremaa, Estonia). In general, the dry, alpine and Mediterranean grasslands were much richer than the studied mesic, wet or saline grasslands at any spatial scale. The presented set of mean, minimum and maximum values and their metadata is publically available and will be continuously updated. These data can serve as a reference of “normal” richness, both in fundamental and applied research. To facilitate the application, we provide an easy formula based on the power-law species-area relationship that allows the estimation of richness values at intermediate grain sizes not included in our dataset. In conclusion, our data emphasise the role of Palaearctic grasslands as global hotspot of small-scale vascular plant diversity, while at the same time highlighting that in some grassland types also the bryophyte and lichen diversity can be extraordinarily high

Бринзоламид/тимолол и латанопрост в лечении псевдоэксфолиативной глаукомы: сравнительное исследование

PURPOSE: To compare the long-term effectiveness of pseudoexfoliative glaucoma (PEG) treatment with a fixed combination (FC) brinzolamide/timolol vs. latanoprost by a comprehensive assessment of structural and functional changes, as well as indicators of arterial ocular blood flow. METHODS: We observed 42 patients with PEG who received FC brinzolamide/timolol (22 patients) 2 times daily or latanoprost once a day (20 patients). The groups were homogeneous for age (66.05±1.241 in brinzolamide/ timolol group and 63.8±2.09 in latanoprost group, p=0.36) and glaucoma stages (MD -6.43±1.51 dB in brinzolamide/ timolol group and -8.02±2.08 dB in latanoprost group, p=0.54), intraocular pressure (IOP) levels were also comparable (19.59±0.79 mm Hg in brinzolamide/timolol group and 19.94±0.88 mm Hg in latanoprost group, p=0.77). The functional and morphometric parameters, studied by means of standard automated perimetry and spectral optical coherence tomography, and ocular blood flow parameters, measured by color Doppler Imaging with impulse Doppler sonography, were subjected to a comparative evaluation. Follow up period was 10.5±0.363 month. RESULTS: A significant IOP reduction, compared with baseline was observed in both groups: 11% from baseline in brinzolamide/timolol group (p=0.005) and 12.5% from baseline in latanoprost group (p=0.011). MD was improved in brinzolamide/timolol group: by 1.2±0.37 dB (p=0.003). No statistically significant difference in RNFL, GlV and GCC was obtained in both groups during the follow up period. However, by the end of 12 months a significant increase of FLV was noted in latanoprost group (p=0.04). By the end of the observation period patients treated with brinzol-amide/timolol showed an increase in diastolic blood flow in the ophthalmic artery (p=0.044) and systolic blood flow in the lateral posterior short ciliary artery (p=0.011). CONCLUSION: FC brinzolamide/timolol and latanoprost demonstrate a significant hypotensive efficacy in PEG, however FC brinzolamide/timolol unlike latanoprost provides stabilization of glaucomatous optic neuropathy, as evidenced by the preservation of visual function and morpho-metric parameters of the retina and optic nerve, as well as an improved arterial ocular blood flow.ЦЕЛЬ. Сравнить долгосрочную эффективность лечения псевдоэксфолиативной глаукомы (ПЭГ) фиксированной комбинацией бринзоламид/тимолол (ФК бринзоламид/ тимолол) с латанопростом на основании комплексной оценки структурных и функциональных изменений, а также показателей артериального глазного кровотока. МЕТОДЫ. В исследовании приняли участие 42 пациента с ПЭГ, получавшие ФК бринзоламид/тимолол (22 больных) 2 раза в день или латанопрост 1 раз в день (20 больных). Группы были однородны по возрасту (66,05±1,24 года в группе, получавшей ФК бринзоламид/тимолол, и 63,8±2,09 года в группе, получавшей латанопрост, р=0,36), по стадиям глаукомы (MD -6,43±1,51 дБ в группе ФК бринзоламид/тимолол и -8,027±2,08 дБ в группе латанопрост, р=0,54), а также по исходному уровню внутриглазного давления (19,59±0,79 и 19,94±0,88 мм рт.ст. соответственно в группах ФК бринзоламид/тимолол и латанопрост, р=0,77). Сравнительной оценке подвергнуты функциональные и морфометрические показатели, полученные при стандартной автоматизированной периметрии и спектральной оптической когерентной томографии, а также параметры регионарной гемодинамики глаза, измеренные в динамике методом цветового доп-плеровского картирования с импульсной допплерогра-фией. Средний срок наблюдения составил 10,5±0,36 мес. РЕЗУЛЬТАТЫ. В обеих группах больных наблюдалось достоверное по сравнению с исходным снижение ВГД, которое составило в группе ФК бринзоламид/тимолол 11% от исходного (p=0,005) и в группе латанопрост 12,5% от исходного (p=0,011). Было отмечено улучшение периметрического индекса MD у больных, получавших ФК бринзоламид/тимолол, на 1,2±0,37 дБ по сравнению с исходным (p=0,003). Статистически значимого изменения морфометрических показателей в динамике не было отмечено ни в одной группе, за исключением достоверного увеличения индекса FLV (p=0,04) у больных, получавших латанопрост. У пациентов, лечившихся ФК бринзоламид/тимолол, к концу наблюдения отмечено увеличение диастолической скорости кровотока в глазной артерии (p=0,044) и систолической скорости кровотока в латеральной задней короткой цилиарной артерии (p=0,011). ЗАКЛЮЧЕНИЕ. ФК бринзоламид/тимолол и латанопрост обладают выраженной гипотензивной эффективностью в лечении ПЭГ, однако ФК бринзоламид/тимолол, но не латанопрост, обеспечивает стабилизацию глаукомной оптической нейропатии, о чем свидетельствует сохранение зрительных функций и морфометрических характеристик сетчатки и зрительного нерва, а также улучшение артериального глазного кровотока

Отдаленные результаты селективной лазерной трабекулопластики при псевдоэксфолиативной глаукоме

PURPOSE: To assess the long-term efficacy of selective laser trabeculoplasty (SLT) in the treatment of pseudoexfoliative glaucoma (PEG) and primary open-angle glaucoma (POAG). METHODS: 75 patients with PEG (64 eyes) and 70 patients with POAG (63 eyes) were included in the study. The groups were homogeneous for age (69.67±0.93 years in PEG group and 65.63±0.33 years in POAG group, p = 0.09) and stages of glaucoma (MD -7.29±1.08 dB in PEG group and -5.95±1.12 dB in POAG group, p=0.39). Baseline IOP was 23.9±0.65 mm Hg in PEG patients and 21.4±0.44 mm Hg in POAG patients (p=0.002). The follow-up period was four years. RESULTS: There was a significant reduction of the IOP level in PEG patients after SLT as compared to the baseline at all stages of the study. By the end of the follow-up period the IOP was 19.00±0.97 mm Hg (p=0.023). A significant reduction of the IOP level in POAG patients occurred only during the first six months after surgery (IOP=18.92±0.46, p=0.000) and by the end of the follow-up period it was 20.8±1.13 (p=0.938). The amounts of topical ocular hypotensive drugs after SLT in the PEG group decreased from 1.69±0.107 to 1.45±0.092 (p=0.05), and in the POAG group - from 1.42±0.091 to 1.2±0.111 (p=0.137). There was no statistically significant progression of glaucomatous neuropathy in both groups: the MD index was not significantly changed in the PEG group during the follow-up period: -7.29±1.08 dB before SLT, and 7.6±1.36 dB in the late postoperative period (p=0.10), in the POAG group the index values were 5.95±1.12 dB and -6.63±1.28 (p=0.37) dB, respectively. CONCLUSION: SLT may be considered an effective and safe treatment for PEG patients, which not only significantly reduces the IOP level, but also helps preserve visual functions at least four years after the surgery.ЦЕЛЬ. Сравнить эффективность селективной лазерной трабекулопластики (СЛТ) в лечении псевдоэксфолиативной глаукомы (ПЭГ) и первичной открытоугольной глаукомы (ПОУГ) в отдаленном периоде. МЕТОДЫ. Под наблюдением находились 75 больных с ПЭГ (64 глаза) и 70 больных ПОУГ (63 глаза). Группы были однородны по возрасту (69,67±0,93 года при ПЭГ и 65,63±0,33 года при ПОУГ, р=0,09) и стадиям глаукомы (MD -7,29±1,08 дБ при ПЭГ и -5,95±1,12 дБ при ПОУГ, р=0,39). При ПЭГ исходное внутриглазное давление (ВГД) составило 23,9±0,65 мм рт.ст., при ПОУГ 21,4±0,44 мм рт.ст. (р=0,002). Отдаленный период наблюдения составил 4 года. РЕЗУЛЬТАТЫ. Достоверное снижение ВГД после СЛТ наблюдалось на всех этапах по сравнению с исходным у больных ПЭГ и к концу срока наблюдения составило 19,00±0,97 мм рт.ст. (р=0,023). При ПОУГ достоверное снижение офтальмотонуса происходило только в первые полгода после операции до 18,92±0,46 мм рт.ст. (р=0,000) и к концу срока наблюдения составило 20,8±1,13 мм рт.ст. (p=0,938). Количество применяемых гипотензивных капель после СЛТ при ПЭГ снизилось с 1,69±0,107 до 1,45±0,092 (р=0,05), а при ПОУГ - от 1,42±0,091 до 1,2±0,111 (р=0,137). В обеих группах больных не отмечалось прогрессирования ГОН: за период наблюдения в группе ПЭГ индекс MD достоверно не изменился: -7,29±1,08 дБ до СЛТ и -7,6±1,36 дБ - в отдаленном периоде после СЛТ (р=0,10); при ПОУГ: -5,95±1,12 и -6,63±1,28 дБ (р=0,37) соответственно. ЗАКЛЮЧЕНИЕ. СЛТ - эффективный и безопасный метод лечения ПЭГ, позволяющий не только снизить ВГД, но и сохранить зрительные функции в течение 4 лет после операции