Úvod: Posouzení významu PET/CT pro iniciální staging karcinomu jícnu s důrazem na metastatické postižení uzlin a průkaz vzdálených metastáz. Dále bylo cílem práce ověření významu PET/CT vyšetření při hodnocení efektu neoadjuvantní léčby. Metody: V prospektivní studii byl sledován soubor 354 nemocných s karcinomem jícnu, kteří byli vyšetřeni na I. chirurgické klinice LF UP a FN Olomouc v letech 2006–2012. Vstupní PET/CT vyšetření bylo provedeno u 349 nemocných. Analyzovali jsme přínos vyšetření ke stanovení stagingu onemocnění a v závislosti na něm jsme stanovovali strategii léčby. Na základě vstupního PET/CT byl u 102 nemocných zjištěn různý stupeň generalizace a byli indikovaní k paliativní či symptomatické terapii. U 247 pacientů bylo zjištěno omezení nádoru na jícen ev. regionální uzliny. Po posouzení celkového stavu a dle přání pacienta byla dále u 188 nemocných indikovaná neoadjuvantní radiochemoterapie (RCHT), léčbu nedokončilo 32 nemocných. U 156 pak bylo v průměrném odstupu 8,4 týdnů od ukončené neoadjuvantní terapie provedeno kontrolní vyšetření PET/CT. Na základě tohoto vyšetření bylo kompletní vymizení známek nádoru (complete response- CR) zjištěno u 38 vyšetřených (24,4 %), regrese u 89 (57,0 %), stacionární nález u 10 (6,4 %) a progrese u 19 (12,2 %). K chirurgické léčbě bylo indikováno 97 pacientů, z toho resekci jícnu bylo možné provést u 85 a u 12 byl výkon pouze paliativní resp. šlo o exploraci. Výsledky: Vstupní PET/CT vyšetření u 349 pacientů u naprosté většiny správně posoudilo rozsah onemocnění v souhlase s histologicky ověřenou diagnózou. Falešně negativní výsledek byl jen u 5 nemocných (1,43 %). Při hodnocení efektu neoadjuvantní léčby byli pacienti rozděleni do skupin dle nálezu při kontrolním PET/CT po neoadjuvanci a bylo vyhodnocováno jejich přežívání. Byl zjištěn signifikantní rozdíl (p=0,0004) v přežívání mezi skupinami s rozdílnou reakcí na neadjuvantní léčbu (CR (n=38), regrese (n=89), stacionární nález (n=10), progrese (n=19)) bez ohledu na další léčbu po neoadjuvanci, ve prospěch pacientů s lepší reakcí na neadjuvantní léčbu. Signifikantní rozdíl v přežívání byl zaznamenán i mezi skupinou pacientů po neoadjuvanci radikálně operovaných (n=85) a neoperovaných (n=59) ve prospěch operovaných (p=0,003). Nejdelšího průměrného přežívání 38,6 měsíců (medián 29,0 měsíců) bylo dosaženo ve skupině operovaných po neoadjuvanci, kde kontrolní PET/CT ukázalo CR. Nebyl však prokázán signifikantní rozdíl (p=0,587) ve výsledcích mezi skupinami operovaných s rozdílnou reakcí na neadjuvantní léčbu (regrese, stacionární nález). Počet případů v jednotlivých hodnocených skupinách není zatím natolik velký, abychom získané výsledky mohli považovat za jednoznačně průkazné a ve sledování a zařazování dalších nemocných do studie budeme dále pokračovat. Závěr: V práci je dokumentován význam a přínos PET/CT v iniciálním stagingu karcinomu jícnu, zejména v průkazu metastatického onemocnění, a to jak v postižení uzlin, tak v odhalení vzdálených metastáz. PET/CT má velký význam pro stanovení léčebné strategie. Dále byl ověřen význam PET/CT vyšetření při hodnocení efektu neadjuvantní léčby., Introduction: To evaluate the significance of PET/CT for the initial staging of esophageal cancer with emphasis on metastatic lymph node affection and detection of distant metastases. Furthermore, the aim of the work was to analyze the significance of PET/CT examination when evaluating the effect of neoadjuvant therapy. Methods: A set of 354 patients with esophageal cancer treated at the 1st Department of Surgery, University Hospital Olomouc and Medical Faculty at Palacky University in Olomouc between the years 2006−2012 were analyzed in a prospective study. The initial PET/CT examination was performed in 349 patients. We analyzed the benefit of this examination in regard to disease staging and based on the result, therapeutic strategy was determined. The initial PET/CT showed varying degrees of disease generalization in 102 patients, these patients were indicated for palliative or symptomatic therapy. In 247 patients, the disease was limited only to the esophagus and /or regional lymph nodes. After considering the patient’s overall condition and taking into account the wishes of the patient, 188 patients were indicated for neoadjuvant chemoradiotherapy (CRT); 32 patients did not complete this treatment. In 156 patients a follow-up PET/CT scan was performed after an average of 8.4 weeks following completion of neoadjuvant therapy. Based on this examination, a complete response- CR, was observed in 38 patients (24.4%), regression of the tumor in 89 (57.0%), stationary findings were seen in 10 (6.4%), and progression in 19 (12.2%). Ninety-seven patients were indicated for surgical resection; however, esophagectomy was only possible in 85 patients, in the remaining 12 patients only an explorative laparotomy was performed due to disease progression. Results: The initial PET/CT examination performed in 349 patients correctly described the extent of the disease in accordance with the histologically confirmed diagnosis in virtually all patients. A false positive result was seen in only 5 patients (1.43%). When evaluating the effect of neoadjuvant therapy, the patients were divided into groups based on the findings of the follow-up PET/CT after neoadjuvant therapy and their overall survival was evaluated. A significant difference (p=0.0004) in survival was observed between the groups based on the different reactions to neoadjuvant therapy (CR (n=38), regression (n=89), stationary findings (n=10), progression (n=19)) without taking into account the following treatment the patient received after neoadjuvant therapy. Patients who had a better response to neoadjuvant therapy had better survival results. There was also a significant difference in survival between the group of patients who completed neoadjuvant therapy and underwent radical surgical resection (n=85) versus those patients who completed neoadjuvant therapy but did not undergo subsequent surgery (n=59). The operated group had a significantly higher overall survival (p=0.003). The longest mean survival, 38.6 months (median 29.0 months), was achieved by the group of patients who completed neoadjuvant therapy, showed a complete response on the follow-up PET/CT, and underwent surgical resection. However, a significant difference was not observed (p=0.587) between the groups who underwent surgical resection and whose follow-up PET/CT results differed (regression or stationary findings). To date, the number of cases in the individual groups is not great enough to consider the obtained results conclusive, and we will continue to include more patients into the study and continue with the analysis. Conclusion: The work documents the significance and benefit of PET/CT in the initial staging of esophageal cancer, especially in detecting metastatic disease- positive lymph nodes as well as distant metastases. PET/CT has great importance in determining therapeutic strategy. Furthermore, the significance of PET/CT in evaluating the effect of neoadjuvant therapy was also studied., and K. Vomáčková, Č. Neoral, R. Aujeský, R. Vrba, M. Stašek, M. Mysliveček, R. Formánek
INTRODUCTION: The male:female ratio at birth (male births divided by total live births - M/T) has been shown to increase in response to ionizing radiation due to gender-biased fetal loss, with excess female loss. M/T rose sharply in 1987 in central-eastern European countries following the Chernobyl accident in 1986. This study analyses M/T and births for the former Soviet Republics and for the countries most contaminated by the event. METHODS: Annual birth data was obtained from the World Health Organisation. The countries with the highest exposure levels (by 137Cs) were identified from an official publication of the International Atomic Energy Agency. All of the former Soviet states were also analysed and the periods before and after 1986 were compared. RESULTS: Except for the Baltic States, all regions in the former USSR showed a significant rise in M/T from 1986. There were significant rises in M/T in the three most exposed (Belarus, Ukraine and the Russian Federation). The birth deficit in the post-Soviet states for the ten years following Chernobyl was estimated at 2,072,666, of which 1,087,924 are accounted by Belarus and Ukraine alone. DISCUSSION: Chernobyl has resulted in the loss of millions of births, a process that has involved female even more than male fetuses. This is another and oft neglected consequence of widespread population radiation contamination. and V. Grech
AIMS: Authors studied potential side effects of fetal calf serum (FCS) in cultivation media on human dental pulp stem cells (DPSC) during long-term cultivation. METHODS: Two lines of DPSC obtained healthy donors (male 22 years, female 23 years) were used. Both lines were cultivated under standard cultivation conditions in four different media containing 10% or 2% FCS and substituted with growth factors. During long-term cultivation proliferation ability, karyotype and phenotype of DPSC were measured. RESULTS: Both lines of DPSC cultivated in a media containing 2% FCS and ITS supplement showed the highest number of population doublings. On the other hand the proliferation rate of DPSC cultivated in a media with 2% FCS without ITS supplement was slowest. Proliferation rate of DPSC cultivated in 10% FCS media with or without FGF-2 was comparable. DPSC cultivated in a media with 10% FCS showed a significantly higher amount of chromosomal aberrations. These chromosomal aberrations do not seem to be clonal but surprisingly we found large amounts of tetraploid cells in the 9th passage in both media containing 10% FCS. CONCLUSIONS: Our study proved that cultivation of DPSC in media containing higher concentration of FCS has critical side effects on cell chromosomal stability. and J. Suchánek, TS. Kleplová, M. Kapitán, T. Soukup
This study aimed to investigate alterations in hemorheology induced by L-carnosine, an anti- oxidant dipeptide, and to determine their relationship to oxidative stress in density-separated erythrocytes of aged and young rats. 28 male Sprague Dawley rats were divided into 4 groups as aged (Aca), young (Yca) L-carnosine groups (250 mg/kg L-carnosine, i.p.) and aged (As), young (Ys) control groups (saline, i.p.). Density separation was further performed to these groups in order to separate erythrocytes according to their age. Blood samples were used for the determination of erythrocyte deformability, aggregation; and oxidative stress parameters. Erythrocyte deformability of Yca group measured at 0.53 Pa was lower than Aca group. Similarly, deformability of least-dense (young) erythrocytes of Yca group was decreased compared to least-dense erythrocytes of Aca groups. Total antioxidant capacity (TAC) of Aca group was higher and oxidative stress index (OSI) lower than As group. Although L-carnosine resulted in an enhancement in TAC of aged rats, this favorable effect was not observed in erythrocyte deformability and aggregation in the dose applied in this study. and G. Erken, M. Bor-Kucukatay, E. KilicToprak, B. Akdag, V. Kucukatay
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