A novel GalR2-specific peptide agonist

The galanin peptide family and its three receptors have with compelling evidence been implicated in several high-order physiological disorders. The co-localization with other neuromodulators and the distinct up-regulation during and after pathological disturbances has drawn attention to this neuropeptide family. In the current study we present data on receptor binding and functional response for a novel galanin receptor type 2 (GalR2) selective chimeric peptide, M1145 [(RG)₂-N-galanin(2-13)-VL-(P)₃-(AL)₂-A-amide]. The M1145 peptide shows more than 90-fold higher affinity for GalR2 over GalR1 and a 76-fold higher affinity over GalR3. Furthermore, the peptide yields an agonistic effect in vitro, seen as an increase in inositol phosphate (IP) accumulation, both in the absence or the presence of galanin. The peptide design with a N-terminal extension of galanin(2-13), prevails new insights in the assembly of novel subtype specific ligands for the galanin receptor family and opens new possibilities to apply the galanin system as a putative drug target.     

One-year outcome after first-ever stroke according to stroke subtype, severity, risk factors and pre-stroke treatment. A population-based study from Tartu, Estonia

The aim of the current study was to evaluate the outcome at 1 year following a first-ever stroke based on a population-based registry from 2001 to 2003 in Tartu, Estonia. The outcome of first-ever stroke was assessed in 433 patients by stroke risk factors, demographic data and stroke severity at onset using the Barthel Index (BI) score and the modified Rankin Score (mRS) at seventh day, 6 months and 1 year. Female sex, older age, blood glucose value >10 mmol/l on admission and more severe stroke on admission were the best predictors of dependency 1 year following the first-ever stroke. At 1 year, the percentage of functionally dependent patients was 20% and the survival rate was 56%. The use of antihypertensive/antithrombotic medication prior to stroke did not significantly affect the outcome. The survival rate of stroke patients in Tartu is lower compared with other studied populations. The outcome of stroke was mainly determined by the initial severity of stroke and by elevated blood glucose value on admission. Patients with untreated hypertension had more severe stroke and trend for unfavourable outcome compared with those who were on treatment.     

Rare epithelial sheets with "cancer-like" nuclei presenting against a background of cytologically normal-appearing endometrial epithelium in endometrial brush samplings: establishing a differential diagnosis

Liquid-fixed Tao brush samples showing small quantities (less than 10%) of endometrial epithelial sheets with cancer-like nuclei that are admixed with benign endometrium raise a concern about false-positive cytology interpretations. This paper details 7 cases along with the outcomes of three prior papers that touch on the differential diagnosis of "small amounts of atypical epithelium with cancer-like nuclei." Liquid-fixed, cytocentrifuge-processed Tao brush endometrial samples from 7 women showing "small amounts of atypical epithelium with cancer-like nuclei" were followed up by hysterectomy. Clinical presentations, diagnostic tests, surgical procedures, and tissue outcomes are detailed. Four women had hyperplastic polyps (three with focal atypical complex hyperplasia, and one with focal atypical simple hyperplasia). One had endometrial microcarcinoma. One had p53-positive endometrial intraepithelial carcinoma (EIC). One had endometrial intraepithelial neoplasia (EIN). The differential diagnosis of the index cytological finding, "small quantities of endometrial epithelial sheets with cancer-like nuclei admixed with benign endometrium," includes hyperplastic polyp, EIC, microcarcinoma/EIN, and carcinoma metastatic to the endometrium. Combining endometrial brushing, endovaginal sonography/sonohysterography, and selective immunostaining may be useful for both detecting and sorting out these lesions. Diagn. Cytopathol. 1999;21:378-386.     

Bulimia and depression

In recent years several lines of evidence have emerged suggesting that eating disorders in general, and bulimia in particular, are in some way linked to affective illness. However, there are few data on the frequency of affective syndromes among patients who have anorexia nervosa or bulimia. This report describes the results of semistructured interviews using the Schedule for Affective Disorders and Schizophrenia (SADS) to evaluate the frequency of the current and lifetime diagnoses of affective illness among 50 female patients meeting DSM-III criteria for bulimia. Seventy percent of the patients had, at some time during their lives, met Research Diagnostic Criteria (RDC) for an episode of major depression and 88% had met RDC at some time during their lives for some affective disturbance. The implications of this high frequency of affective disturbance among patients with bulimia are discussed.     

A novel metalloprotease from Vipera lebetina venom induces human endothelial cell apoptosis.

A novel endothelial cell apoptosis inducing metalloprotease (VLAIP) was found in the snake venom of Vipera lebetina. This metalloprotease is a heterodimeric glycoprotein with molecular mass of about 106 kDa. The protease hydrolyzes azocasein, fibrinogen and oxidized insulin B-chain. The enzyme readily hydrolyzes the Aalpha-chain and more slowly Bbeta-chain of fibrinogen. VLAIP does not cleave fibrin. The complete amino acid sequences of the two different monomers of VLAIP are deduced from the nucleotide sequences of cDNAs encoding these proteins. The full-length cDNA sequences of the VLAIP-A and VLAIP-B encode open reading frames of 616 and 614 amino acids that include signal peptide, propeptide and mature metalloproteinase with disintegrin-like and cysteine-rich domains. VLAIP belongs to the metalloprotease/disintegrin family of reprolysins and has high identity with the proteins that induce apoptosis of endothelial cells. Treatment of HUVEC cells with VLAIP induces changes in the attachment of cells to the substrate and causes cell death. We demonstrated that VLAIP inhibits endothelial cell adhesion to extracellular matrix proteins: fibrinogen, fibronectin, vitronectin, collagen I, and collagen IV. The induction of apoptosis by VLAIP was shown by means of a typical DNA fragmentation pattern of apoptotic cells as well as by monitoring phosphatidylserine externalization using annexin V-FITC staining and flow cytometric analysis.