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Muhammet Furkan Korkmaz, Ahmet Güzel, Mehmet Açıkgöz, Ali Okuyucu, Hasan Alaçam
OBJECTIVES: Community-acquired pneumonia (CAP) in children is one of the most important causes of mortality and morbidity in developing countries. Therefore, it is very important for clinicians to detect the presence and severity of pneumonia. Proadrenomedullin (Pro-ADM) and Interleukin-1β (IL-1β) are thought to have potential for CAP evaluation in children. We sought to investigate the value of Pro-ADM and IL-1β levels for severity assessment and outcome prediction in children with CAP...
January 2018: Annals of Clinical and Laboratory Science
Martyna Szpakowska, Max Meyrath, Nathan Reynders, Manuel Counson, Julien Hanson, Jan Steyaert, Andy Chevigné
The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor...
March 9, 2018: Biochemical Pharmacology
Xiaoling Yang, Hui Shao, Yong Chen, Ning Ding, Anning Yang, Jue Tian, Yuanxu Jiang, Guizhong Li, Yideng Jiang
Cirsium japonicum, a constituent of traditional Chinese medicine, has been shown to exert inflammatory effects as well as to improve the circulation and thus to counteract hematologic stasis. Studies have demonstrated that intermedin (IMD) has protective effects on hypertension in rats by regulating the Ang/NO metabolic pathway. In this study, we investigated whether by regulating the expression of IMD, Cirsium japonicum could improve cardiac function in rats with 2k1c-induced renal hypertension. Renal hypertension was induced in Sprague-Dawley rats by occluding the renal artery...
March 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Christopher Geven, Matthijs Kox, Peter Pickkers
Sepsis remains a major medical challenge, for which, apart from improvements in supportive care, treatment has not relevantly changed over the last few decades. Vasodilation and vascular leakage play a pivotal role in the development of septic shock, with vascular leakage being caused by disrupted endothelial integrity. Adrenomedullin (ADM), a free circulating peptide involved in regulation of endothelial barrier function and vascular tone, is implicated in the pathophysiology of sepsis. ADM levels are increased during sepsis, and correlate with extent of vasodilation, as well as with disease severity and mortality...
2018: Frontiers in Immunology
Hongjin Si, Yao Zhang, Yuqing Song, Lili Li
The poor survival rate of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Adrenomedullin (ADM) has been identified as a potent apoptotic inhibitor. The present study aimed to investigate the protective effects of ADM on MSCs against hypoxia and serum deprivation (H/SD)‑induced apoptosis, and to determine the potential underlying mechanisms. In the present study, a recombinant adenovirus expressing the ADM gene was established and was infected into MSCs...
March 5, 2018: International Journal of Molecular Medicine
Paraskevi L Tsiolaki, Georgia I Nasi, Fotis A Baltoumas, Nikolaos N Louros, Vassiliki Magafa, Stavros J Hamodrakas, Vassiliki A Iconomidou
The Calcitonin-gene related peptide (CGRP) family is a group of peptide hormones, which consists of IAPP, calcitonin, adrenomedullin, intermedin, αCGRP and βCGRP. IAPP and calcitonin have been extensively associated with the formation of amyloid fibrils, causing Type 2 Diabetes and Medullary Thyroid Carcinoma, respectively. In contrast, the potential amyloidogenic properties of αCGRP still remain unexplored, although experimental trials have indicated its presence in deposits, associated with the aforementioned disorders...
March 1, 2018: Journal of Structural Biology
Hans-Dirk Düngen, Verena Tscholl, Danilo Obradovic, Sara Radenovic, Dragan Matic, Lindy Musial Bright, Elvis Tahirovic, Almuth Marx, Simone Inkrot, Djawid Hashemi, Jovan Veskovic, Svetlana Apostolovic, Stephan von Haehling, Wolfram Doehner, Natasa Cvetinovic, Mitja Lainscak, Burkert Pieske, Frank Edelmann, Tobias Trippel, Goran Loncar
AIMS: In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. METHODS AND RESULTS: MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF...
February 24, 2018: ESC Heart Failure
Xiao-Wei Liu, Tao Ma, Wei Liu, Quan Cai, Li Wang, Hong-Wei Song, Liao Yuan, Zhi Liu
PURPOSE: The identification of infection at its early stage in vulnerable patients is challenging. This study aimed to investigate potential biomarkers to distinguish patients progressing to severe sepsis from those with uncomplicated sepsis. MATERIALS AND METHODS: Serum samples were collected from sepsis patients admitted to the emergency department. The mRNA and protein levels of angiopoietin-2 (Ang-2), interleukin-10 (IL-10), heparin-binding protein (HBP), procalcitonin (PCT), adrenomedullin (ADM), and interleukin-6 (IL-6) were evaluated...
January 11, 2018: Journal of Critical Care
Kotb Abbass Metwalley, Hekma Saad Farghaly, Tahra Sherief
BACKGROUND: Obese children are at increased risk for abnormal cardiac structure and function. Little is known about adrenomedullin (AM), a cytokine produced in various organs and tissues, as a biomarker of cardiac hypertrophy in obese children. This study aimed to assess the plasma AM levels in a cohort of obese children and its relationship to left ventricular (LV) functions. METHODS: The study included 60 obese children and 60 non-obese children matched for age and gender as control group...
February 6, 2018: World Journal of Pediatrics: WJP
Michael L Garelja, Christina A Walker, Andrew Siow, Sung H Yang, Paul William R Harris, Margaret A Brimble, Harriet A Watkins, Joseph J Gingell, Debbie L Hay
The calcitonin receptor-like receptor (CLR) is a class B G protein-coupled receptor (GPCR) that forms the basis of three pharmacologically distinct receptors, the calcitonin gene-related peptide (CGRP) receptor, and two adrenomedullin (AM) receptors. These three receptors are created by CLR interacting with three receptor activity-modifying proteins (RAMPs). Class B GPCRs have an N-terminal extracellular domain (ECD) and transmembrane bundle that are both important for binding endogenous ligands. These two domains are joined together by a stretch of amino acids which is referred to as the "stalk"...
February 1, 2018: Biochemistry
Jason M Booe, Margaret L Warner, Amanda M Roehrkasse, Debbie L Hay, Augen A Pioszak
Binding of the vasodilator peptides adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) to the class B GPCR calcitonin receptor-like receptor (CLR) is modulated by receptor activity-modifying proteins (RAMP). RAMP1 favors CGRP, whereas RAMP2 and RAMP3 favor AM. Crystal structures of peptide-bound RAMP1/2-CLR extracellular domain (ECD) heterodimers suggested RAMPs alter ligand preference through direct peptide contacts and allosteric modulation of CLR. Here, we probed this dual mechanism through rational structure-guided design of AM and CGRP antagonist variants...
January 23, 2018: Molecular Pharmacology
Zhihui Xie, Wei-Sheng Chen, Yuzhi Yin, Eunice C Chan, Kaoru Terai, Lauren M Long, Timothy G Myers, Arkadiusz Z Dudek, Kirk M Druey
BACKGROUND: Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life-threatening vascular disorder of unknown etiology. SCLS is characterized by abrupt and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered attention recently because its initial presentation resembles more common vascular disorders including systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses...
January 23, 2018: Journal of Leukocyte Biology
Etienne Gayat, Alain Cariou, Nicolas Deye, Antoine Vieillard-Baron, Samir Jaber, Charles Damoisel, Qin Lu, Xavier Monnet, Isabelle Rennuit, Elie Azoulay, Marc Léone, Heikel Oueslati, Bertrand Guidet, Diane Friedman, Antoine Tesnière, Romain Sonneville, Philippe Montravers, Sébastien Pili-Floury, Jean-Yves Lefrant, Jacques Duranteau, Pierre-François Laterre, Nicolas Brechot, Karine Chevreul, Morgane Michel, Bernard Cholley, Matthieu Legrand, Jean-Marie Launay, Eric Vicaut, Mervyn Singer, Matthieu Resche-Rigon, Alexandre Mebazaa
BACKGROUND: Intensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge. METHODS: FROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium...
January 18, 2018: Critical Care: the Official Journal of the Critical Care Forum
Wenpei Dong, Ping Yu, Tielong Zhang, Chenzhuang Zhu, Jun Qi, Junhao Liang
Remote ischemic preconditioning (RIPC) is a minimally invasive method that provides protection by reducing injury to the heart, kidneys, brain and other tissues or organs. RIPC may improve the outcome in patients undergoing surgery. Although the role of RIPC has been studied, the results remain controversial. It is difficult to confirm whether RIPC has a kidney protective effect and the understanding of the preconditioning signal pathway involved remains unclear. In the present study, the effect of RIPC in urology was evaluated...
January 17, 2018: Molecular Medicine Reports
Christopher Geven, Esther Peters, Mathias Schroedter, Joachim Struck, Andreas Bergmann, Oscar McCook, Peter Radermacher, Matthijs Kox, Peter Pickkers
PURPOSE: Adrenomedullin (ADM) is an important regulator of endothelial barrier function during sepsis. Administration of a murine antibody targeted against the N-terminus of ADM (HAM1101) resulted in improved outcome in models of murine sepsis. We studied the effects of a humanized form of this antibody (HAM8101, also known as Adrecizumab) on vascular barrier dysfunction and survival in rodent models of systemic inflammation and sepsis. METHODS: Rats (n=48) received different dosages of HAM8101 or placebo (n = 8 per group), directly followed by administration of lipopolysaccharide (5 mg/kg)...
January 10, 2018: Shock
Christopher Geven, Andreas Bergmann, Matthijs Kox, Peter Pickkers
Sepsis remains a major scientific and medical challenge, for which, apart from significant refinements in supportive therapy, treatment has barely changed over the last few decades. During sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock. The free circulating peptide adrenomedullin (ADM) is involved in regulation of the endothelial barrier function and tone of blood vessels. Several animal studies have shown that ADM administration improves outcome of sepsis...
January 10, 2018: Shock
Justin J Choi, Matthew W McCarthy
Acute dyspnea is a common chief complaint among patients who visit an emergency room and presents diagnostic challenges for clinicians in both identifying the etiology and determining the clinical severity. The study of biomarkers in the prognostication and risk stratification of these patients has been increasing, including the investigation of the prognostic value for mid-regional pro-adrenomedullin (MR-proADM). Areas Covered: In this review, the authors cover what is known about MR-proADM testing in patients presenting with acute dyspnea and the supporting evidence of its prognostic value in common conditions in medical patients with acute dyspnea, including acute heart failure, community acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease, and acute pulmonary embolism...
January 10, 2018: Expert Review of Molecular Diagnostics
Signe Frøssing, Malin Nylander, Caroline Kistorp, Sven O Skouby, Jens Faber
CONTEXT: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP...
January 2018: Endocrine Connections
Shana Claeys, Geertrui Denecker, Robrecht Cannoodt, Candy Kumps, Kaat Durinck, Frank Speleman, Katleen De Preter
Background: Neuroblastoma is an aggressive childhood malignancy of the sympathetic nervous system. Despite multi-modal therapy, survival of high-risk patients remains disappointingly low, underscoring the need for novel treatment strategies. The discovery of ALK activating mutations opened the way to precision treatment in a subset of these patients. Previously, we investigated the transcriptional effects of pharmacological ALK inhibition on neuroblastoma cell lines, six hours after TAE684 administration, resulting in the 77-gene ALK signature, which was shown to gradually decrease from 120 minutes after TAE684 treatment, to gain deeper insight into the molecular effects of oncogenic ALK signaling...
December 5, 2017: Oncotarget
Fanyang Kong, Li Lei, Yiqi Du, Huiyun Zhu, Zhaoshen Li, Xiangyu Kong
No abstract text is available yet for this article.
December 15, 2017: Gut
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