Prooxidant–antioxidant balance,hsTnI and hsCRP: mortality prediction in haemodialysis patients,two-year follow-up

Oxidative stress and inflammation are highly intertwined pathophysiological processes. We analyzed the markers of these processes and high-sensitive troponin I (hsTnI) for mortality prediction in patients on haemodialysis. This study enrolled a total of 62 patients on regular haemodialysis. The patients were monitored for two years, and the observed outcomes were all-cause and cardiovascular mortality. Blood samples were taken before one dialysis session for analysis of the baseline concentrations of prooxidant–antioxidant balance (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%. By univariate and multivariate logistic regression, our findings suggest that good predictors of all-cause mortality include hsCRP and PAB (p?p?p?p?p?=?.001). Our data suggest that hsCRP and PAB are very good predictors of all-cause mortality. For CVD complications and mortality prediction in HD patients, the most sensitive parameters appear to be hsTnI and hsCRP.     

Left Ventricular Longitudinal Strain in Characterization and Outcome Assessment of Mixed Aortic Valve Disease Phenotypes

ObjectivesThe aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD.BackgroundLittle is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes.MethodsThis observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality.ResultsMean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was –14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear.ConclusionsLV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD.     

Hemostatic problems before, during and after delivery.

Normal pregnancy and childbirth are known to be associated with marked changes in the coagulation and fibrinolytic systems. Generally, enhancement of clotting activity persists to prevent the risk of major hemorrhage. Hemostatic problems, either associated with a specific complication of pregnancy and labor or due to a hereditary or acquired bleeding diathesis or thrombophilias, present a significant cause of maternal and neonatal morbidity and mortality. This article reviews hemostatic disorders in pregnancy and the peripartal period from the standpoint of the obstetrician.     

Ammonium accumulation and chemokine decrease in culture media of Gcdh−/− 3D reaggregated brain cell cultures

Glutaric Aciduria type I (GA-I) is caused by mutations in the GCDH gene. Its deficiency results in accumulation of the key metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body tissues and fluids. Present knowledge on the neuropathogenesis of GA-I suggests that GA and 3-OHGA have toxic properties on the developing brain.We analyzed morphological and biochemical features of 3D brain cell aggregates issued from Gcdh^?/? mice at two different developmental stages, day-in-vitro (DIV) 8 and 14, corresponding to the neonatal period and early childhood. We also induced a metabolic stress by exposing the aggregates to 10 mM l-lysine (Lys).Significant amounts of GA and 3-OHGA were detected in Gcdh^?/? aggregates and their culture media. Ammonium was significantly increased in culture media of Gcdh^?/? aggregates at the early developmental stage. Concentrations of GA, 3-OHGA and ammonium increased significantly after exposure to Lys. Gcdh^?/? aggregates manifested morphological alterations of all brain cell types at DIV 8 while at DIV 14 they were only visible after exposure to Lys. Several chemokine levels were significantly decreased in culture media of Gcdh^?/? aggregates at DIV 14 and after exposure to Lys at DIV 8.This new in vitro model for brain damage in GA-I mimics well in vivo conditions. As seen previously in WT aggregates exposed to 3-OHGA, we confirmed a significant ammonium production by immature Gcdh^?/? brain cells. We described for the first time a decrease of chemokines in Gcdh^?/? culture media which might contribute to brain cell injury in GA-I.     

Supplementation of EPA and DHA in pregnant women with type 1 diabetes mellitus

Background/objectiveLower proportions of n-3 PUFAs have been observed in neonates born to diabetic mothers. We aimed to investigate the association between DHA and EPA supplementation during pregnancy complicated with type 1 diabetes on concentration and proportion of fatty acids in maternal and foetal blood.Subjects and methodsWe conducted a prospective randomized, single-blinded, placebo-controlled trial of 111 eligible pregnant women with type 1 diabetes and presented the results of 84 (intervention arm and control arm comprised 42 participants each) of them who successfully finished the trial in an academic hospital. The initiation of EPA and DHA supplementation or placebo started at randomization visit on gestational week 11–12. Blood samples were taken on the first (screening) visit to the clinic (1st trimester, between 8th and 10th gestational week, GW), then in the second trimester (19–24th GW) and third trimester (30th–33rd GW). On the delivery day, a blood sample was taken on fasting just before birth. The umbilical vein blood sample was taken shortly after the delivery.ResultsWe found a significant increase in the intervention group when compared the first and the third trimester for n-3 PUFAs concentration, 4.3 mg/L (3.3–7.6): 10.0 mg/L (7.1–13.7), p < .001. In the intervention group, the concentration of DHA in maternal vein serum was 11.4 mg/L (7.7–17.5), and in umbilical vein serum, it was 5.1 mg/L (3.0–7.7), which was significantly higher than that in the control group, maternal vein serum: median 9.2 mg/L(6.0–12.3), p = .03 and umbilical vein serum: median 3.4 mg/L (2.1–5.6), p = .009.ConclusionThe increased weight gain in pregnancy and concentration and proportions of DHA, n-3 PUFAs with a decreased proportion of AA, n-6 PUFAs, and AA/DHA ratio in maternal and umbilical vein serum summarize the effect of supplementation with EPA and DHA.     

Implementation of a palliative care team in an Austrian university hospital

Implementation of hospital-based palliative care team is a new subject in German-speaking areas, especially in university hospitals. Our Section of Palliative Care was subsequently built up to a 12-bed palliative care unit, a home-based, and a hospital-based palliative care team. Analysis of the implementation strategies, development of the working profile, and documentation of the hospital-based palliative care team were done. During the first 2 years, quality and number of inquiries for palliative care increased significantly. In our opinion, a high degree of expertise, involvement of the nursing staff, and personal contact play a key role for a successful implementation of a palliative care team in a large university hospital.     

Surface active stabilizer tyloxapol in colloidal dispersions exerts cytostatic effects and apoptotic dismissal of cells

Solid lipid nanoparticles (SLN) have been praised for their advantageous drug delivery properties such as biocompatibility, controlled release and passive drug targeting. However, the cytotoxicity of SLN and their ingredients, especially over a longer time period, has not been investigated in detail. We examined the critical issues regarding the use of a surface active stabilizer Tyloxapol (Tyl) for the preparation of solid lipid particles (SLP) and their effects on cellular functions and viability.SLP composed of behenate, phospholipids and a stabilizer, Tyloxapol or Lutrol (Lut), were prepared by the lipid melt method, labeled with a fluorescent dye and tested on Jurkat or HEK293 cells. The nano-sized particles were rapidly internalized and exhibited cytoplasmic localization. Incubation of cells with SLP-Tyl resulted in a dose- and time-dependent cytostatic effect, and also caused moderate and delayed cytotoxicity. Tyloxapol solution or SLP-Tyl dispersion caused the detachment of HEK293 cells, a decrease in cell proliferation and alterations in cellular morphology. Cell cycle analysis revealed that, while the unfavourable effects of SLP-Tyl and Tyloxapol solution are similar initially, longer incubation results in partial recovery of cells incubated with the dispersion of SLP-Tyl, whereas the presence of Tyloxapol solution induces apoptotic cell death. These findings indicate that Tyloxapol is an unfavourable stabilizer of SLP used for intracellular delivery and reinforce the role of stabilizers in a design of SLP with minimal cytotoxic properties.     

Influence of nanosized delivery systems with benzyl nicotinate and penetration enhancers on skin oxygenation

Many novel nanosized delivery systems have been designed for topical application of drugs since they can overcome the skin barrier and improve drug bioavailability. The increased absorption is often a consequence of a reversibly disrupted barrier function of the skin by the vehicle itself or by specific ingredients that act as penetration enhancers. This paper reports the effects of two nanosized systems (microemulsion and liposomes), in the presence and absence of penetration enhancers (PE), on the topical delivery of a lipophilic drug in vivo and compares that to classical hydrogel formulation. A vasodilator benzyl nicotinate (BN), which increases the blood flow of the skin, was incorporated into the formulations, and skin oxygenation was followed by electron paramagnetic resonance oximetry. It was found that microemulsions and liposomes (with or without PE) accelerate the rate of BN action when compared to hydrogel. However, incorporation of PE in microemulsion also improves the effectiveness of BN action. To understand why PE enhances the action of BN, its effect on the structure of the stratum corneum was investigated in vitro. The increased fluidity of the stratum corneum lipids provides an explanation for the greater penetration of BN into the skin when the drug and PE are together incorporated into the appropriate formulation.