Peptides
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High plasma proenkephalin A level has been associated with ischemic stroke severity and clinical outcomes. This study aimed to assess the relationship between proenkephalin A and disease severity as well as to investigate its ability to predict long-term clinical outcome in patients with aneurysmal subarachnoid hemorrhage. Plasma proenkephalin A concentrations of one hundred and eighty patients and 180 sex- and age-matched healthy controls were measured by chemoluminescence sandwich immunoassay. ⋯ The predictive value of the plasma proenkephalin A concentration was also similar to those of WFNS score and Fisher score (both P>0.05). In a combined logistic-regression model, proenkephalin A improved the AUCs of WFNS score and Fisher score, but the differences were not significant (both P>0.05). Thus, proenkephalin A level may be a useful, complementary tool to predict mortality and functional outcome at 6 months after aneurysmal subarachnoid hemorrhage.
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High plasma levels of adrenomedullin have been associated with stroke severity and clinical outcomes. This study aimed to analyze plasma levels of adrenomedullin in traumatic brain injury and their association with prognosis. One hundred and forty-eight acute severe traumatic brain injury and 148 sex- and age-matched healthy controls were recruited in this study. ⋯ The predictive performance of the plasma adrenomedullin concentration was also similar to that of Glasgow Coma Scale score for the prediction of 6-month mortality and unfavorable outcome of patients. In a combined logistic-regression model, adrenomedullin improved the area under curve of Glasgow Coma Scale score for the prediction of 6-month mortality and unfavorable outcome of patients, but the differences did not appear to be statistically significant. Thus, high plasma levels of adrenomedullin are associated with head trauma severity, and may independently predict long-term clinical outcomes of traumatic brain injury.
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Irisin, myokine secreted by skeletal muscle, was suggested to mediate some of exercise health benefits via "browning" of white adipose tissue. However, mounting evidence contradicts the regulatory role of exercise for muscle irisin production/secretion in humans. Thus, we explored the direct effect of exercise-mimicking treatment on irisin in human primary muscle cells in vitro. ⋯ Moreover, Fncd5 mRNA was increased in myotubes derived from individuals with type-2-diabetes, independent on exercise-mimicking treatment. Fndc5 mRNA in cells was positively related to fasting glycemia (p=0.0001) and negatively to whole-body insulin sensitivity (p<0.05). Collectively, our data do not support the role of exercise-related signaling pathways in irisin regulation in human skeletal muscle and confirm our previous observations on increased Fndc5 expression in muscle cells from individuals with type-2-diabetes.
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As part of our continuing studies on the structure-activity relationships of cyclic pentapeptides based on the structure of endomorphin-2, we report here the synthesis and biological activities of a new series of analogs incorporating 2', 3' or 4'-methylphenylalanine (MePhe) residues into positions 3 or 4 of the parent cyclopeptide, Dmt-c[d-Lys-Phe-Phe-Asp]NH2 (Dmt=2',6'-dimethyltyrosine). Analogs with MePhe in position 4 showed a row of magnitude increased μ-opioid receptor (MOP receptor) affinity as compared with a parent compound. ⋯ All analogs were strong μ/κ (MOP/KOP) receptor agonists and weak δ (DOP) receptor agonists. In the in vivo hot-plate test in mice, the MePhe(4)-modified peptides showed remarkable antinociceptive activity after intracerebroventricular (i.c.v.) administration which was most likely due to the concomitant activation of more than one opioid receptor type.
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Adrenomedullin (AM) is a member of calcitonin gene-related peptide (CGRP) family and a pain-related peptide. We have shown that chronic administration of morphine (20 μg) upregulates AM activity contributing to morphine tolerance. The present study investigated if AM is involved in acute morphine-induced analgesia. ⋯ Furthermore, exposure of ganglion cultures to morphine (3.3 μM) for 30-240, but not 10 min induced an increase in AM content in the culture medium. These results reveal that a single morphine treatment potentiates post-translational change and the release of AM in sensory ganglia masking morphine-induced analgesia. Thus, targeting AM and its receptors should be considered as a novel approach to improve the analgesic potency of opiates during their acute use.