Discovery of a class of potent gap-junction modifiers as novel antiarrhythmic agents

In an effort to discover potent, orally bioavailable compounds for the treatment of atrial fibrillation (AF) and ventricular tachycardia (VT), we developed a class of gap-junction modifiers typified by GAP-134 (1, R¹ = OH, R² = NH₂), a compound currently under clinical evaluation. Selected compounds with the desired in-vitro profile demonstrated positive in vivo results in the mouse CaCl₂ arrhythmia model upon oral administration.     

The cardioprotective effect of different doses of vasopressin (AVP) against ischemia–reperfusion injuries in the anesthetized rat heart

The aim of the present study was to investigate the protective effect of various doses of exogenous vasopressin (AVP) against ischemia–reperfusion injury in anesthetized rat heart. Anesthetized rats were randomly divided into seven groups (n = 4–13) and all of them subjected to prolonged 30 min regional ischemia and 120 min reperfusion. Group I served as saline control with ischemia, in treatment groups II, III, IV and V, respectively different doses of AVP (0.015, 0.03, 0.06 and 1.2 μg/rat) were infused within 10 min prior to ischemia, in group VI, an AVP-selective V1 receptor antagonist (SR49059, 1 mg/kg, i.v.) was administrated prior to effective dose of AVP injection and in group VII, SR49059 (1 mg/kg, i.v.) was only administrated prior to ischemia. Various doses of AVP significantly prevented the decrease in heart rate (HR) at the end of reperfusion compared to their baseline and decreased infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB) and MDA (malondialdehyde) plasma levels], severity and incidence of ventricular arrhythmia, episodes and duration of ventricular tachycardia (VT) as compared to control group. Blockade of V1 receptors by SR49059 attenuated the cardioprotective effect of AVP on ventricular arrhythmias and biochemical parameters, but partially returned infarct size to control. AVP 0.03 μg/rat was known as effective dose. Our results showed that AVP owns a cardioprotective effect probably via V1 receptors on cardiac myocyte against ischemia/reperfusion injury in rat heart in vivo.     

RISK pathway is involved in oxytocin postconditioning in isolated rat heart

The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal transduction cascade in the cardioprotective mechanism of ischemic postconditioning. In the present study, we examined the cardioprotective role of oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt and ERK1/2).Animals were randomly divided into 6 groups. The hearts were subjected under 30 minutes (min) ischemia and 100 min reperfusion. OT was perfused 15 min at the early phase of reperfusion. RISK pathway inhibitors (Wortmannin; an Akt inhibitor, PD98059; an ERK1/2 inhibitor) and Atosiban (an OT receptor antagonist) were applied either alone 10 min before the onset of the ischemia or in the combination with OT during early reperfusion phase. Myocardial infarct size, hemodynamic factors, ventricular arrhythmia, coronary flow and cardiac biochemical marker were measured at the end of reperfusion.OT postconditioning (OTpost), significantly decreased the infarct size, arrhythmia score, incidence of ventricular fibrillation, Lactate dehydrogenase and it increased coronary flow. The cardioprotective effect of OTpos was abrogated by PI3K/Akt, ERK1/2 inhibitors and Atosiban.Our data have shown that OTpost can activate RISK pathway mostly via the PI3K/Akt and ERK1/2 signaling cascades during the early phase of reperfusion.     

Nonlinear synchronization assessment between atrial and ventricular activations series from the surface ECG in atrial fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice. Its presence causes a rapid and irregular ventricular response, being the topic of intensive research in rate control therapies of AF. To this respect, recent studies suggest that ventricular response is notably influenced by atrial activity (AA) temporal organization. However, the interdependency between atrial and ventricular activations has not been adequately explored to date in real-life AF patients. The present work introduces a novel methodology to quantitatively assess synchronization and coupling between real atrial and ventricular activation series. Furthermore, the method operates on surface ECG recordings, thus providing an easy and cost-effective way to be applied. The method is based on a nonlinear index, such as cross-sample entropy (CSE), which estimates the conditional probability to find similar patterns within both activation series. The study has been carried out on patients with paroxysmal and persistent AF in order to be applied over atrial activation series with different properties in their organization. Results showed a statistically significant positive correlation between AA organization and the synchronization between atrial and ventricular activations (R = 0.53, p < 0.01). Furthermore, higher CSE values were observed for persistent (0.759 ± 0.053) than for paroxysmal AF episodes (0.662 ± 0.091), thus suggesting more synchronization between atrial and ventricular activations in paroxysmal AF. As a consequence, CSE provided findings consistent with previous works and could be used to reveal clinically useful information in the improvement of current rate control therapies, which are mainly focused on controlling ventricular rate without paying much attention to the atrial fibrillatory process.     

The effect of feeding expeller-pressed canola meal on growth performance and diet nutrient digestibility in weaned pigs

The effects of feeding increasing levels of expeller-pressed (EP) canola meal in substitution for soybean meal as an energy and amino acid source were evaluated in 240 weaned pigs with an initial body weight of 7.3 ± 0.6 kg. Five pelleted wheat-based diets containing 0, 50, 100, 150 or 200 g EP canola meal/kg were formulated to contain 10.0 MJ net energy (NE)/kg and 1.18 g standardised ileal digestible (SID) lysine/MJ NE and were fed for 4 wk starting 1 wk after weaning at 19 days of age. Expeller-pressed canola meal was added at the expense of soybean meal and the diets were balanced for NE using canola oil and for amino acids using crystalline lysine, methionine, threonine and tryptophan. Increasing inclusion of EP canola meal linearly reduced (P<0.001) the apparent total tract digestibility of energy, dry matter and crude protein and the digestible energy content of diets. From 0 to 28 days on trial, increasing inclusion of EP canola meal did not affect body weight gain, feed intake and feed efficiency. In conclusion, up to 200 g EP canola meal/kg can replace soybean meal in diets formulated to equal NE and SID amino acid content and fed to nursery pigs starting 1 wk after weaning without reducing growth performance.     

Atrial flutter and atrial tachycardia detection using Bayesian approach with high resolution time–frequency spectrum from ECG recordings

Contemporary methods of atrial flutter (AFL), atrial tachycardia (AT), and atrial fibrillation (AF) monitoring, although superior to the standard 12-lead ECG and symptom-based monitoring, are unable to accurately discriminate between AF, AFL and AT. Thus, there is a need to develop accurate, automated, and comprehensive atrial arrhythmia detection algorithms using standard ECG recorders. To this end, we have developed a sensitive and real-time realizable algorithm for accurate AFL and AT detection using any standard electrocardiographic recording. Our novel method for automatic detection of atrial flutter and atrial tachycardia uses a Bayesian approach followed by a high resolution time–frequency spectrum. We find the TQ interval of the electrocardiogram (ECG) corresponding to atrial activity by using a particle filter (PF), and analyze the atrial activity with a high resolution time–frequency spectral method: variable frequency complex demodulation (VFCDM). The rationale for using a high-resolution time–frequency algorithm is that our approach tracks the time-varying fundamental frequency of atrial activity, where AT is within 2.0–4.0 Hz, AFL is within 4.0–5.3 Hz and NSR is found at frequencies less than 2.0 Hz. For classifications of AFL (n = 22), AT (n = 10) and normal sinus rhythms (NSR) (n = 29), we found that our approach resulted in accuracies of 0.89, 0.87 and 0.91, respectively; the overall accuracy was 0.88.     

Synthesis and evaluation of 18F-labeled CJ-042794 for imaging prostanoid EP4 receptor expression in cancer with positron emission tomography

The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with ¹⁸F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. ¹⁸F-CJ-042794 was synthesized via a copper-mediated ¹⁸F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5 ± 1.1% (n = 2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that ¹⁸F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood. The EP4-receptor-expressing LNCaP prostate cancer xenografts were clearly visualized in PET images with 1.12 ± 0.08%ID/g (n = 5) uptake value and moderate tumour-to-muscle contrast ratio (2.73 ± 0.22) at 1 h post-injection. However, the tumour uptake was nonspecific as it could not be blocked by co-injection of cold standard, precluding the application of ¹⁸F-CJ-042794 for PET imaging of EP4 receptor expression in cancer.     

An aromatic amino acid within intracellular loop 2 of the prostaglandin EP2 receptor is a prerequisite for selective association and activation of Gαs

We previously demonstrated that the aromatic moiety of Tyr¹⁴³ within the intracellular loop 2 (ICL2) region of the prostaglandin EP2 receptor plays a crucial role in Gs coupling. Here we investigated whether the ICL2 of the EP2 receptor directly binds to Gαs and whether an aromatic moiety affects this interaction. In Chinese hamster ovary cells, mutations of Tyr¹⁴³ reduced the ability of the EP2 receptor to interact with G proteins as demonstrated by GTPγS sensitivity, as well as the ability of agonist-induced cAMP formation, with the rank order of Phe > Tyr (wild-type) = Trp > Leu > Ala (= 0). We found that the wild-type ICL2 peptide (i2Y) and its mutant with Phe at Tyr¹⁴³ (i2F) inhibited receptor-G protein complex formation of wild-type EP2 in membranes, whereas the Ala-substituted mutant (i2A) did not. Specific interactions between these peptides and the Gαs protein were detected by surface plasmon resonance, but Gαs showed different association rates, with a rank order of i2F > i2Y ≫ i2A, with similar dissociation rates. Moreover, i2F and i2Y, but not i2A activated membrane adenylyl cyclase. These results indicate that the ICL2 region of the EP2 receptor is its potential interaction site with Gαs, and that the aromatic side chain moiety at position 143 is a determinant for the accessibility of the ICL2 to the Gαs protein.     

Efficacy of olmesartan and nifedipine on recurrent hypoxia-induced left ventricular remodeling in diabetic mice

AimsRecurrent hypoxia due to sleep apnea syndrome is implicated in cardiovascular events, especially in diabetic patients, but the underlying mechanisms remain controversial. We previously reported that angiotensin II receptor blockers can improve hypoxia-induced left ventricular remodeling. The aim of this study was to examine the effect on left ventricular remodeling of adding a calcium channel blocker to angiotensin II receptor blocker therapy in diabetic mice exposed to recurrent hypoxia.Main methodsMale db/db mice (8-week-old) and age-matched control db/+ mice were fed a Western diet and subjected to recurrent hypoxia (oxygen at 10 ± 0.5% for 8 h daily during the daytime) or normoxia for 3 weeks. Hypoxic db/db mice were treated with the vehicle, olmesartan (3 mg/kg/day), nifedipine (10 mg/kg/day), or both drugs.Key findingsRecurrent hypoxia caused hypertrophy of cardiomyocytes, interstitial fibrosis, and a significant increase in expression of the oxidative stress marker 4-hydroxy-2-nonenal (4-HNE) in the left ventricular myocardium. Treatment with olmesartan, nifedipine, or both drugs had no effect on systolic blood pressure, and each treatment achieved similar suppression of 4-HNE expression. Olmesartan and the combination with olmesartan and nifedipine significantly prevented cardiomyocyte hypertrophy more than treatment with nifedipine alone. On the other hand, olmesartan combined with nifedipine significantly reduced cytokine expression, superoxide production and matrix metalloproteinase (MMP)-9 activity, and significantly suppressed interstitial fibrosis in the left ventricular myocardium.SignificanceThe combination with olmesartan and nifedipine, as well as a monotherapy with olmesartan, exerts preferable cardioprotection in diabetic mice exposed to recurrent hypoxia.     

Are chronic neck pain,scapular dyskinesis and altered scapulothoracic muscle activity interrelated?: A case-control study with surface and fine-wire EMG

ObjectivesThe function of the scapula is important in normal neck function and might be disturbed in patients with neck pain. The surrounding muscular system is important for the function of the scapula. To date, it is not clear if patients with idiopathic neck pain show altered activity of these scapulothoracic muscles. Therefore, the objective of this study was to investigate differences in deeper and superficial lying scapulothoracic muscle activity between patients with idiopathic neck pain and healthy controls during arm elevation, and to identify the influence of scapular dyskinesis on muscle activity.MethodsScapular dyskinesis was rated with the yes/no method. The deeper lying (Levator Scapulae, Pectoralis Minor (Pm) and Rhomboid major) and superficial lying (Trapezius and Serratus Anterior) scapulothoracic muscles’ activity was investigated with fine-wire and surface EMG, respectively, in 19 female subjects with idiopathic neck pain (age 28.3 ± 10.1 years, average duration of neck pain 45.6 ± 36.3 months) and 19 female healthy control subjects (age 29.3 ± 11.7 years) while performing scaption and towel wall slide. Possible interactions or differences between subject groups, scapular dyskinesis groups or phases of the task were studied with a linear mixed model.ResultsHigher Pm activity during the towel wallslide (p = 0.024, mean difference 8.8 ± 3.3% MVIC) was shown in patients with idiopathic neck pain in comparison with healthy controls. For the MT, a significant group 1 dyskinesis interaction effect was found during scaption which revealed that patients with neck pain and scapular dyskinesis showed lower Middle Trapezius (MT) activity in comparison with healthy controls with scapular dyskinesis (p = 0.029, mean difference 5.1 ± 2.2% MVIC).ConclusionsIn the presence of idiopathic neck pain, higher Pm activity during the towel wallslide was found. Patients with neck pain and scapular dyskinesis showed lower MT activity in comparison with healthy controls with scapular dyskinesis during scaption. Scapular dyskinesis did not have a significant influence on scapulothoracic muscle activity.     

Effect of enzymatic and hydrothermal treatments of rapeseeds on quality of the pressed rapeseed oils: part II. Oil yield and oxidative stability

Response surface methodology was used to evaluate the quantitative effects of three independent variables: rapeseed moisture content (MC), enzymes dosage (ED) and conditioning temperature (T) on rapeseed oil yield (OY), efficiency of pressing (EP), and oxidative stability (OS). The highest OY (16.4%) and EP (42.8%) were obtained from pectolytic enzyme (0.1%) treated seeds (MC = 9%, T = 90 °C). The highest OS (12.6 h) was found for oil pressed from rapeseeds heated at 120 °C (MC = 11%), after the cellulolytic enzyme treatment. Results of OY, EP and OS determinations correlate with the predicted values calculated from the partial cubic models (PCMs) equations (R² = 0.9995, 0.9994, 0.9974 for the cellulolytic enzyme-treated oils and 0.9900, 0.9900, 0.9990 for the pectolytic enzyme-treated oils). The predicted optimum MC = 9.5% and 8.6%, ED = 0.06% and 0.1%, T = 91.2 °C and 90.1 °C resulted in OY = 15.5% and 16.5%, EP = 40.4% and 43.0% for rapeseed oils from seeds treated with cellulolytic and pectolytic enzymes. OS values (12.6 h and 11.8 h) at the optimum conditions of MC = 11.0% and 10.1%, ED = 0.04% and 0.08%, T = 120.0 °C and 119.9 °C for the cellulolytic and pectolytic enzyme-treated oils were also calculated using PCM. Moreover, scanning electron microscopy revealed structural changes in the rapeseed after enzymatic treatment.     

Faisabilité et précision diagnostique d’un protocole de scintigraphie myocardique synchronisée à l’ECG en deux heures : l’étude Myofast

Aim of the studyTo assess the feasibility of early stress and rest myocardial perfusion and function study using a fast 99mTc-tetrofosmin gated-SPECT protocol in patients with known coronary artery disease.Materials and methodsForty-three patients (pts) (37 M, 6 F, mean age 63.8 ± 9.8 years) underwent a 99mTc-Tetrofosmin gated-SPECT (Axis Picker-Philipps^®) myocardial study and a coronary angiography (CA) within 3 months. Images were acquired (LEHR, eight bins, 40 sec per image) after injection of 99mTc-tetrofosmin (200 to 380 MBq) early (15 min) post-stress (36 dipyridamole, two dobutamine and five ergometric stress), and at rest after 99mTc-tetrofosmin reinjection (600 to 1150 MBq), in a total time not exceeding 2 hours. Processing was performed with QGS^® software using the 17-segment model. Pathological study was defined as a summed difference score (SDS) greater than or equal to 4 4, a fixed defect with summed rest score greater than or equal to 4 and/or LV dysfunction defined as myocardial stunning (variation between stress and rest LVEF greater than or equal to 4 5%), stress LVEF less than or equal to 45% or rest LVEF less than or equal to 40%. Results were compared with CA, and stenosis greater than or equal to 4 50% was considered as significant.ResultsFor 100% the quality of SPECT imaging was good or excellent. For six patients gating was impossible because of arrhythmia. The overall sensitivity, specificity and accuracy were 95%, 50%, and 91%, respectively. The concordance between gated SPECT and CA was moderate (kappa = 0.45, SE = 0.15). Interestingly, early-gated acquisition permitted to underline left ventricular dysfunction in 11 cases (30%), of whom eight had polyvascular disease. Stunning was detected in six of 37 cases (16%), of whom six had polyvascular disease.ConclusionA one-day two-hour 99mTc-tetrofosmin gated-SPECT protocol to assess left ventricular perfusion and function is feasible and accurate. Early gated acquisition proves helpful for detecting post-stress stunning, which is a well known crucial prognostic factor of major cardiac events, and could help to speed up clinical management.     

Semi-automated program for analysis of local Ca2+ spark release with application for classification of heart cell type

Local Ca²⁺ spark releases are essential to the Ca²⁺ cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca²⁺ spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope. We validated the algorithm on experimental images from rabbit sinoatrial, atrial, and ventricular cells loaded with Fluo-4 AM. The program characterizes general image parameters of Ca²⁺ transients and sparks: spark duration, which indicates for how long the spark provides Ca²⁺ to the closed intracellular mechanisms (typical value: 25 ± 1, 23 ± 1, 26 ± 1 ms for sinoatrial, atrial, and ventricular cells, respectively); spark amplitude, which indicates the amount of Ca²⁺ released by a single spark (1.6 ± 0.1, 1.6 ± 0.2, 1.4 ± 0.1 F/F₀ for sinoatrial, atrial, and ventricular cells, respectively); spark length, which is the length of the Ca²⁺ wavelets fired out of a row of ryanodine receptors (5 ± 0.1, 5 ± 0.2, 3.4 ± 0.3 μm for sinoatrial, atrial, or ventricular cells, respectively) and number of sparks (0.14 ± 0.02, 0.025 ± 0.01, 0.02 ± 0.01 for 1 μm in 1 s for sinoatrial, atrial, and ventricular cells, respectively). This method is reliable for Ca²⁺ spark analysis of sinoatrial, atrial, or ventricular cells. Moreover, by examining the average value of Ca²⁺ spark characteristics and their scattering around the mean, atrial, ventricular and sinoatrial cells can be differentiated.     

A compensation of angular displacements of the hip joints and lumbosacral spine between subjects with and without idiopathic low back pain during squatting

Low back pain (LBP) is one of the most common symptoms reported in adults. However, the contribution of postural control on the lumbar spine and hips during squatting has not been carefully investigated in individuals with LBP. The aim of this study was to compare three-dimensional kinematic changes of the lumbar spine and hips between subjects with and without idiopathic chronic LBP during squatting activities. In total, 30 subjects enrolled in the study (15 control subjects and 15 subjects with idiopathic chronic LBP). All participants were asked to perform squatting activities five times repeatedly while holding a load of 2 kg in a basket. The outcome measures included the Oswestry Disability Index (ODI) and kinematic angular displacement for the hips and lumbar spine. The LBP group demonstrated increased range of motion (ROM) in flexion of the dominant (T = ?2.14, p = 0.03) and non-dominant (T = ?2.11, p = 0.03) hips during squatting. The lumbar spine flexion ROM significantly decreased (T = 2.20, p = 0.03). The kinematic changes demonstrated interactions with region × group (F = 5.56, p = 0.02), plane × group (F = 4.36, p = 0.04), and region × plane (F = 2292.47, p = 0.001). The ODI level demonstrated significant interaction on combined effects of body region and plane (F = 4.91, p = 0.03). Therefore, the LBP group utilized a compensation strategy to increase hip flexion with a stiffened lumbar spine in the sagittal plane during squatting. This compensatory kinematic strategy could apply to clinical management used to enhance lumbar spine flexibility in subjects with idiopathic chronic LBP.     

Increased plasma levels of osteopontin are associated with activation of the renin–aldosterone system and with myocardial and coronary microvascular damage in dilated cardiomyopathy

In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow (MBF) has been associated with coronary microvascular dysfunction. The aim of this study was to test the hypothesis that osteopontin (OPN) plasma levels could be associated with the activation of the renin–aldosterone system (RAS) in these patients and be involved in mediating myocardial and coronary damage. In 66 patients with idiopathic left ventricular dysfunction of variable severity the plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS activation, myocardial dysfunction and with clinical indexes of left ventricle (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared to controls, patients showed a significant increase of inflammatory markers (OPN: 508 ± 30.8 ng/ml vs. 426.9 ± 16.4, p < 0.05 and interleukin (IL)-6: 1.71 ± 0.29 pg/ml vs. 0.38 ± 0.03 pg/ml, p < 0.001) and of indexes of cardiac damage. OPN levels were significantly correlated with the extent of microvascular dysfunction (MBF at rest: p = 0.01; during dipyridamole: p = 0.0003) and with plasma renin activity (PRA) (r = 0.26, p = 0.04). Both in patients with milder or more severe LV dysfunction lower MBF values were associated with higher OPN levels and PRA. These results suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy.     

Asynchronisme cardiaque chez le sujet à QRS fin. Étude par échocardiographie Doppler tissulaire

ObjectiveTo assess the prevalence of different types of cardiac dyssynchrony by pulsed Doppler ultrasound and Doppler tissue in patients with narrow QRS with or without left ventricular systolic dysfunction.MethodologyProspective, cross-sectional survey at the Institute of Cardiology of Abidjan, from January to April 2012, in subjects with narrow QRS. Group 1: patients with dilated cardiomyopathy with severe left ventricular dysfunction (left ventricular end diastolic diameter greater than 60 mm and/or 30 mm/m² and ejection fraction less than 35% NYHA stage IV). Group 2: normal subjects with normal echocardiography. All patients underwent an evaluation including tissue Doppler search for different types of dyssynchrony (atrioventricular, interventricular and left intraventricular).ResultsPatients in group 1 were significantly older (51.5 ± 15.8 vs. 35.8 ± 7.8, P = 0.03), with larger left ventricular diameters and significantly higher pulmonary systolic pressure. The prevalence of different types of dyssynchrony in group 1 were: atrioventricular dyssynchrony 43.7%, interventricular dyssynchrony 37.5%, left ventricular dyssynchrony 65.6%. Group 2: atrioventricular dyssynchrony 0%, interventricular dyssynchrony 0%, left ventricular dyssynchrony 35%.ConclusionA large proportion of patients with left ventricular systolic dysfunction and narrow QRS have cardiac dyssynchrony and left ventricular dyssynchrony can be found in healthy patients. This raises the problem of the specificity of Doppler ultrasound criteria using cardiac tissue Doppler to assess cardiac dyssynchrony.     

Bioconversion of phenylpyruvic acid to l-phenylalanine by mixed-gel immobilization of Escherichia coli EP8-10

A mixed-gel of κ-carrageenan and gelatin was used in l-phenylalanine production. The mixed-gel, containing 87.5% κ-carrageenan and 12.5% gelatin [the total gel concentration was 4 wt%], showed the best performance and was selected for further study with Escherichia coli EP8-10. The optimum pH and temperature were 8.5 and 37 °C, respectively. The effects of trehalose and Mg²⁺ were studied in the mixed-gel immobilization. Their optimum concentrations were 5 × 10^?2 and 2 × 10^?3 mol/L, respectively. Under the optimal conditions, 98.3% of the phenylpyruvic acid (PPA) was converted to l-phenylalanine. The activity recovery of the transaminase enzyme in the mixed-gel immobilization was higher than that in single κ-carrageenan immobilization, which was 93.6%. The total PPA conversion rate was over 80% in all 15 batches, suggesting great sustainability in the mixed-gel immobilization. The maximum reaction rate (r_max) was calculated to be 4.75 × 10^?2 mol/(L g h).     

Cholinergic modulation of activation sequence in the atrial myocardium of non-mammalian vertebrates

Cholinergic changes of electric activity were studied in isolated atrium preparations from fishes (cod and carp), amphibians (frog) and reptilians (lizard) using the microelectrode technique and high-resolution optical mapping. Perfusion of isolated atrium with acetylcholine (10^? 6–5 · 10^? 5 M) caused gradual suppression of action potential generation and, eventually, completely blocked the excitation in a part of the preparation. Other regions of atrium, situated close to the sinoatrial and atrioventricular junctions, remained excitable. Such cholinergic suppression of electric activity was observed in the atrial myocardium of frog and in both fish species, but not in reptilians. Ba²⁺ (10^? 4 M), which blocks the acetylcholine-dependent potassium current (I_KACh), prevented cholinergic reduction of action potential amplitude. In several preparations of frog atrium, cholinergic suppression of excitation coincided with episodes of atrial fibrillation. We conclude that the phenomenon of cholinergic suppression of electric activity is typical for atria of fishes and amphibians. It is likely to be caused by I_KACh activation and may be important for initiation of atrial arrhythmias.     

Lignocaine Therapy for Ventricular Ectopic Activity after Acute Myocardial Infarction: A Double-blind Trial

The effectiveness of intravenous lignocaine in suppressing ventricular ectopic activity after acute myocardial infarction was examined in a double-blind trial in 82 patients. Whereas suppression of unifocal ventricular ectopics was achieved by lignocaine in 90% of patients, other forms of potentially more dangerous ectopic activity (multifocal or R-on-T ectopics) seemed more resistant to therapy. Cessation of ectopic activity was also observed in about one-third of the patients in the control group. The incidence of ventricular tachycardia and fibrillation and the mortality during and after the trial period were similar in the lignocaine-treated and control groups, whether or not the initial ventricular ectopics had been suppressed.This study provides no evidence to support the routine use of intravenous lignocaine in the management of ventricular ectopic activity after acute myocardial infarction.     

Hirtellanines A and B,a pair of isomeric isoflavonoid derivatives from Campylotropis hirtella and their immunosuppressive activities

A pair of isomeric isoflavonoid derivatives, Hirtellanines A (1) and B (2), has been isolated from the roots of Campylotropis hirtella (Franch.) Schindl. and their structures were elucidated on the basis of spectroscopic methods, with special emphasis on 1D and 2D NMR techniques. The in vitro assay showed that Hirtellanine A had strong B lymphocyte suppression activity (IC₅₀: 0.06 μM) and T lymphocyte suppression activity (IC₅₀: 0.92 μM). Hirtellanine B showed moderate B lymphocyte suppression activity (IC₅₀: 3.00 μM) and T lymphocyte suppression activity (IC₅₀: 9.55 μM). Due to the potent immunosuppressive activities and lower cytotoxicity, Hirtellanine A could be a promising lead towards novel immunosuppressive agents.