Delayed rectifier potassium current in undiseased human ventricular myocytes

Objective: The purpose of the study was to investigate the properties of the delayed rectifier potassium current (I-K) in myocytes isolated from undiseased human left ventricles. Methods: The whole-cell configuration of the patch-clamp technique was applied in 28 left ventricular myocytes from 13 hearts at 35 degrees C. Results: An E-4031 sensitive tail current identified the rapid component of I-K (I-Kr) in the myocytes, but there was no evidence for an E-4031 insensitive slow component of I-K (I-Kb). When nifedipine (5 mu M) was used to block the inward calcium current (I-Ca), I-Kr activation was fast (tau=31.0+/-7.4 ms, at +30 mV, n=5) and deactivation kinetics were biexponential and relatively slow (tau(1) =600.0+/-53.9 ms and tau(2)-6792.2+/-875.7 ms, at -40 mV, n=7). Application of CdCl2 (250 mu M) to block I-Ca altered the voltage dependence of the I-Kr considerably, slowing its activation (tau=657.1+/-109.1 ms, at +30 mv n=5) and accelerating its deactivation ( tau=104.0+/-18.5 ms, at -40 mV, n=8). Conclusions: In undiseased human ventricle at 35 degrees C I-Kr exists having fast activation and slow deactivation kinetics; however, there was no evidence found for an expressed I-Ks. I-Kr probably plays an important role in the frequency dependent modulation of repolarization in undiseased human ventricle, and is a target for many Class III antiarrhythmic drugs

Fermi GBM transient searches with ADWO

We present the method called Automatized Detector Weight Optimization (ADWO). This method searches for non-triggered, short-duration transients in the data-set of the Fermi's Gamma-ray Burst Monitor. The data of all available detectors and energy channels are combined. Therefore, ADWO is ideal to search for electromagnetic counterparts of gravitational wave events. We present the successful identification of all short-duration gamma-ray bursts, as well as that of the possible electromagnetic counterparts of gravitational wave transients GW150914 and LVT151012

Miscellanea. Folyóirat-referátumok. Könyvismertetések

Folyóirat-referátumok. Hepatológia A kávéfogyasztás védőhatása az összmortalitásra francia, HIV-HCV koinfekcióban szenvedő betegekben (Protective effect of coffee consumption on all-cause mortality of French HIV-HCV co-infected patients) Carrieri MP, Protopopescu C, Marcellin F, et al. (Aix Marseille Univ, INSERM, IRD, SESSTIM, 27 bd Jean Moulin, 13385 Marseille Cedex 5, Franciaország; e-mail: [email protected]): J. Hepatol. 2017; 67: 1157–1167. | A jövő medicinája A robotsebészet rövid története (A short history of robotic surgery) Lane T. (Lister Hospital, Coreys Mill Lane, Stevenage SG1 4AB, Egyesült Királyság): Ann R Coll Surg Eng. 2018 (Suppl): 5–7. | Sportorvostan Állóképességi edzés cardiovascularis betegeknek – gyakorlati szempontok (Endurance training in cardiovascular patients – practical aspects) Mayer-Berger W. (Ärztlicher Direktor, Klinik Roderbirken, Rehabilitationsklinik für Herz-, Kreislauf-, Gefäßerkrankungen und Psychokardiologie der Dt. Rentenversicherung Rheinland, Roderbirken 1, 42799 Leichlingen, Németország; e-mail: wolfgang. [email protected]): Dtsch Z Sportmed. 2018; 69: 87–92. | Könyvismertetések. Kiss László Égnek legszebb ajándéka Barangolás a himlő elleni védőoltás magyarországi kultúrtörténetében Magyar Tudománytörténeti és Egészségtudományi Intézet, Budapest, 2017 141 oldal, ármegjelölés nélkül | Julesz Máté Orvosi jog működés közben A hálapénztől a kártérítésig Medicina Könyvkiadó, Budapest, 201

Antiandrogén kardenolid analógok szintézise és biológiai hatásvizsgálata = Synthesis and biological effect investigations of antiandrogen cardenolide analogues

A 17?-hidroxiláz-C17,20-liáz (P45017?) az androgén bioszintézis kulcsenzime, amely a 21 szénatomos szteroidok esetén mind a 17?-hidroxilezést, mind pedig a C17?C20 kötés hasítását katalizálja. Ezen enzim gátlása az androgének szintézisét korai fázisban gátolja, így a prosztatarák kezelésében hasznos lehet. Új 17?-dihidrooxazinil-szteroidokat állítottunk elő. Ezen vegyületek gátló hatását in vitro radioinkubációs technikával, patkányhere-C17,20-liáz enzimen végeztük. Egyes 17?-(2-oxazolidon-5-il)-androszt-4-én-3-on származékok hatásos inhibítornak bizonyultak. A D-gyűrűhöz kondenzált, ösztránvázas dioxafoszforinánok és oxazafoszforinánok epimerjeit szintetizáltuk; térszerkezetüket és jellemző konformációjukat NMR-es és számításos kémiai módszerekkel határoztuk meg. Alkenil-fenilhidrazonok Lewis-sav-katalizálta 1,3-dipoláris cikloaddíciós reakciójával androszt-5-én-kondenzált arilpirazolinokhoz jutottunk. A pirazolinok proliferációgátló hatását három humán ráksejtvonalon vizsgáltuk. Egy származék a ciszplatinnál is hatékonyabb citotoxicitást mutatott. | 17?-Hydroxylase-C17,20-lyase (P45017?) is a key enzyme regulating the androgen biosynthetic pathway, catalyzing both 17?-hydroxylation and cleavage of the C17?C20 bond of 21-carbon steroids. Inhibition of this enzyme can block androgen synthesis at an early stage, and may therefore be useful in the treatment of prostatic carcinoma. New 17?-dihydrooxazinyl steroids were synthetized. The inhibitory effects of these compounds on rat testicular C17,20-lyase were investigated with an in vitro radioincubation technique. Some 17?-(2-oxazolidon-5-yl)-androst-4-en-3-one derivatives were found to be potent inhibitors for this enzime. D-ring-fused dioxaphosphorinanes and oxazaphosphorinanes in the estrone series were synthetized as epimeric pairs and investigated by NMR and computational methods in order to determine their stereostructures and predominant conformations. Lewis acid induced intramolecular 1,3-dipolar cycloadditions of alkenyl phenylhydrazones were carried out to furnish androst-5-ene-fused arylpyrazolines. The antiproliferative activities of the pyrazoline derivatives were tested in vitro on three malignant human cell lines. One of the derivatives displayed higher cytotoxic activity, than cisplatin

Steroidal Ferrocenes as Potential Enzyme Inhibitors of the Estrogen Biosynthesis

The potential inhibitory efect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenylalkynes using our efcient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities was investigated with in vitro radiosubstrate incubations. Some of the test compounds were found to be potent inhibitors of the STS. A compound bearing ferrocenyl side chain on the C-2 displayed a reversible inhibition, whereas C-16 and C-17 derivatives displayed competitive irreversible binding mechanism toward the enzyme. 17α-Triazolyl-ferrocene derivatives of 17β-estradiol exerted outstanding inhibitory efect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding afnity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most efective STS inhibitors published so far. STS inhibitory potential of the steroidal ferrocenes may lead to the development of novel compounds able to suppress in situ biosynthesis of 17β-estradiol in target tissues

Synthesis of novel 13 α-estrone derivatives by Sonogashira coupling as potential 17 β-HSD1 inhibitors

Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC50 values

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

17α-hydroxylase-C17,20-lyase (P45017α) is a key regulator enzyme of the steroid hormone biosynthesis in both the adrenals and the testes. Inhibition of this enzyme can block androgen synthesis in an early step, and may thereby be useful in the treatment of several androgen-dependent diseases. We developed radio-substrate in vitro incubation methods for the determination of the distinct 17α-hydroxylase and C17,20-lyase activities of the enzyme using rat testicular homogenate as enzyme source. With this method we have studied the inhibiting activity of selected steroidal picolyl and picolinylidene compounds. Tests revealed a substantial inhibitory action of the 17-picolinyliden-androst-4-en-3-one compound

Comprehensive frailty assessment with multidimensional frailty domains as a predictor of mortality among vascular and cardiac surgical patients

Purpose: The frailty concept has become a fundamental part of daily clinical practice. In this study our purpose was to create a risk estimation method with a comprehensive aspect of patients’ preoperative frailty. Patients and methods: In our prospective, observational study, patients were enrolled between September 2014 and August 2017 in the Department of Cardiac Surgery and Department of Vascular Surgery at Semmelweis University, Budapest, Hungary. A comprehensive frailty score was built from four main domains: biological, functional-nutritional, cognitive-psychological and sociological. Each domain contained numerous indicators. In addition, the EUROSCORE for cardiac patients and the Vascular POSSUM for vascular patients were calculated and adjusted for mortality. Results: Data from 228 participants were included for statistical analysis. A total of 161 patients underwent vascular surgery, and 67 underwent cardiac surgery. The preoperatively estimated mortality was not significantly different (median: 2.700, IQR (interquartile range): 2.000–4.900 vs. 3.000, IQR: 1.140– 6.000, P 5 0.266). The comprehensive frailty index was significantly different (0.400 (0.358–0.467) vs. 0.348 (0.303–0.460), P 5 0.001). In deceased patients had elevated comprehensive frailty index (0.371 (0.316–0.445) vs. 0.423 (0.365–0.500), P < 0.001). In the multivariate Cox model an increased risk for mortality in quartiles 2, 3 and 4 compared with quartile 1 as a reference was found (AHR (95% CI): 1.974 (0.982–3.969), 2.306 (1.155–4.603), and 3.058 (1.556–6.010), respectively). Conclusion: The comprehensive frailty index developed in this study could be an important predictor of long-term mortality after vascular or cardiac surgery. Accurate frailty estimation could make the traditional risk scoring systems more accurate and reliable