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

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

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

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

Discriminant analysis of intermediate brain atrophy rates in longitudinal diagnosis of alzheimer's disease

Diagnosing Alzheimer's disease through MRI neuroimaging biomarkers has been used as a complementary marker for traditional clinical markers to improve diagnostic accuracy and also help in developing new pharmacotherapeutic trials. It has been revealed that longitudinal analysis of the whole brain atrophy has the power of discriminating Alzheimer's disease and elderly normal controls. In this work, effect of involving intermediate atrophy rates and impact of using uncorrelated principal components of these features instead of original ones on discriminating normal controls and Alzheimer's disease subjects, is inspected. In fact, linear discriminative analysis of atrophy rates is used to classify subjects into Alzheimer's disease and controls. Leave-one-out cross-validation has been adopted to evaluate the generalization rate of the classifier along with its memorization. Results show that incorporating uncorrelated version of intermediate features leads to the same memorization performance as the original ones but higher generalization rate. As a conclusion, it is revealed that in a longitudinal study, using intermediate MRI scans and transferring them to an uncorrelated feature space can improve diagnostic accuracy

Analysis of metallothionein and vimentin immunoreactivity in pharyngeal squamous cell carcinoma and its microenvironment

Metallothionein (MT) has been shown to have pro-proliferative anti-apoptotic activity and to be involved in microenvironment remodeling. The aim of this study has been to determine whether the changes in MT and vimentin immunoreactivity observed in cancer and its microenvironment are related to the local spread of the disease. The immunoreactivity levels of both MT and vimentin were evaluated together with CD56 and CD57 antigens in 49 tissue samples taken from patients with squamous cell carcinoma originating from the palatine tonsils and in 20 tissue samples derived from patients with chronic tonsillitis (the reference group). MT immunoreactivity levels were statistically significantly higher in the tissue samples from squamous cell carcinoma than in those of the reference group and also higher in the squamous cell carcinoma samples compared with the stromal samples. Moreover, stromal fibroblasts exhibited high vimentin and MT immunoreactivity levels. Statistically significantly higher MT immunoreactivity levels within the tumor cells were identified in patients with the presence of lymph node metastases in contrast to those patients without such metastases. Vimentin was detected in both the tumor and the stromal tissue samples and presented an interesting pattern of staining strongly expressed within the stroma and the septal architecture of the tumor. The number of CD56- and CD57-positive lymphocytes identified in tissue samples both from squamous cell carcinoma and from the stroma was statistically significantly lower than that in the reference group. MT expression by tumor cells is thus associated with an aggressive phenotype of the tumor and the ability to create metastases