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Tochukwu C Okwuosa, Cindy Soares, Verena Golwitzer, Rober Habashy, Peter Timmins, Mohamed A Alhnan
A method for the production of liquid capsules with the potential of modifying drug dose and release is presented. For the first time, the co-ordinated use of fused deposition modelling (FDM), 3D printing and liquid dispensing to fabricate individualised dosage form on demand in a fully automated fashion has been demonstrated. Polymethacrylate shells (Eudragit EPO and RL) for immediate and extended release were fabricated using FDM 3D printing and simultaneously filled using a computer-controlled liquid dispenser loaded with model drug solution (theophylline) or suspension (dipyridamole)...
March 11, 2018: European Journal of Pharmaceutical Sciences
Joanna Y Huang, Paul Monagle, M Patricia Massicotte, Christina J VanderPluym
INTRODUCTION: Ventricular Assist Devices (VADs) are increasingly utilised in children with end-stage heart failure, and experience high bleeding and clotting rates. In particular, pediatric VAD patients are more challenging than adults to anticoagulate due to developmental hemostasis, lack of suitable drug preparations, and difficult anticoagulation monitoring often due to poor vascular access; in addition to difficulties of VAD design in smaller children. This review aims to summarize the current evidence related to antithrombotic therapy in pediatric VAD patients...
February 28, 2018: Thrombosis Research
Rune Kleppe, Inge Jonassen, Stein Ove Døskeland, Frode Selheim
Platelet activation contributes to normal haemostasis but also to pathologic conditions like stroke and cardiac infarction. Signalling by cGMP and cAMP inhibit platelet activation and are therefore attractive targets for thrombosis prevention. However, extensive cross-talk between the cGMP and cAMP signalling pathways in multiple tissues complicates the selective targeting of their activities. We have used mathematical modelling based on experimental data from the literature to quantify the steady state behaviour of nitric oxide (NO)/cGMP/cAMP signalling in platelets...
February 19, 2018: International Journal of Molecular Sciences
Ko-Lin Kuo, Szu-Chun Hung, Wei-Cheng Tseng, Jia-Sin Liu, Ming-Huang Lin, Chih-Cheng Hsu, Der-Cherng Tarng
Introduction: Dipyridamole decreases proteinuria and improves renal function progression in patients with glomerular disease through its inhibition of platelet activation and enhanced nitric oxide expression. Few studies have evaluated the effects of dipyridamole on renal outcome or survival in CKD stage 5 patients who have not yet received dialysis (CKD 5 ND). Materials and Methods: A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database...
January 12, 2018: Oncotarget
Lorenzo Valerio, Jawaad Sheriff, Phat L Tran, William Brengle, Alberto Redaelli, Gianfranco B Fiore, Federico Pappalardo, Danny Bluestein, Marvin J Slepian
INTRODUCTION: Continuous flow ventricular assist devices (cfVADs) continue to be limited by thrombotic complications associated with disruptive flow patterns and supraphysiologic shear stresses. Patients are prescribed complex antiplatelet therapies, which do not fully prevent recurrent thromboembolic events. This is partially due to limited data on antiplatelet efficacy under cfVAD-associated shear conditions. MATERIALS AND METHODS: We investigated the efficacy of antiplatelet drugs directly acting on three pathways: (1) cyclooxygenase (aspirin), (2) phosphodiesterase (dipyridamole, pentoxifylline, cilostazol), and (3) glycoprotein IIb-IIIa (eptifibatide)...
December 5, 2017: Thrombosis Research
Kentaro Ando, Akira Takahara, Yuji Nakamura, Takeshi Wada, Koki Chiba, Ai Goto, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kiyotaka Hoshiai, Yasuki Akie, Atsuhiko T Naito, Atsushi Sugiyama
Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal...
February 1, 2018: Journal of Pharmacological Sciences
Jin-Bao Zhou, Bao-Yang Luo, Chi-Wen Liu, Feng Zhu
BACKGROUND: This study aimed to explore the effects of early antiplatelet therapy (APT) for portal vein thrombosis (PVT) in patients with cirrhotic portal hypertension after splenectomy with gastro-oesophageal devascularization. METHODS: We retrospectively analysed 139 patients who underwent splenectomy with gastro-oesophageal devascularization for portal hypertension due to cirrhosis between April 2010 and December 2016. Based on the post-operative platelet values, we used two different APT regimens: APT was started when platelet counts were increased to 200 × 109 /L or above (group A, n = 64) or 300 × 109 /L or above (group B, n = 75)...
February 3, 2018: ANZ Journal of Surgery
Sujita W Narayan, Prasad S Nishtala
AIM: To examine the patterns of preventive medicines (PM) use in the last year of life of older adults. METHODS: This study cohort included individuals (n = 99 809) aged ≥75 years who were in their last year of life. PM examined in this study included low-dose aspirin (≤325 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates. Logistic regression models examined the influence of age, sex, multimorbidity, socioeconomic status, and a diagnosis of cancer on the number and type of PM prescribed from 2007 to 2012...
February 2, 2018: Geriatrics & Gerontology International
Denise Mayumi Tanaka, Luciano Fonseca Lemos de Oliveira, José Antônio Marin-Neto, Minna Moreira Dias Romano, Eduardo Elias Vieira de Carvalho, Antonio Carlos Leite de Barros Filho, Fernando Fonseca França Ribeiro, Jorge Mejia Cabeza, Carla Duque Lopes, Camila Godoy Fabricio, Norival Kesper, Henrique Turin Moreira, Lauro Wichert-Ana, André Schmidt, Maria de Lourdes Higuchi, Edécio Cunha-Neto, Marcus Vinícius Simões
BACKGROUND: Myocardial perfusion defects (MPD) due to coronary microvascular dysfunction is frequent in chronic Chagas cardiomyopathy (CCC) and may be involved with development of myocardial damage. We investigated whether MPD precedes left ventricular systolic dysfunction and tested the hypothesis that prolonged use of dipyridamole (DIPY) could reduce MPD in an experimental model of CCC in hamsters. METHODS AND RESULTS: We investigated female hamsters 6-months after T...
February 1, 2018: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
Rasmi Rekha Mishra, Nevin Belder, Suhail A Ansari, Merve Kayhan, Hilal Bal, Umar Raza, Pelin Gülizar Ersan, Ünal M Tokat, Erol Eyüpoğlu, Özge Saatci, Pouria Jandaghi, Stefan Wiemann, Ayşegül Üner, Caglar Cekic, Yasser Riazalhosseini, Özgür Şahin
PURPOSE: Tamoxifen remains an important hormonal therapy for ER-positive breast cancer (BC); however, development of resistance is a major obstacle in clinics. Here, we aimed to identify novel mechanisms of tamoxifen resistance and provide actionable drug targets overcoming resistance. EXPERIMENTAL DESIGN: Whole transcriptome sequencing, downstream pathway analysis and drug repositioning approaches were used to identify novel modulators (here: PDE4D) of tamoxifen resistance...
January 31, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Nina A Hilkens, Ale Algra, L Jaap Kappelle, Philip M Bath, László Csiba, Peter M Rothwell, Jacoba P Greving
OBJECTIVE: To study the early time course of major bleeding and its subtypes in patients with cerebral ischemia on dual and single antiplatelet therapy. METHODS: We performed a post hoc analysis on individual patient data from 6 randomized clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of Atherothrombosis With Clopidogrel in High-Risk Patients [MATCH], Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic stroke...
February 20, 2018: Neurology
Roberto Nery Dantas, Antonildes Nascimento Assuncao, Ismar Aguiar Marques, Mateus Guimaraes Fahel, Cesar Higa Nomura, Luiz Francisco Rodrigues Avila, Maria Clementina Pinto Giorgi, Jose Soares, Jose Claudio Meneghetti, Jose Rodrigues Parga
OBJECTIVES: Despite advances in non-invasive myocardial perfusion imaging (MPI) evaluation, computed tomography (CT) multiphase MPI protocols have not yet been compared with the highly accurate rubidium-82 positron emission tomography (82RbPET) MPI. Thus, this study aimed to evaluate agreement between 82RbPET and 320-detector row CT (320-CT) MPI using a multiphase protocol in suspected CAD patients. METHODS: Forty-four patients referred for MPI evaluation were prospectively enrolled and underwent dipyridamole stress 82RbPET and multiphase 320-CT MPI (five consecutive volumetric acquisitions during stress)...
January 19, 2018: European Radiology
Zareen Amtul, Wasimul Haque, David F Cechetto
BACKGROUND AND PURPOSE: The objective of this work is to study the dose-dependent effect of combination therapy with dipyridamole and triflusal over that of triflusal alone on infarct size after middle cerebral artery occlusion (MCAO) ischemia. MATERIALS AND METHODS: Male Wistar rats were subjected to a permanent MCAO in the right hemisphere. Rats received triflusal alone and with dipyridamole via oral route. Three days after surgery, infarct volumes were measured...
January 12, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Youko Takakuwa, Masayoshi Sarai, Hideki Kawai, Akira Yamada, Kenji Shiino, Kayoko Takada, Yasuomi Nagahara, Meiko Miyagi, Sadako Motoyama, Hiroshi Toyama, Yukio Ozaki
Objectives: The current management of coronary artery disease (CAD) relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW) therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance...
2018: Asia Oceania Journal of Nuclear Medicine & Biology
Chen-Shu Chang, Hsuan-Ju Chen, Chun-Hui Liao
BACKGROUND: Medical complications following stroke often result in significant morbidity. This study was designed to investigate the prevalence and risk of gastroesophageal reflux disease (GERD) between patients with stroke and those without stroke in Taiwan. METHODS AND RESULTS: This retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. The study included 18,412 patients newly diagnosed as having stroke during 2000-2006 and 18,412 patients without stroke frequency-matched by sex, age, and index year...
January 8, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Zifei Qin, Shishi Li, Zhihong Yao, Xiaodan Hong, Baojian Wu, Kristopher W Krausz, Frank J Gonzalez, Hao Gao, Xinsheng Yao
Active efflux transport of glucuronides out of cells is a critical process in elimination of drugs and food-derived compounds. Wushanicaritin, a natural polyphenol from Epimedium species, has shown many biological activities. However, the transporters responsible for excretion of wushanicaritin glucuronides still remain undefined. Herein, chemical inhibitors (Ko143, MK571, dipyridamole and leukotriene C4) and single stable knocked-down efflux transporters (BCRP, MRP1, MRP3 and MRP4) were used to determine the contributions of efflux transporters to glucuronide efflux and cellular glucuronidation in UGT1A1-overexpressing HeLa cells (HeLa1A1)...
January 10, 2018: Food & Function
Philip M Bath, Lisa J Woodhouse, Jason P Appleton, Maia Beridze, Hanne Christensen, Robert A Dineen, Lelia Duley, Timothy J England, Katie Flaherty, Diane Havard, Stan Heptinstall, Marilyn James, Kailash Krishnan, Hugh S Markus, Alan A Montgomery, Stuart J Pocock, Marc Randall, Annemarei Ranta, Thompson G Robinson, Polly Scutt, Graham S Venables, Nikola Sprigg
BACKGROUND: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset...
December 20, 2017: Lancet
Markus Zilker, Fritz Sörgel, Ulrike Holzgrabe
Pharmaceutical manufacturers have to study the stability of drug products before marketing according to ICH guideline Q1A(R2); data of those investigations aim to set expiry dates. The expiry date on the container of a remedy assures the physician and the patient a stability of the drug in its formulation i.e. within a specification of 95-105%. Only few studies show that shelf-lives of pharmaceutical products are often longer than expiration dates. The objective of the study presented here was determining the content of nine expired ampoules manufactured in the last century and identifying the impurity profile by means of HPLC-UV and HPLC-MS, respectively...
December 13, 2017: Journal of Pharmaceutical and Biomedical Analysis
Eun Jee Chung, Nikolaos E Efstathiou, Eleni K Konstantinou, Daniel E Maidana, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Age related macular degeneration is the leading cause of blindness in the developed world. Although its precise cause remains elusive, dysfunction of the retinal pigment epithelium (RPE) and dysregulation of complement have been implicated in its pathogenesis. The goal of this study was to evaluate the role of an AMP-dependent kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide riboside (AICAR), on tumor necrosis factor alpha (TNF-α) induction of complement factor B (CFB) in RPE cells. We found that AICAR inhibited TNF-α-induced CFB expression in ARPE-19 and human primary RPE cells in a dose-dependent fashion...
December 15, 2017: Scientific Reports
Kent Yamaguchi, Justin Mathew, James M Lhi, Don Young Park
CASE: Spontaneous spinal epidural hematoma (SSEH) is a known, although rare, clinical entity that may be challenging to diagnose. This case report describes the rapid development of a large SSEH in an elderly patient on aspirin-dipyridamole combination therapy after she shifted her position in bed. Magnetic resonance imaging obtained 4 hours after the onset of symptoms demonstrated a large spinal epidural hematoma that extended from T4 to L1. CONCLUSION: With early diagnosis, the patient was successfully treated with a laminectomy and evacuation of the hematoma, and there was full neurological recovery...
January 2017: JBJS Case Connector
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