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Dyslipidemia is present in every other patient with arterial hypertension. With increasing blood pressure and cholesterol levels, the risk of cardiovascular events increases proportionally. Treatment of dyslipidemia appears to lower cardiovascular mortality to a greater extent than treatment of hypertension. A significant proportion of patients with dyslipidemia indicated for drug therapy are not treated at all or treated insufficiently and do not reach the target values. Concurrent treatment of hypertension and dyslipidemia reduces the incidence of cardiovascular events significantly more than treating only one of these diseases. An even better efficacy of combined treatment of hypertension and dyslipidemia can be achieved by improving patient adherence using fixed drug combinations.Key words: arterial hypertension - cardiovascular events - dyslipidemia - fixed combinations -treatment.

Objectives: Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients' heart rates to their serum beta-blocker levels., Methods: We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4 vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p = .041) in comparison to adherent patients., Results: Heart rate above 75.5 beats per minute predicted non-adherence to beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate cutoff might be applicable for nebivolol but was not determined due to the low number of patients treated with nebivolol., Conclusions: We concluded that heart rate was shown to be a good predictor of non-adherence to beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.

This paper presents a method for the determination of acebutolol, betaxolol, bisoprolol, metoprolol, nebivolol and sotalol in human serum by liquid-liquid extraction and ultra-high-performance liquid chromatography coupled with ultra-high-resolution TOF mass spectrometry. After liquid-liquid extraction, beta blockers were separated on a reverse-phase analytical column (Acclaim RS 120; 100 × 2.1 mm, 2.2 μm). The total run time was 6 min for each sample. Linearity, limit of detection, limit of quantification, matrix effects, specificity, precision, accuracy, recovery and sample stability were evaluated. The method was successfully applied to the therapeutic drug monitoring of 108 patients with hypertension. This method was also used for determination of beta blockers in 33 intoxicated patients., (Copyright © 2016 John Wiley & Sons, Ltd.)

These review article presents the results of major recent studies in cardiovascular prevention. HOPE-3 study showed that people with medium cardiovascular risk who have not experienced a cardiovascular event, and have normal blood pressure, benefit from deploying a statin, and in the presence of hypertension benefit from deploying a combination of a statin and antihypertensive drugs. Studies evaluating genetic predisposition brought new evidence that both LDL cholesterol and systolic blood pressure are independent and multiplicative causal risk factors for cardiovascular events. A mild long-term reduction in blood pressure and LDL cholesterol has the potential to significantly reduce the lifetime risk of cardiovascular events. In the final section the article discusses options for improving patient adherence to antihypertensive and lipid treatment and the new available fixed combinations for these diseases.Key words: arterial hypertension - cardiovascular prevention - dyslipidemia - fixed combinations - treatment.

Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new-generation reagents were used in bioconjugation with an artificial retro-aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine-selective bioconjugation., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data., Methods: A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients., Results: Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001)., Conclusion: In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.

Tetrafluoroalkyl bromides are metalated with equimolar iPrMgCl·LiCl (Turbo Grignard) to form organomagnesium compounds which are stable at low temperatures and react with various electrophiles (aldehydes, ketones, CO 2 , cyclic sulfate and sulfamidate, N-sulfonylimines, nitrone, chlorophosphate, nonaflyl azide) to afford novel functionalized tetrafluoroethylene-containing products. Ease of operation, excellent selectivity, high nucleophilicity, and enhanced stability of the reactive species together with a broad substrate scope comprise a highly attractive nucleophilic tetrafluoroethylation protocol affording unique synthetic building blocks.

This general article discusses the problems of beta-blockers use in patients with chronic obstructive pulmonary disease (COPD). Its aim is to refute exaggerated concerns of physicians over possible undesirable effects of beta-blockers on the patient respiratory functions and present new data on the effects of beta-blockers on the extent of COPD exacerbations, bronchial reactivity and mortality of patients.

This study was done to identify the content compounds of Achillea wilhelmsii (A. wilhelmsii) and to evaluate its hypoglycemic and anti-hypercholesterolemic activity and effect on inflammatory mediators. The extracts and fractions of A. wilhelmsii were thoroughly analyzed using high performance liquid chromatography (HPLC), and the total content of phenols and flavonoids was determined. The hypoglycemic activity was evaluated in vivo using alloxan-induced diabetic mice. The effect upon inflammatory mediators was evaluated in vitro using the human monocytic leukemia cell line (THP-1). The anti-hypercholesterolemic activity was evaluated in vitro using the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase assay kit. The water extract (WE)-treated group showed the highest reduction in the fasting blood glucose levels (FBGL). The chloroform fraction (CF) and ethyl acetate fraction (EAF) both showed a significant ability to reduce the secretion of tumor necrosis factor alpha (TNF-α). The EAF, however, also attenuated the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The CF showed the most significant 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibition activity. The five main compounds in the CF were isolated and identified. Out of the five compounds in the CF, 1β,10β-epoxydesacetoxymatricarin (CP1) and leucodin (CP2) showed the highest anti-hypercholesterolemic potential. A molecular docking study provided corresponding results.

This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction., (© 2015 American Heart Association, Inc.)

Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3-(pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid.

A series of new hypervalent iodine reagents based on the 1,3-dihydro-3,3-dimethyl-1,2-benziodoxole and 1,2-benziodoxol-3-(1H)-one scaffolds, which contain a functionalized tetrafluoroethyl group, have been prepared, characterized, and used in synthetic applications. Their corresponding electrophilic fluoroalkylation reactions with various sulfur, oxygen, phosphorus, and carbon-centered nucleophiles afford products that feature a tetrafluoroethylene unit, which connects two functional moieties. A related λ(3) -iodane that contains a fluorophore was shown to react with a cysteine derivative under mild conditions to give a thiol-tagged product that is stable in the presence of excess thiol. Therefore, these new reagents show a significant potential for applications in chemical biology as tools for fast, irreversible, and selective thiol bioconjugation., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Eleven new C-geranylated flavonoids, tomentodiplacones L, M, and N (1, 2, 10), tomentodiplacol B (3), 3',4'-O-dimethyl-5'-hydroxydiplacone (4), mimulones F, G, and H (5, 6, 7), paulowniones A (8) and B (9), tomentone (11), and 3',4',5'-trimethoxyflavanone (12), together with 11 known flavonoids (13-23), were isolated from fruits of Paulownia tomentosa. The structures of the compounds isolated were determined by spectroscopic data interpretation. The ability of compounds 1-23, together with the nonprenylated flavanones eriodictyol (24) and naringenin (25), to reduce the production of the pro-inflammatory cytokine TNF-α in THP-1 cells after bacterial lipopolysaccharide stimulation was evaluated using an in vitro screening test. The preliminary structure-activity relationships of these derivatives were also studied, and the correlation of their TNF-α inhibitory activity with their lipophilicity was investigated. The mechanism of action of compounds with significant antiphlogistic potential (4, 7, 10, 14, 22) was investigated. These compounds reduced both the secretion of TNF-α and the level of its corresponding mRNA. Compounds 4, 7, 10, 14, and 22 inhibited the nuclear translocation of NF-κB, which controls the expression of TNF-α, by blocking the degradation of IκB.

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (-8.6 [95% cofidence interval: -11.8, -5.3] mm Hg; P<0.001 in renal denervation versus -8.1 [95% cofidence interval: -12.7, -3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (-12.4 [95% cofidence interval: -17.0, -7.8] mm Hg; P<0.001 in renal denervation versus -14.3 [95% cofidence interval: -19.7, -8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy., (© 2014 American Heart Association, Inc.)

To improve blood pressure (BP) control of their patients, physicians either adjust or switch antihypertensive medication. Currently, there is only limited information available on why physicians decide to switch antihypertensive medications. A questionnaire-based survey was performed between November 2011 and March 2012 in the Czech Republic. General practitioners were asked to fill in questionnaires about their hypertensive patients whose antihypertensive medication they were planning to change. These questionnaires recorded data about patient demographic information, cardiovascular risk factors, BP values, and reasons for switching antihypertensive medication. Two hundred eight-six general practitioners surveyed a total of 4341 hypertensive patients. The mean age of the patients was 59.8 years, 68.9% of patients were overweight or obese. Uncontrolled office systolic and diastolic BP >140/90 mm Hg was present in 89.6% and 81.5% of patients, respectively, despite the fact that 49.4% of patients used a combination of 2 or more antihypertensive drugs. The most common reasons for switching medication were insufficient BP control (73.7%), followed by aiming for a better 24-hour effect (38.4%) and increased cardiovascular risk of the patients (37.7%). The major reason for switching antihypertensive treatment in general practice was insufficient BP control. Switching medication because of adverse drug effects is less frequent than reported a decade ago.

This study was designed to assess the effect of the addition of low-dose spironolactone on blood pressure (BP) in patients with resistant arterial hypertension. Patients with office systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicentre trial. One hundred sixty-one patients in outpatient internal medicine departments of 6 hospitals in the Czech Republic were randomly assigned to receive 25 mg of spironolactone (N = 81) or a placebo (N = 80) once daily as an add-on to their antihypertensive medication, using simple randomization. This study was registered with ClinicalTrials.gov, number NCT00524615. A nalyses were done with 150 patients who finished the follow-up (74 in the spironolactone and 76 in the placebo group). At 8 weeks, BP values were decreased more by spironolactone, with differences in mean fall of SBP of -9.8, -13.0, -10.5, and -9.9 mm Hg (P < 0.001 for all) in daytime, nighttime, and 24-hour ambulatory BP monitoring and in the office. The respective DBP differences were -3.2, -6.4, -3.5, and -3.0 mm Hg (P = 0.013, P < 0.001, P = 0.005, and P = 0.003). Adverse events in both groups were comparable. The office SBP goal <14 mm Hg at 8 weeks was reached in 73% of patients using spironolactone and 41% using placebo (P = 0.001). Spironolactone in patients with resistant arterial hypertension leads to a significant decrease of both SBP and DBP and markedly improves BP control.

The asymmetric transfer hydrogenation (ATH) of imines catalyzed by the Noyori-Ikariya [RuCl(η6-arene)(N-arylsulfonyl-DPEN)] (DPEN=1,2-diphenylethylene-1,2-diamine) half-sandwich complexes is a research topic that is still being intensively developed. This article focuses on selected aspects of this catalytic system. First, a great deal of attention is devoted to the N-arylsulfonyl moiety of the catalysts in terms of its interaction with protonated imines (substrates) and amines (components of the hydrogen-donor mixture). The second part is oriented toward the role of the η6-coordinated arene. The final part concerns the imine substrate structural modifications and their importance in connection with ATH. Throughout the text, the summary of known findings is complemented with newly-presented ones, which have been approached both experimentally and computationally.

Initial risk stratification in patients with acute heart failure (AHF) is poorly validated. Previous studies tended to evaluate the prognostic significance of only one or two selected ECG parameters. The aim of this study was to evaluate the impact of multiple ECG parameters on mortality in AHF. The Acute Heart Failure Database (AHEAD) registry collected data from 4,153 patients admitted for AHF to seven hospitals with Catheter Laboratory facilities. Clinical variables, heart rate, duration of QRS, QT and QTC intervals, type of rhythm and ST-T segment changes on admission were collected in a web-based database. 12.7 % patients died during hospitalisation, the remainder were discharged and followed for a median of 16.2 months. The most important parameters were a prolonged QRS and a junctional rhythm, which independently predict both in-hospital mortality [QRS > 100 ms, odds ratio (OR) 1.329, 95 % CI 1.052-1.680; junctional rhythm, OR 3.715, 95 % CI 1.748-7.896] and long-term mortality (QRS > 120 ms, OR 1.428, 95 % CI 1.160-1.757; junctional rhythm, OR 2.629, 95 % CI 1.538-4.496). Increased hospitalisation mortality is predicted by ST segment elevation (OR 1.771, 95 % CI 1.383-2.269) and prolonged QTC interval >475 ms (OR 1.483, 95 % CI 1.016-2.164). Presence of atrial fibrillation and bundle branch block is associated with increased unadjusted long-term mortality, but mostly reflects more advanced heart disease, and their predictive significance is attenuated in the multivariate analysis. ECG in patients admitted for acute heart failure carries significant short- and long-term prognostic information, and should be carefully evaluated.

This review is oriented toward the asymmetric transfer hydrogenation (ATH) of imines regarding mostly fundamental, yet important topics from the practical point of view. Development of analytical methods for the monitoring of ATH (i.e., kinetics and stereoselectivity) belongs to those topics, as well as studies on the influence of reaction conditions and structural variations on the reaction performance. The second part is devoted to the reaction mechanism with the emphasis on imine ATH and catalyst behaviour under acidic conditions. The review also addresses the asymmetric hydrogenation (AH) of ketones and imines using molecular hydrogen and the application of ATH in pharmaceutical projects. The contributions of our group to each area are included.

Asymmetric transfer hydrogenation (ATH) of cyclic imines using [RuCl(η(6)-p-cymene)TsDPEN] (TsDPEN = N-tosyl-1,2-diphenylethylenediamine) was tested with various aliphatic (secondary, tertiary) and aromatic amines employed in the HCOOH-base hydrogen donor mixture. Significant differences in reaction rates and stereoselectivity were observed, which pointed to the fact that the role of the base in the overall mechanism could be more significant than generally accepted. The hydrogenation mixture was studied by nuclear magnetic resonance (NMR), Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and vibrational circular dichroism (VCD) with infrared spectroscopy. The results suggested that the protonated base formed an associate with the active ruthenium-hydride species, most probably via a hydrogen bond with the sulfonyl group of the complex. It is assumed that the steric and electronic differences among the bases were responsible for the results of the initial ATH experiments.

Perindopril is a long acting ACE inhibitor with a 24- hour lasting effect. Its positive effect on a reduction in cardiovascular events has been confirmed in a range of large randomized clinical trials and in a wide spectrum of patients: hypertonic patients, diabetics, patients with stable ischaemic heart disease, elderly patients, or patients who have undergone a cerebrovascular accident. The extending range of various fixed combinations as well as new pharmaceutical dosage forms, including the newly introduced orodispersible tablets of perindopril, enables optimization of treatment for every patient, an increase in the patients treatment adherence, and also improvement in longterm blood pressure control with a consequent effect on reduction of morbidity and mortality.

A 68-year-old woman with resistant essential arterial hypertension despite the regular use of four antihypertensive drugs was referred to the catheter-based renal sympathetic denervation. Due to the complicated anatomy, insertion of the guiding catheter into the left renal artery was not stable. Thus, renal denervation of only the right renal artery was performed. Before and after renal denervation, the patient's blood pressure was monitored by home blood pressure (BP) telemonitoring. The average 7-day home BP telemonitoring values before and 1, 2, and 3 months after denervation were 187.1/124.1, 193.3/123.1, 198.3/129.6, and 195.2/128.0 mm Hg. After unilateral renal denervation, no BP decrease occurred. This unique case suggests that unilateral catheter-based renal sympathetic denervation in resistant arterial hypertension shows no BP-lowering effect. Therefore, when treating resistant hypertension by catheter-based renal denervation, it seems advisable to try always to perform an effective bilateral procedure.

This paper presents a digital holographic method for measurement of periodic asymmetric temperature fields. The method is based on a modified Twyman-Green setup having double sensitivity. For measurement only one precisely synchronized and triggered digital camera is used. The periodicity and self-similarity of each cycle of the measured phenomenon combined with the precisely synchronized camera capture allow one to obtain data later used for three-dimensional (3D) measurement. The reconstruction of 3D temperature field is based on tomographic approach.

Objective: Even though several studies described a positive influence of elevated initial blood pressure on the outcome in acute heart failure (AHF), data specifically addressed to a population with severe AHF associated with antecedent hypertension, regardless of admission blood pressure values, are missing., Methods and Results: From the 4153 consecutive patients enrolled in the Czech AHF registry we selected 1343 patients who suffered from pulmonary oedema or cardiogenic shock and compared them according to the presence of antecedent hypertension. Demographic, clinical, laboratory, treatment profiles and mortality rates were assessed and predictors of short- and long-term outcome were identified. Patients with antecedent hypertension (n = 1053, 78%) were older (P < 0.001), more often women (P = 0.001), having more co-morbidities and a worse laboratory profile. A trend for worse survival of hypertensive patients was observed when compared to a non-hypertensive cohort (1-, 2-, 3-year survival 70.0, 61.5, 55.5% vs. 72.6, 68.2, 64.0%, P = 0.062). Age and creatinine levels were independently associated with mortality during the whole follow-up period (P < 0.001). Low left ventricular ejection fraction, need of mechanical ventilation, inotropic and vasopressor support, were adversely related to in-hospital mortality (P < 0.001). On the other hand, presence of initial tachycardia improved short-term outcome (P = 0.007). Long-term survival was worsened by initial atrial fibrillation (P = 0.036) and anaemia (P < 0.001) while the presence of de-novo AHF improved it (P = 0.009)., Conclusions: Long-term antecedent hypertension is not significantly correlated with mortality after an episode of severe AHF, but probably still participates in vascular and end-organ damage. Survival of these patients is determined by other associated co-morbidities.

This paper analyzes the possibility of increasing the acoustic transmission loss of sound transmitted through planar or curved glass shells using attached piezoelectric macro fiber composite (MFC) actuators shunted by active circuits with a negative capacitance. The key features that control the sound transmission through the curved glass shells are analyzed using an analytical approximative model. A detailed analysis of the particular arrangement of MFC actuators on the glass shell is performed using a finite element method (FEM) model. The FEM model takes into account the effect of a flexible frame that clamps the glass shell at its edges. A method is presented for the active control of the Young's modulus and the bending stiffness coefficient of the composite sandwich structure that consists of a glass plate and the attached piezoelectric MFC actuator. The predictions of the acoustic transmission loss frequency dependencies obtained by the FEM model are compared with experimental data. The results indicate that it is possible to increase the acoustic transmission loss by 20 and 25 dB at the frequencies of the first and second resonant modes of the planar and curved glass shells, respectively, using the effect of the shunt circuit with a negative capacitance.

Syncope is a symptom, defined as transient loss of consciousness and postural tone with spontaneous and mostly prompt recovery. At first it is necessary to differentiate other non-syncopal transient loss of consciousness and simple falls, where thorough history taking is pivotal. EGSYS and OESIL risk scores seem to be contributional in initial risk stratification, however they are neither widely accepted nor a part of national guidelines. They are part of the European society of cardiology guidelines, though. Next it is essential expert ECG evaluation, thorough physical status examination, supine and standing blood pressure measurement and carotid sinus massage, if not contraindicated. Successively one has to decide if hospitalization or outpatient management is more suitable. Recently it has been shown, that so-called syncope management units (aimed for short-term hospitalization or fast outpatient examination, including vital function monitoring, echocardiography and facile cathlab access) are effective in fast syncope evaluation. Echocardiography, ECG monitoring and head-up tilt test should be a part of complex diagnostic evaluation. If syncope is not clarified by upon stated methods moreover syncope is recurrent, electrophysiological study, ILR implantation or both are justified. Despite of entire health practitioner's effort, more than 1/3 of syncopes remain unexplained.

Methods for the asymmetric transfer hydrogenation (ATH) of ketones and imines are still being intensively studied and developed. Of foremost interest is the use of Noyori's [RuCl(η⁶-arene)(N-TsDPEN)] complexes in the presence of a hydrogen donor (i-PrOH, formic acid). These complexes have found numerous practical applications and have been extensively modified. The resulting derivatives have been heterogenized, used in ATH in water or ionic liquids and even some attempts have been made to approach the properties of biocatalysts. Therefore, an appropriate modification of the catalyst that suits the specific requirements for the reaction conditions is very often readily available. The mechanism of the reaction has also been explored to a great extent. Model substrates, acetophenone (a ketone) and 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline (an imine), are both reduced by this Ru catalytic system with almost perfect selectivity. However, in each case the major product is a different enantiomer (S- for an alcohol, R- for an amine when the S,S-catalyst is used), which demanded an in-depth mechanistic investigation. Full-scale molecular modelling of this system enabled us to visualize the plausible 3D structures of the transition states, allowing the proposition of a viable explanation of previous experimental findings.

There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (n=59) or a placebo (n=58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was -5.4 mm Hg (95%CI -10.0; -0.8) for systolic BP (P=0.024) and -1.0 mm Hg (95% CI -4.0; 2.0) for diastolic BP (P=0.358). The APBM nighttime systolic, 24-hour ABPM systolic, and office systolic BP values were significantly decreased by spironolactone (difference of -8.6, -6.6, and -6.5 mm Hg; P=0=0.011, 0.004, and 0.011 [corrected]), whereas the fall of the respective diastolic BP values was not significant (-3.0, -1.0, and -2.5 mm Hg; P=0.079, 0.405, and 0.079). The adverse events in both groups were comparable. In conclusion, spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension.

The current practice of withdrawing aspirin 7-10 days preoperatively may be dangerous in certain groups of patients. The risk of cardiovascular events increases 3-fold after aspirin withdrawal. The average time between aspirin withdrawal and the manifestation of acute coronary syndrome is 8 to 11 days. The withdrawal of clopidogrel earlier than 4-6 weeks after bare metal stent implantation or less than 12 months after drug-eluting stent implantation is very risky and poses a high risk of stent thrombosis and high perioperative mortality. Continuing aspirin perioperatively leads to a 1.5-fold increase in perioperative bleeding complications but it does not lead to a higher severity of bleeding complications or higher mortality. The article analyzes current European and American guidelines for perioperative antiplatelet treatment and suggests an algorithm based on the guidelines to help make clinical decisions., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

The automatic building of protein structures with tripeptidic and tetrapeptidic fragments was investigated. The oligopeptidic conformers were positioned in the electron-density map by a phased rotation, conformation and translation function and refined by a real-space refinement. The number of successfully located fragments lay within the interval 75-95% depending on the resolution and phase quality. The overlaps of partially located fragments were analyzed. The correctly positioned fragments were connected into chains. Chains formed in this way were extended directly into the electron density and a sequence was assigned. In the initial stage of the model building the number of located fragments was between 60% and 95%, but this number could be increased by several cycles of reciprocal-space refinement and automatic model rebuilding. A nearly complete structure can be obtained on the condition that the resolution is reasonable. Computer graphics will only be needed for a final check and small corrections.

We present a case of 60 years old patient with the history of repeated sinusitis and bronchial asthma, who developed Churg-Strauss syndrome (CSS) with mono-neuritis multiplex, skin laesions on the head and acute perimyocarditis, which led to suspicion on myocardial infarction. Diagnosis of CSS was based on clinical manifestations, blood hypereosinophilia and histological examination of nasal mucous membrane biopsy. Subsequent immunosuppressive therapy led to regression of symptoms and improvement of temporarily decreased left ventricular function.

Objectives: Detection of free plasma metanephrines seems to be the most exact method for biochemical diagnosis of pheochromocytoma, but their diagnostic efficacy in the common low-risk clinical settings is debated., Methods: A cross-sectional multicentre study including 1260 subjects assessed the diagnostic efficacy of free plasma metanephrine and normetanephrine in low-risk patients screened for resistant or markedly accelerated hypertension, paroxysmal hypertension, 'flushes' and, in a small proportion, for adrenal incidentaloma or genetic predisposition to pheochromocytoma., Results: Pheochromocytoma was identified and verified by histology in 25 subjects (2%), with the diagnosis not confirmed by long-term follow-up or use of imaging techniques in the remaining 1235 individuals. The combined assay of free plasma metanephrines was a highly sensitive (100%) and specific (96.7%) measure, yielding a negative predictive value of 100%., Conclusion: The satisfactory diagnostic efficacy of free plasma metanephrines allows their use as a single screening test in cases of suspected pheochromocytoma in the population with a low pretest probability.

Background: Aspirin resistance appears to be an important prognostic factor in patients with coronary artery disease, yet there is no standardized method to measure it and limited data on its correlation to clinical outcomes., Methods: In a prospective study we followed 103 patients (mean age 64 years) with acute coronary syndrome (ACS) without ST segment elevation who were treated with 100 mg of aspirin (ASA) daily. Optical platelet aggregometry using cationic propyl gallate (CPG) as an inductor was measured at ACS onset and after 3, 12, 24, 36, and 48 months. ASA responsiveness was defined both by the slope of the aggregation curve (<53%/min) and by spontaneous aggregation (<5%). The primary outcomes were the recurrence of ACS or stroke., Results: Patients with ACS exhibited a greater prevalence of ASA resistance (55%) than healthy volunteers (4%; p<0.01). ASA resistance occurred more often in patients with type 2 diabetes, hypertriacylglycerolemia, and decreased HDL levels, and in smokers (p<0.05). A single assessment of platelet aggregometry was sufficient to identify ASA-resistant patients. During the 4-year follow-up, the patients with ASA resistance had an 88% incidence of recurrent cardiovascular events versus 46% for the patients without ASA resistance (p<0.01). In the subgroup with recurrent cardiovascular (CV) events, significantly more patients were ASA-resistant than in the subgroup without recurrent CV events (72% vs. 8%, p<0.01)., Conclusion: ASA resistance measured by CPG-induced platelet aggregometry is more common among patients with ACS and some metabolic risk factors, and ASA-resistant patients have a significantly higher recurrence of cardiovascular events.

Oxidative stress and especially its connection with many diseases has been discussed much recently. Among markers of oxidative stress there appear new and quite specific ones called advanced oxidation protein products (AOPPs). We tried to influence the level of AOPPs by an antioxidant therapy with N-acetylcysteine. Fourteen individuals with many cardiovascular risk factors were examined. All these patients were administered acetylcysteine (NAC) 600 mg/day orally during 20 days. Before starting the therapy we determined AOPP, albumin cobalt binding (ACB), glucose, creatinine, urea, ALT, AST, cholesterol, LDL, HDL and triglycerides values in peripheral venous blood in all individuals. After finishing our intervention we determined AOPP, ACB and glucose level again. Our results show a statistically significant decrease in AOPP levels after 20-day N-acetylcysteine therapy (medians, initially 82.2, at study end 74.3 umol/l, p = 0.039). We demonstrate a significant decrease in AOPP levels after 20-day N-acetylcysteine therapy in dose 600 mg/day.