Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11 β -hydroxysteroid dehydrogenase 1 (11 β -HSD 1), an enzyme that regenerates active cortisol from inert cortis one. Increased expression of 11 β - HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11 β - HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-ox o-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7 α -OH-DHEA, 7 β -OH- DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04- 15.67 years, BMI greater than 90 th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7 α -OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854 , transformed mean with 95 % confidence interval) to 1.530 nm ol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1. 842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1. 132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7 β -OH-DHEA levels was observed. In conclusions, diminished levels of 7 α -OH-DHEA indicate its possible effect on activity of 11 β -HSD 1. Further studies are necessary to clarify whether competitive substrates for 11 β -HSD 1 such as 7 α -OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity., L. Máčová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein ki nase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of isch emia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166±40; AS 1.6±0.2 vs . 550±60 and 3.2±0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92±25; AS 1.7±0.2; P<0.05 vs . non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 % as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart., T. Ravingerová, J. Matejíková, D. Pancza, F. Kolář., and Obsahuje bibliografii
Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats., N. N. Hamouda, M. A. Qureshi, J. M. Alkaabi, M. Oz, F. C. Howarth., and Obsahuje bibliografii
It has been reported that the virulence of axenically cultivated Entamoeba histolytica increases following growth with cholesterol. The purpose of this study was to determine whether cholesterol would enhance the virulence of axenically cultivated Naegleria fowleri. Amoebae were cultivated in axenic medium with (100 pg/ml) or without cholesterol for 6 months and tested in mice for changes in virulence. After 6 months of continuous cultivation, N. fowleri grown with cholesterol was less virulent for mice than the same strain grown without cholesterol.
Staging a restaging nemalobuněčného karcinomu plic levého horního laloku představuje separátní multidisciplinární výzvu v široké problematice diagnostiky a terapie tohoto závažného onemocnění. Neoadjuvantní terapie je etablovanou terapeutickou metodou v multimodální terapii nemalobuněčného karcinomu plic s předoperačně prokázaným uzlinovým postižením mediastinálního kompartmentu. Autonomie lymfatické drenáže levého horního laloku způsobuje, že nádorové buňky tvoří primární lymfatické metastázy v oblasti uzlin aorto-pulmonálního okna. Tyto lymfatické uzliny jsou rovněž součástí uzlinového kompartmentu mezihrudí. Jsou však lokalizovány mimo dosahu konvenčních stagingových metod. Proto i přes negativní mediastinoskopii a počítačovou tomografii může být intraoperačně prokázáno N2 postižení v oblasti A-P okna. Zavedení invazivního stagingu při suponované pozitivitě uzlin A-P okna by mohlo mít pro selektovanou skupinu pacientů terapeutický benefit ve smyslu primární indukční terapie před chirurgickou resekcí. Přehledová práce autorů si klade za cíl poukázat na problematiku stagingu a restagingu nemalobuněčného karcinomu plic levého horního laloku v intencích revidovaných doporučení Evropské společnosti hrudní chirurgie a našich zkušeností., Staging and re-staging of non-small cell lung carcinoma of the left upper lobe represents a multidisciplinary challenge for diagnostics and therapy of this serious disease. Neoadjuvant therapy is an established therapeutic approach for multimodal therapy of non-small cell lung carcinoma with pre-surgery diagnosed nodal spreading into the mediastinal compartment. The autonomy of lymphatic drainage of the upper left lobe causes that the cancer cells produce primary lymphatic metastases in the aorta-pulmonary (A-P) window area. These lymphatic nodes are also a part of nodal compartment of the mediastinum. However, they are localized beyond the reach of the conventional staging methods. Therefore, even in spite of negative mediastinoscopy and CT, N2 spreading into the A-P window area can be proven intra-operationally. Establishment of invasive staging during suspected positivity of the A-P window nodes might be of therapeutic benefit for selected patients, in terms of primary induction therapy prior to surgical resection. The aim of this review is to pinpoint and highlight the known issues with staging and re-staging of non-small cell lung carcinoma of the upper left lobe based on revised guidelines of the European Association of Thoracic Surgery and our experience., Michal Benej, Ivan Čapov, Jan Wechsler, Adam Peštál, Zdeněk Chovanec, Martin Páral, Stanislav Špelda, and Literatura
Refluxní choroba jícnu je onemocnění způsobené návratem žaludečního obsahu zpět do jícnu. Tento stav označujeme jako gastroezofageální reflux. Nejčastějším důsledkem gastroezofageálního refluxu je zánět jícnu (refluxní ezofagitida). Zánět může být viditelný při endoskopickém vyšetření jako různě rozsáhlé eroze nebo může být prokázán pouze mikroskopicky z odebraných bioptických vzorků (mikroskopická ezofagitida). Gastroezofageální choroba se může manifestovat i v orgánech mimo jícen. Jedná se o tzv. extraezofageální refluxní chorobu, u které bývají postiženy refluxátem především orgány dýchacích cest., Gastro‑oesophageal reflux disease is caused by the return of stomach contents back into the oesophagus. This condition is called gastro‑oesophageal reflux. The most frequent consequence of gastro‑oesophageal reflux is an inflammation of the oesophagus (reflux oesophagitis). The inflammation may be visible during endoscopy as variously extensive erosions or may be established only by microscopy from biopsy (microscopic oesophagitis). Gastro‑oesophageal disease can even be manifested in organs outside the oesophagus as extraoesophageal reflux disease, which often affects mainly the pulmonary system., and Stefanová M.
In the 18th century there were disputes over appointments to the vacant canonries in the Olomouc chapter. One of the reforms of Maria Theresa was the Chapter Statutes, which she approved in 1772 and which came into force on 1 st January 1773. The new statutes confirmed both the privilege of the free election of bishops by canons and the practice of appointing only aristocrats as canons, including so-called domicelars (non-resident Canons). The Chapter of Olomouc gained the status of an exclusively aristocratic chapter at a time when this privilege (because of secularization and other factors) was beginning to disappear. While the requirement that aspirants should have right of abode (inkolat) favoured the landed nobility, the requirement that they be of aristocratic origin favoured "only" the higher nobility, regardless of their origin or suitability for the office - a circumstance that later met with considerable criticism. The Chapter also received a new canonical seal from Maria Theresa, which its canons use to this day. Maria Theresa’s successor, Josef II, intervened again in the Chapter Statutes, limiting the influence of the Holy See over the appointment of canons and thereby enhancing the Sovereign’s influence in the Chapter., Jitka Jonová., and Obsahuje bibliografické odkazy