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https://www.readbyqxmd.com/read/28641140/effect-of-c1-inh-on-ischemia-reperfusion-injury-in-a-porcine-limb-ex-vivo-perfusion-model
#1
Mai M Abdelhafez, Jane Shaw, Damian Sutter, Jonas Schnider, Yara Banz, Hansjörg Jenni, Esther Voegelin, Mihai A Constantinescu, Robert Rieben
Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28640753/mechanism-of-antihypertensive-effect-of-mucuna-pruriens-l-seed-extract-and-its-isolated-compounds
#2
Mohammad Yaseen Khan, Vimal Kumar
Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done...
June 21, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#3
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28627122/a-biotinylated-peptide-bp21-as-a-novel-potent-anti-anaphylactic-agent-targeting-platelet-activating-factor
#4
Akira Sato, Keiichi Ebina
Platelet-activating factor (PAF) is an important mediator of anaphylaxis and is therefore an anti-anaphylactic drug target. We recently reported that synthetic N-terminally biotinylated peptides (BP4-BP29) inhibit PAF by directly interacting with PAF and its metabolite/precursor lyso-PAF. In this study, we investigated whether the biotinylated peptides can inhibit anaphylactic reactions in vivo. In mouse models of anaphylaxis, one of the peptides, BP21, markedly and dose-dependently inhibited hypothermia with a maximum dose-response within 30 min after administration, even at doses 20 times lesser than doses of the known PAF antagonist CV-3988...
June 19, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28622690/exploiting-cancer-s-phenotypic-guise-against-itself-targeting-ectopically-expressed-peptide-g-protein-coupled-receptors-for-lung-cancer-therapy
#5
REVIEW
Mahjabin Khan, Tao Huang, Cheng-Yuan Lin, Jiang Wu, Bao-Min Fan, Zhao-Xiang Bian
Lung cancer, claiming millions of lives annually, has the highest mortality rate worldwide. This advocates the development of novel cancer therapies that are highly toxic for cancer cells but negligibly toxic for healthy cells. One of the effective treatments is targeting overexpressed surface receptors of cancer cells with receptor-specific drugs. The receptors-in-focus in the current review are the G-protein coupled receptors (GPCRs), which are often overexpressed in various types of tumors. The peptide subfamily of GPCRs is the pivot of the current article owing to the high affinity and specificity to and of their cognate peptide ligands, and the proven efficacy of peptide-based therapeutics...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28616554/alpha2a-adrenergic-receptor-and-enos-genetic-polymorphisms-are-associated-with-exercise-muscle-vasodilatation-in-apparently-healthy-individuals
#6
Rafael Amorim Belo Nunes, Lucia Pereira Barroso, Alexandre da Costa Pereira, Maria Urbana Pinto Brandão Rondon, Carlos Eduardo Negrão, José Eduardo Krieger, Alfredo José Mansur
PURPOSE: Muscle vasodilatation during exercise has been associated with cardiovascular health and may be influenced by genetic variability. The purpose of this study was to evaluate functional genetic polymorphisms of physiologic pathways related to the regulation of the cardiovascular function (alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin B2 receptor) and exercise muscle vasodilatation in apparently healthy men and women. METHODS: We enrolled 689 individuals without established cardiovascular disease that had attended a check-up program...
December 2016: IJC Heart & Vasculature
https://www.readbyqxmd.com/read/28615126/unveiling-the-participation-of-avian-kinin-ornithokinin-and-its-receptors-in-the-chicken-inflammatory-response
#7
Rodrigo Guabiraba, Damien Garrido, Geoffrey Bailleul, Angélina Trotereau, Mélanie Pinaud, Anne-Christine Lalmanach, Nathalie K Chanteloup, Catherine Schouler
Vasoactive peptides are key early mediators of inflammation released through activation of different enzymatic systems. The mammalian kinin-kallikrein (K-KLK) system produces bradykinin (BK) through proteolytic cleavage of a kininogen precursor by enzymes named kallikreins. BK acts through specific ubiquitous G-protein coupled receptors (B1R and B2R) to participate in physiological processes and inflammatory responses, such as activation of mononuclear phagocytes. In chickens, the BK-like nonapeptide ornithokinin (OK) has been shown to promote intracellular calcium increase in embryonic fibroblasts and to be vasodilatory in vivo...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28605681/a-vote-for-robustness-monitoring-serum-enzyme-activity-by-thin-layer-chromatography-of-dabsylated-bradykinin-products
#8
Malte Bayer, Simone König
High-end analytical methods provide excellent data but may lack the robustness required in large analytical studies. In particular complex chemical matrices may cause difficulties and increase the need for extensive sample preparation. For screening of patients we thus developed a low-tech assay to monitor bradykinin degradation by serum proteases. The bradykinin concentration mirrors the activity of angiotensin-converting enzyme (ACE). Dabsylated bradykinin (DBK) and its labeled fragments DBK1-8 and DBK1-5 were visualized by thin-layer chromatography using only 3μL of serum...
June 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28597074/early-metabolic-markers-identify-potential-targets-for-the-prevention-of-type-2-diabetes
#9
Gopal Peddinti, Jeff Cobb, Loic Yengo, Philippe Froguel, Jasmina Kravić, Beverley Balkau, Tiinamaija Tuomi, Tero Aittokallio, Leif Groop
AIMS/HYPOTHESIS: The aims of this study were to evaluate systematically the predictive power of comprehensive metabolomics profiles in predicting the future risk of type 2 diabetes, and to identify a panel of the most predictive metabolic markers. METHODS: We applied an unbiased systems medicine approach to mine metabolite combinations that provide added value in predicting the future incidence of type 2 diabetes beyond known risk factors. We performed mass spectrometry-based targeted, as well as global untargeted, metabolomics, measuring a total of 568 metabolites, in a Finnish cohort of 543 non-diabetic individuals from the Botnia Prospective Study, which included 146 individuals who progressed to type 2 diabetes by the end of a 10 year follow-up period...
June 8, 2017: Diabetologia
https://www.readbyqxmd.com/read/28596298/sex-differences-in-pulmonary-vascular-control-focus-on-the-nitric-oxide-pathway
#10
Daphne P M de Wijs-Meijler, A H Jan Danser, Irwin K M Reiss, Dirk J Duncker, Daphne Merkus
Although the incidence of pulmonary hypertension is higher in females, the severity and prognosis of pulmonary vascular disease in both neonates and adults have been shown to be worse in male subjects. Studies of sex differences in pulmonary hypertension have mainly focused on the role of sex hormones. However, the contribution of sex differences in terms of vascular signaling pathways regulating pulmonary vascular function remains incompletely understood. Consequently, we investigated pulmonary vascular function of male and female swine in vivo, both at rest and during exercise, and in isolated small pulmonary arteries in vitro, with a particular focus on the NO-cGMP-PDE5 pathway...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28594791/-prospects-of-clinical-application-of-pharmacological-imitation-of-the-phenomenon-of-ischaemic-postconditioning-of-the-heart
#11
S Iu Tsibul'nikov, L N Maslov
Pharmacological imitation of the phenomenon of ischaemic postconditioning of the heart appears to exert a cardioprotective effect in the reperfusion period. It was determined that the protective effect may be carried out resulting from activation of the adenosine, opioid and bradykinin receptors. However, there is yet no common point of view concerning the question as to the activation of what subtypes of the receptors the cardioprotective effect of adenosine, opioids and bradykinin is associated with. The clinical findings strongly suggest that further studies are required, since the data obtained in the hitherto carried out trials are ambiguous, scarce, and sometimes yield contradicting results...
2017: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/28587989/hypertension-alters-the-endothelial-dependent-biphasic-response-of-bradykinin-in-isolated-microminipig-basilar-artery
#12
Md Zahorul Islam, Hiroaki Kawaguchi, Naoki Miura, Noriaki Miyoshi, Emi Yamazaki-Himeno, Mitsuya Shiraishi, Atsushi Miyamoto, Akihide Tanimoto
Angiotensin (Ang) II is known to promote vascular disease and hypertension, partly through its effect on vascular endothelium. Bradykinin (BK) is an endothelium-dependent agonist that induces relaxation followed by contraction of the porcine basilar artery through release of NO and PGF2α, respectively. In this study, we evaluated the effect of Ang II-induced hypertension on basilar artery responsiveness to BK in the Microminipig (MMPig). Ang II (200ng/kg/min) or vehicle was infused into MMPigs for 14days using an osmotic mini-pump and blood pressure was monitored regularly...
June 3, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28585839/solid-phase-synthesis-of-oxetane-modified-peptides
#13
Jonathan D Beadle, Astrid Knuhtsen, Alex Hoose, Piotr Raubo, Andrew G Jamieson, Michael Shipman
Solid-phase peptide synthesis (SPPS) is used to create peptidomimetics in which one of the backbone amide C═O bonds is replaced by a four-membered oxetane ring. The oxetane containing dipeptide building blocks are made in three steps in solution, then integrated into peptide chains by conventional Fmoc SPPS. This methodology is used to make a range of peptides in high purity including backbone modified derivatives of the nonapeptide bradykinin and Met- and Leu-enkephalin.
June 6, 2017: Organic Letters
https://www.readbyqxmd.com/read/28580520/enzyme-immunoassay-of-antibodies-to-endogenous-bioregulators-for-evaluating-the-risk-of-heart-disease
#14
V S Morozova, S N Petrochenko, M A Myagkova, S O Bachurin
The levels of natural antibodies to β-endorphin, bradykinin, histamine, dopamine, and serotonin were measured in 271 cardiological patients in order to evaluate the severity of their clinical status. The patients were distributed into groups differing by the course of the pathological process. The levels of natural antibodies to all antigens were maximum in patients with cardiosclerosis: the content of antibodies to β-endorphin surpassed the control by 46%, to histamine by 62%, to bradykinin by 36%, to dopamine by 49%, and to serotonin by 65%...
June 5, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28578650/snake-venom-from-deadly-toxins-to-life-saving-therapeutics
#15
Humera Waheed, Syed Faraz Moin, M Iqbal Choudhary
Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated...
June 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28572980/the-role-of-contact-system-in-septic-shock-the-next-target-an-overview-of-the-current-evidence
#16
REVIEW
Henrique Nicola
BACKGROUND: Septic shock remains challenging to intensive care units worldwide, despite recent documented improvement in mortality over the years. Multiple new therapies have been attempted without success in large clinical trials. Evidence concerning the role of the contact system and bradykinin on septic shock physiological manifestations is shown by this article. OBJECTIVES: The objective of the study is to review the current evidence linking contact system activation and septic shock, as well as efficacy of available therapies targeting this pathophysiological pathway and to evaluate the potential of further researching the matter...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28566000/peripheral-kv7-channels-regulate-visceral-sensory-function-in-mouse-and-human-colon
#17
Madusha Peiris, James Rf Hockley, David E Reed, Ewan St John Smith, David C Bulmer, L Ashley Blackshaw
Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1-KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry, gut-nerve electrophysiological recordings in both mouse and human tissues, and single-cell qualitative real-time polymerase chain reaction of gut-projecting sensory neurons, to investigate the contribution of peripheral KV7 channels to visceral nociception...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28560465/-lanadelumab-future-plasma-independent-subcutaneous-prophylaxis-for-bradykinin-mediated-angioedema
#18
B Wedi
No abstract text is available yet for this article.
May 30, 2017: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
https://www.readbyqxmd.com/read/28554847/panicolytic-like-action-of-bradykinin-in-the-dorsal-periaqueductal-gray-through-%C3%AE-opioid-and-b2-kinin-receptors
#19
Caio César Sestile, Jhonatan Christian Maraschin, Vanessa Scalco Gama, Hélio Zangrossi, Frederico Guilherme Graeff, Elisabeth Aparecida Audi
A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin-mediated neurotransmission suggest that the μ-opioid receptor (MOR) synergistically interacts with the 5-HT1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone...
May 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28552382/randomized-trial-of-icatibant-for-angiotensin-converting-enzyme-inhibitor-induced-upper-airway-angioedema
#20
Richard Sinert, Phillip Levy, Jonathan A Bernstein, Richard Body, Marco L A Sivilotti, Joseph Moellman, Jennifer Schranz, Jovanna Baptista, Alan Kimura, Wolfram Nothaft
BACKGROUND: Upper airway angioedema is a rare, unpredictable, and at times life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACE-Is) with no existing effective pharmacologic treatment. Icatibant is a bradykinin B2 receptor antagonist that may be beneficial in patients with ACE-I-induced angioedema. OBJECTIVE: We aimed to evaluate the efficacy of icatibant in subjects with ACE-I-induced angioedema. METHODS: At 31 centers in 4 countries, adults on ACE-Is who presented within 12 hours of the onset of at least moderately severe angioedema were randomized 1:1 to icatibant 30 mg or placebo administered subcutaneously...
May 25, 2017: Journal of Allergy and Clinical Immunology in Practice
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