Neuroprotective Potential of Biphalin, Multireceptor Opioid Peptide, Against Excitotoxic Injury in Hippocampal Organotypic Culture

Biphalin is a dimeric opioid peptide that exhibits affinity for three types of opioid receptors (MOP, DOP and KOP). Biphalin is undergoing intensive preclinical study. It was recognized that activation of δ-opioid receptor elicits neuroprotection against brain hypoxia and ischemia. We compare the effect of biphalin and morphine and the inhibition of opioid receptors by naltrexone on survival of neurons in rat organotypic hippocampal cultures challenged with NMDA. Findings: (1) 0.025–0.1 μM biphalin reduces NMDA-induced neuronal damage; (2) biphalin neuroprotection is abolished by naltrexone; (3) reduced number of dead cells is shown even if biphalin is applied with delay after NMDA challenge

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

A three-level M-quantile model for poverty mapping in Poland

Poverty mapping is of crucial signicance in many countries all over the world, including Poland. EU-SILC is the main source of information about poverty but data from this survey are only sucient to publish poverty indicators at country and regional level (NUTS 1). This is the consequence of small sample sizes in dierent domains, which causes a low precision of estimation. Given the small sample size in relevant cross clas- sications of the EU-SILC survey, it is, therefore, necessary to use the latest techniques of indirect estimation and draw on alternative data sources to estimate the parameters of interest at low levels of spatial aggregation with acceptable precision. One of the methods which can be practically employed for deriving small area estimates of poverty and inequality is the M-quantile technique

A strong neuroprotective effect of the autonomous Cterminal peptide of IGF-1 Ec (MGF) in brain ischemia

Published online September 6, 2005 ©2005 FASEBThe ischemic stroke is the third leading cause of death in developed countries. The C-terminal peptide of mechano-growth factor (MGF), an alternatively spliced variant of insulin-like growth factor 1 (IGF-1), was found to function independently from the rest of the molecule and showed a neuroprotective effect in vivo and in vitro. In vivo, in a gerbil model of transient brain ischemia, treatment with the synthetic MGF C-terminal peptide provided very significant protection to the vulnerable neurons. In the same model, ischemia evoked increased expression of endogenous MGF in the ischemia-resistant hippocampal neurons, suggesting that the endogenous MGF might have an important neuroprotective function. In an in vitro organotypic hippocampal culture model of neurodegeneration, the synthetic peptide was as potent as the full-length IGF-1 while its effect lasted significantly longer than that of recombinant IGF-1. While two peptides showed an additive effect, the neuroprotective action of the C-terminal MGF was independent from the IGF-1 receptor, indicating a new mode of action for this molecule. Although MGF is known for its regenerative capability in skeletal muscle, our findings demonstrate for the first time a neuroprotective role against ischemia for this specific IGF-1 isoform. Therefore, the C-terminal MGF peptide has a potential to be developed into a therapeutic modality for the prevention of neuronal damage.Joanna Dluzniewska, Anna Sarnowska, Malgorzata Beresewicz, Ian Johnson, Surjit K. S. Srai, Bala Ramesh, Geoffrey Goldspink, Dariusz C. Górecki, and Barbara Zablock

Changes in Ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction

Background— Heart failure (HF) causes a decline in the function of the pacemaker of the heart—the sinoatrial node (SAN). The aim of the study was to investigate HF-induced changes in the expression of the ion channels and related proteins underlying the pacemaker activity of the SAN. Methods and Results— HF was induced in rats by the ligation of the proximal left coronary artery. HF animals showed an increase in the left ventricular (LV) diastolic pressure (317%) and a decrease in the LV systolic pressure (19%) compared with sham-operated animals. They also showed SAN dysfunction wherein the intrinsic heart rate was reduced (16%) and the corrected SAN recovery time was increased (56%). Quantitative polymerase chain reaction was used to measure gene expression. Of the 91 genes studied during HF, 58% changed in the SAN, although only 1% changed in the atrial muscle. For example, there was an increase in the expression of ERG, K v LQT1, K ir 2.4, TASK1, TWIK1, TWIK2, calsequestrin 2, and the A1 adenosine receptor in the SAN that could explain the slowing of the intrinsic heart rate. In addition, there was an increase in Na + -H + exchanger, and this could be the stimulus for the remodeling of the SAN. Conclusions— SAN dysfunction is associated with HF and is the result of an extensive remodeling of ion channels; gap junction channels; Ca 2+ -, Na + -, and H + -handling proteins; and receptors in the SAN. </jats:sec