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
Few studies concerning the importance of wheat allergy affecting the course of atopic eczema in adolescents and adult patients exist. Aim: The evaluation if wheat allergy can deteriorate the course of atopic eczema. Follow-up of patients with confirmed food allergy to wheat. Method: Altogether 179 persons suffering from atopic eczema were included in the study: 51 men and 128 women entered the study with an average age of 26.2 (s.d. 9.5 years) Dermatological and allergological examinations were performed, including skin prick tests, atopy patch tests, and specific serum IgE for wheat, open exposure test and double-blind, placebo-controlled food challenge test with wheat flour. Results: Wheat allergy affecting the coures of atopic eczema was confirmed in eight patients (4.5%) out of 179 patients enrolled in this study by double-blind, placebo controlled food challenge test. The course of atopic eczema showed a positive trend in patients with confirmed food allergy at 3, 6, 9, 12 month follow-up (statistical evaluation with paired t-test) after the elimination of wheat flour. Conclusion: Wheat allergy may play an important role in the worsening of atopic eczema (acting as a triggering exacerbating factor) only in a minority of adolescents and adult patients (4.5% in our study). The diagnostic methods (skin prick test, specific IgE, atopy patch test, history) cannot be used as separated tests for the determination of food allergy to wheat in patients with atopic eczema.Open exposure tests and double-blind, placebo-controlled food challenge should be used for the confirmation of wheat allergy affecting the course of atopic eczema., Jarmila Čelakovská, Květuše Ettlerová, Karel Ettler, Jaroslava Vaněčková, Josef Bukač, and Literatura 34
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
The oribatid mite Galumna elimata was reared under laboratory conditions on algae (Protacoccus spp.) at different temperatures (5, 15 and 20°C). Higher weight-specific amylolytic activity was found in the whole body homogenates of mites exposed to cold acclimation (5°C, 21 days) in comparison with individuals acclimated to 15 and 20°C. Accompanying parameters (live body weight, content of total soluble proteins in the body, protein-specific amylolytic activity, presence and composition of food boluses, activity of mesenteric and caecal wall cells, gregarinid parasitisation, number of glycogen granulae and guanine deposits in mesenchymal tissue, presence of proventricular glands) were investigated at all three acclimation temperatures to explain mechanisms of this change. The acclimation response of weight-specific amylolytic activity was accompanied by elevation of protein-specific amy lolytic activity. Microanatomical features did not confirm any increased secretion activity of mesenteric and caecal cells in cold acclimated animals. Granulation and apocrine secretion of these cells increased with increasing temperature as with food ingestion. The food boluses contained algae or algae mixed with unknown fungal hyphae in individuals acclimated to 15 and 20°C. The concentrated mucoid substances prevailed in animals exposed to cold, indicating lower feeding activity at 5°C. Based on these findigs, Lye hypothesised that specific amylolytic activity reflected passively the different changes in protein composition of the body at different temperatures and its elevation is without direct adaptive importance., Vladimír Šustr, Jan Hubert, and Lit
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
The male of Tetanoptera leucodactyla Verbèke, a genus and species of Sciomyzidae known until now only from one female specimen from the Congo, is described, and the genus is more fully characterized. The external morphology is illustrated and the male genitalia are described and figured for the first time. The relationships of Tetanoptera to genera of the Sepedon group and certain other genera of Tetanocerini are discussed. Tetanoptera appears to be related to Verbekaria, and intermediate in an evolutionary lineage between the relatively primitive Tetanocera and the advanced Thecomyia., Lloyd V. Knutson, Jean-Claude Vala, and Lit
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