The efficacy and safety of the combination of β-blocker bisoprolol and if inhibitor I(f) ivabradine in patients with stable angina and chronic obstructive pulmonary disease

The study was aimed to assess the efficacy and safety of treating coronary heart disease (CHD) patients complicated with COPD using the combination of tolerable doses of -blocker bisoprolol and inhibitor If-channel ivabradine, compared with bisoprolol alone. A total of 50 patients were included (88% men, mean age 62.8+/-7.2 years) with stable angina and clinical signs of bronchoobstruction (84% with COPD and 16% with bronchial asthma in remission phase). At the study start, all patients received bisoprolol, the dose of which was titrated until the clinical signs of intolerance (most common - bronchoobstruction) appeared or worsened. Average dose of bisoprolol at the time of forced titration stop was 6.3+/-2.2 mg/day, mean heart rate (HR) decreased from 82.1+/-8.4 to 72.2+/-8.5 bpm. Then, the patients were randomized into two groups: patients of the first group (n=25) continued to take bisoprolol in tolerable dose, and patients of the second group were added ivabradine (5-15 mg, mean dose 10.7+/- 3.1 mg/day). In contrast to the bisoprolol alone, combination therapy resulted in further decrease of HR to an average of 62.6+/-4.1 bpm over 6 month of follow-up. This was associated with additional decrease of the number of angina attacks (by 4.68+/-4.40 per week vs. 2.48+/-4.70, <0.05), nitrates consumption (by 206.0+/-153.6 mg/week vs. 95.6+/-134.2 mg/week, <0.01) and score of negative components of quality of life (by 5.16+/-3.3 vs. 2.24+/-4.5, <0.05), compared with the first group, respectively. In combination therapy group there was also the decrease of the inhaled broncholytics consumption (from 2.88+/-3.23 to 1.88+/-2.65 per week, <0.05), that was not evident in the first group. Average number of hospitalizations per 1 patient decreased over 6 months of follow-up, compared to the same period before the trial, in both groups, but more prominently in the combination therapy group (-0.31+/-0.55 vs. -0.56+/-0.76, accordingly, <0.1). Therefore, in the treatment of patients with CHD, stable angina and concomitant bronchoobsrtuctive manifestations, if not possible to administer -blockers in the adequate HR-reducing dose, the addition of ivabradine to the treatment could be the treatment of choice. The combination of tolerable doses of bisoprolol and ivabradine is s afe and allows to achieve adequate HR decrease. This is a ssociated with maximal antianginal effect, decrease in the need for broncholytic therapy, improvement of the quality of life and decrease of the number of hospitalizations, compared with the treatment with bisoprolol alone.     

Variations in tissue resistivity and in the extension of activated neuron domains shape the voltage signal during spreading depression in the CA1 in vivo

Spreading depression (SD), a wave of neuron activity related to migraine and the ischaemic penumbra, features a moving shell of extracellular negative potential shift ( V _o) whose generators are poorly understood. We investigated its subcellular correlates in the hippocampal CA1 in vivo by localizing the neuron domains that generate transmembrane current ( I _m) using field analysis, and the local changes of tissue resistivity, a major determinant of extracellular current flow. A large increase of tissue resistivity occurred in times and dendritic strata displaying large V _o, albeit with different rates. Typically, SD is composed of basal and apical dendritic components. The apical SD lasts much longer, while it becomes gradually restricted to a narrow dendritic region. Strikingly, pyramidal cells displayed a strong surge of inward current only when SD affected a small dendritic region. However, when the V _o signal covered most of the main neuron axis, only smaller surges of inward current developed at the outer dendritic rims of a wide null current zone. Computational reconstruction showed that this effect was due to strong spatial cancellation of the inward and outward currents in SD-activated isopotential and shunted regions of individual neurons. Consequently, despite former accounts of large conductance increase, the net I _m is small and the large Δ V _o amplitude mostly due to increased tissue resistivity. The particular subcellular evolution indicates an initial explosive opening of conductance along most of the pyramidal neuron followed by a wave-like centripetal closure towards the apical dendrites. The applicability of these mechanisms to SD in other brain regions is discussed.     

Effect of bacteriophage on the serum level of iron and copper in pregnant women with pyelonephritis

Eighty-nine pregnant women, including 62 pregnant females with pyelonephritis, were examined. After bacteriophage treatment for pyelonephritis, there was an increase in the content of iron, a decrease in the level of soluble transferrin receptor without iron therapy, suggesting iron redistribution in pregnant woman. The blood levels of copper, ceruloplasmin, and transferrin in pregnant women with pyelonephritis point to antioxidative defense activation in both healthy pregnant women and pregnant females with pyelonephritis. The serum concentration of ceruloplasmin is of importance for prognosis and evaluation of ceruloplasmin in pregnant women. The higher content of ceruloplasmin in pregnancy is indicative of the involvement of protective mechanisms from autoaggression.     

Determination of the solute removal index for urea by using a partial spent dialysate collection method

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.