A QM-MD simulation approach to the analysis of FRET processes in (bio)molecular systems. A case study: complexes of E. coli purine nucleoside phosphorylase and its mutants with formycin A.

Predicting FRET pathways in proteins using computer simulation techniques is very important for reliable interpretation of experimental data. A novel and relatively simple methodology has been developed and applied to purine nucleoside phosphorylase (PNP) complexed with a fluorescent ligand - formycin A (FA). FRET occurs between an excited Tyr residue (D*) and FA (A). This study aims to interpret experimental data that, among others, suggests the absence of FRET for the PNPF159A mutant in complex with FA, based on novel theoretical methodology. MD simulations for the protein molecule containing D*, and complexed with A, are carried out. Interactions of D* with its molecular environment are accounted by including changes of the ESP charges in S1, compared to S0, and computed at the SCF-CI level. FRET probability W F depends on the inverse six-power of the D*-A distance, R da . The orientational factor 0 < k(2) < 4 between D* and A is computed and included in the analysis. Finally W F is time-averaged over the MD trajectories resulting in its mean value. The red-shift of the tyrosinate anion emission and thus lack of spectral overlap integral and thermal energy dissipation are the reasons for the FRET absence in the studied mutants at pH 7 and above. The presence of the tyrosinate anion results in a competitive energy dissipation channel and red-shifted emission, thus in consequence in the absence of FRET. These studies also indicate an important role of the phenyl ring of Phe159 for FRET in the wild-type PNP, which does not exist in the Ala159 mutant, and for the effective association of PNP with FA. In a more general context, our observations point out very interesting and biologically important properties of the tyrosine residue in its excited state, which may undergo spontaneous deprotonation in the biomolecular systems, resulting further in unexpected physical and/or biological phenomena. Until now, this observation has not been widely discussed in the literature.

[Genetic basis of cardiac diseases leading to heart failure]. / Genetyczne uwarunkowania chorób ukladu krazenia prowadzacych do niewydolnosci serca.

In the last few years medical genetics is assuming a much more prominent position in the etiology of cardiac diseases. The article presents the current state of the molecular and genetic basis of diseases leading to heart failure, such as coronary artery disease, idiopathic cardiomyopathy, valvular abnormalities, essential hypertension and other rare cardiac diseases. Looking for the molecular basis is followed by practical advice on the role of genetic testing, expanding of the methods of prophylaxis, modification of medical managing and treatment.

[Effects of thrombolysis on left and right ventricular diastolic function in patients after myocardial infraction. One-year follow-up]. / Wplyw leczenia trombolitycznego na czynnosc rozkurczowa lewej i prawej komory u pacjentów po zawale sciany przedniej. Obserwacja roczna.

UNLABELLED: It has been shown, that successful reperfusion of the infarctrelated artery by thrombolysis can prevent left ventricular (LV) dilatation and dysfunction. To date no study has shown the impact of thrombolytic therapy on LV and RV diastolic filling. The aim of the study was to assess the effects of thrombolysis on LV and RV diastolic inflow and systolic function of LV in patients (pts) after anterior myocardial infarction MI. METHODS: Echocardiographic and Doppler-derived measurements of LV systolic function, RV and LV diameters and diastolic function at rest and after treadmill exercise test (TET) were assessed prospectively in 21 patients (pts) after MI treated with streptokinase and 10 pts treated without thrombolysis during one-year follow-up. They were compared with 31 age-matched controls. RESULTS: LV and RV filling indices in both groups of pts after MI were impaired compared to controls but in pts without thrombolysis were more abnormal compared to pts treated with thrombolysis. Among several echocardiographic variables most consistent alteration was shortening of E-deceleration time of mitral as well as RV inflow, more abnormal in pts without thrombolysis. There was strong inverse relation between degree of impairment of diastolic variables and exercise capacity. CONCLUSIONS: These data indicates beneficial effect of thrombolysis on RV and LV diastolic function in patients after AMI. E-deceleration was the most sensitive marker of diastolic dysfunction.

[Psychological factors in coronary heart disease]. / Czynniki psychologiczne w chorobie niedokrwiennej serca.

Looking for pathophysiological factors in coronary heart disease involves genetics, environmental factors and difficult to estimate psychological and sociological factors, which may cause coronary heart disease as well as affect survival among patients. Randomized controlled trials are to support correlation between coronary heart disease and psychological factors and help to find such factors, which could be influenced in order to improve prognosis. There is a strong evidence for aetiological and prognostic role for depression and less evidence for anxiety and type A behaviour.

[The role of sodium in prevention and treatment of essential hypertension]. / Udzial sodu w zapobieganiu i leczeniu nadcisnienia tetniczego pierwotnego.

In the last few years there has been an increasing interest in restricting dietary sodium intake to prevent and treat essential hypertension. The article presents the role of sodium in etiopathogenesis of essential hypertension, in relation to sodium sensitivity. It also evaluates the dietary sodium restriction and puts an attention on the influence of antihypertensive drugs on the sodium balance.

[Effect of digoxin on atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic 3', 5'-guanosine monophosphate (cGMP) in patients with chronic congestive heart failure]. / Wplyw digoksyny na stezenie przedsionkowego peptydu natriuretycznego, mózgowego peptydu natriuretycznego i cyklicznego 3', 5'-guanozynomonofosforanu u chorych na przewlekla, zastoinowa niewydolnosc serca.

UNLABELLED: Neurohumoral factors play important role in the pathogenesis of congestive heart failure (CHF) and digoxin (dig) is one of the most frequently used drugs in this condition. The aim of this study was to assess the effects of dig on atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their "second messenger" cyclic 3',5'-guanosine monophosphate (cGMP). MATERIAL AND METHOD: The study group consisted of 25 patients (pts) aged 25-81 with CHF (NYHA II/III), 13 women and 12 men. Control group consisted of 10 healthy volunteers, 2 women and 8 men. The blood samples for evaluation of ANP, BNP and cGMP plasma level was taken at baseline conditions and 3 hours (h) after intravenous injection of 0.25 mg of dig. From the next day 0.25 mg dig was administrated orally for 6 days and plasma levels of ANP, BNP and cGMP were assessed on the 3rd and 6th day of treatment. Medium serum dig concentration on the 6th day was 0.98 ng/mL. RESULTS: The baseline ANP, BNP and cGMP plasma level was significantly higher in pts with CHD than in control group (ANP 144.4 vs 98.8 pg/ml p < 0.001; BNP 130.0 vs 97.2 pg/ml p < 0.001; cGMP 1.44 vs 0.86 pg/ml p < 0.001). In pts with CHF there was a significant increase ANP, BNP and cGMP plasma level 3 h after dig intravenous injection (ANP 205.2 vs 144.4 pg/ml p < 0.01; BNP 227.1 vs 130.0 pg/ml p < 0.01; cGMP 1.84 vs 1.44 pg/ml p < 0.01). The ANP and BNP plasma level after 3 days of oral dig was still significantly increased (ANP 171.1 vs 144.4 pg/ml p < 0.05; BNP 223.7 vs 130.0 pg/ml p < 0.01). ANP, BNP and cGMP plasma level was higher in pts with CHF also after 6 days of oral dig, but the difference was statistically significant. After 6 days of digoxin treatment there was a significant increase of ejection fraction (p < 0.005), with reduction of end-diastolic diameter of left ventricle (p < 0.05) and diameter of left atrium (p < 0.01). ANP at baseline correlated positively with baseline cGMP (r = 0.702 p < 0.05). On the 6th day BNP correlated positively with cGMP (r = 0.628 p < 0.05). 3 h after dig intravenous injection ANP correlated positively with BNP (r = 0.881 p < 0.05), but on the 3rd day of oral dig ANP correlated negatively with BNP (r = -0.536 p < 0.05). On the 6th day of oral dig end-diastolic diameter of left ventricle correlated negatively with BNP (r = -0.483 p < 0.05) and cGMP (r = -0.824 p < 0.05). CONCLUSIONS: 1. In pts with CHF a single intravenous digoxin injection increases ANP, BNP and cGMP plasma level. 2. Oral digoxin administration supports this beneficial neurohumoral effect and improves hemodynamic parameters of left ventricle as well as reduces left atrium diameter.

[Incidence of myocardial ischemia in patients with ischemic heart disease tested with 48-hour Holter monitoring]. / Wystepowanie incydentów niedokrwienia miesnia sercowego u chorych na chorobe niedokrwienna serca w 48-godzinnym badaniu holterowskim.

The aim of the work was to examine the frequency, duration and times of occurrence of painful and painless episodes of heart muscle ischaemia in patients suffering from ischaemic heart disease as well as to evaluate its variations during 24-hour period. Out of all 30 subjects, altogether 104 episodes of myocardial ischaemia were recorded in 18 patients. 67 episodes (in 16 patients) were recorded in the first 24-hour period, and 37 episodes (11 patients) were recorded in the second 24-hour period. 7 patients revealed the incidence of episodes only during the first 24-hour period and 2 patients recorded episodes only in the second 24-hour period. Out of 9 patients in whom ischaemic episodes were observed both in the first as well as in the second 24-hour period, more episodes occurred in the first 24-hour period in 5 patients, more episodes in the second 24-hour period were observed in 3 patients and the same number of episodes in both 24-hour periods was observed in 1 subject. Average duration of the episode was significantly longer in the first 24-hour period. Characteristic 24-hour distribution of ischaemic episodes was observed with peak incidence between 6.00:8.00, 8.00:10.00 and between 18.00:20.00. The times of occurrence of ischaemic episodes on 24-hour monitoring resemble these registered on 48-hour monitoring. Differences in occurrence of ischaemic episodes between first and second 24-hour period were observed, but they reached the level of statistical significance only in the time of their peak incidence, between 8.00 and 10.00 a.m. and 18.00 and 20.00 (p < 0.05). Characteristic pattern of distribution of the episodes of myocardial ischaemia was observed. The number of episodes of myocardial ischaemia is higher in the first 24-hour period of monitoring, although the level of statistical significance was achieved only for episodes occurring between 8.00:10.00 and 18.00:20.00. Duration of ischaemic episodes on 48-hour Holter monitoring is statistically significantly longer during the first 24-hours of monitoring. Majority of ischaemic episodes are painless.

[Neurohumoral mechanisms in pathophysiology of chronic heart failure]. / Mechanizmy neurohumoralne w patofizjologii przewleklej niewydolnosci serca.

Pathogenic mechanisms of chronic systolic heart failure are constantly of great interest. In recent years the neurohumoral theory of heart failure has gained attraction. According to this theory, neurohumoral mechanisms play the main role in the pathogenesis of heart failure, especially in its progression. These mechanisms can be divided into 2 categories: vasoconstrictive, mitogenic and antinatriuretic on the one hand and vasodilative, antimitogenic and natriuretic on the other one. The former consists of sympathetic nervous system, renin-angiotensin-aldosterone system, vasopressin, endothelin, cytokines. The latter comprises natriuretic peptides, prostaglandins and nitric oxide. Undoubtedly unfavourable roles of sympathetic system and renin-angiotensin-aldosteron have been shown in the progression of heart failure. Data are being also gathered confirming harmful effects of endothelin and cytokines and possibly of neuropeptide Y and vasopressine. Extensive data exist that demonstrate beneficial influence of natriuretic peptide on heart failure. The roles of nitric oxide as well as recently discovered adrenomedullin and medullipin are far from clear.

[The effect of intravenous magnesium on the arrhythmias in patients after electrical cardioversion]. / Wplyw dozylnie podawanego roztworu magnezu na zaburzenia rytmu serca u chorych po kardiowersji elektrycznej.

The aim of this study was to examine the effect of magnesium, applied by intravenous infusion, on supraventricular and ventricular cardiac arrhythmias in patients after effective electric cardioversion. 30 patients examined were: 4 women and 26 men aged from 24 to 84 years (the average age being 56.1). All patients had previously been treated successfully by electric cardioversion. Patients were divided into two groups: group 1 of 15 patients aged 24 through 74 years, group 2 of 15 patients aged 25 through 76 years. After effective cardioversion, in the first group of patients, the infusion of 500 ml 0.9% NaCl was applied; whereas the other group of patients received 500 ml 0.9% NaCl with 5g MgSO4 and 20 mEq KCl. After electric cardioversion all patients had 24-hour Holter monitoring. After successful electric cardioversion in all the examined patients, supraventricular and ventricular cardiac arrhythmias were observed. However, in group 2 numerous premature supraventricular beats, episodes of atrial fibrillation, numerous premature ventricular beats, multifocal premature ventricular beats and pairs of ventricular beats were rarer than in the 1st group. In conclusion, it should be stated that the intravenous application of magnesium can be an effective method of treating supraventricular et ventricular cardiac arrhythmias occurring with patients after electric cardioversion.

[Obesity and cardiovascular diseases]. / Otylosc a choroby ukladu krazenia.

Obesity is a chronic complex disorder, which requires long-term treatment. The aim of this study was to estimate on the basis of current literature the coexistence of the cardiovascular system diseases and overweight. It was concluded that obesity is an independent risk factor for coronary heart disease, hypertension and heart failure.

[Studies of arrhythmia incidence and heart rate variability in patients suffering from cerebral stroke]. / Badania nad czestoscia wystepowania zaburzen rytmu serca i zmiennoscia rytmu serca u chorych na udar mózgu.

Patients with cerebral stroke develop electrocardiographic changes concerning the period of ventricular muscle repolarization and cardiac arrhythmias, which may results in the possibility of acute circulatory arrest. ECG monitoring by means of Holter method provides not only information concerning arrhythmias, episodes of ischaemia of the cardiac muscle, but it is also a recognised and generally accepted method of investigation of the autonomic system. The aim of the study was to assess the incidence of arrhythmias and heart rate variability in patients suffering from recent cerebral stroke. The studies involved 36 patients, in that 22 women (mean age 67.7 +/- 7.2 years) and 14 men (mean age 66.5 +/- 11.3 years) within first 24 hours after cerebral stroke confirmed by computerised tomography (CT). One the basis of CT scan haemorrhagic stroke was diagnosed in 7 patients and ischaemic stroke, after ruling out haemorrhagic stroke and neurological consultations, in 29 patients. Moreover, all patients revealed hypertension, 12 of them mild degree (1 degree), and 21 of moderate degree (2 degrees), and 3 of severe degree (3 degrees). The control group comprised 65 patients suffering from primary hypertension without concomitant cerebral stroke, matching the study group as to sex and age as well as the degree of hypertension. All of them were submitted to 24-hour Holter monitoring on tape by means of 3-channel registrator MR45, analysis of ECG tracings was carried out according to Optima Jet system manufactured by Oxford. In order to facilitate further analysis, the automatic recording was verified visually and next heart rate variability (HRV) was estimated within 24 hours and separately for day hours 6:00-22:00 and night hours 22:00-6:00. In comparison to patients with hypertension, but without stroke, subjects with hypertension and accompanying cerebral stroke more often reveal premature supraventricular beats, pairs of ventricular beats as well as episodes of nonsustained ventricular tachycardia; they also reveal lower 24-hours heart rate variability.

[QT dispersion in patients with acute myocardial infarction]. / Dyspersja QT u chorych ze swiezym zawalem miesnia serca.

The aim of the study was the evaluation of the QT dispersion interval in patients with acute myocardial infarction, taking into consideration its location, treatment provided and coronary artery reperfusion. Investigations were performed in 75 patients treated because of acute myocardial infarction, including 57 men and 18 women, age 40-84 years. Acute myocardial infarction was recognised on a base of generally accepted criteria. At the reception standard 12-outputs ECG was performed. Next ECG testing was performed after 3 hours from the start of the thrombolytic therapy. In case of patients which were not qualified for thrombolytic therapy next ECG was applied within 3 hours after reception. For further observation of changes in QT dispersion ECG generally provided within 2, 3, 4 and 5 day of hospitalization were used. Taking as a location criterium of infarction the method of provided treatment and obtained reperfusion in the infarcted area, patients were classified to the one of 6 groups. To the first group (I)-patients with inferior wall infarction, treated thrombolytically with obtained reperfusion-15 patients were included, age 41-69 years. To the second group (II)-patients with inferior wall infarction, treated thrombolytically without obtained reperfusion-18 persons were included, age 43-84 years. To the third group (III)-patients with inferior wall infarction, not treated thrombolytically-9 patients were included, age 49-72 years. To the fourth group (IV)-patients with anterior wall infarction, treated thrombolytically with obtained reperfusion-9 persons were included, age 40-73 years. To the fifth group (V)-patients with anterior wall infarction, treated thrombolytically without obtained reperfusion-10 persons were included, age 47-78 years. To the sixth group (VI)-patients with anterior wall infarction, not treated thrombolytically-14 patients were included, age 44-81 years. Control group for the comparison of initial evaluation of the QT and QTc dispersion interval was group of 11 healthy persons, age 27-64 years. There was proved, that in patients with acute myocardial infarction, independently of its location, QT and QTc dispersion was increased. Thrombolytic therapy in patients with acute inferior wall myocardial infarction with reperfusion obtained causes extension of QT dispersion. In patients with acute anterior wall myocardial infarction thrombolytic therapy with obtained reperfusion causes reduction of QT and QTc dispersion. In patients not treated thrombolytically, which had anterior wall myocardial infarction, in first days of observation QT and QTc dispersion was increased. This effect was not observed in patients with inferior wall infarction.

[Ventricular arrhythmias in patients with mitral valve prolapse and spurious cords in heart ventricles]. / Wystepowanie komorowych zaburzen rytmu serca u chorych z wypadaniem platka zastawki dwudzielnej i strunami rzekomymi w komorach serca.

The aim of the work to assess the frequency of ventricular arrhythmias in patients with isolated mitral valve prolapse isolated spurious cords in heart ventricles as well as in those patients who had both, mitral valve prolapse and spurious cord in heart ventricle. Out of 4156 successive electrocardiographic investigations carried out at the Department and Clinic of Cardiology, Medical Academy in Wroclaw, coexistence of spurious cords in heart ventricle and mitral valve prolapse was diagnosed in 32 patients (0.8% of all subjects), isolated mitral valve prolapse--in 184 patients (4.4%) and presence of isolated spurious cords not accompanied by mitral valve prolapse--in 91 patients (2.2%). In 20 patients with coexistence of spurious cords in heart ventricles and mitral valve prolapse, ventricular arrhythmias occurred in 12 subjects (60.0%) and in 5 of them they were significant. In the group of 29 patients with isolated spurious cords, disturbances of the ventricular rhythm occurred in 13 subjects (44.8%), while significant ventricular arrhythmias were found in 6 patients (20.7%). Out of 60 subjects with isolated mitral valve prolapse disturbances of the ventricular rhythm were found in 20 patients (33.3%) and significant arrhythmias--in 12 subjects (20.0%). The observations did not reveal increased prevalence of significant ventricular disturbances of the heart rhythm in patients with coexisting mitral valve prolapse and spurious cords in the heart ventricles.

[Angiotensin converting enzyme inhibitors for hypertension]. / Leki blokujace enzym konwertujacy w nadcisnieniu tetniczym.

The review paper presents modern opinions upon angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension. It describes their hypotensive properties and therapeutic efficacy. The review discusses also using of ACE inhibitors for disorders often coexisting with hypertension, likewise it presents ACE inhibitors in combination with other hypotensive drugs. The paper discusses also side effects of ACE inhibitors as well as diseases, in which ACE inhibitors are contraindicated.

[Myoglobin concentration in serum as an early marker of reperfusion in patients with acute myocardial infarction after thrombolytic therapy]. / Stezenie mioglobiny w surowicy jako wczesny wskaznik udroznienia tetnic wiencowych u chorych ze swiezym zawalem serca leczonych trombolitycznie.

Detection of coronary artery reperfusion in patients after thrombolytic therapy because of acute myocardial infarction includes, except angiography, disappearance of anginal pain, regression of electrocardiographic and echocardiographic myocardial ischaemia symptoms, increased activity of creatine kinase (CPK) and its isoenzyme CK-MB. The aim of the study was to check whether changes in myoglobin serum concentration could be an early marker of coronary artery reperfusion after thrombolysis in patients with acute myocardial infarction. The studies comprised 50 patients treated by thrombolysis due to threatening myocardial infarction, including 29 men and 21 women aged 43-84 years. The patients were divided into 2 groups: the first (i)-patients without symptoms of coronary artery reperfusion and the second (ii)-those with symptoms of coronary artery reperfusion. It was assumed that the basis for successful reperfusion would be the reduction of total elevations of the ST segment 70% or more in electrocardiographic recording performed 3 hours after the start of thrombolytic treatment. Reperfusion was considered completely unsuccessful when reduction of total elevations was less than 30%. In patients with reperfusion after thrombolysis the concentrations of myoglobin were much higher and the activity of CPK and CK-MB significantly more intensive in comparison with patients without reperfusion symptoms in electrocardiographic assay. The evaluation of myoglobin concentration, CPK and CK-MB activity in the 3rd hour after the start of thrombolytic treatment in relation to maximum values is characterised by high sensitivity and specificity in the prediction of reperfusion onset Maximum myoglobin concentration in serum appears significantly earlier than maximum CPK and CK-MB activity and this marker is characterised by higher sensitivity and specificity in the evaluation of coronary artery reperfusion than the activity of CPK and CK-MB.

Utilization of standards generated in the process of thermal decomposition chemically modified silica gel for a single point calibration of a GC/FID system.

The utilization of a multicomponent gaseous standard mixture, containing CO and CO(2) and obtained by thermal decomposition of a so-called immobilized compound, for a single point calibration of a GC/FID system are described. The generation of such a mixture takes place as a result of thermal decomposition of a sample of chemically modified silica gel placed in a heated chamber of thermal desorber coupled with the device being calibrated via a catalytic methanizer. The mean amount of the analyte librated from unit mass of the gel was 0.71 mg g(-1) (RSD = 3%) for carbon monoxide and 0.86 mg g(-1) (RSD = 3%) for carbon dioxide.

[QT dispersion]. / Dyspersja QT.

The study presents the modern concepts on QT dispersion which is regarded as one of the reasons of potentially dangerous cardiac arrhythmias. The measurement of QT interval is based on standard 12-lead electrocardiogram or 24-hours Holter monitoring record. The study describes the rules of QT dispersion measurement and the most common problems connected with it. The changes of QT dispersion in ischaemic heart disease, heart failure, cardiac arrhythmia and prolonged QT interval syndrome were discussed. The study presents also the influence of such drugs as amiodarone, sotalol, beta-adrenolytics on QT dispersion. It was found out that QT dispersion measurement in patients with cardiac diseases seems to be the easy predictor of life-threatening cardiac arrhythmias. The problem is still very controversial and needs further clinical investigations.

[Propafenone, flecainide, procainamide in the treatment of a fresh attack of atrial fibrillation]. / Propafenon, Flekainid i prokainamid w leczeniu swiezego napadu migotania przedsionków.

The purpose of the present work was an assessment of the effectiveness of intravenously administered propafenone, flecainide and procainamide in restoration of sinus rhythm in patients with atrial fibrillation attack lasting not more than 48 hours, The studies were carried out in 95 patients, including 30 treated with propafenone, 27 with flecainide, and 38 with procainamide. Propafenone turned out to be effective in 23 patients (76.7%), flecainide in 19 patients (70.4%), and procainamide in 14 patients (36.8%). Each of the drugs more effectively restored sinus rhythm in patients with smaller size of the left atrium and with shorter duration of atrial fibrillation attack, and propafenone and flecainide were also more effective in younger patients. The return of sinus rhythm was accompanied a reduction of the size of the left atrium. None of the studied drugs caused any more important adverse effects.

[Effect of propranolol on arrhythmia in individuals with false chordae in heart ventricles]. / Wplyw propranololu na zaburzenia rytmu u osób ze strunami rzekomymi w komorach serca.

In 4156 echocardiographic examinations, false chordae were observed in 91 persons (2.2%). It was shown that false chordae without evidence of traction caused no increase of the risk of development of ventricular arrhythmia (class II and over according to Lown). In 50% of persons with false chordae and the evidence of traction significant ventricular arrhythmia occurred. It was found that administration of the drugs with negative inotropic action may increase arrhythmia in persons with false chordae in the heart ventricles.