Cíl studie: Cílem studie bylo zjištění vztahů mezi manifestací tinnitu, nálezem na sluchových evokovaných potenciálech a genetickým pozadím u receptoru pro gamaaminomáselnou kyselinu typu A (GABA(A) receptor), podporující desinhibiční hypotézu vzniku tinnitu. Soubor a metodika: Bylo vyšetřeno 131 pacientů z hlediska sluchové ztráty, provedena kvantifikace tinnitu, sluchové evokované potenciály střední latence (MLR) a kmenové sluchové evokované potenciály (BAEP) a dále stanovení genotypu (CA)n repetitivní sekvence pro beta‑3 podjednotku GABA(A) receptoru. Následně byly hledány vztahy mezi jednotlivými výsledky a manifestací tinnitu. Výsledky: Byla nalezena korelace tinnitus skóre s amplitudovým poměrem vln V/III v BAEP (R = 0,22, p < 0,001) a s průměrným sluchovým prahem (R = 0,22, p = 0,17). Rovněž byla nalezena korelace tinnitus skóre s amplitudou vlny PA v MLR (R = 0,31–0,37; p < 0,001). Výsledky MLR neukázaly žádný vztah k průměrnému sluchovému prahu. U skupiny s kratší anamnézou tinnitu (méně než devět měsíců) byl prokázán rozdíl v manifestaci tinnitu na genotypu pro (CA)n repetitivní sekvenci genu pro beta‑3 podjednotku GABA(A) receptoru (p = 0,002). Tento výsledek byl rovněž konzistentní s rozložením amplitudy vlny PA v dané subpopulaci. Závěr: Tyto výsledky svědčí o existenci dvou hlavních regulačních mechanizmů vzniku tinnitu: první, který je závislý na velikosti sluchové ztráty, je na úrovni mozkového kmene, zatímco druhý je na úrovni korové s možnou souvislostí s genotypem (CA)n repetitivní sekvence pro beta‑3 podjednotku GABA(A) receptoru., Study aim:Study objective was to explore associations between manifestation of tinnitus, auditory evoked potentials and genetic background of gamma‑aminobutyric acid type A (GABA(A) receptors) to support the disinhibited feedback hypothesis of tinnitus generation. Materials and methods: A population of 131 patients was assessed for severity of hearing loss, quantification of tinnitus, mid‑latency responses (MLR) and brainstem auditory evoked potentials (BAEP), and (CA)n tandem repeat polymorphism in GABA(A) Beta‑3 subunit gene to establish any correlation with manifestation of tinnitus. Results: It was observed that tinnitus score correlates with V/III amplitude ratio in BAEP (R = 0.22, p < 0.001) and with mean pure tone audiometry (PTA) threshold (R = 0.22, p = 0.017). Analysis of the MLR results showed a significant correlation between the PA wave amplitude and the tinnitus score (R = 0.31–0.37; p < 0.001). MLR result analysis showed no statistically significant correlation between the wave amplitudes and the mean auditory threshold. An analysis of a subgroup with shorter clinical history (less than nine months) revealed a statistically significant difference in the tinnitus score in relation to the genotype of (CA)n tandem repeat of the GABRß3 receptor subunit gene (p = 0.002). This result was also consistent with the distribution of the PA wave amplitude in the given subpopulation. Conclusion: Our findings indicate existence of two main regulatory mechanisms of tinnitus generation: first, the brainstem mechanism is dependent on the severity of the hearing loss; second, the cortical mechanism is likely to be dependent on the genotype of (CA)n tandem repeat in GABA(A) beta‑3 subunit gene., and J. Rottenberg, M. Zallmann, R. Kostrica, M. Jurajda, T. Talach
We aimed to investigate in detail the structural mutations after influence of actellic insecticide at different doses and different temperature conditions. We tested effects of single introduction of different doses of actellic: 48, 96, 192, and 384 mg/kg. Cytogenetic effect of actellic in bone marrow cells at different temperature regimens was studied. Following actellic administration, animals were being in two temperature regimes: normal (18-20°C) and high (37-38°C). After treatment with actellic, animals were kept within 1, 2, 4 and 8 hours at high temperature (37-38°C), i.e. in a thermostat (TV-80) with access of air. In experiments, the animals were divided into seven groups. The animals of the 1st group were administered actellic at a dose 384 mg/kg and kept under normal temperature until slaughtering. The animals of the 2nd group after administration of actellic were immediately placed in an environment with a temperature of 37-38°C. Animals of the 3rd, 4th, 5th, and 6th groups after treatment with actellic were transferred to conditions with high temperature, respectively, for 1, 2, 4 and 8 hours. The 7th group of mice was under normal temperature conditions without treatment with actellic. Our results have shown that in normal temperature conditions single exposure of actellic (384 mg/kg) did not affect the genetic apparatus of somatic cell, evidenced by the frequency of chromosome aberrations in bone marrow cells that were within the control levels. However, at high temperatures (37-38°C) the pesticide caused 6-fold larger number of chromosome aberrations in bone marrow cells, in comparison with normal conditions., Anvarjon Rakhmankulovich Shermuratov, and Literatura
Introduction: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. Aim: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. Methods: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. Results: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). Conclusion: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated. and M. Tošovský, P. Bradna, C. Andrýs, K. Andrýsová, E. Čermáková, T. Soukup