Erektilná dysfunkcia, ktorú charakterizuje vysoká prevalencia a progresívny priebeh, znižuje kvalitu života muža a aj jeho sexuálnej partnerky. Jestvuje dostatok poznatkov na to, aby sme erektilnú dysfunkciu považovali u väčšiny pacientov za znak genitálnovaskulárnej choroby. Erektilná dysfunkcia môže byť považovaná za klinickú manifestáciu cievnej choroby penisu (genitálnovaskulárnu artériovú chorobu muža) podobne, ako je angína pektoris typickou manifestáciou cievnej choroby srdca (kardiovaskulárnej artériovej ischemickej choroby). Niekoľko štúdií potvrdilo predpoklad, že symptómy erektilnej dysfunkcie predchádzajú vznik stenokardií u 60–95 % pacientov s kardiovaskulárnou chorobou v intervale 2–3 rokov a obdobne u pacientov aj so všetkými ďalšími orgánovovaskulárnymi chorobami. Európska lieková agentúra (EMA) schválila 4 inhibítory fosfodiesterázy 5 (PDE5-I) pre liečbu erektilnej dysfunkcie. Lekári by sa vyhľadávaniu pacientov s erektilnou dysfunkciou mali systematicky venovať hlavne u pacientov s vaskulárnymi rizikovými faktormi., Erectile dysfunction is a highly prevalent and progressive condition affecting the quality of life of man and his sexual partner. Evidence is accumulating in favour of erectile dysfunction as a sign of a genitovascular disease (GVD) in the majority of patients. Erectile dysfunction may be considered as the clinical manifestation of a organovascular disease affecting penis (male genitovascular disease – MGVD) as well as angina pectoris is the typical manifestation of a vascular disease affecting coronary arteries of a heart (cardiovascular disease – CVD). Several studies confirm the assumption that erectile dysfunction symptoms were found to come prior to cardiovascular disease symptoms in 60–95 % of CVD patients with mean interval of 2–3 years and likewise of all organovascular diseases (OVD). Four potent selective PDE5Is have been approved by the EMA for the treatment of erectile dysfunction. Physicians should systematically look for erectile dysfunction in any male with vascular risk factors., and Peter Gavorník, Andrej Dukát, Ľudovít Gašpar, Denisa Medová, Xénia Faktorová, Eva Gavorníková
Moderní léčba erektilní dysfunkce, která spočívá v první linii v podávání inhibitorů fosfodiesterázy 5 (PDE5‑I), je bezpečná a dobře tolerovaná. Avanafil, nový PDE5‑I, je vysoce účinný a selektivní PDE5 inhibitor. Výsledky fáze III klinických studií ukázaly, že avanafil je efektivní a dobře tolerovaná léčba erektilní dysfunkce širokého spektra příčin a závažnosti. Zlepšení sexuální funkce a snášenlivost jsou spojeny s rychlým nástupem účinku a trváním efektu, které činí avanafil plně indikovaným pro on-demand léčbu erektilní dysfunkce., Modern ED therapy, which in the first line consists of PDE5 inhibitors (PDE5-I) application, is safe and effective and is well tolerated. Avanafil, a new agents, is a highly potent PDE5 inhibitor and highly selective for PDE5. Results of phase III clinical trials suggest that avanafil is an effective and well tolerated treatment for ED of broad-spectrum aetiology and severity. The improvement in sexual function and tolerability coupled with the rapid onset of action and durability of effect make avanafil a viable tool for on demand treatment of ED., and Šrámková T.
We study ergodic properties of stochastic geometric wave equations on a particular model with the target being the 2D sphere while considering only solutions which are independent of the space variable. This simplification leads to a degenerate stochastic equation in the tangent bundle of the 2D sphere. Studying this equation, we prove existence and non-uniqueness of invariant probability measures for the original problem and obtain also results on attractivity towards an invariant measure. We also present a structure-preserving numerical scheme to approximate solutions and provide computational experiments to motivate and illustrate the theoretical results., Ľubomír Baňas, Zdzisłlaw Brzeźniak, Mikhail Neklyudov, Martin Ondreját, Andreas Prohl., and Obsahuje seznam literatury
Eribulin je netaxanový inhibitor dynamiky mikrotubulů. Je syntetickým analogem halichondrinu B. Působením na mikrotubuly eribulin účinkuje antimitoticky v G2/M fázi buněčného cyklu, ničí mitotické vřeténko a způsobuje apoptózu. Specificky inhibuje růstovou fázi mikrotubulů a sekvestruje tubulin v neproduktivní agregáty. V poslední době byly publikovány výsledky preklinického výzkumu „nemitotického“ mechanizmu účinku eribulinu (zejm. vliv na vaskularizaci nádoru, epiteliálně mezenchymální přechod, invazivitu a schopnost migrace)., Eribulin is a non-taxane microtubule dynamics inhibitor. It is a synthetic analogue of halichondrin B. By acting on microtubules, eribulin has an antimitotic effect in the G2/M phase of cell cycle, disrupting the mitotic spindle and inducing apoptosis. It specifically inhibits the growth phase of microtubules and sequesters tubulin in non-productive aggregates. Recently, the results of preclinical research of “non-mitotic” mechanism of action of eribulin (particularly the effect on tumour vascularization, epithelial-mesenchymal transition, invasiveness, and migration ability) have been published., Jitka Abrahámová, Zuzana Donátová, and Literatura
One of the most significant insults that jeopardize cardiomyocyte homeostasis is a surge of reactive oxygen species (ROS) in the failing myocardium. Early growth response factor-1 (Egr-1) has been found to act as a transcriptional regulator in multiple biological processes known to exert deleterious effects on cardiomyocytes. We thus investigated the signaling pathways involved in its regulation by H2O2. Egr-1 mRNA levels were found to be maximally induced after 2 h in H2O2-treated H9c2 cells. Egr-1 respective response at the protein level, was found to be maximally induced after 2 h of treatment with 200 μM H2O2, remaining elevated for 6 h, and declining thereafter. H2O2- induced upregulation of Egr-1 mRNA and protein levels was ablated in the presence of agents inhibiting ERKs pathway (PD98059) and JNKs (SP600125, AS601245). Immunofluorescent experiments revealed H2O2-induced Egr-1 nuclear sequestration to be also ERK- and JNK-dependent. Overall, our results show for the first time the fundamental role of ERKs and JNKs in regulating Egr-1 response to H2O2 treatment in cardiac cells at multiple levels: mRNA, protein and subcellular distribution. Nevertheless, further studies are required to elucidate the specific physiological role of Egr-1 regarding the modulation of gene expression and determination of cell fate., I.-K. S. Aggeli, I. Beis, C. Gaitanaki., and Obsahuje bibliografii a bibliografické odkazy
This paper focuses on Ernst Mach's contributions to teaching on the one side and technology-oriented research on the other side. The first part sums up Mach's views concerning the role of natural sciences and humanities within the curriculum and, in particular, culture in general. The second part deals with Mach's contribution to applied sciences and technology, mentioning some of his most original inventions in that field., Emilie Těšínská, Ivan Landa, Jiří Drahoš., and Obsahuje bibliografii
We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulating the axons with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same., E. Kuriščák, S. Trojan, Z. Wünsch., and Obsahuje bibliografii
a_1 We sought to examine the association between maternal erythrocyte omega-3, omega-6 and trans fatty acids and risk of preeclampsia. We conducted a case-control study of 170 women with proteinuric, pregnancy-induced hypertension and 185 normotensive pregnant women who delivered at Harare Maternity Hospital, Harare, Zimbabwe. We measured erythrocyte omega-3, omega-6 and trans fatty acid as the percentage of total fatty acids using gas chromatography. After multivariate adjustment for confounding factors, women in the highest quartile group for total omega-3 fatty acids compared with women in the lowest quartile experienced a 14 % reduction in risk of preeclampsia (odds ratio 0.86, 95 % confidence interval 0.45 to 1.63). For total omega-6 fatty acids the odds ratio was 0.46 (95 % confidence interval 0.23 to 0.92), although there was suggestion of a slight increase in risk of preeclampsia associated with high levels of arachidonic acid. Among women in the highest quartile for arachidonic acid the odds ratio was 1.29 (95 % confidence interval 0.66 to 2.54). A strong statistically significant positive association of diunsaturated fatty acids with a trans double bond with risk of preeclampsia was observed. Women in the upper quartile of 9-cis 12-trans octadecanoic acid (C18:2n6ct) compared with those in the lowest quartile experienced a 3-fold higher risk of preeclampsia (odds ratio = 3.02, 95 % confidence interval 1.41 to 6.45). Among women in the highest quartile for 9-trans 12-cis octadecanoic acid (C18:2n6tc) the odds ratio was 3.32 (95 % confidence interval 1.55 to 7.13)., a_2 Monounsaturated trans fatty acids were also positively associated with the risk of preeclampsia, although of much reduced magnitude. We observed a strong positive association of trans fatty acids, particularly diunsaturated trans fatty acids, with the risk of preeclampsia. We found little support for the hypothesized in verse association between omega-3 fatty acids and preeclampsia risk in this population. Polyunsaturated fatty acids, particularly omega-3 fatty acids, were comparatively lower in Zimbabwean than among US pregnant women. Given the limited inter-person variation in omega-3 fatty acids among Zimbabwean women, our sample size may be too small to adequately assess the relation in this population., K. Mahomed, M. A. Williams, I. B. King, S. Mudzamiri., and Obsahuje bibliografii a bibliografické odkazy