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https://www.readbyqxmd.com/read/28326642/neprilysin-inhibition-in-heart-failure-mechanisms-and-substrates-beyond-modulating-natriuretic-peptides
#1
REVIEW
Emilia D'Elia, Attilio Iacovoni, Muthiah Vaduganathan, Ferdinando L Lorini, Stefano Perlini, Michele Senni
The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II...
March 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28322750/supradural-inflammatory-soup-in-awake-and-freely-moving-rats-induces-facial-allodynia-that-is-blocked-by-putative-immune-modulators
#2
Julie Wieseler, Amanda Ellis, Andrew McFadden, Kendra Stone, Kimberley Brown, Sara Cady, Leandro F Bastos, David Sprunger, Niloofar Rezvani, Kirk Johnson, Kenner C Rice, Steven F Maier, Linda R Watkins
Facial allodynia is a migraine symptom that is generally considered to represent a pivotal point in migraine progression. Treatment before development of facial allodynia tends to be more successful than treatment afterwards. As such, understanding the underlying mechanisms of facial allodynia may lead to a better understanding of the mechanisms underlying migraine. Migraine facial allodynia is modeled by applying inflammatory soup (histamine, bradykinin, serotonin, prostaglandin E2) over the dura. Whether glial and/or immune activation contributes to such pain is unknown...
March 16, 2017: Brain Research
https://www.readbyqxmd.com/read/28315456/mechanisms-underlying-the-diuretic-effect-of-gomphrena-celosioides-mart-amaranthaceae
#3
Paulo Cesar de Paula Vasconcelos, Danilo Ramos Spessotto, Jane Vasconcelos Marinho, Marcos José Salvador, Arquimedes Gasparotto Junior, Candida Aparecida Leite Kassuya
ETHNOPHARMACOLOGICAL RELEVANCE: Gomphrena celosioides (Amaranthaceae) is a native medicinal plant found in Mato Grosso do Sul State that is used for treating urinary tract and kidney stones. This study aimed to evaluate the diuretic effects of ethanolic extract from G. celosioides (EEGC) on acute and extended diuresis to provide a pharmacological basis for its use in traditional medicine. AIM OF THE STUDY: To evaluate the diuretic and natriuretic activity of EEGC and its mechanism of action in an animal model...
March 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28315051/development-of-antibody-modified-chitosan-nanoparticles-for-the-targeted-delivery-of-sirna-across-the-blood-brain-barrier-as-a-strategy-for-inhibiting-hiv-replication-in-astrocytes
#4
Jijin Gu, Karam Al-Bayati, Emmanuel A Ho
RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands...
March 17, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28299349/gabapentin-inhibits-protein-kinase-c-epsilon-translocation-in-cultured-sensory-neurons-with-additive-effects-when-coapplied-with-paracetamol-acetaminophen
#5
Vittorio Vellani, Chiara Giacomoni
Gabapentin is a well-established anticonvulsant drug which is also effective for the treatment of neuropathic pain. Although the exact mechanism leading to relief of allodynia and hyperalgesia caused by neuropathy is not known, the blocking effect of gabapentin on voltage-dependent calcium channels has been proposed to be involved. In order to further evaluate its analgesic mechanisms, we tested the efficacy of gabapentin on protein kinase C epsilon (PKCε) translocation in cultured peripheral neurons isolated from rat dorsal root ganglia (DRGs)...
2017: TheScientificWorldJournal
https://www.readbyqxmd.com/read/28299332/relationship-between-angiotensin-converting-enzyme-apelin-and-new-onset-atrial-fibrillation-after-off-pump-coronary-artery-bypass-grafting
#6
Shu Xu, Jian Zhang, Yin-Li Xu, Hai-Bo Wu, Xiao-Dong Xue, Hui-Shan Wang
It has been shown that inflammation and oxidative stress are important factors in postoperative atrial fibrillation (POAF). Angiotensin converting enzyme (ACE) and apelin have a close relationship with inflammation and oxidative stress. The effect of ACE and apelin on POAF after off-pump coronary artery bypass grafting (OPCABG) remains a question. The concentrations of serum ACE, angiotensin II (Ang II), apelin, bradykinin (BK), malondialdehyde (MDA), and C reactive protein (CRP) were measured in the perioperative period of OPCABG...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28295341/exercise-training-reverses-age-induced-diastolic-dysfunction-and-restores-coronary-microvascular-function
#7
Kazuki Hotta, Bei Chen, Bradley J Behnke, Payal Ghosh, John N Stabley, Jeremy A Bramy, Jaime L Sepulveda, Michael D Delp, Judy M Muller-Delp
The risk for diastolic dysfunction increases with advancing age. Regular exercise training ameliorates age-related diastolic dysfunction; however, the underlying mechanisms have not been identified. We investigated whether 1) microvascular dysfunction contributes to the development of age-related diastolic dysfunction, and 2) initiation of late-life exercise training reverses age-related diastolic and microvascular dysfunction. Young and old rats underwent 10 weeks of exercise training or remained as sedentary, cage-controls...
March 10, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28288820/resveratrol-inhibits-bk-induced-cox-2-transcription-by-suppressing-acetylation-of-ap-1-and-nf-%C3%AE%C2%BAb-in-human-rheumatoid-arthritis-synovial-fibroblasts
#8
Chuen-Mao Yang, Yu-Wen Chen, Pei-Ling Chi, Chih-Chung Lin, Li-Der Hsiao
Bradykinin (BK) induces inflammation in rheumatoid arthritis (RA). Resveratrol is a potent activator of Sirt1 which could modulate inflammation through deacetylating histones of transcription factors. Here, we investigated the mechanisms underlying BK-induced COX-2 expression which is modulated by resveratrol/Sirt1 in human rheumatoid arthritis synovial fibroblasts (RASFs). We found that BK-induced COX-2 protein and mRNA expression associated with PGE2 synthesis, and promoter activity was mediated through B2R receptors, which were attenuated by selective B2R antagonist Hoe140 or transfection with B2R siRNA...
March 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28284848/angiotensin-converting-enzymes-in-fish-venom
#9
Dávida Maria Ribeiro Cardoso Dos Santos, Cledson Barros de Souza, Hugo Juarez Vieira Pereira
Animal venoms are multifaceted mixtures, including proteins, peptides and enzymes produced by animals in defense, predation and digestion. These molecules have been investigated concerning their molecular mechanisms associated and possible pharmacological applications. Thalassophryne nattereri is a small venomous fish inhabiting the northern and northeastern coast of Brazil, and represents a relatively frequent cause of injuries. Its venom causes severe inflammatory response followed frequently by the necrosis of the affected area...
March 8, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28283888/kinin-receptors-sensitize-trpv4-channel-and-induce-mechanical-hyperalgesia-relevance-to-paclitaxel-induced-peripheral-neuropathy-in-mice
#10
Robson Costa, Maíra A Bicca, Marianne N Manjavachi, Gabriela C Segat, Fabiana Chaves Dias, Elizabeth S Fernandes, João B Calixto
Kinin B1 (B1R) and B2 receptors (B2R) and the transient receptor potential vanilloid 4 (TRPV4) channel are known to play a critical role in the peripheral neuropathy induced by paclitaxel (PTX) in rodents. However, the downstream pathways activated by kinin receptors as well as the sensitizers of the TRPV4 channel involved in this process remain unknown. Herein, we investigated whether kinins sensitize TRPV4 channels in order to maintain PTX-induced peripheral neuropathy in mice. The mechanical hyperalgesia induced by bradykinin (BK, a B2R agonist) or des-Arg(9)-BK (DABK, a B1R agonist) was inhibited by the selective TRPV4 antagonist HC-067047...
March 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28238904/proteomic-toxicological-and-immunogenic-characterization-of-mexican-west-coast-rattlesnake-crotalus-basiliscus-venom-and-its-immunological-relatedness-with-the-venom-of-central-american-rattlesnake-crotalus-simus
#11
Álvaro Segura, María Herrera, Francisco Reta Mares, Claudia Jaime, Andrés Sánchez, Mariángela Vargas, Mauren Villalta, Aarón Gómez, José María Gutiérrez, Guillermo León
The venom of the Mexican west-coast rattlesnake (Crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. This venom is composed of 68% Zn(2+)-dependent metalloproteinases (SVMPs), 14% phospholipases A2 (PLA2s), 11% serine proteinases, 4% SVMPs-inhibitor tripeptides (SVMP-ITs), 2% bradykinin-potentiating peptides (BPPs), 0.6% cysteine-rich secretory proteins (CRISPs), and 0.2% l-amino acid oxidases (LAAOs). SVMPs present in the venom are responsible for azocasein hydrolysis and hemorrhagic activity, but their contribution to the lethal activity of the venom in mice is masked by the neurotoxic activity of PLA2s, which in addition are also responsible for myotoxic activity...
February 24, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28226311/effects-of-root-extracts-of-eurycoma-longifolia-jack-on-corpus-cavernosum-of-rat
#12
Bae Huey Tee, See Ziau Hoe, Swee Hung Cheah, Sau Kuen Lam
OBJECTIVE: This study was conducted to investigate the mechanisms of action of Eurycoma longifolia in rat corpus cavernosum. MATERIALS AND METHODS: Tincture of the roots was concentrated to dryness by evaporating the ethanol in vacuo. This ethanolic extract was partitioned into five fractions sequentially with hexane, dichloromethane, ethyl acetate, butanol and water. The corpus cavernosum relaxant activity of each fraction was investigated. Dichloromethanic (DCM) fraction which showed the highest potency in relaxing phenylephrine-precontracted corpora cavernosa was purified by column chromatography...
February 22, 2017: Medical Principles and Practice: International Journal of the Kuwait University, Health Science Centre
https://www.readbyqxmd.com/read/28225674/inhibiting-plasma-kallikrein-for-hereditary-angioedema-prophylaxis
#13
RANDOMIZED CONTROLLED TRIAL
Aleena Banerji, Paula Busse, Mustafa Shennak, William Lumry, Mark Davis-Lorton, Henry J Wedner, Joshua Jacobs, James Baker, Jonathan A Bernstein, Richard Lockey, H Henry Li, Timothy Craig, Marco Cicardi, Marc Riedl, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel J Sexton, Christopher TenHoor, Jon A Kenniston, Ryan Faucette, J Gordon Still, Harvey Kushner, Robert Mensah, Chris Stevens, Joseph C Biedenkapp, Yung Chyung, Burt Adelman
Background Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency. Methods We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial...
February 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28223053/diabetes-upregulation-of-cyclooxygenase-2%C3%A2-contributes-to-altered-coronary-reactivity-after-cardiac-surgery
#14
Jun Feng, Kelsey Anderson, Arun K Singh, Afshin Ehsan, Hunter Mitchell, Yuhong Liu, Frank W Sellke
BACKGROUND: We hypothesized that upregulation of inducible cyclooxygenase 2 (COX-2) contributes to altered coronary arteriolar reactivity early after cardioplegic arrest and cardiopulmonary bypass (CP/CPB) in patients with diabetes mellitus who are undergoing cardiac surgery. METHODS: The right atrial tissue samples of nondiabetes (ND), controlled diabetes (CDM), and uncontrolled diabetes (UDM) patients undergoing cardiac surgery were harvested before and after CP/CPB...
February 18, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28222330/hereditary-c1-inhibitor-deficiency-is-associated-with-high-spontaneous-amidase-activity
#15
Delphine Charignon, Arije Ghannam, Denise Ponard, Christian Drouet
BACKGROUND: Angioedema diagnosis classically targets the complement system (via C1 inhibitor (C1Inh) function and antigenic C4 level) and contact phase activation (via amidase activity). Bradykinin is responsible for angioedema attacks and is produced from contact phase activation secondary to failed C1Inh control. OBJECTIVE: We aimed to compare the diagnostic performances of spontaneous amidase activity and antigenic C4 level in C1Inh hereditary angioedema (C1Inh-HAE) patients...
February 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28220244/resetting-of-renal-tissular-renin-angiotensin-and-bradykinin-kallikrein-systems-after-unilateral-kidney-denervation-in-rats
#16
Jürgen M Bohlender, Jürg Nussberger, Frédéric Birkhäuser, Eric Grouzmann, George N Thalmann, Hans Imboden
The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems in rats 6 days after left kidney denervation (DNX, n = 8) compared to sham-operated controls (CTR, n = 8). Plasma renin concentration was unchanged in DNX vs. CTR (p = NS). Kidney bradykinin (BK) and angiotensin (Ang) I and II concentrations decreased bilaterally in DNX vs...
February 20, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28219400/alleviation-of-secondary-brain-injury-posttraumatic-inflammation-and-brain-edema-formation-by-inhibition-of-factor-xiia
#17
Sarah Hopp, Marc W Nolte, Christian Stetter, Christoph Kleinschnitz, Anna-Leena Sirén, Christiane Albert-Weissenberger
BACKGROUND: Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in the plasma is triggered by activated factor XII. Hence, we set out to study in detail the influence of activated factor XII on the abovementioned pathophysiological features of TBI...
February 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28215026/separation-of-peptides-on-superficially-porous-particle-based-macrocyclic-glycopeptide-liquid-chromatography-stationary-phases-consideration-of-fast-separations
#18
Rasangi M Wimalasinghe, Zachary S Breitbach, Jauh T Lee, Daniel W Armstrong
Macrocyclic glycopeptide based liquid chromatography stationary phases are known for their highly selective peptide separations. Fast and ultrafast (t R < 1 min) high-efficiency separations were achieved with superficially porous particle (SPP)-based stationary phases. Separations of pharmaceutically important classes of peptides such as enkephalins and bradykinins have been achieved in less than 5 min in isocratic elution modes. Selectivity for peptides structurally similar to one another was increased with use of teicoplanin-based stationary phases compared with commercial C18 stationary phases...
February 18, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28201967/dipeptidyl-peptidase-4-inhibitor-induced-angioedema-an-overlooked-and-potentially-lethal-adverse-drug-reaction
#19
Susanne Irene Scott, Michelle Fog Andersen, Lise Aagaard, Christian Von Buchwald, Eva Rye Rasmussen
Introduction Angioedema is a potentially fatal adverse drug reaction of some medications, as swellings of the upper airways can cause death by asphyxiation. Angiotensin converting enzyme-inhibitors are widely known to cause angioedema but less is known about the association between dipeptidyl peptidase-4 inhibitors (gliptins) and angioedema. Dipeptidyl peptidase-4 inhibitors are anti-diabetic drugs used to improve glycaemic control. They, as a class effect, inadvertently affect the degradation of the vasoactive kinins bradykinin and substance P, both of which can cause angioedema due to vasodilatation and increase in vascular permeability in the capillaries...
February 14, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28196712/ipomoea-pes-caprae-l-r-br-convolvulaceae-as-a-topical-herbal-medicine-to-relieve-pain-and-inflammation-promising-tool-against-effects-due-to-toxin-skin-contact
#20
Cristiane da Silva Barth, Hugo Guilherme Tolentino de Souza, Lilian W Rocha, Gislaine Francieli da Silva, Mariana Ferreira Dos Anjos, Veronica D'Avila Pastor, Tania Mari Belle Bresolin, Angelica Garcia Couto, José Roberto Santin, Nara Lins Meira Quintão
ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoea pes-caprae is known as bayhops, beach morning glory or goat's foot, and in Brazil as salsa-de-praia. Its leaves are used in worldwide folk medicine for the relief of jellyfish-stings symptoms. The literature only reports the anti-inflammatory and neutralizing effects of a nonpolar plant derived, without validating the popular use or exploring the mechanism of action. AIM OF THE STUDY: This study aimed to evaluate and validate the topical effects of a semisolid containing hydroethanolic extract obtained from the aerial parts of I...
February 11, 2017: Journal of Ethnopharmacology
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