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41. Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants Full Text available with Trip Pro

Enhancing Plasticity of the Central Nervous System: Drugs, Stem Cell Therapy, and Neuro-Implants Stroke represents the first cause of adult acquired disability. Spontaneous recovery, dependent on endogenous neurogenesis, allows for limited recovery in 50% of patients who remain functionally dependent despite physiotherapy. Here, we propose a review of novel drug therapies with strong potential in the clinic. We will also discuss new avenues of stem cell therapy in patients with a cerebral (...) lesion. A promising future for the development of efficient drugs to enhance functional recovery after stroke seems evident. These drugs will have to prove their efficacy also in severely affected patients. The efficacy of stem cell engraftment has been demonstrated but will have to prove its potential in restoring tissue function for the massive brain lesions that are most debilitating. New answers may lay in biomaterials, a steadily growing field. Biomaterials should ideally resemble lesioned brain

2017 Neural plasticity

42. Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy Full Text available with Trip Pro

Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through (...) the course of antibacterial therapy. Multi-drug resistance (MDR) has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative

2017 International journal of molecular sciences

43. A novel strategy to co-target estrogen receptor and nuclear factor κB pathways with hybrid drugs for breast cancer therapy Full Text available with Trip Pro

inhibition of ER and NFκB via a single bifunctional hybrid drug may represent a viable approach to improve the anti-inflammatory activity and prevent therapy resistance of ER-targeted anti-cancer drugs. (...) A novel strategy to co-target estrogen receptor and nuclear factor κB pathways with hybrid drugs for breast cancer therapy Nearly 75% of breast tumors express estrogen receptor (ER), and will be treated with endocrine therapy, such as selective estrogen receptor modulator (SERM), tamoxifen, or aromatase inhibitors. Despite their proven success, as many as 40-50% of ER+ tumors fail to respond to endocrine therapy and eventually recur as aggressive, metastatic cancers. Therefore, preventing

2017 Hormones & cancer

44. Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing Full Text available with Trip Pro

Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing Resistance-associated variant (RAV) is one of the most significant clinical challenges in treating HCV-infected patients with direct-acting antivirals (DAAs). We investigated the viral dynamics in patients receiving DAAs using third-generation sequencing technology. Among 283 patients with genotype-1b HCV receiving (...) daclatasvir + asunaprevir (DCV/ASV), 32 (11.3%) failed to achieve sustained virological response (SVR). Conventional ultra-deep sequencing of HCV genome was performed in 104 patients (32 non-SVR, 72 SVR), and detected representative RAVs in all non-SVR patients at baseline, including Y93H in 28 (87.5%). Long contiguous sequences spanning NS3 to NS5A regions of each viral clone in 12 sera from 6 representative non-SVR patients were determined by third-generation sequencing, and showed the concurrent

2017 Scientific reports

45. Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling Full Text available with Trip Pro

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling Constitutive JAK/STAT3 signaling contributes to disease progression in many lymphoproliferative disorders. Recent genetic analyses have revealed gain-of-function STAT3 mutations in lymphoid cancers leading to hyperactivation of STAT3, which may represent a potential therapeutic target. Using a functional reporter assay, we screened 306 compounds with selective activity (...) against various target molecules to identify drugs capable of inhibiting the cellular activity of STAT3. Top hits were further validated with additional models including STAT3-mutated natural killer (NK)-cell leukemia/lymphoma cell lines and primary large granular lymphocytic (LGL) leukemia cells to assess their ability to inhibit STAT3 phosphorylation and STAT3 dependent cell viability. We identified JAK, mTOR, Hsp90 and CDK inhibitors as potent inhibitors of both WT and mutant STAT3 activity

2017 Oncotarget

46. Sterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design Full Text available with Trip Pro

Sterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design Ergosterol biosynthesis pathways essential to pathogenic protozoa growth and absent from the human host offer new chokepoint targets. Here, we present characterization and cell-based interference of Acanthamoeba spp sterol 24-/28-methylases (SMTs) that catalyze the committed step in C28- and C29-sterol synthesis. Intriguingly, our kinetic analyses suggest that 24-SMT (...) prefers plant cycloartenol whereas 28-SMT prefers 24(28)-methylene lophenol in similar fashion to the substrate preferences of land plant SMT1 and SMT2. Transition state analog-24(R,S),25-epiminolanosterol (EL) and suicide substrate 26,27-dehydrolanosterol (DHL) differentially inhibited trophozoite growth with IC50 values of 7 nM and 6 µM, respectively, and EL yielded 20-fold higher activity than reference drug voriconazole. Against either SMT assayed with native substrate, EL exhibited tight binding

2017 Journal of lipid research

47. Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma Full Text available with Trip Pro

activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer therapies in preclinical or clinical models are essential and the multimodal molecular imaging approach may represent a new stage for pharmacologic development in cancer. Monitoring the progress of lymphoma therapy with imaging modalities will help patients. Identifying and addressing key (...) Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug

2017 International journal of molecular sciences

48. Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy Full Text available with Trip Pro

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (...) in this study to be a promising nanocarrier for anti-atherogenic therapy, in the light of efficient iMΦ-targeted drug delivery and excellent function of mediating cellular cholesterol efflux.

2017 International journal of nanomedicine

49. Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy Full Text available with Trip Pro

Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only (...) a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug. Results show that microbubbles can provide excellent detectability through MRI relaxometry and accurately represent drug distribution during CED infusion. Compared with the short half-life of Gd-DTPA (1-2 hours

2017 Oncotarget

50. Prevalence and Clinical Profile of Drug Eruptions among Antiretroviral Therapy-Exposed HIV Infected People in Yaoundé, Cameroon Full Text available with Trip Pro

Prevalence and Clinical Profile of Drug Eruptions among Antiretroviral Therapy-Exposed HIV Infected People in Yaoundé, Cameroon Prevalence and incidence of drug eruptions vary around the world and are influenced by some key factors including HIV infection.This study aimed to find the peculiarities of drug eruptions in people living with HIV (PLHIV) and on antiretroviral therapy (ART).This was a retrospective cross-sectional study including ART-taking PLHIV, aged 15+ years, followed up between (...) January 2010 and December 2014 at the day-care unit of the Yaoundé Central Hospital, and who presented with drug eruptions after ART initiation.Of 6,829 ART-experiencing PLHIV, 41 presented with drug eruptions, giving a prevalence of 0.6%. The M/F sex ratio equaled 0.17. The mean age was 41.07 ± 11.36 years. Benign drug eruptions accounted for 83.3%. Milder forms were essentially maculopapular exanthema (36.6%), fixed pigmented erythema (7.3%), and urticaria (4.9%). Severe forms were represented

2017 Dermatology research and practice

51. Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections. (Abstract)

Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections. The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter (...) was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.Copyright © 2016. Published by Elsevier Ltd.

2017 Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Controlled trial quality: uncertain

52. Inverse remodelling of K2P3.1 K+ channel expression and action potential duration in left ventricular dysfunction and atrial fibrillation: implications for patient-specific antiarrhythmic drug therapy. Full Text available with Trip Pro

Inverse remodelling of K2P3.1 K+ channel expression and action potential duration in left ventricular dysfunction and atrial fibrillation: implications for patient-specific antiarrhythmic drug therapy. Atrial fibrillation (AF) prevalence increases with advanced stages of left ventricular (LV) dysfunction. Remote proarrhythmic effects of ventricular dysfunction on atrial electrophysiology remain incompletely understood. We hypothesized that repolarizing K2P3.1 K+ channels, previously implicated (...) in AF pathophysiology, may contribute to shaping the atrial action potential (AP), forming a specific electrical substrate with LV dysfunction that might represent a target for personalized antiarrhythmic therapy.A total of 175 patients exhibiting different stages of LV dysfunction were included. Ion channel expression was quantified by real-time polymerase chain reaction and Western blot. Membrane currents and APs were recorded from atrial cardiomyocytes using the patch-clamp technique. Severely

2017 European Heart Journal

53. Respect your elders: how often are the very elderly represented in drug therapy trials?

Respect your elders: how often are the very elderly represented in drug therapy trials? Print | PDF PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites. Email salutation (e.g. "Dr Smith" or "Joanne") for correspondence: Organisation web address: Timing (...) of the eligible articles for final inclusion. In each phase, 2 observers will independently assess each article. Discrepancies will be resolved through discussion, or by consulting a third investigator. ">Procedure for study selection Example : Title-abstract screening: 1. Not an original full research paper (e.g. review, editorial) 2. Not an in vivo animal study 3. No metastases/ only primary tumor 4. No control group 5. Combination therapy or contamination 6. Not about analgesics used in the clinic Full

2017 PROSPERO

54. Novel Synthetic Opioids in Counterfeit Pharmaceuticals and Other Illicit Street Drugs

synthetic opioids as reported in the media and in other sources of information in Canada and the United States. Finally, the bulletin includes a discussion of the implications of this phenomenon for those working in: ? Public health and harm reduction ? Emergency medical services and emergency response services ? Laboratories ? Poison control centres ? Law enforcement Reports of Novel Synthetic Opioids in Counterfeit Pharmaceuticals and Other Illicit Street Drugs The following table provides a non (...) Bulletin: Novel Synthetic Opioids in Counterfeit Pharmaceuticals and Other Illicit Street Drugs Canadian Centre on Substance Abuse • Centre canadien de lutte contre les toxicomanies Page 12 Pag e 12 1 U.S. Food and Drug Administration. (2016). Counterfeit Medicine. Retrieved June 2, 2016, from www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/CounterfeitMedicine/ 2 Canadian Community Epidemiology Network on Drug Use. (2014). CCENDU Drug Alert: Increasing Availability of Counterfeit

2016 Canadian Centre on Substance Abuse

55. Ustekinumab for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic, or have medical contrai

Ustekinumab for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic, or have medical contrai October 2019 EUnetHTA Joint Action 3 WP4 1 EUnetHTA Joint Action 3 WP4 Version 1.0, 22/10/2019 Relative effectiveness assessment of pharmaceutical technologies USTEKINUMAB FOR THE TREATMENT OF ADULT PATIENTS WITH MODERATELY TO SEVERELY ACTIVE (...) and Pharmaceutical Benefits Agency (TLV). Relative effectiveness assessment of pharmaceutical technologies. Ustekinumab for the treat- ment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic, or have medical contraindications to such therapies. EUnetHTA Project ID: PTJA07. 2019. PTJA07 - Ustekinumab for active ulcerative colitis October 2019 EUnetHTA Joint Action 3

2020 EUnetHTA

56. Association Between Academic Medical Center Pharmaceutical Detailing Policies and Physician Prescribing. Full Text available with Trip Pro

Association Between Academic Medical Center Pharmaceutical Detailing Policies and Physician Prescribing. In an effort to regulate physician conflicts of interest, some US academic medical centers (AMCs) enacted policies restricting pharmaceutical representative sales visits to physicians (known as detailing) between 2006 and 2012. Little is known about the effect of these policies on physician prescribing.To analyze the association between detailing policies enacted at AMCs and physician (...) of policies regulating pharmaceutical salesperson visits to attending physicians.The monthly within-drug class market share of prescriptions written by an individual physician for detailed and nondetailed drugs in 8 drug classes (lipid-lowering drugs, gastroesophageal reflux disease drugs, diabetes drugs, antihypertensive drugs, hypnotic drugs approved for the treatment of insomnia [sleep aids], attention-deficit/hyperactivity disorder drugs, antidepressant drugs, and antipsychotic drugs) comparing the 10

2017 JAMA

57. Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial (Abstract)

Behavioural outcomes of subthalamic stimulation and medical therapy versus medical therapy alone for Parkinson's disease with early motor complications (EARLYSTIM trial): secondary analysis of an open-label randomised trial Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess (...) changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone.We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical

2018 EvidenceUpdates

58. Pharmaceutical policies: effects of cap and co-payment on rational use of medicines. (Abstract)

Pharmaceutical policies: effects of cap and co-payment on rational use of medicines. Growing expenditures on prescription medicines represent a major challenge to many health systems. Cap and co-payment policies are intended as an incentive to deter unnecessary or marginal utilisation, and to reduce third-party payer expenditures by shifting parts of the financial burden from insurers to patients, thus increasing their financial responsibility for prescription medicines. Direct patient payment (...) policies include caps (maximum numbers of prescriptions or medicines that are reimbursed), fixed co-payments (patients pay a fixed amount per prescription or medicine), co-insurance (patients pay a percentage of the price), ceilings (patients pay the full price or part of the cost up to a ceiling, after which medicines are free or are available at reduced cost) and tier co-payments (differential co-payments usually assigned to generic and brand medicines). This is the first update of the original

2015 Cochrane

59. Herbal cannabis and pharmaceutical cannabinoid treatment following motor vehicle accidents: A state of the science review

of prescription drug therapy 1 1.2 ICBC prescription medication funding policy 2 1.3 Herbal cannabis and pharmaceutical cannabinoids in clinical medical practice in Canada 2 2.0 An overview of a graduated evidence-informed, ICBC funding model 3 2.1 Funding policy decisions within a graduated, evidence informed ICBC funding model 5 2.2 Pharmaceutical cannabinoid medications for regulatory approved indications (LEVEL 1) 6 2.3 Pharmaceutical cannabinoids for indications without regulatory approval (LEVEL 2) 6 (...) and a doctor’s prescription which, to some extent, it adjudicates as to the appropriateness of diagnosis and the type and volume of drugs prescribed. Decisions regarding funding of herbal cannabis and pharmaceutical cannabinoidss fit within this well established ICBC funding policy framework. 1.3 Herbal cannabis and pharmaceutical cannabinoids in clinical medical practice in Canada The application of scientific medical knowledge of herbal cannabis and pharmaceutical cannabinoid therapy to clinical medical

2020 Therapeutics Letter

60. [IBENTO][IBENTO]Report of the PMDA-ATC Pharmaceuticals Review Seminar 2017 in Bangkok, Thailand

of the PMDA-ATC Pharmaceuticals Review Seminar 2017 in Bangkok, Thailand PMDA-ATC Pharmaceuticals Review Seminar 2017 in Bangkok, Thailand Pharmaceuticals and Medical Devices Agency (PMDA) completed the PMDA-Asia Training Center for Pharmaceuticals and Medical Devices Regulatory Affairs (ATC) Pharmaceuticals Review Seminar 2017 in Bangkok, Thailand on December 12-15, 2017. This seminar was designed for new drug application reviewers from overseas regulatory agencies. Total of 20 regulators from Sri Lanka (...) of the seminar, the Course completion certificates were handed to each participant by Dr. Junko Sato. Photos and participant comments Lectures were provided by experts of product review, relief services and drug safety. There were also presentations by representatives from Sri Lanka and Thailand about their own pharmaceuticals review systems and regulations. Participants enthusiastically asked many questions and all the lecturers answered those questions. Comments from the participants: “I have

2018 Pharmaceuticals and Medical Devices Agency, Japan

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