Levosimendan has an inhibitory effect on platelet function

Levosimendan enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilatation. Although studies have evaluated the efficacy of levosimendan in heart failure, it is not clear whether it might produce functional influence on platelet response. In this study, the effect of levosimendan on platelet aggregation was investigated. Platelet function tests were performed in 12 healthy male volunteers. Three concentrations of levosimendan solution were prepared that would result in 10, 25, and 45 ng/ml levosimendan concentrations in the blood similar to that observed after clinical therapeutic intravenous application of 0.05-0.1 microg/kg/min. Each concentration of levosimendan solution and a control diluent without levosimendan were incubated with whole blood at 37 degrees C. After incubation for 15 min, aggregation responses were evaluated with adenosine diphosphate (ADP) (5 and 10 microM) and collagen (2 and 5 microg/ml) in platelet-rich plasma. Preincubation with all dilutions of levosimendan inhibited aggregation of platelets induced by ADP and collagen significantly. Levosimendan also inhibited significantly the secondary wave of platelet aggregation induced by ADP. The results showed that there was a relationship between levosimendan concentration and inhibition of platelet aggregation. In conclusion, this study with an in vitro model showed that levosimendan had a significant inhibitory effect on platelets in clinically relevant doses.     

Comparison of initial efficacy and long-term follow-up of heparin-coated Jostent with conventional NIR stent

The implantation of heparin-coated stents was reported to be well tolerated, but there are conflicting results about acute in-hospital complications. (sub)acute thrombosis rates, and long-term follow-up compared to uncoated stents. We compared the angiographic and clinical results after coronary placement of two stent models: the heparin-coated premounted Jostent and the uncoated premounted NIR stent. Of 710 patients revascularized, a total of 426 patients received Jostent (n = 230) or NIR stent (n = 196) implantation. The primary end points were acute or subacute thrombosis, urgent CABG, AMI or death, while the secondary end points were the comparison of the restenosis rates of the stents at the 6th month and of the functional angina classification of the stent groups at the 1st, 6th and 12th months. There were no significant differences between the Jostent and NIR stent groups regarding angiographic and procedural success. Acute thrombosis rates in the Jostent and NIR stent groups were similar while no subacute thrombosis was observed in either group. The major adverse cardiac event rates of the groups also did not differ. Angiographic restenosis occurred in 17% of the Jostent group and 16% of the NIR stent group (NS). The combined clinical and angiographic restenosis rate was also similar between the Jo and NIR groups (19% and 18%, respectively). Comparison of functional angina classes at the 1st, 6th and 12th months revealed no significant difference between the study groups. In conclusion, when compared with implantation of an uncoated premounted NIR stent, implantation of a heparin-coated premounted Jostent does not provide any more benefit with respect to initial efficacy, sub(acute) thrombosis and 6-month restenosis rates and 12-month clinical outcomes.     

Examination of fabrication conditions of acrylate-based hydrogel formulations for doxorubicin release and efficacy test for hepatocellular carcinoma cell

The objective of the present study was to develop 2-hydroxypropyl methacrylate-co-polyethylene methacrylate [p(HPMA-co-PEG–MEMA)] hydrogels that are able to efficiently entrap doxorubicin for the application of loco-regional control of the cancer disease. Systemic chemotherapy provides low clinical benefit while localized chemotherapy might provide a therapeutic advantage. In this study, effects of hydrogel properties such as PEG chains length, cross-linking density, biocompatibility, drug loading efficiency, and drug release kinetics were evaluated in vitro for targeted and controlled drug delivery. In addition, the characterization of the hydrogel formulations was conducted with swelling experiments, permeability tests, Fourier transform infrared, SEM, and contact angle studies. In these drug-hydrogel systems, doxorubicin contains amine group that can be expected a strong Lewis acid–base interaction between drug and polar groups of PEG chains, thus the drug was released in a timely fashion with an electrostatic interaction mechanism. It was observed that doxorubicin release from the hydrogel formulations decreased when the density of cross-linking, and drug/polymer ratio were increased while an increase in the PEG chains length of the macro-monomer (i.e. PEG–MEMA) in the hydrogel system was associated with an increase in water content and doxorubicin release. The biocompatibility of the hydrogel formulations has been investigated using two measures: cytotoxicity test (using lactate dehydrogenase assay) and major serum proteins adsorption studies. Antitumor activity of the released doxorubicin was assessed using a human SNU398 human hepatocellular carcinoma cell line. It was observed that doxorubicin released from all of our hydrogel formulations which remained biologically active and had the capability to kill the tested cancer cells.     

Is there a role for surgery in the management of isolated secundum atrial septal defect in adults?

Isolated atrial septal defect (ASD) is the most common form of congenital heart abnormalities in adults and approximately 80% are located in the region of the fossa ovalis (ostium secundum ASD).1 Indications for closure are in cases where the ratio of pulmonary-to-systemic flow (Qp/Qs) is higher than 1.5, without significant elevation of pulmonary vascular resistance.Surgical closure of ASDs has been performed for over 60 years and techniques have steadily improved, using smaller incisions and minimally invasive techniques. On the other hand, in the last 20 years, various transcatheter ASD closure techniques and devices have been developed, among which, percutaneous treatment with a septal occluder device is the most popular.2,3Despite increasing use of occluder devices and the fact that studies have been published internationally pointing out some of the advantages and disadvantages compared with surgery in adults, no formal comparison of efficacy, morbidity and complications has been published.2-4 We present a retrospective comparison of short-term (three months) results for transcatheter and surgical closure of 163 ostium secundum ASD patients in a university hospital.     

Estrogen Receptor Alpha Expression and Liver Fibrosis in Chronic Hepatitis C Virus Genotype 1b: A Clinicopathological Study

Background:

Hepatic damage due to chronic hepatitis C virus (HCV) genotype 1b infection varies widely.

Objectives:

We aimed to investigate whether estrogen receptor alpha (ERα) plays a role in liver fibrosis in patients infected with HCV genotype 1b.

Patients and Methods:

All the consecutive patients who received the same standard treatment protocol for HCV genotype 1b were subdivided into two subgroups according to their fibrosis scores as fibrotic stages < 2 in mild fibrosis group and fibrotic stages ≥ 2 in advanced fibrosis group, depending on the presence of septal fibrosis. ERα was stained in liver biopsy specimens. Demographics and clinical properties were compared between the groups. Multivariate logistic regression analysis was performed to predict advanced fibrosis.

Results:

There were 66 patients in the mild fibrosis group and 24 in the advanced fibrosis group. Among the mild and advanced fibrosis groups, 65.1% and 50%were female, respectively (P = 0.19). There was an inverse correlation between ERα and fibrotic stage (r: -0.413; P < 0.001). Age, platelet counts, neutrophil counts, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma glutamyl transferase (GGT) and ERα were statistically significant in the univariate analysis. In multivariate logistic regression analyses, ERα expression continued to be an independent predicting factor of liver fibrosis in patients infected with chronic HCV genotype 1b (OR: 0.10; 95% CI: 0.018-0.586; P < 0.001).

Conclusions:

ERα expression in liver was inversely correlated with liver fibrosis among patients infected with chronic HCV genotype 1b.