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Převodní systém srdce je důležitý pro tvorbu a synchronizaci srdeční činnosti. Počínaje Tawarou, Einthovenem a dalšími průkopníky bylo během posledních 100 let nasbíráno množství informací o histologických, morfologických a fyziologických charakteristikách specializovaných srdečních tkání. V posledních deseti letech bylo značné úsilí vynaloženo na pochopení buněčných a molekulárních mechanizmů řídících vývoj převodního systému srdce. Během tohoto období vznikly určité kontroverze o povaze mechanizmů signalizace působících na vznik a diferenciaci převodního systému, zvláště u savců. V tomto přehledném článku se pokusíme shrnout současný stav znalostí v této oblasti a poukázat na některé zbývající otázky.

The cardiac conducting system is vital for generating and synchronizing the heartbeat. Beginning with Tawara, Einthoven and other pioneering workers, a wealth of information has been collected over the last 100 years on the histologic, morphologic and physiologic characteristics of specialized cardiac tissues. However, in the last ten years considerable effort has been put into understanding the cellular and molecular mechanisms governing its development. During this latter period, controversies have also arisen as to the nature of the signaling mechanisms involved in induction and patterning of the conducting system, particularly with respect to the pathways functioning in mammals. In this review, we will try to summarize the current state of knowledge in this field and point out some of the remaining questions.

Článek

Raloxifen prevents bone loss in castrated male mice

Physiological research. 2007 ; 56 (4) : 443-447.

ISSN 0862-8408
Medvik
Zdroj

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.

Článek

Chronic oral administration of beta-adrenoceptor agonist clenbuterol affects myosin heavy chain (MHC) expression in adult mouse heart

Physiological research. 2007 ; 56 (3) : 275-283.

ISSN 0862-8408
Medvik
Zdroj

The aim of this study was to analyze the effects of chronic administration of the ß-adrenoceptor agonist clenbuterol (2 mg/kg body weight/day for a period of 30 days) on the major contractile protein (myosin) in the left ventricular muscle of the adult mouse heart. Separation of myosin heavy chain (MHC) isoforms on 7.5 % glycerol SDS-PAGE and subsequent quantification of the gels by laser densitometry showed a 6.5-fold increase in the ß-isoform of MHC in the clenbuterol-treated group. The ?: ß ratio of these two isoforms in the control group was 98.16±0.14 %: 1.83±0.14 %, whereas in the treated group it was 88.05±1.15 %: 11.95±1.15 %. Actomyosin ATPase activity assay demonstrated a significant (20 %) decline in ATPase activity of the tissue in the ß-agonist-treated group. These results suggest that chronic clenbuterol treatment is capable to induced the transformation of MHC isoforms increasing the slow ß-MHC isoform, which may contribute to the altered contractile mechanics of clenbuterol-treated hearts.

Článek

Sequential expression of vascular endothelial growth factor, Flt-1, and KDR/Flk-1 in regenerating mouse skeletal muscle

Physiological research. 2006 ; 55 (6) : 633-640.

ISSN 0862-8408
Medvik
Zdroj

We investigated the expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and KDR/Flk-1) during muscle regeneration by immunohistochemistry and real-time RT-PCR. On days 5 and 7 after the induction of injury, VEGF and Flt-1 were detected in the cytoplasm and KDR/Flk-1 in the cytoplasm and on cell membranes of the same regenerating muscle fibers. The levels of these proteins in the regenerating muscle fibers gradually decreased until day 20. In contrast, these proteins were not detected in the fibers of normal muscle. This suggests that regenerating muscle fibers express VEGF and its receptors in response to injury. In addition, we found that the VEGF mRNA transcript transiently increased after 12 h of muscle injury and then returned to the basal levels observed in normal muscles on day 1. The expression of Flt-1 and KDR/Flk-1 mRNA transcripts also peaked on day 3 and then returned to the basal levels observed in normal muscles on day 10. These findings suggest that regenerating muscle fibers are an important source of VEGF and that VEGF signaling through Flt-1 and KDR/Flk-1 may be involved in the process of muscle regeneration in vivo.