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https://www.readbyqxmd.com/read/28917289/imaging-of-convective-drug-delivery-in-the-nervous-system
#1
REVIEW
Russell R Lonser
Convection-enhanced delivery permits the direct homogeneous delivery of small- and large-molecular-weight putative therapeutics to the nervous system in a manner that bypasses the blood-nervous system barrier. The development of co-infused surrogate imaging tracers (for computed tomography and MRI) allows for the real-time, noninvasive monitoring of infusate distribution during convective delivery. Real-time image monitoring of convective distribution of therapeutic agents insures that targeted structures/nervous system regions are adequately perfused, enhances safety, informs efficacy (or lack thereof) of putative agents, and provides critical information regarding the properties of convection-enhanced delivery in normal and various pathologic tissue states...
October 2017: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/28904343/engineered-factor-xa-variants-retain-procoagulant-activity-independent-of-direct-factor-xa-inhibitors
#2
Daniël Verhoef, Koen M Visscher, C Ruben Vosmeer, Ka Lei Cheung, Pieter H Reitsma, Daan P Geerke, Mettine H A Bos
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28903884/successful-outcome-of-severe-intra-cerebral-bleeding-associated-with-acquired-factor-v-inhibition-utilization-of-multiple-therapeutic-agents
#3
Panagiotis Andreadis, Katerina Kafantari, Aleka Agapidou, Sofia Vakalopoulou, Efthymia Vlachaki
BACKGROUND: Acquired coagulation Factor inhibitors are antibodies that either inhibit the activity or increase the clearance of a clotting factor leading to an increased risk of bleeding. Most of the times, the disorder is attributed to Factor VIII inhibition (Acquired Hemophilia A), however other coagulation factors could also be implicated. CASE REPORT: We herein would like to report an interesting case of a patient who underwent Coronary Artery Bypass Graft and received antibiotic treatment after surgery with a third-generation cephalosporin...
September 13, 2017: Balkan Medical Journal
https://www.readbyqxmd.com/read/28887666/the-potential-of-multi-compound-nanoparticles-to-bypass-drug-resistance-in-cancer
#4
REVIEW
C G Da Silva, Godefridus J Peters, Ferry Ossendorp, Luis J Cruz
PURPOSE: The therapeutic efficacy of conventional chemotherapy against several solid tumors is generally limited and this is often due to the development of resistance or poor delivery of the drugs to the tumor. Mechanisms of resistance may vary between cancer types. However, with current development of genetic analyses, imaging, and novel delivery systems, we may be able to characterize and bypass resistance, e.g., by inhibition of the right target at the tumor site. Therefore, combined drug treatments, where one drug will revert or obstruct the development of resistance and the other will concurrently kill the cancer cell, are rational solutions...
September 8, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28867360/the-use-of-tmz-embedded-hydrogels-for-the-treatment-of-orthotopic-human-glioma-xenografts
#5
Bandita Adhikari, Jie Li, Michael G Brandel, Diahnn Futalan, Johnny Akers, Timothy Deming, Clark C Chen, Bob S Carter
The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves...
August 31, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28860786/risk-factors-and-early-outcomes-of-acute-renal-injury-after-thoracic-aortic-endograft-repair-for-type-b-aortic-dissection
#6
Songyuan Luo, Huanyu Ding, Jianfang Luo, Wei Li, Bing Ning, Yuan Liu, Wenhui Huang, Ling Xue, Ruixin Fan, Jiyan Chen
BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become an emerging treatment modality for acute type B aortic dissection (TBAD) patients in recent years. The risk factors and impacts of acute kidney injury (AKI) after percutaneous TEVAR, however, have not been widely established. METHODS: We retrospectively studied the clinical records of 305 consecutive patients who admitted to our institution and had TEVAR for TBAD between December 2009 and June 2013...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28841684/infection-with-purified-piscine-orthoreovirus-demonstrates-a-causal-relationship-with-heart-and-skeletal-muscle-inflammation-in-atlantic-salmon
#7
Øystein Wessel, Stine Braaen, Marta Alarcon, Hanne Haatveit, Norbert Roos, Turhan Markussen, Torstein Tengs, Maria K Dahle, Espen Rimstad
Viral diseases pose a significant threat to the productivity in aquaculture. Heart- and skeletal muscle inflammation (HSMI) is an emerging disease in Atlantic salmon (Salmo salar) farming. HSMI is associated with Piscine orthoreovirus (PRV) infection, but PRV is ubiquitous in farmed Atlantic salmon and thus present also in apparently healthy individuals. This has brought speculations if additional etiological factors are required, and experiments focusing on the causal relationship between PRV and HSMI are highly warranted...
2017: PloS One
https://www.readbyqxmd.com/read/28830606/thrombin-generation-assays-for-global-evaluation-of-the-hemostatic-system-perspectives-and-limitations
#8
Rita Carolina Figueiredo Duarte, Cláudia Natália Ferreira, Danyelle Romana Alves Rios, Helton José Dos Reis, Maria das Graças Carvalho
The existing techniques to evaluate hemostasis in clinical laboratories are not sensitive enough to detect hypercoagulable and mild hypocoagulable states. Under different experimental conditions, the thrombin generation test may meet these requirements. This technique evaluates the overall balance between procoagulant and anticoagulant forces and has provided new insights in our understanding of the coagulation cascade, as well as of the diagnosis of hypocoagulability and hypercoagulability conditions. Thrombin generated in the thrombin generation test can be quantified as platelet-rich or platelet-poor plasma using the calibrated automated thrombogram method, which monitors the cleavage of a fluorogenic substrate that is simultaneously compared to the known thrombin activity in a non-clotting plasma sample...
July 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/28820359/clinical-outcomes-of-direct-oral-anticoagulants-after-lower-extremity-arterial-procedures
#9
Afsha Aurshina, Pavel Kibrik, Justin Eisenberg, Ahmad Alsheekh, Anil Hingorani, Natalie Marks, Enrico Ascher
Objectives The use of postoperative anticoagulation is not uncommon for patients undergoing lower extremity arterial procedures as adjunctive therapy. Longer postoperative length of stay is necessary to achieve adequate therapeutic international normalized ratio with traditional protocols that call for the use of unfractionated heparin and warfarin therapy. We hypothesized the direct oral anticoagulants are an attractive alternative to provide adequate anticoagulation in patients who undergo lower extremity arterial procedures...
January 1, 2017: Vascular
https://www.readbyqxmd.com/read/28816833/perioperative-use-of-erythromycin-reduces-cognitive-decline-after-coronary-artery-bypass-grafting-surgery-a-pilot-study
#10
Evanthia Thomaidou, Helena Argiriadou, Georgios Vretzakis, Kalliopi Megari, Nikolaos Taskos, Georgios Chatzigeorgiou, Kyriakos Anastasiadis
OBJECTIVES: Adverse neurologic outcome can be a debilitating complication after cardiac surgery. The aim of this study was to investigate the potential neuroprotective action of erythromycin, a well known antibiotic agent, regarding postoperative cognitive decline in patients undergoing cardiac surgery. METHODS: Forty patients scheduled for elective coronary artery bypass grafting surgery were prospectively randomly assigned in 2 groups: the erythromycin group (n = 19) who received erythromycin at a dose of 25 mg/kg before and after surgery and the control group (n = 21) who did not receive it...
September 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28815418/availability-of-angiography-and-therapeutic-embolization-for-the-treatment-of-acute-bleeding-in-patients-with-hemophilia
#11
Mi Jin Kim, Ji Young Oh, Young Shil Park
Clotting factor replacement therapy alone is often inadequate for acute bleeding in hemophilia patients, and surgery for such patients poses significant clinical challenges. Arterial angiographic intervention is used to control bleeding in local blood vessels. In the present study, we examined the clinical course and prognosis of hemophilia patients with bleeding who had undergone angiography, and evaluated the validity of diagnostic angiography and therapeutic embolization in these patients. Angiography was performed in five hemophilia patients, who experienced bleeding that was difficult to control even after treatment with clotting factor replacement or bypassing agent therapy...
August 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28814242/antimicrobial-peptides-a-promising-therapeutic-strategy-in-tackling-antimicrobial-resistance
#12
Ramya Nuti, Sridhar Goud, A Prasanth Saraswati, Ravi Alvala, Mallika Alvala
BACKGROUND: Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules...
August 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28791355/pegylation-of-lumbrokinase-improves-pharmacokinetic-profile-and-enhances-anti%C3%A2-thrombotic-effect-in-a-rat-carotid-artery-thrombosis-model
#13
Mingji Jin, Guangming Jin, Wei Huang, Zhonggao Gao
The present study aimed to prepare injectable Lumbrokinase (LK) with long circulation time in addition to enhanced anti-thrombotic efficacy. Following preparation, the pharmacokinetic and anti‑thrombotic effect of the drug in a rat carotid artery thrombosis model was evaluated. The drug was prepared by conjugation of LK with mPEG‑SC20000 as previously reported. The pharmacokinetics of the mPEG‑SC20000‑LK were then examined and the anti‑thrombotic activity in an artery‑vein bypass thrombosis rat model was evaluated...
October 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28789610/management-of-refractory-bleeding-post-cardiopulmonary-bypass-in-an-acute-heparin-induced-thrombocytopenia-type-ii-renal-failure-patient-who-underwent-urgent-cardiac-surgery-with-bivalirudin-angiox-%C3%A2-anticoagulation
#14
Kimberly Hassen, Maria R Maccaroni, Haytham Sabry, Smitangshu Mukherjee, Shankari Serumadar, Inderpaul Birdi
Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy...
August 1, 2017: Perfusion
https://www.readbyqxmd.com/read/28776894/persept-1-a-phase-3-trial-of-activated-eptacog-beta-for-on-demand-treatment-of-haemophilia-inhibitor-related-bleeding
#15
M Wang, J B Lawrence, D V Quon, J Ducore, M L Simpson, L N Boggio, I S Mitchell, G Yuan, W A Alexander, J-F Schved
INTRODUCTION: Haemophilia A or B patients with inhibitors have been treated with FVIIa-containing bypassing agents for over 20 years. However, due to uncertainty regarding dose response and thrombotic risk, the use of a gradual, titrated, minimal dosing strategy remains prevalent, potentially hampering early haemostasis. AIM: Evaluate the dose-dependent efficacy, safety and immunogenicity of activated eptacog beta (rhFVIIa), a new recombinant inhibitor bypassing agent for the treatment of bleeding episodes (BEs)...
August 3, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/28774798/drug-combination-approach-to-overcome-resistance-to-egfr-tyrosine-kinase-inhibitors-in-lung-cancer
#16
REVIEW
Christy W S Tong, William K K Wu, Herbert H F Loong, William C S Cho, Kenneth K W To
The discovery of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) has led to unprecedented clinical response in a subset of lung cancer patients carrying the sensitizing EGFR mutations (L858R or exon 19 deletion). However, disease progression invariably occurs within a year after the initial TKI treatment, predominantly due to the development of acquired resistance caused by the secondary EGFR T790 M mutation. Numerous second generation irreversible and third generation EGFR T790 M selective EGFR TKIs have been developed to overcome resistance...
October 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28771230/hyperosmotic-stress-enhances-cytotoxicity-of-smac-mimetics
#17
Sebastian Bittner, Gertrud Knoll, Martin Ehrenschwender
Inhibitors of apoptosis (IAP) proteins contribute to cell death resistance in malignancies and emerged as promising targets in cancer therapy. Currently, small molecules mimicking the IAP-antagonizing activity of endogenous second mitochondria-derived activator of caspases (SMAC) are evaluated in phase 1/2 clinical trials. In cancer cells, SMAC mimetic (SM)-mediated IAP depletion induces tumor necrosis factor (TNF) secretion and simultaneously sensitizes for TNF-induced cell death. However, tumor cells lacking SM-induced autocrine TNF release survive and thus limit therapeutic efficacy...
August 3, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28770424/predictors-of-long-term-remission-and-relapse-of-type-2-diabetes-mellitus-following-gastric-bypass-in-severely-obese-patients
#18
Vanessa Lopes Preto de Oliveira, Gianluca P Martins, Cláudio C Mottin, Jacqueline Rizzolli, Rogério Friedman
BACKGROUND: Diabetes remission is not observed in all obese patients with type 2 diabetes submitted to bariatric surgery. Relapses occur in patients in whom remission is achieved. We investigated the factors associated with long-term (≥3 years) remission and relapse of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) in these patients. METHODS: By a retrospective review, we analyzed data from 254 patients with type 2 diabetes who had undergone RYGB from May 2000 to November 2011 and had at least 3 years of follow-up...
August 2, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28763308/revascularization-strategies-and-in-hospital-management-in-acute-coronary-syndromes-complicated-by-hemophilia-a-or-hemophilia-b
#19
Matthew J Reilley, Anne Blair, William H Matthai, Rolando Vega, Meghan Buckley, Phyllis A Gimotty, Patrick F Fogarty
: Among adult patients with hemophilia A and hemophilia B the emergent management of acute coronary syndromes (ACSs) is challenging, and exposure to antithrombotic agents and/or revascularization procedures may confer an enhanced risk of bleeding. We sought to identify clinical characteristics and in-hospital outcomes among ACS patients with hemophilia A/hemophilia B, compared with matched noncoagulopathic ACS controls. Case discharges from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality (1998-2011) had International Classification of Diseases, 9th Revision codes for hemophilia A/hemophilia B and ACS...
July 29, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28762929/-risk-factors-of-cardiovascular-complications-after-beating-heart-coronary-artery-bypass-grafting-in-patients-with-type-two-diabetes
#20
S Y Borodashkina, K V Protasov, V A Podkamennyi
AIM: to determine risk factors of early cardiovascular complications after beating-heart coronary artery bypass grafting (CABG) in patients with ischemic coronary disease (IHD) and type two diabetes (D2). MATERIALS AND METHODS: We included into this study 188 patients (mean age 59 years, 85.1% men) with IHD and D2 who underwent off-pump CABG. The following cardiovascular complications (CVC) registered within 7 days after surgery were analyzed: myocardial infarction (MI), stroke/transient ischemic attack (S/TIA), atrial fibrillation (AF)...
March 2017: Kardiologiia
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