Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure in the dog

A noninvasive test is needed to assess the severity of encephalopathy during fulminant hepatic failure. This feasibility study was designed to compare a noninvasive test, brain lactate measurement by magnetic resonance spectroscopy, with intracranial pressure monitoring in a large animal model of fulminant hepatic failure. Five dogs received an intraventricular catheter for intracranial pressure measurement. Liver injury was induced by intravenous bolus of D-galactosamine. Brain lactate concentrations were determined by magnetic resonance spectroscopy for up to 48 hours after D- galactosamine administration (t = 0 hour). A dose of D-galactosamine exceeding 1.5 g/kg resulted in fulminant hepatic failure. Brain lactate levels increased to >10 mmol/L in the two dogs that developed severe intracranial hypertension of >50 mm Hg and sustained cerebral perfusion pressures of <40 mm Hg. Both dogs experienced brain death, 42 and 48 hours after the administration of D-galactosamine. Brain lactate concentrations determined by magnetic resonance spectroscopy were in agreement with brain tissue concentrations of lactate determined by high-performance liquid chromatography at necropsy. Plasma lactate concentrations were only mildly elevated (3.2 and 4.2 mmol/L) at the time of brain death. Elevated levels of brain lactate are associated with intracranial hypertension and poor neurological outcome during fulminant hepatic failure

Noble metal nanoparticles networks stabilized by rod-like organometallic bifunctional thiols

Rod-like organometallic dithiol containing square-planar Pt(II) centers, i. e., trans,trans-[(H3COCS)Pt(PBu3)(2)(C equivalent to C-C6H4-C6H4-C equivalent to C)(PBu3)(2)Pt(SCOCH3)] was used as bifunctional stabilizing agent for the synthesis of Pd-, Au-, and AgNPs (MNPs). All the MNPs showed diameters of about 4 nm, which can be controlled by carefully modulating the synthesis parameters. Covalent MNPs stabilization occurred through a single S bridge between Pt(II) and the noble metal nanocluster surfaces, leading to a network of regularly spaced NPs with the formation of dyads, as supported by SR-XPS data and by TEM imaging analysis. The chemical nature of NPs systems was also confirmed by EDS and NMR. Comparison between SR-XPS data of MNPs and self-assembled monolayers and multilayers of pristine rod-like dithiols deposited onto polycrystalline gold surfaces revealed an electronic interaction between Pt(II) centers and biphenyl moieties of adjacent ligands, stabilizing the organic structure of the network. The possibility to obtain networks of regularly spaced MNPs opens outstanding perspectives in optoelectronics

Catestatin Improves Post-Ischemic Left Ventricular Function and Decreases Ischemia/Reperfusion Injury in Heart

The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium

The crisis sensitivity of European countries and regions: stylized facts and spatial heterogeneity

We investigate the impact of the recent global recession on European countries and regions. We first identify the heterogeneous impact of the global recession on individual European countries and regions. We then discuss three classes of explanations for spatial heterogeneity in the severity of the crisis: (i) the extent to which countries are integrated in the global economy via financial and trade linkages, (ii) differences in the institutional framework of countries and (iii) differences in their sectoral composition. We show that especially variation in the sectoral composition contributes to the variation in the effects of the current crisis, both at the country level and at the detailed regional level across Europe. © The Author 2011. Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved

Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: A retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Aims Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. Methods and results We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). Conclusion In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas

Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α

<p>Abstract</p> <p>Background</p> <p>Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.</p> <p>Results</p> <p>The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).</p> <p>Conclusion</p> <p>The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.</p