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
This study was aimed to evaluate the role of commensal Gram-negative bacterium Bacteroides ovatus in murine model of chronic intestinal inflammation. The attempt to induce chronic colitis was done in Bacteroides ovatus-monoassociated, germ-free and conventional mice either in immunocompetent (BALB/c) mice or in mice with severe combined immunodeficiency (SCID), using 2.5 % dextran-sodium sulfate (DSS) in drinking water (7 days DSS, 7 days water, 7 days DSS). Conventional mice developed chronic colitis. Some of germ-free BALB/c and the majority of germ-free SCID mice did not survive the long-term treatment with DSS due to massive bleeding into the intestinal lumen. However, monocolonization of germ-free mice of both strains with Bacteroides ovatus prior to long-term treatment with DSS protected mice from bleeding, development of intestinal inflammation and precocious death. We observed that though DSS-treated Bacteroides ovatus-colonized SCID mice showed minor morphological changes in colon tissue, jejunal brush-border enzyme activities such as γ-glutamyltranspeptidase, lactase and alkaline phosphatase were significantly reduced in comparison with DSS-untreated Bacteroides ovatus-colonized mice. This modulation of the enterocyte γ-glutamyltranspeptidase localized to the brush border membrane has been described for the first time. This enzyme is known to reflect an imbalance between pro-oxidant and anti-oxidant mechanisms, which could be involved in protective effects of colonization of germ-free mice with Bacteroides ovatus against DSS injury., T. Hudcovic ... [et al.]., and Obsahuje seznam literatury
We have previously shown that chronic renal failure in rats induces changes in motor activity and behavior. Similar work on the possible effects of acute renal failure (ARF) induced by cisplatin (CP) is lacking. This is the subject matter of the current work. CP was injected intraperitoneally (i.p.) at a single dose of 20 mg/kg to induce a state of ARF, and three days later, its effects on motor activity, thermal and chemical noci ceptive tests, neuromuscular coordination, pentobarbitone-sleeping time, exploration activity and tw o depression models were investigated. The platinum concentration in the kidneys and brains of mice was also measured. The occurrence of CP-induced ARF was ascertained by standard physiological, biochemical and histo-pathological methods. CP induced all the classical biochemical, physiological and histopathological signs of ARF. The average renal platinum concen tration of CP-treated mice was 5.16 ppm, but there was no measurable concentration of platinum in the whole brains. CP treatment significantly decreased motor and exploration activities, and increased immobility time in depression models, suggesting a possible depression-like state. There was also a significant decrease in neuromuscular coordination in CP-treated mice. CP, given at a nephrotoxic dose, induced several adverse motor and behavioral alterations in mice. Further behavioral tests and molecular and biochemical investigations in the brains of mice with CP-induced ARF are warranted., B. H. Ali ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
An interaction between N-methyl-D-aspartate (NMDA) and MK-801 was examined in mice using a modified elevated plus-maze paradigm that allows assessment of the adaptive form of spatial memory. NMDA administered (s.c.) immediately after the acquisition session protected the animals against the amnesia induced by MK-801 given shortly before the retention session. Behavioral performance, expressed as the transfer latency, and therefore spatial memory potency of NMDA plus MK-801 treated animals was comparable with that of both NMDA-treated animals and the controls., Z. Hliňák, I. Krejčí., and Obsahuje bibliografii
Raloxifen is a selective estrogen receptor modulator which prevents bone loss in ovariectomized female mice in a fashion similar to estrogens. Since testosterone-deficient male mice also lose bone mass, we were interested in testing the effects of raloxifen on bones in intact and castrated male mice. Bone density was significantly reduced in castrated animals (1.36±0.04 g/ml) as compared to intact animals (1.42±0.03 g/ml) (p<0.01). When castrated mice with extraordinarily low concentrations of testosterone and with reduced weight of seminal vesicles were treated with raloxifen, the changes in bone density and bone minerals resulting from castration (1.36±0.04 g/ml) were entirely prevented (1.40±0.01 g/ml). Cortical bone was lost in orchidectomized mice, and this decrease in cortical thickness of the femur was prevented by raloxifen administration. Raloxifen in a dose used in humans for treatment of osteoporosis decreased the weight of seminal vesicles, an organ which is highly sensitive to the androgenic effect, decreased the concentration of testosterone (12.5±2.8 μmol/l) (p<0.01) but not to the same level as in the case of castrated animals (0.6±0.3 μmol/l), and did not have any effect on bone density or mineral content in intact mice. The results of the present study may thus be interpreted as supporting the hypothesis that raloxifen is an effective agent against the deleterious effects of castration-induced osteopenia in male mice and also support the hypothesis that estrogens may have physiological skeletal effects in male mice., P. D. Broulík, K. Broulíková., and Obsahuje bibliografii a bibliografické odkazy
Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this s tudy we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non - specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal inje ction of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP suc cessfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non -specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS., B. Bender, M. Baranyi, A. Kerekes, L. Bodrogi, R. Brands, P. Uhrin, Z. Bösze., and Obsahuje bibliografii