Současné studie naznačují možnou důležitou úlohu melatoninu v Huntingtonově nemoci (HN) a jeho možné terapeutické využití při léčbě této nemoci. HN je dědičné neurodegenerativní onemocnění, které doprovází snižování hladiny melatoninu s postupem onemocnění. U normálních (nenádorových) buněk působí melatonin antiapoptoticky díky svým antioxidačním vlastnostem a schopnosti zabránit aktivaci proteinu p53. Dále melatonin zvyšuje expresi BDNF (brain derived neurotrophic factor) a dalších neuroprotektivních faktorů. Cílem této studie bylo stanovit netoxickou dávku melatoninu pro primární kožní fibroblasty izolované z transgenních miniprasat pro N‑koncovou část lidského mutovaného huntingtinu (TgHD) a popsat efekt tohoto ošetření na tyto buňky vystavené genotoxickému stresu. Buňky byly kultivovány v médiu obohaceném různými dávkami melatoninu. Analýzou proliferačních křivek získaných mikroskopováním živých buněk v pravidelných časových intervalech jsme stanovili efekt různých koncentrací melatoninu.Ukázali jsme, že vyšší dávky melatoninu jsou pro primární prasečí buňky toxické. Je zajímavé, že TgHD buňky byly oproti kontrolním buňkám více citlivé k tímto dávkám melatoninu. Stanovili jsme efektivní dávku melatoninu a současně jsme ukázali její efekt na proliferaci u buněk vystavených genotoxickému stresu. Klíčová slova: Huntingtonova choroba – melatonin – mikroskopie buněk v čase – miniprasečí model –proliferační křivky – kožní fibroblasty Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů., According to the recent studies, melatonin might play an important role in Huntington’s disease (HD) and act as a novel therapeutic approach in the treatment of the disease. HD, the inherited neurodegenerative disorder, is accompanied by gradual melatonin reduction as it progresses. Melatonin in normal cells (non‑tumor) has the anti‑apoptotic ability due to its antioxidant property and its ability to prevent the activation of p53. Furthermore, melatonin increases the expression of BDNF (brain derived neurotrophic factor) and other neuroprotective factors. The aim of this study was to evaluate the nontoxic dose of melatonin for primary skin fibroblasts isolated from minipigs transgenic for the N‑terminal part of human mutated huntingtin (TgHD), and the effect of melatonin treatment to these cells exposed to genotoxic stress. Cells were cultured in medium supplemented with different doses of melatonin. Using time lapse microscopy, we estimated the effect of decreasing melatonin concentrations by analyzing the proliferation curves. We show that higher doses of melatonin are toxic for primary porcine fibroblasts. Interestingly, TgHD cells were more sensitive to these doses of melatonin treatment than wild type cells. We evaluated the effective dose of melatonin and demonstrated its rescue proliferative effect on porcine primary cells exposed to genotoxic stress., and P. Rausova, J. Valasek, Z. Ellederová, J. Motlik
Introduction: We studied influence of mud-bath on bone status in male Wistar rats with subchronic arthritis. Methods: Arthritis was induced by 2 subplantar injections of Freund’s adjuvans with heat-killed Streptoccocus pyogenes into paw. Groups: intact (int) on chippings; (con) arthritis on chippings; (san38) arthritis on hot sand; (mu38) arthritis on hot mud; (mu21) arthritis on mild mud. Bone mineral density (BMD, g/cm2) was measured by dual energy X-ray absorptiometry and femurs were tested biomechanically. Bone markers osteocalcin (OC), PINP and CTX were analysed in bone. Results: BMD of right femur decreased vs. left in san38 (p = 0.030) and mu38 (p = 0.047). Fracture load of right/left femur (N) decreased in experimental groups, significantly in san38 (p = 0.05). Fracture threshold of neck decreased in right vs. left in experimental groups, but significantly in san38 (p = 0.05). OC decreased in mu38 vs. con (1.84 ± 0.14/2.62 ± 0.23). PINP decreased in int vs. san38 (p = 0.005) and mu21 (p < 0.001). CTX decreased in int vs. mu38 (p = 0.006) and mu21 (p = 0.005). Conclusion: The hot bath appears indifferent in relation to osteoporosis, while cold mud-bath shows good effect on bone metabolism. The cold mud-baths help to reduce arthritic inflammation and pain and thereby lead to higher mobility with positive consequence on bone., Helena Živná, Ljiljana Maric, Iveta Gradošová, Klára Švejkovská, Soňa Hubená, Pavel Živný, and Literatura 19
AIM: The ability of two newly developed oximes (K727, K733) to reduce tabun-induced acute neurotoxic signs and symptoms was evaluated and compared with currently available trimedoxime in rats. METHODS: The neuroprotective effects of the oximes studied combined with atropine on Wistar rats poisoned with tabun at a lethal dose (380 µg/kg i.m.; 90% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery consisting of 38 measurements of sensory, motor and autonomic nervous functions at 2 hours following tabun challenge. RESULTS: All tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K727, K733) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of lethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. CONCLUSION: The ability of both novel bispyridinium oximes to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes such as trimedoxime in the treatment of acute tabun poisonings. and J. Kassa, J. Hatlapatková, J. Žďárová Karasová
Competencies develop and changes throughout a persons life, they can gain or lose, going through various age stages. Their development does not end in youth, but continue on through the adult life. The ability to thing and reflect those thoughts specifically come forward in the center of structure of competency, which grows at the same time as the individual matures. One of the competency types is health competency. Health competency is a relatively new concept; it is not sufficiently researched. Aim of the study was to determine the factors of an adult individual health competency. 827 respondents participated in the study, in the processing of data was used SPSS. Was used factor analysis, analysis of variance with ANOVA and KruskalWallis test and Pearsons correlation. It was found that health competency is affected by several factors. These are: health education, health behavior, and the value of the environment. Each of the sets was distributed to key factors. It is the main factors affecting the health competence, but additional factors are: gender, education and income., Inara Upmale, Andrejs Geske, and Literatura
Large animal models to explore the safety and tolerability of novel therapeutic approaches for Huntington’s disease (HD) are in exploration to achieve higher translational reliability in future studies. Recently, a Libechov minipig has been established as one new transgenic (Tg) large animal model for HD. We here discuss the advantages and limitations in using this model in HD with regards to breeding, housing, handling, and with respect to homology to humans and ethical considerations. A group of TgHD and wild type (WT) female minipigs (n = 36) was used to gain first evidence about abovementioned aspects. It is concluded that Libechov minipigs may fulfill an important role to bridge the gap between rodents and non‑human primates in the translation to humans. and S. Schramke, R. Schubert, F. Frank, M. Wirsig, M. Fels, N. Kemper, V. Schuldenzucker, R. Reilmann
Charcot foot neuropathic osteoarthropathy is a disorder affecting the soft tissues, joints, and bones of the foot and ankle. The disease is triggered in a susceptible individual through a process of uncontrolled inflammation leading to osteolysis, progressive fractures and articular malpositioning due to joint subluxations and dislocations. The progression of the chronic deformity with a collapsed plantar arch leads to plantar ulcerations because of increased pressure on the plantar osseous prominences and decreased plantar sensation. Subsequent deep soft tissue infection and osteomyelitis may result in amputation. The Charcot foot in diabetes represents an important diagnostic and therapeutic challenge in clinical practice. Conservative treatment remains the standard of the care for most patients with neuropathic disorder. Offloading the foot and immobilization based on individual merit are essential and are the most important recommendations in the active acute stage of the Charcot foot. Surgical realignment with stabilization is recommended in severe progressive neuropathic deformities consisting of a collapsed plantar arch with a rocker-bottom foot deformity. and P. Sponer, T. Kucera, J. Brtková, J. Srot
Regulatory T cells (Treg) are a specialized subpopulation of T cells that act to suppress inadequate immune response. Psoriasis is recognized as a T -cell driven immune-mediated systemic inflammatory disease with skin manifestation. Effective therapeutical approach to treat psoriasis is Goeckerman therapy (GT ). The aim of this study was to compare the number of Treg in the peripheral blood of 27 psoriatic patients and 19 controls and to evaluate the influence of GT on Treg population in peripheral blood of patients with psoriasis. There was no significant difference in the relative number of Treg cells in the peripheral blood of healthy blood donors and patients with psoriasis before initiation of GT (P = 0.2668). In contrary, the relative number of Treg cells in peripheral blood of patients with psoriasis after GT was significantly higher than those found in healthy blood donors (P = 0.0019). Moreover, the relative number of Treg is significantly increased in psoriatic patients after Goeckerman therapy compared to the pre-treatment level (P = 0.0042). In conclusion, this significant increase in Treg count after GT is probably associated with amelioration of inflammation by GT , as disease activity expressed as PASI decreased in our patients by GT (P = 0.0001)., Kateřina Kondělková, Doris Vokurková, Jan Krejsek, Lenka Borská, Zdeněk Fiala, Květa Hamáková, Ctirad Andrýs, and Literatura 39
The aim of this study was to determine the prevalence of musculoskeletal problems among Czech dentists and to analyze the factors that affect these disorders. Information was gathered through questionnaire completed by 581 physicians. The questionnaire ascertained general information about physicians including their work habits and the characteristics of their work environment along with the occurrence of musculoskeletal problems as well as their intensity. In the past year the occurrence of at least mild difficulties associated with the locomotive system was reported by 96.9% of dentists surveyed (n = 557), with 66.3% of respondents (n = 381) reporting difficulties ofa moderate or major nature. Most respondents of both sexes indicated neck pain. A statistically significant correlation with the occurrence of musculoskeletal complaints of medium and major intensity was demonstrated for the following factors: sex, age, running a private practice, past injury or musculoskeletal diseases, and the perception of work as psychologically demanding. Musculoskeletal disorders in dentists in Czech Republic are relatively frequent and serious health problem. The causes of these diseases must be identified and appropriate preventive interventions undertaken that will contribute to a reduction in the incidence of these problems. and Z. Sustová, L. Hodacová, M. Kapitán
Cíl práce: Lipoperoxidace je dávána do příčinné souvislosti s rozvojem nejdůležitějších rizikových faktorů kardiovaskulárních onemocnění. Lipoperoxidační procesy jsou důsledkem reakcí lipidů s volnými radikály bez ohledu na jejich původ. Vztah mezi triacylglyceroly (TAG) a volnými radikály (VR) není zcela jasný. Může se dokonce stát, že hypertriacylglycerolémie je doprovázena nízkými koncentracemi VR a naopak. Jedno z možných vysvětlení spočívá ve vztahu lipoperoxidace a složení mastných kyselin v molekulách TAG. Cílem této studie bylo analyzovat vztah složení mastných kyselin v TAG a produkci VR u pacientů trpících diabetes mellitus 2. typu. Typ studie: observační s kontrolní skupinou Materiál a metody: Studie zahrnovala 18 normotriacylglycerolemických (NTG) jedinců (M/F 12/6) a 24 hypertriacylglycerolemických (HTG) jedinců (M/F 16/8). Pacienti v obou skupinách byli diabetici 2. typu. Analýzu mastných kyselin v triacylglycerolech plazmy jsme provedli kapilární plynovou chromatografií a koncentrace volných radikálů byly změřeny přímou spektrofotometrií. Statistické analýzy (parametrické i neparametrické) byly provedeny pomocí statistického software STATISTICA pro Windows. Výsledky: Ve skupině HTG jsme pozorovali nižší zastoupení kyseliny myristové (14:0) (1.62 [1.23-2.07] vs. 1.90 [1.72-2.79], p = 0.022, [medián (1.-3. kvartil]) a vyšší poměr alfa-linolenové kyseliny (18:3n-3) (1.51 [1.21-1.86] vs 1.16 [1.02-1.42], p = 0.021). Poměr kyselin arachidonové/eikosapentaenové byl ve skupině HTG nižší (5.54 [3.62-7.98] vs 7.25 [5.98-15.12], p = 0.027). Když jsme HTG skupinu dále rozdělili podle koncentrací VR na tercily, prokázali jsme nižší hodnoty poměru kyseliny arachidonová/eikosapentaenová ve druhém tercilu (4.05 [2.66-4.67] vs 7.64 [5.83-11.00], 1. tercil, a 6.21 [3.20-8.31], 3. tercil p = 0.019). V spojených HTG+NTG skupinách jsme zaznamenali negativní korelaci mezi MA a TAG (r = -0.3153, p = 0.045). V triaclylglycerolech jsme prokázali pozitivní korelace VR a kyseliny stearové (p < 0.001) spolu s negativní korelací některých n-6 vícenenasycených mastných kyselin (18:3n-6, p < 0.05, 22:5n-6, p < 0.01). Závěr: Zastoupení mastných kyselin v molekulách TAG je spojeno s tvorbou VR. Nicméně do tohoto vztahu vstupují i jiné faktory., Objective: The lipoperoxidation plays a causal role in the development of most important risk factors of cardiovascular disease. The lipoperoxidation results from the reaction of lipid molecules with free radicals, regardless of their origin. The relationship between triacylglycerols (TAG) and the free radicals (FR) amount is not clear. Thus, it can turn up that the hypertriacylglyceridaemia is accompanied with the low values of FR, or vice versa. One possible explanation of this phenomenon is that the degree of lipoperoxidation of TAG is dependent on the composition of fatty acids (FA) in their molecule. Therefore, the aim of this study was to analyze FA composition in TAG and its relationship to FR production in type 2 diabetes mellitus. Design: observational study with internal control group Material and Methods: 18 normotriacylglycerolemic (NTG) individuals (12M/6F) and 24 hypertriacylglycerolemic (HTG) patients (16M/8F). Patients in both groups were persons, suffering from type 2 diabetes mellitus. Fatty acid analysis of plasma triacylglycerols was performed by gas chromatography and free radicals were determined by direct spectrophotometric method. Statistical analyses (both parametric and non-parametric) were performed with the statistical software STATISTICA for Windows. Results: We found lower content of myristic acid (14:0) (1.62 [1.23-2.07] vs. 1.90 [1.72-2.79], p = 0.022, [median (1st-3rd quartile)]) and higher content of alpha-linolenic acid (18:3n-3) (1.51 [1.21-1.86] vs. 1.16 [1.02-1.42], p = 0.021) in HTG group. The ratio of arachidonic/eicosapentaenoic acid was in HTG group lower (5.54 [3.62-7.98] vs. 7.25 [5.98-15.12], p = 0.027). When the HTG group was stratified into the tertiles by the FR concentrations, we observed lower values in the second tertile for ratios based on arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3) (4.05 [2.66-4.67] vs. 7.64 [5.83-11.00], 1st tertile, and 6.21 [3.20-8.31], 3rd tertile, p = 0.019). In pooled groups, we proved negative correlation between MA and TAG (r = -0.3153, p = 0.045) and the link between FR and FA composition of TAG expressed as positive relationship of FR with content of stearic acid (p < 0.001) and negative correlation with some n-6 polyunsaturated fatty acids (18:3n-6, p < 0.05, 22:5n-6, p < 0.01). Conclusion: The composition of FA in TAG molecules has undoubtedly some relationship to the FR generation. However, the other factors seem to play a role, since the relationship is not straightforward within entire FR range., and Vecka M., Tvrzická E., Votruba M.
The management of chronic diseases shall be considered a priority in the work of the global international institutions, which are related to health policies. In the search for effective and efficient solutions for the treatment of chronic diseases, scientists are developing different programs. In Bulgaria the continuous monitoring of chronically ill people is defined with the term dispensarization. The objective of the research is to analyze the place and the role of patients in the monitoring of their chronic diseases and how the concept of quality of life relates to this process. Method The research in focus groups is planned within a research project on the monitoring of chronic diseases. Five group discussions were held. The number of participants in all focus groups was sixty. Results The two discussed directions - the active role of the patient and the focus on the results are weak links in the current organization of the care for the chronically ill people. The topic of creating and adopting an Act of the patient was also presented, in which to be paid attention to the evaluation of the quality of life. In general was brought the need for a clear delineation of the roles and the competencies of everyone involved in the monitoring process of chronic diseases. The chronic disease cannot be defined only as a medical problem, as there are economic and social, including political consequences. Conclusions The management of the chronic disease requires coordination of doctor-patient interaction, a model of partnership and trust in the relations, self-management of the condition by the patients and their inclusion in the health team. The most important step to achieve this goal is the education of the patients, increasing their knowledge and motivation, psycho-emotional support, instilling hope and faith in the capacity of the patients., Teodora Dimcheva, Gergana Foreva, Radost Аsenova, Nonka Маteva, Todor Stoev, Rosica Dimova, and Literatura