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https://www.readbyqxmd.com/read/28820396/the-role-of-mtor-inhibitors-and-hmg-coa-reductase-inhibitors-on-young-and-old-endothelial-cell-functions-critical-for-re-endothelialisation-after-percutaneous-coronary-intervention-an-in-vitro-study
#1
K Korybalska, E Kawka, A Breborowicz, J Witowski
Percutaneous coronary intervention (PCI) has become a standard treatment in patients with acute coronary syndrome. However, it is associated with endothelial cell denudation, which may predispose to in-stent thrombosis and restenosis. Pharmacological methods which prevent restenosis can delay post-PCI re-endothelialisation. We have therefore examined how atorvastatin (HMG-CoA reductase inhibitor), sirolimus and everolimus (mTOR inhibitors) affect young and old endothelial cell functions which are responsible for wound healing after PCI...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820069/apixaban-effective-and-safe-in-preventing-thromboembolic-events-in-patients-with-atrial-fibrillation-and-renal-failure
#2
Francesca Cortese, Pietro Scicchitano, Michele Gesualdo, Gabriella Ricci, Santa Carbonara, Carlo Franchini, Brigida Immacolata Pia Schiavone, Filomena Corbo, Marco Matteo Ciccone
Thromboembolic events, principally stroke, represent among the leading causes of morbidity and mortality of subjects with atrial fibrillation, with an incidence about 5 times higher compared to healthy subjects. Chronic kidney disease, frequently associated with atrial fibrillation, determines itself a further increase of thromboembolic events, bleeding and mortality. In addition, the presence of renal failure complicates the pharmacological management of these patients, mainly due to the side effects of antiarrhythmic and anticoagulant drugs with renal excretion, due to their accumulation...
August 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28820067/a-comprehensive-review-on-ebola-ebov-virus-future-prospects
#3
Dr Abdru Rauf, Muhammad, Abdur Rauf, Ahsan Khan, Muhammad Rizwan, Seema Patel, Haroon Khan, Adel Mahasneh, Mohammad S Mubarak
Ebola virus (EBOV) was discovered for the first time in 1976. It belongs to the family Filoviridae, which causes hemorrhagic fever that could lead to death in a few days. West Africa faced a major outbreak where symptoms appeared in the form of chills, myalgia, fever, diarrhea, and vomiting, and the disease finally reached a severe state as a result of hemorrhagic complications and failure of multiple organs. EBOV spreads by contact with body fluids of an infected person such as blood, saliva, urine, and seminal fluid, and also spreads by a contact with contaminated surfaces...
August 16, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28819225/cytochrome-p450-abc-transporter-inhibition-simultaneously-enhances-ivermectin-pharmacokinetics-in-the-mammal-host-and-pharmacodynamics-in-anopheles-gambiae
#4
Carlos J Chaccour, Felix Hammann, Marta Alustiza, Sandra Castejon, Brian B Tarimo, Gloria Abizanda, Ángel Irigoyen Barrio, Helena Martí Soler, Rafael Moncada, José Ignacio Bilbao, Azucena Aldaz, Marta Maia, José Luis Del Pozo
Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818532/myricetin-solid-lipid-nanoparticles-stability-assurance-from-system-preparation-to-site-of-action
#5
Dina M Gaber, Noha Nafee, Osama Y Abdallah
Myricetin - a natural flavonoid - has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids...
August 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28818511/vitamin-d-enhances-antiepileptic-and-cognitive-effects-of-lamotrigine-in-pentylenetetrazole-kindled-rats
#6
Ali F Abdel-Wahab, Mohamed A Afify, Amal M Mahfouz, Naiyer Shahzad, Ghazi A Bamagous, Saeed S Al Ghamdi
Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine...
August 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28818421/erbb-signaling-antagonist-ameliorates-behavioral-deficit-induced-by-phencyclidine-pcp-in-mice-without-affecting-metabolic-syndrome-markers
#7
Hagar Tadmor, Idit Golani, Ravid Doron, Ilana Kremer, Alon Shamir
Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated...
August 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28817540/association-of-olfactory-function-with-the-intensity-of-self-reported-physical-activity-in-adults-with-type-1-diabetes
#8
Bogusz Falkowski, Maciej Chudziński, Ewa Jakubowska, Anna Duda-Sobczak
INTRODUCTION    Olfactory function is impaired in patients with type 1 diabetes and can be recognized as a form of diabetic neuropathy. Physical activity has various beneficial effects on type 1 diabetes. OBJECTIVES    The aim of this study was to assess a relation between physical activity and olfactory function in patients with type 1 diabetes. PATIENTS AND METHODS    We enrolled 120 patients with type 1 diabetes referred to an outpatient diabetes clinic. Patients with diabetes duration of less than 5 years, age above 65 years, concomitant diabetic ketoacidosis, and those using drugs affecting nasal mucosa were excluded...
August 9, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28816119/clinical-presentation-and-management-of-dyskinetic-cerebral-palsy
#9
REVIEW
Elegast Monbaliu, Kate Himmelmann, Jean-Pierre Lin, Els Ortibus, Laura Bonouvrié, Hilde Feys, R Jeroen Vermeulen, Bernard Dan
Cerebral palsy is the most frequent cause of severe physical disability in childhood. Dyskinetic cerebral palsy (DCP) is the second most common type of cerebral palsy after spastic forms. DCP is typically caused by non-progressive lesions to the basal ganglia or thalamus, or both, and is characterised by abnormal postures or movements associated with impaired tone regulation or movement coordination. In DCP, two major movement disorders, dystonia and choreoathetosis, are present together most of the time. Dystonia is often more pronounced and severe than choreoathetosis, with a major effect on daily activity, quality of life, and societal participation...
September 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28815933/an-%C3%AE-iib-%C3%AE-3-antagonist-prevents-thrombosis-without-causing-fc%C3%AE-riia-mediated-thrombocytopenia
#10
Yu-Ju Kuo, Ying-Ru Chen, Chun-Chieh Hsu, Hui-Chin Peng, Tur-Fu Huang
BACKGROUND: Thrombocytopenia, a common side effect of Arg-Gly-Asp (RGD)-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb β3 . OBJECTIVE: To explore the correlation between αIIb β3 binding epitopes and induction of DDAb binding to conformation-altered αIIb β3 , we examined whether two purified disintegrins TMV-2 and TMV-7 with distinct binding motifs that have different effects on induction of αIIb β3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory monoclonal antibody (mAb) raised against αIIb β3 ...
August 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28815569/glucose-dependent-leukocyte-activation-in-familial-hypercholesterolemia
#11
Natasja Koks, Marijke A de Vries, Erwin Birnie, Arash Alipour, Manuel Castro Cabezas
BACKGROUND: Leukocyte activation is an obligatory factor in the development of atherosclerosis. The postprandial situation has been associated to increased leukocyte activation in several disorders, such as type 2 diabetes mellitus and familial combined hyperlipidemia. Our study aim was to evaluate the effect of post-OGTT hyperglycemia on leukocyte activation in patients with familial hypercholesterolemia (FH). MATERIALS AND METHODS: Patients who met the diagnostic criteria for heterozygous FH and healthy volunteers were asked to undergo an oral glucose tolerance test...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28815510/inhibition-of-%C3%AE-secretase-leads-to-an-increase-in-presenilin-1
#12
Aitana Sogorb-Esteve, María-Salud García-Ayllón, Marta Llansola, Vicente Felipo, Kaj Blennow, Javier Sáez-Valero
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other γ-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression...
August 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28814831/schiff-base-derived-from-thiosemicarbazone-and-anthracene-showed-high-potential-in-overcoming-multidrug-resistance-in-vitro-with-low-drug-resistance-index
#13
Jie Bai, Rui-Hui Wang, Yan Qiao, Aidong Wang, Chen-Jie Fang
Multidrug resistance (MDR) is a huge obstacle in cancer chemotherapeutics. Overcoming MDR is a great challenge for anticancer drug discovery. Here, DNA binding and cytotoxicity of Schiff base L1 and L2 were explored to assess their efficiency in fighting cancer and overcoming the MDR. L1 and L2 could treat extremely chemoresistant MCF-7/ADR cell as drug-sensitive cell, with drug resistance index (DRI) <2.13, showing high potential in overcoming the MDR. The apoptotic ratio induced by L1 and L2 was low for both MCF-7 and MCF-7/ADR cells...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814513/escape-of-tick-borne-flavivirus-from-2-c-methylated-nucleoside-antivirals-is-mediated-by-a-single-conservative-mutation-in-ns5-that-has-a-dramatic-effect-on-viral-fitness
#14
Ludek Eyer, Hirofumi Kondo, Darina Zouharova, Minato Hirano, James J Valdés, Memi Muto, Tomas Kastl, Shintaro Kobayashi, Jan Haviernik, Manabu Igarashi, Hiroaki Kariwa, Marketa Vaculovicova, Jiri Cerny, Rene Kizek, Andrea Kröger, Stefan Lienenklaus, Milan Dejmek, Radim Nencka, Martin Palus, Jiri Salat, Erik De Clercq, Kentaro Yoshii, Daniel Ruzek
Tick-borne encephalitis virus (TBEV) causes a severe and potentially fatal neuroinfection in humans. Despite its high medical relevance, no specific antiviral therapy is currently available. Here we demonstrate that treatment with a nucleoside analog, 7-deaza-2' -C-methyladenosine (7-deaza-2' -CMA), substantially improved disease outcome, increased survival, and reduced signs of neuroinfection and viral titers in the brains of mice infected with a lethal dose of TBEV. To investigate the mechanism of action of 7-deaza-2' -CMA, two drug-resistant TBEV clones were generated and characterized...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814481/plausibility-criteria-for-putative-pathophysiological-mechanisms-in-functional-gastrointestinal-disorders-a-consensus-of-experts
#15
Jan Tack, Maura Corsetti, Michael Camilleri, Eamonn Mm Quigley, Magnus Simren, Hidekazu Suzuki, Nicholas J Talley, Hans Tornblom, Lukas Van Oudenhove
BACKGROUND AND AIMS: The functional gastrointestinal disorders (FGIDs) are extremely common conditions associated with a considerable personal, social and health economic burden. Managing FGIDs in clinical practice is challenging because of the uncertainty of symptom-based diagnosis, the high frequency of overlap between these conditions and the limited efficacy of available therapies. It has often been argued that successful drug development and management of FGIDs requires knowledge of the underlying pathophysiology...
August 16, 2017: Gut
https://www.readbyqxmd.com/read/28814475/developmental-pathway-genes-and-neural-plasticity-underlying-emotional-learning-and-stress-related-disorders
#16
Marissa E Maheu, Kerry J Ressler
The manipulation of neural plasticity as a means of intervening in the onset and progression of stress-related disorders retains its appeal for many researchers, despite our limited success in translating such interventions from the laboratory to the clinic. Given the challenges of identifying individual genetic variants that confer increased risk for illnesses like depression and post-traumatic stress disorder, some have turned their attention instead to focusing on so-called "master regulators" of plasticity that may provide a means of controlling these potentially impaired processes in psychiatric illnesses...
September 2017: Learning & Memory
https://www.readbyqxmd.com/read/28813109/assessment-of-inhibitory-control-in-crack-and-or-cocaine-users-a-systematic-review
#17
Fernanda Rasch Czermainski, Alice Rodrigues Willhelm, Álvaro Zaneti Santos, Mayra Pacheco Pachado, Rosa Maria Martins de Almeida
Objective: Impairments involving inhibitory control have been considered central deficits in drug users, but it appears that dysfunctions may be specific to users' drug of choice. This article aims to review recent findings on inhibitory control impairment in samples of crack and/or cocaine users. Methods: Searches were conducted on the PubMed, PsycINFO, and Web of Knowledge databases in two stages according to eligibility criteria. Initially, databases were searched and the titles and abstracts of results were analyzed and then selected articles were read in full...
August 14, 2017: Trends in Psychiatry and Psychotherapy
https://www.readbyqxmd.com/read/28812061/behavioral-comorbidities-and-drug-treatments-in-a-zebrafish-scn1lab-model-of-dravet-syndrome
#18
Brian P Grone, Tiange Qu, Scott C Baraban
Loss-of-function mutations in SCN1A cause Dravet syndrome (DS), a catastrophic childhood epilepsy in which patients experience comorbid behavioral conditions, including movement disorders, sleep abnormalities, anxiety, and intellectual disability. To study the functional consequences of voltage-gated sodium channel mutations, we use zebrafish with a loss-of-function mutation in scn1lab, a zebrafish homolog of human SCN1A. Homozygous scn1lab(s552/s552) mutants exhibit early-life seizures, metabolic deficits, and early death...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28811713/clinical-significance-of-glycemic-parameters-on-venous-thromboembolism-risk-prediction-in-gastrointestinal-cancer
#19
Fiorella Guadagni, Silvia Riondino, Vincenzo Formica, Girolamo Del Monte, Anna Maria Morelli, Jessica Lucchetti, Antonella Spila, Roberta D'Alessandro, David Della-Morte, Patrizia Ferroni, Mario Roselli
AIM: To investigate the possible predictive role of routinely used glycemic parameters for a first venous thromboembolism (VTE) episode in gastrointestinal (GI) cancer ambulatory patients - with or without clinically diagnosed type 2 diabetes (T2D) or obesity - treated with chemotherapy. METHODS: Pre-treatment fasting blood glucose, insulin, glycated hemoglobin (HbA1c) and homeostasis model of risk assessment (HOMA) were retrospectively evaluated in a cohort study of 342 GI cancer patients...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28811386/trimetazidine-protects-retinal-ganglion-cells-from-acute-glaucoma-via-the-nrf2-ho-1-pathway
#20
Peixing Wan, Wenru Su, Yingying Zhang, Zhidong Li, Caibin Deng, Yehong Zhuo
Acute glaucoma is one of the leading causes of irreversible vision impairment characterized by the rapid elevation of intraocular pressure and consequent retinal ganglion cell (RGC) death. Oxidative stress and neuro-inflammation have been considered critical for the pathogenesis of RGC death in acute glaucoma. Trimetazidine (TMZ), an anti-ischemic drug, possesses anti-oxidative and anti-inflammatory properties, contributing to its therapeutic potential in tissue damage. However, the role of TMZ in acute glaucoma and the underlying molecular mechanisms remain elusive...
August 15, 2017: Clinical Science (1979-)
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