Úvod: Radioimunoterapie patří mezi rychle se rozvíjející klinické metody. Často je nejvhodnější možností terapie u pacientů s relabujícím lymfomem, případně u starších pacientů. Vývoj nových typů imunokonjugátů patří proto v posledních letech mezi klíčová témata ve vývoji radiofarmak. Metody: Imunoglobulin G M75 byl značen metodou elektrofilní jodace radionuklidem 125I, který je optimální pro vývoj metody značení a také pro stanovení vlastností značeného preparátu (vazebná aktivita, imunospecifita). Výhody 125I jsou zejména jeho dlouhý poločas (59,408 dne) a nízká radiační zátěž. Zachování vazby aktivního místa na antigen bylo testováno metodou ELISA, koncentrace byla stanovena modifikovanou metodou podle Bradfordové. Fyziologická distribuce byla testována na myších CD1-Foxn1nu. Výsledky: Stanovená kumulace značené protilátky v nádorové tkáni byla > 7 % podané radioaktivity, vazebná aktivita protilátky byla první den po značení vyšší než 90 % ve srovnání s vazebnou aktivitou neznačené protilátky. Závěr: Připravený radioimunokonjugát IgG M75 s 125I si zachovává dostatečnou schopnost vazby antigenu, a má proto potenciál v terapii tumorů exprimujících karbonátdehydratasu. Pro použití v radioterapii je třeba otestovat analogický radioimunokonjugát značený radionuklidem 131I., x, Lenka Marešová, Ondřej Lebeda, Daniel Seifert, Irena Sieglová, Vlastimil Král, and Literatura
The cell culture became an invaluable tool for studying cell behaviour, development, function, gene expression, toxicity of compounds and efficacy of novel drugs. Although most results were obtained from cell cultivation in two-dimensional (2D) systems, in which cells are grown in a monolayer, three-dimensional (3D) cultures are more promising as they correspond closely to the native arrangement of cells in living tissues. In our study, we focused on three types of 3D in vitro systems used for cultivation of one cell type. Cell morphology, their spatial distribution inside of resulting multicellular structures and changes in time were analysed with histological examination of samples harvested at different time periods. In multilayered cultures of WRL 68 hepatocytes grown on semipermeable membranes and non-passaged neurospheres generated by proliferation of neural progenitor cells, the cells were tightly apposed, showed features of cell differentiation but also cell death that was observable in short-term cultures. Biogenic scaffolds composed of extracellular matrix of the murine tibial anterior muscle were colonized with C2C12 myoblasts in vitro. The recellularized scaffolds did not reach high cell densities comparable with the former systems but supported well cell anchorage and migration without any signs of cell regression. and H. Hrebíková, D. Čížková, J. Chvátalová, R. Pisal, R. Adamčik, P. Beznoska, D. Díaz-Garcia, J. Mokrý
Seminal vesicle secretion is important for increasing the stability of sperm chromatin, inhibition of the immune activity in the female reproductive tract and so on. Metronidazole (MTZ), a drug used for treatment of infections caused by anaerobic bacteria and protozoa, may have negative effects on the genital gland including the seminal vesicles. Curcumin exhibits antioxidant as well as anti-inflammatory properties. The present study aims to evaluate the negative effects of MTZ on the seminal vesicle structure and ameliorative effects of curcumin using stereological methods. Thirty balb/c mice were divided into six groups. The control group was received distilled water. The second and the third received higher doses of MTZ (500 mg/kg body weight/day) and MTZ (500 mg/kg/day) + 100 mg/kg/day curcumin, respectively. The fourth and the fifth were treated with lower doses of MTZ (165 mg/kg body weight/day) and MTZ (165 mg/kg body weight/day) + curcumin (100 mg/kg body weight/day), respectively. The sixth group received 100 mg/kg body weight/day curcumin. All the administrations were done by oral gavages for 14 days. After 30 days, seminal vesicles were removed. Stereological study of the seminal vesicle structure revealed a significant reduction in gland and vesicular fluid volume in MTZ-treated (higher or lower doses) animals. Curcumin protected the reduction of both parameters in therapeutic-dose treated animals. Metronidazole treatment does not induce structural changes in the seminal gland; however, it can have a significant impact on its secretion ability. Importantly, these deteriorations might be preventable by curcumin co-treatment., Ali Noorafshan, Saied Karbalay‑Doust, and Literatura 30
Melatonin is a hormone with strong antioxidant properties. In this experiment, Freund's complete adjuvant was used as a stressogenic substance given to laboratory outbred mice, whereas melatonin was investigated as a protectant against the stressogenic effect. Levels of low molecular weight antioxidants, thiobarbituric acid reactive substances, and tumor necrosis factor α and activity of glutathione reductase were determined in blood from the animals. Surprisingly, melatonin was not involved in direct regulation of antioxidants, thiobarbituric acid reactive substances and tumor necrosis factor α. On the other hand, melatonin regulated glutathione reductase activity. We can conclude on regulation of metabolism caused by melatonin in the model. The effect was more important than the expected regulation of immunity and basal oxidative homeostasis. and M. Pohanka, B. Ruttkay-Nedecký, J. Fusek, V. Adam, R. Kizek
Pohybová inaktivita je průkazně spojena s manifestací chronických, kvalitu a prognózu života člověka významně negativně modifikujících onemocnění. Benefity pohybové aktivity zprostředkovává jistě mnoho více či méně provázaných patofyziologických mechanizmů, které dosud nebyly ve své složitosti zcela prozkoumány. Koncem 20. století se podařilo prokázat, že pracující příčně pruhovaný sval skutečně reguluje metabolickou a fyziologickou odezvu v ostatních orgánech. Jedná o několik stovek substancí, které mají autokrinní, parakrinní a endokrinní účinek. Tyto proteiny a peptidy, jsou-li vylučovány do krevního oběhu, ovlivňují významným způsobem metabolizmus vzdálených orgánů. Byly klasifikovány jako „myokiny“ (cytokiny produkované myocyty). Mezi identifikované myokiny lze zařadit např.: interleukiny – IL4, IL6, IL7, IL15, myostatin, LIF (leucemia inhibitory factor), BDNF (brain-derived neurotropic factor), IGF1 (insulin-like growth factor), FGF2 (fibroblastový růstový faktor 2), FGF21, FSTL1 (folistatin-related protein 1), irisin, EPO (erytropoetin) a BAIBA (β-aminoisobutyric acid). Myokiny mají v lidském organizmu v prvé řadě imunoregulační roli. Další významnou úlohou myokinů je, shodou okolností rovněž v interakci s tukovou tkání, regulace energetické homeostázy. Ovlivňují také růst svalových vláken a jejich regeneraci, stimulují angiogenezi, uplatňují se v regulaci metabolizmu glukózy a mají prokázaný efekt na lipidy. S ohledem na svoji rozmanitou funkci představují myokiny do budoucna terapeutický cíl v léčbě poruch svalového růstu regenerace a také obezity. Další recentní výzkum směřuje k odhalení tzv. myokinové rezistence jako rezultátu dlouhodobé svalové inaktivity a její asociaci s chronickým subklinickým zánětem., Physical inactivity is demonstrably related to the manifestation of chronic diseases which significantly modify the quality and prognosis of life in a negative way. The benefits of exercise are surely mediated by many pathophysiological mechanisms interrelated in varying degrees, which have not yet been fully examined in their complexity. In the late 20th century it was positively proven that a working striated muscle really regulates the metabolic and physiological response in the other organs. These involve several hundred substances with autocrine, paracrine and endocrine effects. These proteins and peptides, if released into the blood stream, substantially affect the metabolism of distant organs. They were classified as “myokines“ (cytokines produced by myocytes). The identified myokines include e.g. IL4, IL6, IL7, IL15, myostatin, LIF (leukemia inhibitory factor), BDNF (brain-derived neurotrophic factor), IGF1 (insulin-like growth factor), FGF2 (fibroblast growth factor 2), FGF21, FSTL1 (follistatin-related protein 1), irisin, EPO (erythropoetin) and BAIBA (β-aminoisobutyric acid). Myokines have first of all an immunoregulatory role in the human body. Another important effect of myokines is, coincidentally also in the interaction with adipose tissue, the regulation of energy homeostasis. They also affect the growth of muscle fibres and their regeneration, stimulate angiogenesis, they are involved in the regulation of glucose metabolism and have a proven effect on lipids. Considering their diverse function, myokines present a prospective therapeutic goal in the treatment of disorders of muscle growth and regeneration as well as obesity. Another recent research moves toward uncovering of the “myokine resistance” as a result of long-term muscle inactivity and its association with chronic subclinical inflammation., and Zuzana Stránská, Štěpán Svačina
Our study aimed to investigate subacute exposure to alcohol in relation to bone microstructure of mice. Animals from experimental (E) group drank a solution composed of 15 % ethanol and water for 14 days (one remodeling cycle), while those from control (C) group drank only water. In the compact bone of E group, decreased bone formation and increased porosity were observed which corresponds with lower levels of serum alkaline phosphatase and glutathione. Alcohol significantly increased sizes of primary osteon's vascular canals and decreased those of secondary osteons, Haversian canals. Relative bone volume, bone mineral density (BMD), relative bone volume without marrow cavity were also lower in E group. On the contrary, trabecular bone microstructure did not differ significantly between E and C groups. Liver function test showed higher levels of alanine aminotransferase, aspartate aminotransferase in alcohol-fed mice. Serum calcium, phosphate were significantly lower in E group. According to our study, only changes in compact bone microstructure of mice following one remodeling cycle were observed due to both direct and indirect effects of alcohol., A. Sarocka, V. Kovacova, R. Omelka, M. Bauerova, E. Kapusta, Z. Goc, G. Formicki, M. Martiniakova., and Obsahuje bibliografii
The reactivating and therapeutic efficacy of two combinations of oximes (HI‑6 + trimedoxime and HI‑6 + K203) was compared with the effectiveness of antidotal treatment involving single oxime (HI‑6, trimedoxime, K203) using in vivo methods. In vivo determined percentage of reactivation of cyclosarin‑inhibited blood and tissue acetylcholinesterase in poisoned rats showed that the reactivating efficacy of both combinations of oximes is slightly higher than the reactivating efficacy of the most effective individual oxime in blood, diaphragm as well as in brain. Moreover, both combinations of oximes were found to be slightly more efficacious in the reduction of acute lethal toxic effects in cyclosarin‑poisoned mice than the antidotal treatment involving single oxime. Based on the obtained data, we can conclude that the antidotal treatment involving chosen combinations of oximes brings a beneficial effect for its ability to counteract the acute poisoning with cyclosarin., Jiří Kassa, Jana Zdarová Karasová, Růžena Pavlíková, Filip Caisberger, Jiří Bajgar, and Literatura 36
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