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https://www.readbyqxmd.com/read/28922723/protective-effects-of-mirtazapine-and-chrysin-on-experimentally-induced-testicular-damage-in-rats
#1
Alaa E El-Sisi, Magda E El-Sayad, Nermine M Abdelsalam
Mirtazapine is an antidepressant with prominent antioxidant effects. Chrysin, a natural flavone, exhibits multiple pharmacological actions. This study was designed to investigate the potential protective effects of chrysin and mirtazapine against nitrofurazone-induced testicular damage in rats. Possible underlying mechanisms such as oxidative stress, inflammation and apoptosis were also investigated. Testicular damage was induced by oral administration of nitrofurazone (50mg/kg/day) for two weeks. Chrysin (25 and 50mg/kg/day, p...
September 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28922692/phosphodiesterase-4-inhibitors-for-chronic-obstructive-pulmonary-disease
#2
REVIEW
Jimmy Chong, Bonnie Leung, Phillippa Poole
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013...
September 19, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28922066/the-effect-of-lysozyme-on-reducing-biofilms-by-staphylococcus-aureus-pseudomonas-aeruginosa-and-gardnerella-vaginalis-an-in-vitro-examination
#3
Mirsada Hukić, Dzenita Seljmo, Amra Ramovic, Monia Avdić Ibrišimović, Serkan Dogan, Jasna Hukic, Elma Feric Bojic
Two basic questions about lysozyme activities on the selected microorganisms were investigated, namely whether lysozyme inhibits biofilm production and which concentrations of the enzyme have the ability to change the natural biofilm producing capacity of different strains of Staphylococcus aureus (methicillin sensitive and resistant), Streptococcus pyogenes, Pseudomonas aeruginosa, and Gardnerella vaginalis. The effect of lysozyme on biofilm formation capacities of 16 strains of selected microorganisms was investigated, whereby four testing replicates have been performed in vitro using the Test Tube method, and the potential of lysozyme to change biofilm forming capacities depending on its concentration, species, and strains of microorganisms is demonstrated...
September 18, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28922023/fatty-acid-synthase-fasn-as-a-therapeutic-target-in-breast-cancer
#4
Javier A Menendez, Ruth Lupu
Ten years ago, we put forward the metabolo-oncogenic nature of fatty acid synthase (FASN) in breast cancer. Since the conception of this hypothesis, which provided a model to explain how FASN is intertwined with various signaling networks to cell-autonomously regulate breast cancer initiation and progression, FASN has received considerable attention as a therapeutic target. However, despite the ever-growing evidence demonstrating the involvement of FASN as part of the cancer-associated metabolic reprogramming, translation of the basic science-discovery aspects of FASN blockade to the clinical arena remains a challenge...
September 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28921919/oral-glucose-lowering-with-linagliptin-and-metformin-compared-with-linagliptin-alone-as-initial-treatment-in-asian-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia-subgroup-analysis-of-a-randomized-clinical-trial
#5
Ronald Cw Ma, Stefano Del Prato, Baptist Gallwitz, Vyankatesh K Shivane, Diane Lewis-D'Agostino, Zelie Bailes, Sanjay Patel, Jisoo Lee, Maximilian von Eynatten, Maximiliano Di Domenico, Stuart A Ross
AIMS/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enrol predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed T2DM patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed T2DM patients with glycated hemoglobin A1c (HbA1c) 8...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28921915/weekly-glucagon-like-peptide-1-receptor-agonist-albiglutide-as-monotherapy-improves-glycemic-parameters-in-japanese-patients-with-type-2-diabetes-mellitus-a-randomized-double-blind-placebo-controlled-study
#6
Antonio Nino, Inaha Okuda, Timothy H Wilson, Lin Yue, Hiromu Nakajima, Maho Tsuboi, Molly C Carr, Yutaka Seino
AIMS/INTRODUCTION: This phase 3, randomized, double-blind 24-week study with extension to 1 year assessed efficacy and safety of albiglutide compared with placebo in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise with or without a single oral antidiabetic drug. MATERIALS AND METHODS: Patients received weekly albiglutide 30 mg (n=160), albiglutide 50 mg (n=150), or placebo switched to albiglutide 30 mg after 24 weeks (n=77)...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28921642/clinical-pharmacology-tools-and-evaluations-to-facilitate-comprehensive-dose-finding-in-oncology-a-continuous-risk-benefit-approach
#7
Julie M Bullock, Tiffany Lin, Sanela Bilic
Targeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity-guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity-driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk-benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk-benefit assessment and establish the right dose...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921641/pharmacokinetic-guided-dosing-of-new-oral-cancer-agents
#8
Catherine J Lucas, Jennifer H Martin
Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921558/safety-and-efficacy-of-intravenous-iron-polymaltose-iron-sucrose-and-ferric-carboxymaltose-in-pregnancy-a-systematic-review
#9
REVIEW
Alaa Qassim, Ben W Mol, Rosalie M Grivell, Luke E Grzeskowiak
BACKGROUND: Intravenous (IV) iron in pregnancy is useful where oral iron is not tolerated or a rapid replenishment of iron is required. AIMS: To review the literature on the efficacy and safety of different IV iron preparations in the management of antenatal iron-deficiency anaemia (IDA). MATERIALS AND METHODS: We searched MEDLINE, Embase and Scopus from inception to June 2016. Eligible studies were randomised controlled trials (RCTs) and observational studies, involving administration of IV iron (ferric carboxymaltose (FCM), iron polymaltose (IPM) or iron sucrose (IS)), regardless of comparator, to manage antenatal IDA...
September 18, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28921512/dacomitinib-induced-diarrhea-targeting-chloride-secretion-with-crofelemer
#10
Ysabella Z A Van Sebille, Rachel J Gibson, Hannah R Wardill, Imogen A Ball, Dorothy M K Keefe, Joanne M Bowen
Dacomitinib, an irreversible small-molecule pan-ErbB TKI, has a high incidence of diarrhea which has been suggested to be due to chloride secretory mechanisms. Based on this hypothesis, crofelemer, an anti-secretory agent may be an effective intervention. T84 monolayers were treated with 1µM dacomitinib and 10µM crofelemer, and mounted into Ussing chambers for electrogenic ion analysis. Crofelemer attenuated increases in chloride secretion in cells treated with dacomitinib. Albino Wistar rats (n=48) were treated with 7...
September 16, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28921057/dvt-prevention-in-stroke
#11
REVIEW
Christopher Goshgarian, Philip B Gorelick
PURPOSE OF REVIEW: The purpose of this review is to discuss the prevention of venous thromboembolism (VTE) in stroke patients. We discuss use of oral anticoagulation and other interventions for the prevention of VTE. A new class of medications, non-vitamin K antagonist oral anticoagulants (NOACs), have been successfully trialed for the prevention of VTE. We review the data and guidance statements for VTE prevention. RECENT FINDINGS: Warfarin and vitamin K antagonist drugs have been the mainstay of VTE prevention for decades...
September 18, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28920805/pharmacokinetics-of-piroxicam-in-cranes-family-gruidae
#12
Naomi L Keiper, Sherry K Cox, Grayson A Doss, Betsy Elsmo, Dana Franzen-Klein, Barry K Hartup
To investigate the pharmacokinetics of the nonsteroidal anti-inflammatory drug (NSAID) piroxicam in cranes, three brolgas (Antigone rubicunda) were administered piroxicam as a single oral dose at 0.5 mg/kg and 1.0 mg/kg during separate trials. Serial blood samples were collected for quantification of piroxicam in plasma. Piroxicam was readily absorbed at both dosages, and no adverse effects were observed. Plasma concentrations peaked at 3.67 hr with a concentration of 4.00 μg/ml for the lower dosage, and at 0...
September 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28920464/absorption-sites-of-orally-administered-drugs-in-the-small-intestine
#13
Teruo Murakami
In pharmacotherapy, drugs are mostly taken orally to be absorbed systemically from the small intestine, and some drugs are known to have preferential absorption sites in the small intestine. It would therefore be valuable to know the absorption sites of orally administered drugs and the influencing factors. Areas covered:In this review, the author summarizes the reported absorption sites of orally administered drugs, as well as, influencing factors and experimental techniques. Information on the main absorption sites and influencing factors can help to develop ideal drug delivery systems and more effective pharmacotherapies...
September 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28919810/a-comparison-between-the-administration-of-oral-prolonged-release-oxycodone-naloxone-and-transdermal-fentanyl-in-patients-with-moderate-to-severe-cancer-pain-a-propensity-score-analysis
#14
A Roberto, M T Greco, L Legramandi, F Galli, M Galli, O Corli
BACKGROUND: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF) and oral prolonged-release oxycodone-naloxone (OXN-PR) are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared. PATIENTS AND METHODS: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28919776/safety-pharmacokinetics-and-pharmacodynamics-of-oral-omaveloxolone-rta-408-a-synthetic-triterpenoid-in-a-first-in-human-trial-of-patients-with-advanced-solid-tumors
#15
Ben C Creelan, Dmitry I Gabrilovich, Jhanelle E Gray, Charles C Williams, Tawee Tanvetyanon, Eric B Haura, Jeffrey S Weber, Geoffrey T Gibney, Joseph Markowitz, Joel W Proksch, Scott A Reisman, Mark D McKee, Melanie P Chin, Colin J Meyer, Scott J Antonia
BACKGROUND: Omaveloxolone is a semisynthetic oleanane triterpenoid that potently activates Nrf2 with subsequent antioxidant function. We conducted a first-in-human Phase I clinical trial (NCT02029729) with the primary objectives to determine the appropriate dose for Phase II studies, characterize pharmacokinetic and pharmacodynamic parameters, and assess antitumor activity. METHODS: Omaveloxolone was administered orally once daily continuously in a 28-day cycle for patients with stage 4 relapsed/refractory melanoma or non-small cell lung cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919757/once-monthly-paliperidone-palmitate-in-early-stage-schizophrenia-a-retrospective-non-interventional-1-year-study-of-patients-with-newly-diagnosed-schizophrenia
#16
Robin Emsley, Ludger Hargarter, Paul Bergmans, Boran Uglešić, Abdullah Cem Sengül, Antonino Petralia, Angelina Khannanova, Pierre Cherubin, Andreas Schreiner
BACKGROUND: Long-acting antipsychotic therapy may be best suited for patients in the early stage of schizophrenia, when the most can be done before disease progression associated with poor adherence occurs. We explored the patterns of use of once-monthly paliperidone palmitate (PP1M), concomitant medication use, hospitalization, and clinical outcomes of adult, newly diagnosed patients with schizophrenia receiving continuous treatment with PP1M for at least 12 months. METHODS: This was an international, multicenter, exploratory, retrospective chart review of medical records of adult patients who were newly diagnosed (not more than 1 year before initiation of PP1M treatment) with schizophrenia and who had received continuous treatment with PP1M for ≥12 months in naturalistic clinical settings...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28919705/new-insight-into-the-pathogenesis-of-nail-psoriasis-and-overview-of-treatment-strategies
#17
REVIEW
Alessandra Ventura, Mauro Mazzeo, Roberta Gaziano, Marco Galluzzo, Luca Bianchi, Elena Campione
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population. The prevalence of nail involvement in psoriasis patients varies between 15% and 79%. While the nails represent a small portion of the body surface area, psoriasis in these areas can have a disproportionate influence on a patient's physical and psychosocial activities. Differential diagnosis between an onychomycosis and a psoriatic nail could be challenging; nevertheless, coexistence of onychomycosis and nail psoriasis also occurs and both are common disorders in the general population...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28919541/drugs-for-treating-opioid-induced-constipation-a-mixed-treatment-comparison-network-meta-analysis-of-randomized-controlled-clinical-trials
#18
Kannan Sridharan, Gowri Sivaramakrishnan
CONTEXT: Opioid-induced constipation is a common problem associated with chronic use of opioid analgesics. OBJECTIVES: To compare available interventions for the treatment of opioid-induced constipation, using principles of network meta-analysis. METHODS: Electronic databases were searched for randomized controlled clinical trials evaluating drugs used in opioid induced constipation. Number of patients with rescue-free bowel movements (RFBM) was the primary outcome and time for achieving RFBM, adverse events and changes in the analgesic activity of the opioid analgesics were the secondary outcomes...
September 14, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28919359/human-intestine-and-liver-microsomal-metabolic-differences-between-c19-diester-and-monoester-diterpenoid-alkaloids-from-the-roots-of-aconitum-carmichaelii-debx
#19
Min Zhang, Chong-Sheng Peng, Xiao-Bo Li
The roots of Aconitum carmichaelii Debx. show excellent effects against rheumatism and cardiovascular diseases, but the effective compounds, C19-diester and monoester diterpenoid alkaloids (DDAs and MDAs) are toxic for their narrow therapeutic windows. It is noteworthy to investigate intestinal metabolism of these toxic compounds mainly by oral administration, because gut also express drug-metabolizing enzymes as well as liver. This study initially focused on phase I and phase II metabolism of DDAs (including aconitine, mesaconitine and hypaconitine) and MDAs (including benzoylaconine, benzoylmesaconine and benzoylhypaconine) in human intestine microsomes (HIM), with comparison of metabolism in human liver microsomes (HLM)...
September 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28919201/macitentan-for-the-treatment-of-inoperable-chronic-thromboembolic-pulmonary-hypertension-merit-1-results-from-the-multicentre-phase-2-randomised-double-blind-placebo-controlled-study
#20
Hossein-Ardeschir Ghofrani, Gérald Simonneau, Andrea M D'Armini, Peter Fedullo, Luke S Howard, Xavier Jaïs, David P Jenkins, Zhi-Cheng Jing, Michael M Madani, Nicolas Martin, Eckhard Mayer, Kelly Papadakis, Dominik Richard, Nick H Kim
BACKGROUND: Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. METHODS: The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm(5) and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo...
September 8, 2017: Lancet Respiratory Medicine
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