The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL 1-3 receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL 1 and GAL 2 receptors in anxiety-and depression-related behavior. However, to date, there is sparse literature implicating GAL 3 receptors in behavioral functions. Therefore, we studied the behavior of GAL 3 receptor-deficient (GAL 3 -KO) mice to elucidate whether GAL 3 receptors are involved in mediating behavior-associated actions of GAL. The GAL 3 -KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL 3 -KO mice exhibited an anxietylike phenotype in the elevated plus maze, open field, and light/ dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL 3 receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders.T hirty years ago, Tatemoto et al. (1) isolated the neuropeptide galanin (GAL), a 29-aa (30-aa in humans) peptide, from porcine intestine. The peptide is highly conserved throughout evolution and found in many other species. GAL is widely distributed in the CNS and peripheral nervous system, and it has a variety of biological and physiological functions, ranging from energy homeostasis, reproduction, and feeding to cognition and learning (2). In the murine brain, GAL mRNA is extensively expressed in the hypothalamic and brainstem areas. The highest expression levels were observed in the preoptic, periventricular, and dorsomedial hypothalamic nuclei; bed nucleus of the stria terminalis (BNST); medial and lateral amygdala; locus coeruleus; and nucleus of the solitary tract (3). Furthermore, GAL coexists with the serotonin and norepinephrine systems in the rodent brain and acts as an inhibitory neuromodulator of norepinephrine, serotonin, dopamine, glutamate, and acetylcholine function (4). The expression pattern and neuromodulatory functions of GAL suggest a role for this neuropeptide in mood disorders like anxiety and depression. Accordingly, administration of GAL via the intracerebroventricular (i.c.v.) route or into the dopaminergic ventral tegmental area induced depression-like behavior in the rat forced swim test (FST) (5, 6). Several studies in GAL-overexpressing transgenic mice reported an increased depression-like behavior in the FST (7, 8) but found no differences in anxiety-related behavior und...

Galanin can be regarded as an immunomodulatory peptide as it can sensitize polymorphonuclear neutrophils towards pro-inflammatory cytokines in humans and mice.

It is over 30years since the regulatory peptide galanin was discovered by Professor Mutt and co-workers. Galanin exerts its effects by binding to three galanin G-protein coupled receptors, namely GALR, GALR and GALR. Each galanin receptor has a different distribution in the central nervous system and the peripheral nervous system as well as distinctive signaling pathways, which implicates that the receptors are involved in different biological- and pathological effects. The delineation of the galaninergic system is however difficult due to a lack of stable, specific galanin receptor ligands. Herein, a new short GALR specific ligand, Ala-galanin (2-11), is presented. The galanin (2-11) modified analogue Ala-galanin (2-11) was tested in I-galanin competitive binding studies for the three galanin receptors and the G-protein coupled receptor signaling properties was tested by the ability to influence second-messenger molecules like inositol phosphate and cyclic adenosine monophosphate. In addition, two different label-free real-time assays, namely EnSpire® based on an optical biosensor and xCELLigence® based on an electric biosensor, were used for evaluating the signaling properties using cell lines with different levels of receptor expression. Ala-galanin (2-11) was subsequently found to be a full agonist for GALR with more than 375-fold preference for GALR compared to both GALR and GALR. The single amino acid substitution of serine to alanine at position 5 in the short ligand galanin (2-11) resulted in a ligand subsequently unable to bind neither GALR nor GALR, even at concentrations as high as 0.1mM.

Background: A questionnaire-based prospective study was conducted to evaluate the current use of complementary and alternative medicine (CAM) in a hemato-oncological outpatient clinic. Methods: A multiple-choice questionnaire was designed to assess the use of CAM in a hemato-oncological outpatient clinic. It consisted of questions on sociodemographic and general patient data, and of different kind of questions concerning the use of CAM, including disclosure rates to oncologists and general physicians. The data was analyzed with SAS and a p-value < 0.05 was considered as statistically significant. Results: 46 out of 251 patients (18%) indicated to use CAM. 62 out of all patients (25%) discussed the topic with their general physician or oncologist. Praying or nutritional supplements were the most often used type of CAM. 95 of all participating patients found that the use of CAM could be helpful. Conclusions: The findings of our monocentric study in an outpatient setting do not support the relatively high percentage of CAM users described in the current literature. Nevertheless, CAM needs to be defined more clearly, in order to increase the patients' awareness of CAM.

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There is some evidence that long-term high-intensity endurance training might be associated with deterioration in cardiac function and might impose a potential risk for cardiovascular events. Thus, the intention was to retrospectively evaluate the cardiac status in former endurance athletes, particularly right ventricular (RV) dimension and function, to reveal potential cardiac damage. A group of 12 former world-class swimmers (45 ± 1.5 years) was examined 24.9 ± 4.3 years after cessation of high-intensity endurance training. They underwent history taking, physical examination, ECG, exercise testing and echocardiography. Furthermore, functional and echocardiography data that were also available from former evaluations were included in the analysis. There was a significant decline in exercise capacity. LV function was normal with a decrease in septal thickness to 9.1 ± 1.3 (p < 0.05) and LV diastolic diameter to 48.9 ± 5.6 (p < 0.05). Still, there was a remaining septal hypertrophy. RV function was 55.3 ± 4.2% and there were normal RV dimensions adjusted for body surface area. 25 years after the cessation of endurance training there was a normal RV and LV function with a normalization of almost all diameters, still there was a mild LV hypertrophy in some athletes. Consequently, no relevant long-term cardiac remodeling after intensive endurance training was depicted in this group of athletes.

The neuropeptide galanin is widely distributed in the central and peripheral nervous systems and part of a bigger family of bioactive peptides. Galanin exerts its biological activity through three G-protein coupled receptor subtypes, GAL1-3R. Throughout the last 20years, data has accumulated that galanin can have a neuroprotective effect presumably mediated through the activation of GAL1R and GAL2R. In order to test the pharmaceutical potential of galanin receptor subtype selective ligands to inhibit excitotoxic cell death, the GAL1R selective ligand M617 and the GAL2R selective ligand M1145 were compared to the novel GAL1/2R ligand M1154, in their ability to reduce the excitotoxic effects of intracerebroventricular injected kainate acid in rats. The peptide ligands were evaluated in vitro for their binding preference in a competitive (125)I-galanin receptor subtype binding assay, and G-protein signaling was evaluated using both classical signaling and a label-free real-time technique. Even though there was no significant difference in the time course or severity of the kainic acid induced epileptic behavior in vivo, administration of either M617 or M1154 before kainic acid administration significantly attenuated the neuronal cell death in the hippocampus. Our results indicate the potential therapeutic value of agonists selective for GAL1R in the prevention of neuronal cell death.

Health service research needs coded diagnoses of outpatients. The morbidity treated by physicians in ambulatory care is analysed every quarter on the basis of the diagnoses of about 1,2 Mio. patients by a randomised panel. Patient data combined with diagnoses, encounters and procedures demonstrate the variety of medical care provided. Relevant research questions are for instance the influence of co-payment on the structure of diagnoses or the prevalence of heart diseases in the offices of general practitioners. The comparison of prescribing patterns and diagnoses demonstrates the predominantly probatory therapy with proton pump-inhibitors in the case of gastroesophegal reflux disease. The plausibility and validity of disease documentation are permanently observed by regular checks.