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Bypassing agent

John B Gordon, Jane C Burns
Background: A growing population of young adults is presenting to cardiologists with late manifestations of Kawasaki disease (KD) that include cardiomyopathy, ischemia, and infarction. The management of these conditions differs in important ways from atherosclerotic heart disease, and yet there is little awareness in the adult cardiology community regarding the special challenges posed by the cardiovascular sequelae of KD. Methods: Observations were made on a population of 140 adult KD patients enrolled in the San Diego Adult KD Collaborative Study...
October 31, 2017: Global Cardiology Science & Practice
Mariana Carla Mendes, Maria Lúcia Bonfleur, Rosane Aparecida Ribeiro, Camila Lubaczeuski, Ana Flavia Justino Fêo, Rodrigo Vargas, Everardo Magalhães Carneiro, Antonio Carlos Boschero, Allan Cezar Faria Araujo, Sandra Lucinei Balbo
PURPOSE: Duodeno-jejunal bypass (DJB) operation improves glucose homeostasis in morbid obesity, independently of weight loss or reductions in adiposity, through mechanisms not yet fully elucidated. Herein, we evaluated the effects of DJB upon glucose homeostasis, endocrine pancreatic morphology, and β-cell responsiveness to potentiating agents of cholinergic and cAMP pathways, in western diet (WD) obese rats, at 2 months after operation. METHODS: From 8 to 18 weeks of age male Wistar rats fed on a WD...
March 19, 2018: Endocrine
Shakthi Rk Devan, Suresh Vasu, Yogesha Mallikarjuna, Ramkumar Ponraj, Gireesh Kamath, Suresh Poosala
Biodecontamination is important for eliminating pathogens at research animal facilities, thereby preventing contamination within barrier systems. We enhanced our facility's standard biodecontamination method to replace the traditional foggers, and the new system was used effectively after creating bypass ducts in HVAC units so that individual rooms could be isolated. The entire system was controlled by inhouse-developed supervisory control and data-acquisition software that supported multiple cycles of decontamination by equipment, which had different decontamination capacities, operated in parallel, and used different agents, including H2O2 vapor and ClO2 gas...
March 1, 2018: Journal of the American Association for Laboratory Animal Science: JAALAS
Alexander Kulik, Amy M Abreu, Viviana Boronat, Nicholas T Kouchoukos, Marc Ruel
RATIONALE: Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). Up to 20% of vein grafts will occlude within the first year after CABG despite standard aspirin antiplatelet therapy. However, more potent postoperative platelet inhibition with ticagrelor may improve graft patency. The goal of this study will be to evaluate the efficacy of ticagrelor, as compared to aspirin, for the prevention of saphenous vein graft occlusion following CABG...
March 15, 2018: Contemporary Clinical Trials
Élodie Chrabaszcz, Luisa Laureti, Vincent Pagès
The genome of all organisms is constantly threatened by numerous agents that cause DNA damage. When the replication fork encounters an unrepaired DNA lesion, two DNA damage tolerance pathways are possible: error-prone translesion synthesis (TLS) that requires specialized DNA polymerases, and error-free damage avoidance that relies on homologous recombination (HR). The balance between these two mechanisms is essential since it defines the level of mutagenesis during lesion bypass, allowing genetic variability and adaptation to the environment, but also introduces the risk of generating genome instability...
February 26, 2018: Nucleic Acids Research
Katja M Gist, David S Cooper, Julia Wrona, Sarah Faubel, Christopher Altmann, Zhiqian Gao, Bradley S Marino, Jeffrey Alten, Kristal M Hock, Tomoyuki Mizuno, Alexander A Vinks, Melanie S Joy, Michael F Wempe, Michael R Bennett, Stuart L Goldstein
BACKGROUND: Milrinone, an inotropic agent used ubiquitously in children after cardiac surgery, accumulates in acute kidney injury (AKI). We assessed if urinary AKI biomarkers are predictive of an increase in milrinone concentrations in infants after cardiac surgery. METHODS: Multicenter prospective pilot study of infants undergoing cardiac surgery. Urinary AKI biomarkers were measured in the urine at specific time intervals after cardiopulmonary bypass initiation...
April 2018: Therapeutic Drug Monitoring
Kazuhiro Toyama, Atsushi Yasumoto, Fumihiko Nakamura, Shunya Arai, Mineo Kurokawa
Acquired hemophilia A (AHA) is a hemorrhagic disorder. Whether or not severe thrombotic events can develop without the use of bypassing agents in AHA patients is unclear. An 80-year-old woman with AHA underwent immunosuppressive therapy with prednisolone at 1 mg/kg daily. After achieving remission, she suddenly developed multiple organ failure due to acute systemic thrombosis and died within a few hours of the diagnosis. Patients with AHA, especially those with risk factors for thrombosis, have a considerable risk of developing thrombosis during the recovery phase of factor VIII activity and should be carefully monitored by coagulation testing...
March 9, 2018: Internal Medicine
Andrea Erxleben
Since the serendipitous discovery of the antitumor activity of cisplatin, there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs attract increasing interest. In cancer cells the mitochondrial metabolism is deregulated. Impaired apoptosis, insensitivity to anti-growth signals and unlimited proliferation have been linked to mitochondrial dysfunction...
March 6, 2018: Current Medicinal Chemistry
Massimo Franchini, Pier Mannuccio Mannucci
One of the most challenging issues facing us in the treatment of haemophilia is the development of alloantibodies against infused factor VIII (FVIII) or factor IX (FIX). Inhibitors render factor replacement therapy ineffective, exposing patients to an unacceptably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in a new class of therapeutic agents which act by enhancing coagulation (i...
February 14, 2018: Blood Transfusion, Trasfusione del Sangue
Jiabin Wu, Pengcheng Wang, Yinsheng Wang
Exposure to many endogenous and exogenous agents can give rise to DNA alkylation, which constitutes a major type of DNA damage. Among the DNA alkylation products, alkyl phosphotriesters have relatively high frequencies of occurrence and are resistant to repair in mammalian tissues. However, little is known about how these lesions affect the efficiency and fidelity of DNA replication in cells or how the replicative bypass of these lesions is modulated by translesion synthesis DNA polymerases. In this study, we synthesized oligodeoxyribonucleotides containing four pairs (Sp and Rp) of alkyl phosphotriester lesions at a defined site, and examined how these lesions are recognized by DNA replication machinery in Escherichia coli cells...
March 5, 2018: Nucleic Acids Research
Mehdi Dehghani Firoozabadi, Mohammad Ali Sheikhi, Hossein Rahmani, Ahmad Ebadi, Amanollah Heidari, Behnam Gholizadeh, Khosrow Sharifi
Sulfur mustard (SM) is a toxic chemical agent that belongs to a class of vesicant compounds. In the 1980s it was used by the Iraqi army against Iranian forces. Sulfur mustard severely irritates the skin, eyes and lungs. The highest side effects seen in patients affected by this gas are pulmonary complications including different types of lung diseases such as bronchiolitis. It has also led to a certain type of chronic obstructive pulmonary disease called mustard lung. Similar extra-pulmonary, molecular and hormonal effects can be observed in these patients and patients with chronic obstructive pulmonary disease...
October 2017: Postȩpy Dermatologii i Alergologii
Douglas M Bennion, Chad H Jones, Alex N Dang, Jacob D Isenberg, Justin T Graham, Lena Lindblad, Oliver Domenig, Michael F Waters, Marko Poglitsch, Colin Sumners, U Muscha Steckelings
Significant neuroprotective effects of angiotensin II type 2 (AT2 ) receptor agonists in ischemic stroke have been previously demonstrated in multiple studies.  However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular and systemic administration, are unsuitable for translation to humans; in the latter case because AT2 receptor agonists are blood brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the blood brain barrier and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1-induced ischemic stroke...
March 2, 2018: Clinical Science (1979-)
Rajesh N Gacche, Yehuda G Assaraf
Angiogenesis research in the past two decades has contributed significantly towards understanding the molecular pathophysiology of cancer progression and inspired target-oriented research and pharma industry for the development of novel anti-angiogenic agents. Currently, over eleven drugs targeting angiogenesis have been approved by the FDA for the treatment of various malignancies. Of the registered anti-angiogenic clinical trials until the end of 2017 (, over 47% were completed, 10% were terminated, 3% withdrawn, over 0...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Masashi Toyama, Tomonobu Abe, Masato Nakayama, Tetsuyuki Takahashi, Tomoka Shiba, Chihiro Nakajima
We present herein a patient with rocuronium anaphylaxis, which had been identified using skin test, underwent conventional coronary artery bypass surgery without any neuromuscular blocking agent. Immobility was achieved with sedatives and analgesics.
February 2018: Kyobu Geka. the Japanese Journal of Thoracic Surgery
Dorthe Viemose Nielsen, Christian Torp-Pedersen, Regitze Kuhr Skals, Thomas A Gerds, Zidryne Karaliunaite, Carl-Johan Jakobsen
BACKGROUND: Several choices of inotropic therapy are available and used in relation to cardiac surgery. Comparisons are necessary to select optimal therapy. In Denmark, dobutamine and milrinone are the two inotropic agents most commonly used to treat post-bypass low cardiac output syndrome. This study compares all-cause mortality with these drugs. METHODS: In a retrospective observational study we investigated 10,700 consecutive patients undergoing cardiac surgery from 1 April 2006 to 31 December 2013 at Aarhus and Aalborg University Hospitals in the Central and Northern Denmark Region...
February 26, 2018: Critical Care: the Official Journal of the Critical Care Forum
Martina Sundqvist, Karin Christenson, André Holdfeldt, Michael Gabl, Jonas Mårtensson, Lena Björkman, Regis Dieckmann, Claes Dahlgren, Huamei Forsman
GPR84 is a recently de-orphanized member of the G-protein coupled receptor (GPCR) family recognizing medium chain fatty acids, and has been suggested to play important roles in inflammation. Due to the lack of potent and selective GPR84 ligands, the basic knowledge related to GPR84 functions is very limited. In this study, we have characterized the GPR84 activation profile and regulation mechanism in human phagocytes, using two recently developed small molecules that specifically target GPR84 agonistically (ZQ16) and antagonistically (GLPG1205), respectively...
February 22, 2018: Biochimica et Biophysica Acta
Shamir R Mehta, Kevin R Bainey, Warren J Cantor, Marie Lordkipanidzé, Guillaume Marquis-Gravel, Simon D Robinson, Matthew Sibbald, Derek Y So, Graham C Wong, Joseph G Abunassar, Margaret L Ackman, Alan D Bell, Raymond Cartier, James D Douketis, Patrick R Lawler, Michael S McMurtry, Jacob A Udell, Sean van Diepen, Subodh Verma, G B John Mancini, John A Cairns, Jean-François Tanguay
Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence...
March 2018: Canadian Journal of Cardiology
Yesim Dargaud, Anne Lienhart, Maissaa Janbain, Sandra LeQuellec, Nathalie Enjolras, Claude Negrier
Emicizumab is a recombinant, humanized, bispecific, monoclonal antibody that bridges activated factor IX and factor X to restore the function of deficient factor VIII. Treatment of bleeding in patients with hemophilia and inhibitors involves the use of bypassing agents (BPA).These molecules are also used for the management of breakthrough bleeds in patients on prophylaxis with emicizumab, with increased concerns about the risks of combining two procoagulant drugs. Using thrombin generation assay, we tailored the dosage of activated prothrombin complex concentrate (APCC) and successfully treated an acute spontaneous arterial bleeding in a patient on prophylaxis with emicizumab 1...
February 22, 2018: Haematologica
Qian Liu, Shengnan Yu, Weiheng Zhao, Shuang Qin, Qian Chu, Kongming Wu
Tyrosine kinase inhibitors (TKIs)-treatments bring significant benefit for patients harboring epidermal growth factor receptor (EGFR) mutations, especially for those with lung cancer. Unfortunately, the majority of these patients ultimately develop to the acquired resistance after a period of treatment. Two central mechanisms are involved in the resistant process: EGFR secondary mutations and bypass signaling activations. In an EGFR-dependent manner, acquired mutations, such as T790 M, interferes the interaction between TKIs and the kinase domain of EGFR...
February 19, 2018: Molecular Cancer
Min Shen, Rosita Asawa, Ya-Qin Zhang, Elizabeth Cunningham, Hongmao Sun, Alexander Tropsha, William P Janzen, Eugene N Muratov, Stephen J Capuzzi, Sherif Farag, Ajit Jadhav, Julie Blatt, Anton Simeonov, Natalia J Martinez
Drug repurposing approaches have the potential advantage of facilitating rapid and cost-effective development of new therapies. Particularly, the repurposing of drugs with known safety profiles in children could bypass or streamline toxicity studies. We employed a phenotypic screening paradigm on a panel of well-characterized cell lines derived from pediatric solid tumors against a collection of ∼3,800 compounds spanning approved drugs and investigational agents. Specifically, we employed titration-based screening where compounds were tested at multiple concentrations for their effect on cell viability...
January 12, 2018: Oncotarget
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