Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

Background and Aims

To evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC).

Methods

Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation.

Results

On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments.

Conclusions

Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation.     

Short-term effects of alcohol consumption on the hormonal milieu and mood states in nulliparous women.

The present study was designed to determine the short-term effects of alcohol consumption on hormonal responses and mood states in nulliparous women who have regular menstrual cycles. To this aim, we conducted a within-subjects design study in which eight women consumed a 0.4-g/kg dose of alcohol in orange juice during one test session (alcohol condition) and an equal volume of orange juice (control condition) during the other. Changes in plasma prolactin, oxytocin and cortisol levels, blood alcohol concentrations (BACs), and mood states were compared. BAC peaked at approximately 36.7+5.4 min after the consumption of the alcoholic beverage and decreased thereafter. Alcohol consumption significantly increased the area under the concentration-time curve (AUC) of prolactin (P<.01) and decreased the oxytocin AUC (P=.04) when compared to the control condition. Cortisol AUCs were not different across the two experimental conditions. Similar to that previously observed in lactating women, changes in prolactin and oxytocin paralleled changes in feelings of drunkenness. The magnitude and persistence of the alcohol-induced hormonal changes in nulliparous women were significantly less pronounced than those observed in lactating women, further highlighting the dynamics of the system under study during lactation.     

Immune response to Neospora caninum live tachyzoites in prepubertal female calves

Parasitology Research - The aim of the present study was to characterize the specific immune response in prepubertal female calves inoculated with Neospora caninum. Forty-eight N....     

The endothelium modulates the arterial wall mechanical response to intra-aortic balloon counterpulsation: in vivo studies

Intra-aortic balloon pump (IABP) benefits could depend on variations in the cardiovascular biomechanical properties associated with blood flow-induced endothelium-dependent changes. However, if IABP results in changes in the peripheral artery biomechanics and if the endothelium plays a role in these potential changes remains unknown. The aim of this study is to characterize acute IABP effects on peripheral artery biomechanics in control and acute heart failure (AHF) states and the role of the endothelium in IABP effects on peripheral artery biomechanics. Pressure and diameter were recorded in sheep (n= 7) iliac arteries (IAs), before and during 1:2 IABP, during four states: (i) control with intact IA; (ii) AHF with intact IA; (iii) control with de-endothelialized (DE) (mechanical rubbing) IA; and (iv) AHF with DE IA. Arterial distensibility, elastic modulus, and conduit function (CF) (1/characteristic impedance) were calculated. The results of this study include: (i) during control conditions, IABP resulted in intact IA dilatation, stiffness reduction, and CF increase; (ii) AHF induction determined a reduction in intact IA diameter and CF, and a stiffness increase. These changes reverted during IABP; (iii) the increase in IA stiffness observed after DE remained unchanged during IABP; (iv) in DE IA, AHF did not result in diameter or stiffness changes; and (v) IABP during AHF did not associate changes in diameter or stiffness in the DE IA. In conclusion, during control and AHF states, IABP results in IA dilatation and stiffness reduction. The integrity of the endothelial layer would be critical for the IABP-associated changes in IA biomechanics.     

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group). Since biperiden permeability was higher than those obtained for high permeability drugs, we classified it as a BCS class I compound. On the other hand, as no differences were obtained for permeability values when apical to basolateral and basolateral to apical fluxes were studied, this drug cannot act as a substrate of efflux transporters. As a consequence of our results, we suggest that the widely used antiparkinsonian drug, biperiden, should be candidate for a waiver of in vivo bioequivalence studies.     

Risk factors associated to clinical deterioration during the transport of sick newborn infants

Adequate neonatal transport is a key component in the care of newborn infants that require transfer. Objective. To determine the characteristics and risk of clinical deterioration during neonatal transport. Material and Methods. This was an observational and prospective study that consecutively included newborn infants transferred to the Neonatal Intensive Care Unit (NICU) of the Hospital Garrahan. The TRIPS (Transport Risk Index of Physiology Stability) risk score was measured pre- and post-transport. A diagnosis of clinical deterioration was made when the post-transport TRIPS score was higher than the pre-transport score. Newborns characteristics, transport distance, newborns status upon admission, need for immediate cardiorespiratory support (ICRS), and death before the 7th day and at discharge were recorded. Bivariate and multivariate analyses were used to assess the associations with clinical deterioration . Results. A total of 160 transferred newborn infants were enrolled, gestational age (GA) was 35 ± 3 weeks; birth weight (BW) 2482 ± 904 g and median age 2 days. Most were referred due to cardiorespiratory (50%) or surgical (34%) illnesses. Of them, 91 (57%) had clinical deterioration and 46% hypothermia. Forty nine neonates required ICRS and 28 died (twelve before 7 days after admittance). Variables assessed were not associated with the risk of clinical deterioration. Mortality was higher in the group with clinical deterioration (OR: 3.34; 95% CI: 1.2-8.7), even when severity of the clinical picture was considered (OR A: 3; 95% CI: 1.2-8.3). Clinical deterioration during transport was associated with the need for ICRS (OR: 2.4; 95% CI: 1.2-5). Conclusions. In our experience transferred newborn infants often suffered loss of stability or clinical deterioration, regardless of their characteristics, and this was related to a higher mortality. Therefore, it is critical to optimize care strategies during all neonatal transports.     

Detection of resistance to second-line antituberculosis drugs by use of the genotype MTBDRsl assay: a multicenter evaluation and feasibility study

The rate of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has been steadily increasing in countries of the former USSR. The availability of rapid and reliable methods for the detection of drug resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the Genotype MTBDRsl assay compared to that of phenotypic drug susceptibility testing (Becton Dickinson Bactec MGIT 960 system) with a test panel of 200 Mycobacterium tuberculosis isolates at four sites in Eastern Europe. The interpretability of the Genotype MTBDRsl assay was over 95%. The sensitivity for the detection of resistance to fluoroquinolones, ethambutol, amikacin, and capreomycin varied between 77.3% and 92.3%; however, it was much lower for kanamycin (42.7%). The sensitivity for the detection of XDR TB was 22.6%. The test specificity was over 82% for all drugs. The assay presents a good screening tool for the rapid detection of resistance to individual second-line drugs and can be recommended for use in countries with a high burden of MDR/XDR TB. The sensitivity for the detection of kanamycin resistance needs improvement.