Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. Given that endothelial cells are the main source of ET-1 and ET-1 from other cells may encounter difficulty penetrating vascular compartments, we hypothesize that endothelial-derived ET-1 promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They were given intratracheal bleomycin and euthanized at day 28. We quantified pulmonary fibrosis, measured lung ET-1 and its receptors’ expression, and assessed pulmonary vascular remodeling by calculating medial wall index, muscularization index, adventitial collagen and adventitial fibroblast and macrophage accumulation. Right ventricle remodeling was also assessed. Both VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p<0.01). Expression of both ET-1 receptors mRNAs were increased in fibrosis models. Bleomycin-induced fibrosis VEETKO mice had significantly less muscularized arterioles, lower muscularization index and attenuated adventitial collagen, fibroblast and macrophage accumulation as compared to that of Wild type mice. Right ventricular pressure, hypertrophy and fibrosis did not increase both in VEETKO and Wild type mice despite the more enhanced vascular remodeling in Wild type. In conclusion, endothelialderived endothelin-1 promotes pulmonary vascular remodeling secondary to bleomycin-induced pulmonary fibrosis., A. B. Hartopo, N. Arfian, K. Nakayama, Y. Suzuki, K. Yagi, N. Emoto., and Seznam literatury
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects. The vasodilator response to the ET-1 antagonist BQ123 (1 μM) was significantly higher in arteries from obese hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries from obese hypertensive patients. The present study show that hypertension yet prevail after gastric bypass surgery and the ETA receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients., K. Gradin, B. Persson., and Seznam literatury
The global epidemic of diabetes is of significant concern. Diabetes associated vascular disease signifies the principal cause of morbidity and mortality in diabetic patients. It is also the most rapidly increasing risk factor for cognitive impairment, a silent disease that causes loss of creativity, productivity, and quality of life. Small vessel disease in the cerebral vasculature plays a major role in the pathogenesis of cognitive impairment in diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors (ETA and ETB), is a likely candidate that may be involved in many aspects of the diabetes cerebrovascular disease. In this review, we took a brain-centric approach and discussed the role of the ET system in cerebrovascular and cognitive dysfunction in diabetes., W. Li, Y. Abdul, R. Ward, A. Ergul., and Seznam literatury
Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system., R. Ward, Y. Abdul, A. Ergul., and Seznam literatury
Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5’ UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies., S. Biswas, B. Feng, A. Thomas, S. Chen, E. Aref-Eshghi, B. Sadikovic, S. Chakrabarti., and Seznam literatury
Díky neustálému zdokonalování technologií slaví endoskopické řešení urologických onemocnění značné úspěchy. Při léčbě ureterálních striktur dosahuje endoskopická léčba dobrých výsledků. Zásadní otázkou zůstává volba vhodného přístupu: retrográdního, antegrádního nebo kombinovaného přístupu. Po identifikaci striktury lze provádět dilataci balonkem nebo endoureterotomii. Úspěch intervence závisí na lokalizaci, délce a povaze ureterální striktury. Tyto faktory rovněž rozhodují o volbě nejvhodnějšího přístupu. Pečlivé monitorování je nezbytnou podmínkou pro úspěch operace a celkovou spokojenost pacienta., With improvement in technology, endoscopic management of urologic disease has growing success. Ureteral strictures are a disease process with good outcomes associated with endoscopic treatment. An early challenge is determining the best approach to the stricture, via a retrograde, antegrade, or combined approach. Once the stricture is encountered, balloon dilation or endoureterotomy can be performed. The location, the length, and the nature of the ureteral stricture, with a variety of success rates dependent upon these factors, best determine the decision on approach and treatment. Careful follow up is paramount to treatment success and patient satisfaction., and Syan R., Shah O.
Cíl: Cílem je zhodnotit zkušenosti s léčbou aneurysmatu podkolenní tepny stentgraftem. Metodika: V období od června 2011 do října 2014 jsme na našem pracovišti léčili 18 aneurysmat podkolenní tepny u 14 pacientů pomocí stentgraftu. Jednalo se o 13 mužů a jednu ženu ve věku od 50 do 90 let. Věkový průměr byl 70 let, medián 69,5 let. Léčili jsme tři aneurysmata o průměru menším než 2 cm, 12 aneurysmat o průměru 2-5 cm a tři výdutě o průměru větším než 5 cm. Výsledky: Pacienti byli sledováni 2-35 měsíců, průměrná doba sledování byla 13, 4 měsíce, medián 10 měsíců. Technická úspěšnost byla 100 %. Primární průchodnost byla 78 %, sekundární průchodnost byla 94 %. Podle Kaplanovy-Maierovy analýzy byly pravděpodobnost primární průchodnosti za 6 a 12 měsíců po implantaci stentgraftu stejná, a to 75,8 % (95 % CI: 54,6-97,0 %), pravděpodobnost sekundární průchodnosti za 6 a 12 měsíců 94,4 % (95 % CI: 83, 8-100 %). Závěr: Endovaskulární léčba stentgraftem je možnou alternativou chirurgické léčby aneurysmatu podkolenní tepny. Endovaskulární léčba je jednoduchá, bezpečná a účinná., Aim: To evaluate the experience in the treatment of popliteal artery aneurysm with stentgraft. Method: From June 2011 to October 2014, we were treated 18 aneurysms of the popliteal artery in 14 patients using the stentgraft at our department. There were 13 men and one woman aged from 50 to 90 years. The mean age was 70 years. We treated three aneurysms with a diameter of less than 2 cm, 12 aneurysms 2-5 cm in diameter and 3 aneurysms with a diameter greater than 5 cm. Results: Patients were followed-up 2-35 months, mean follow-up was 13.4 months. The technical success rate was 100%. Primary patency was 78%, secondary patency was 94%. According to Kaplan-Maier analysis the probability of primary patency at 6 and 12 months after stentgraft implantation was 75.8 % (95% CI: 54.6 to 97.0%), the probability of secondary patency at 6 and 12 months was 94.4% (95% CI: 83,8-100%). Conclusion: Endovascular treatment with stentgraft is a possible alternative of surgical treatment of popliteal artery aneurysm. Endovascular treatment is simple, safe, and effective., Marie Černá, Martin Köcher, Ondřej Hrbáček, Jana Zapletalová, Vojtěch Prášil, Martin Hazinger, Petr Bachleda, Petr Utíkal, Petr Dráč, Pavel Xinopulos, Jana Janečková, Jiří Herman, Zdeněk Sekanina, and Literatura
Cíl: Stále více literárních údajů přináší přesvědčivé informace o tom, že EVAR může být indikována i u nemocných s rupturou aneurysmatu abdominální aorty (RAAA). Výhodou EVAR při léčbě RAAA je, že umožňuje vyhnout se laparotomii, a předchází tak výraznému snížení krevního tlaku vedoucímu až k cirkulačnímu kolapsu při uvolnění retroperitonea, snižuje kardiorespirační zátěž a minimalizuje ztráty krve. Cílem práce je zhodnotit vlastní zkušenosti s akutní endovaskulární léčbou rupturovaných aneurysmat abdominální aorty či aneurysmat společné kyčelní tepny. Metodika: Od roku 2011 do konce roku 2014 jsme léčili celkem deset nemocných s RAAA nebo rupturou aneurysmatu arteria iliaca communis (RAAIC). Průměrný věk nemocných zahrnutých do souboru byl 69,3 let v rozmezí od 61 do 79 let (medián věku nemocných - 68 let). Sedm nemocných bylo léčeno pro RAAA, tři nemocní pro RAAIC. Výsledky: Celkem u osmi nemocných jsme použili bifurkační stentgraft - u všech sedmi nemocných s RAAA a jednoho nemocného s RAAIC U jednoho ze sedmi nemocných s RAAA byla pro délku proximálního krčku 5 mm použita chimney technika. U dvou nemocných bylo možné řešit RAAIC pouze pomocí tubulárního stentgraftu. Primární technická úspěšnost dosáhla v našem souboru 100%, perioperační letalita 20 %. Průměrná doba dalšího sledování nemocných v době zpracování souboru byla 13,5 měsíců, v rozmezí od 10 do 38 měsíců. Déle než 1 rok bylo sledováno sedm nemocných. Z pozdních komplikací jsme u jednoho nemocného zaznamenali endoleak typu II bez zvětšování vaku aneurysmatu. Jedenkrát jsme zaznamenali uzávěr raménka bifurkačního stentgraftu. Závěr: Na základě našich zkušeností a literárních výsledků jsou na našem pracovišti v současné době hemodynamicky stabilní pacienti s RAAA a RAAIC a vhodnou morfologií indikováni k endovaskulární léčbě., Aim: In comparison with open surgery the endovascular treatment of ruptured abdominal aortic aneurysm can avoid laparotomy with subsequent significant blood pressure drop leading to the circulation collapse while releasing of the retroperitoneum, can reduce cardiopulmonary complications and minimize blood loss. The aim of the study is to evaluate our own experience with acute endovascular treatment of ruptured abdominal aortic aneurysm and common iliac artery aneurysm. Methods: From the year 2011 to December 2014 10 patients with average age of 69.3 years (range 61-79 years, median - 68 years) were treated for ruptured abdominal aortic aneurysm and common iliac artery aneurysm (RCIAA). Seven patients were treated for ruptured abdominal aortic aneurysm and three patients for ruptured common iliac artery aneurysm. Results: We used the bifurcated stentgraft in eight patients Results: in all seven patients with RAAA and in one patient with RCIAA. In one of the seven patients with RAAA chimney technique was used. In two patients with RAAIC tubular stent-graft only can be used. Primary technical success was achieved in 100% of patients, perioperative mortality 20%. Patients were followed-up 10-38 months, mean follow-up was 13.5 months. Seven patients were observed more than one year. Secondary endoleak type II was found at follow-up CT in one patient. In one patient thrombosis stent-graft leg was found during follow-up. Conclusion: Based on our experience and literature results in our department currently all hemodynamically stable patients with ruptured abdominal aortic aneurysm or ruptured common iliac artery aneurysm and suitable morphology are indicated for endovascular treatment., Martin Köcher, Petr Utíkal, Petr Dráč, Marie Černá, Petr Bachleda, Vojtěch Prášil, Martin Hazlinger, and Literatura
The formation of S-aminolevulmic acid (ALA), energy-dependent steps ffom ALA to protoporphyrin IX (Proto) and from Proto to protochlorophyllide (PChlide) formation, the roles of NADPH in PChlide photoreduction and geranylgeraniol hydrogenation, the source of adenylates and reduced pyridine nucleotides for the reactions of chlorophyll biosynthesis, and the compartmentation and interrelationships of porphyrin biosynthesis pathways are reviewed.
Využitie kombinovaného systému na báze pyrolýzy biomasy, resp. triedeného komunálneho odpadu, v kombinácii s čistením exhalátov za pomoci elektrického výboja, poskytuje zaujímavú možnosť znižovania skleníkotvorného CO2 a súčasne rozvoja niektorých foriem obnoviteľných zdrojov energie. Testovaný pilotný systém z hľadiska veľkosti zodpovedá približne potrebám bežne stavaných rodinných domov., Marcela Morvová., and Obsahuje bibliografii