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.     

Pathologische Anatomie (Sektionstechnik) und Physiologie

Ohne Zusammenfassung     

Post‐traumatic reactions among rescue personnel 96 hours after the Hilton Hotel bombing in Sinai: The effect of previous exposure

This paper considers the immediate post‐traumatic reactions of rescue personnel who were exposed to the Hilton Hotel bombing in Sinai. The entire rescue personnel (n = 26) were assessed and separated into two groups on the basis of previous exposure to the same type of trauma. The results suggest that among rescue personnel, those with previous exposure had a lower level of post‐traumatic symptoms than those who were being exposed for the first time. This supports the hypothesis that previous exposure to the same type of trauma has an immunizing effect for subsequent same type of traumatic event among rescue personnel. Copyright © 2005 John Wiley & Sons, Ltd.     

Learning-induced enhancement of postsynaptic potentials in pyramidal neurons

We studied the effect of olfactory learning-induced modifications in piriform (olfactory) cortex pyramidal neurons on the propagation of postsynaptic potentials (PSPs). Rats were trained to distinguish between odors in pairs, in an olfactory discrimination task. Three days after training completion, PSPs were evoked in layer II pyramidal cells in piriform cortex brain slices by electrical stimulation of two pathways. Stimulation of layer Ib activated the intra-cortical fibers that terminate on the proximal region of the apical and basal dendrites. Stimulation of layer Ia activated the afferent axons that originate from the olfactory bulb and terminate on the distal apical dendrites. We have previously shown that olfactory training is accompanied by enhanced synaptic transmission in the intrinsic pathway, but not in the afferent pathway at 3 days after training. Here we show that at this stage, in both pathways PSPs evoked in neurons from trained rats had significantly faster rise time measured at the soma compared with PSPs in neurons from pseudo-trained and naive rats. Activation of the slow afterhyperpolarization (AHP), which is generated by potassium channels probably located at the proximal region of both apical and basal dendrites, reduced the amplitude measured at the soma of the proximal intrinsic pathway PSPs more effectively than PSPs that were generated distally by the afferent fibers. Thus the amount of reduction by AHP was used as a measure for the relative distance of PSP-generating sites from the soma. In neurons from trained rats, despite the previously reported reduction in AHP amplitude, AHP conductance shunted the PSPs from both synaptic pathways more efficiently compared with neurons from the control rats. We suggest that in neurons from trained rats PSPs are electrotonicly closer to the soma.     

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.     

Reliable atrial septostomy by stenting of the atrial septum.

The aim of this report was to describe our experience with creating an interatrial communication by stenting the interatrial septum. In many forms of congenital heart disease, the presence of an appropriate interatrial shunt is critical. After the first several weeks of life, balloon atrial septostomy is not effective, and success with other methods is limited. Clinical records, echocardiograms, and catheterization data in patients who had an atrial septal stent placed between 2001 and 2004 at UCLA were reviewed. Changes in atrial pressures and systemic saturations were analyzed. Follow-up data and explant pathology were reviewed as available. Thirteen patients had stenting of the atrial septum (four restrictive, nine nonrestrictive). In patients with elevated right and left atrial pressures, there was a mean reduction of 2.4 and 7.4 mm Hg in right atrial and left atrial pressures, respectively. In patients with transposition physiology, there was a mean increase in oxygen saturation of 11.3%. Follow-up echocardiograms revealed patent stents with excellent position relative to the atrial septum. In six cases, the stents were removed during subsequent surgery and appeared endothelialized and patent. Stenting of the atrial septum is safe and effective in selected cases, allowing for a reliable, long-lasting, restrictive or nonrestrictive interatrial communication.     

Prevention of Mother-to-Child Transmission of HIV: Compliance with the Recommendations of the Brazilian National STD/AIDS Control Program for Prenatal and Perinatal HIV Testing in Porto Alegre, Brazil

In order to benefit from antiretroviral therapy, pregnant women infected with HIV must be tested and diagnosed. Not infrequently, however, women present in labor without prior prenatal care and are thus unable to benefit fully from HIV testing and, if infected, antiretroviral therapy. In this study we evaluated the need for rapid perinatal HIV testing for untested mothers presenting in labor in a public maternal–child hospital that provides care for metropolitan Porto Alegre, Brazil, and potentially modifiable risk factors for noncompliance with national recommendations. We surveyed a consecutive sample of women who gave birth at Hospital Materno–Infantil Presidente Vargas (Presidente Vargas Mother-and-child Hospital) in August–October 2001and administered a structured questionnaire to consenting participants. The questionnaire consisted of demographic data, information on health-seeking behavior, knowledge of HIV infection, and testing during pregnancy. We confirmed information on HIV testing, syphilis, and hepatitis B by examination of the patient's prenatal records. We also obtained data regarding laboratory testing and treatment during labor and delivery (e.g., HIV testing, antiretroviral treatment, and suppression of lactation) from hospital inpatient charts. Of 214 eligible participants, 209 (98%) agreed to participate in the study. Overall 173 (83%) of the 209 participants had had a previous HIV test and 36 (17%) had not. Women with fewer pregnancies were more likely to have been tested (p = .017), as were women with lower family incomes (p = .007). No women had received rapid tests in the delivery room. Of the 209 participants, 201 (96%) had had at least one prenatal visit and 169 (81%) had had three or more visits; 12 (6%) of these reported that they had not been offered an HIV test, 5 (2%) did not know if testing had been offered or not, and 191 (95%) reported that they had been offered a test. We were able to obtain prenatal records for 190 (95%) of the 201participants who had received prenatal care. HIV testing was not mentioned in 9% of charts. Results of syphilis tests were recorded on prenatal records or hospital charts for 167 (80%)participants, and results of hepatitis B surface antigen were found for 93 (45%). Women who to 30pchad had three or more prenatal visits were significantly more likely to have been tested for to 30pcHIV (OR 46.96, 95% CI, 15.92–144.85, .0001), syphilis (OR 31.64, 95% CI, 11.81–87.42, p < .0001) or HBsAg (OR, 4.88, 95% CI, 1.91–12.99, p < .0001) than women who had had two prenatal visits or fewer. Our study showed shown that in 12% of the pregnancies included in our sample national recommendations for prenatal or perinatal testing were not followed, and in an additional 5%, HIV testing, though offered, was not obtained. These women could potentially have benefited from rapid HIV testing. As knowledge of HIV and risk factors for transmission were almost universal in our sample, we believe that the passive health-seeking behavior we observed may offer an opportunity for targeting new efforts to promote the importance of prenatal care and prenatal diagnosis of HIV.     

Melatonin affects the temporal pattern of vocal signatures in birds

In humans and other animals, melatonin is involved in the control of circadian biological rhythms. Here, we show that melatonin affects the temporal pattern of behavioral sequences in a noncircadian manner. The zebra finch (Taeniopygia guttata) song and the crow of the Japanese quail (Coturnix japonica) are courtship vocalizations composed of a stereotyped sequence of syllables. The zebra finch song is learned from conspecifics during infancy, whereas the Japanese quail crow develops normally without auditory input. We recorded and analyzed the complete vocal activity of adult birds of both species kept in social isolation for several weeks. In both species, we observed a shortening of signal duration following the transfer from a light-dark (LD) cycle to constant light (LL), a condition known to abolish melatonin production and to disrupt circadian rhythmicity. This effect was reversible because signal duration increased when the photoperiod was returned to the previous LD schedule. We then tested whether this effect was directly related to melatonin by removal of the pineal gland, which is the main production site of circulating melatonin. A shortening of the song duration was observed following pinealectomy in LD. Likewise, melatonin treatment induced changes in the temporal structure of the song. In a song learning experiment, young pinealectomized finches and young finches raised in LL failed to copy the temporal pattern of their tutor's song. Taken together, these results suggest that melatonin is involved in the control of motor timing of noncircadian behavioral sequences through an evolutionary conserved neuroendocrine pathway.