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drug dose

Tristan Pascart, Frédéric Lioté
This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management...
March 13, 2018: Rheumatology
Rada M Savic, Prasanna Jagannathan, Richard Kajubi, Liusheng Huang, Nan Zhang, Moses Were, Abel Kakuru, Mary K Muhindo, Norah Mwebaza, Erika Wallender, Tamara D Clark, Bishop Opira, Moses Kamya, Diane V Havlir, Philip J Rosenthal, Grant Dorsey, Francesca T Aweeka
Background: Dihydroartemsinin-piperaquine is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies. Methods: HIV-uninfected pregnant women were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks gestation and randomized to: sulfadoxine-pyrimethamine every 8 weeks (n=106), dihydroartemsinin-piperaquine every 8 weeks (n=94), or dihydroartemsinin-piperaquine every 4 weeks (n=100) during pregnancy...
March 14, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Jana Tchekalarova, Keylla da Conceição Machado, Antonio Luiz Gomes Júnior, Ana Amélia de Carvalho Melo Cavalcante, Albena Momchilova, Rumyana Tzoneva
PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test...
March 12, 2018: Seizure: the Journal of the British Epilepsy Association
Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
February 27, 2018: Biomaterials
Hong-Jie Li, Dong-Sheng Gao, Yong-Tao Li, Yong-Sheng Wang, Hong-Ying Liu, Jun Zhao
Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. Severe outbreaks of PEDV variants have re-emerged in Asia and North America since 2010, causing tremendous economic losses to the swine industry. The lack of effective therapeutic treatment promotes the research for new antivirals. Lithium chloride (LiCl) has been reported as a potential antiviral drug for certain viruses. In this study, the antiviral effect of LiCl on PEDV in Vero cells was evaluated...
March 5, 2018: Research in Veterinary Science
Sherine Ismail, Mohamed Osman, Rayf Abulezz, Hani Alhamdan, K H Mujtaba Quadri
Pharmacists possess pivotal competencies and expertise in developing clinical pathways (CPs). We present a tertiary care facility experience of pharmacists vis-a-vis interprofessional collaboration for designing and implementing CPs. We participated in the development of CPs as leading members of a collaborative team of healthcare professionals. We reviewed literature, aligning it with hospital formulary and institutional standards, and participated in weekly team meetings for six months. Several tools and services were adapted to guide prescribing and standardization of care through time-bound order sets...
March 16, 2018: Pharmacy (Basel, Switzerland)
Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3 / *3 . The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation...
March 16, 2018: International Journal of Molecular Sciences
Rogério M Pinto, Susan S Witte, Prema L Filippone, C Jean Choi, Melanie Wall
The U.S. Centers for Disease Control and Prevention (CDC) Diffusion of Effective Behavioral Interventions project has disseminated HIV behavioral interventions (EBIs) across the United States since the 1990s. In 2011, the CDC launched the High-Impact HIV Prevention (HIP) project, providing EBIs plus high-impact services (HIV testing, primary care, and support services). Providers (nurses, social workers, educators) are unable to consistently make linkages; thus, numerous at-risk individuals are not benefitting from HIP...
March 1, 2018: Health Education & Behavior: the Official Publication of the Society for Public Health Education
C Lavanya, Manjunatha M Venkataswamy, M K Sibin, M M Srinivas Bharath, G K Chetan
Increased telomerase activity can be blocked by targeting the hTERT activity at both RNA and catalytic subunits. Various inhibitors had been used to regulate hTERT activity in glioblastoma cell lines and showed promising results. The present study hypothesized that the telomerase specific inhibitor BIBR1532 can effectively down-regulate the telomerase activity in LN18 glioblastoma cell line. LN18 glioblastoma cell line was treated with various concentrations of BIBR1532 at different time intervals. MTT assay was performed to determine cell viability after BIBR1532 treatment...
March 15, 2018: Cytotechnology
Michaël R Laurent
An overview of selected papers related to bone published in 2017 is provided. PURPOSE: This paper accompanies a lecture at the 2018 Belgian Bone Club annual Clinical Update Symposium held in Brussels on January 20th, discussing the best papers (in the opinion of the author) published in the previous year. METHODS: A PubMed search using the keyword "bone" and articles published in 2017. RESULTS: Hot topics include screening for osteoporosis, novel anabolic drugs such as romosozumab and abaloparatide for osteoporosis and rare metabolic bone diseases, as well as long-term efficacy of denosumab and possible risk of multiple vertebral fractures following its discontinuation...
March 15, 2018: Archives of Osteoporosis
Thomas Tängdén, Pier Giorgio Cojutti, Jason A Roberts, Federico Pea
BACKGROUND AND OBJECTIVES: Valganciclovir is used as oral prophylaxis for cytomegalovirus (CMV) infection in kidney transplant recipients. However, limited pharmacokinetic data exist to guide dosing in this patient group. This study aimed to describe the population pharmacokinetics of valganciclovir in a large sample of kidney transplant recipients and predict optimal dosing based on Monte Carlo simulations. METHODS: Therapeutic drug monitoring (TDM) data from adult kidney transplant recipients who received valganciclovir prophylaxis during a 10-year study period were collected retrospectively...
March 15, 2018: Clinical Pharmacokinetics
Weiwei Chen, Jiajia An, Jiwei Guo, Yan Wu, Lijuan Yang, Juanjuan Dai, Kaikai Gong, Shuang Miao, Sichuan Xi, Jing Du
PURPOSE: Sodium selenite (SS) has been widely reported to induce apoptosis in various cancer cell types. However, the underlying molecular mechanisms governing SS-mediated repression of lung cancer stem cells remain largely undefined. METHODS: In vitro assays of cell proliferation, clonal formation, apoptosis, migration and cancer stemness cell sphere formation were performed to examine the inhibitory effects of SS on lung adenocarcinoma (LAD) cells with or without the overexpression of SRY-related high-mobility-group box 2 (SOX2)...
March 15, 2018: Cancer Chemotherapy and Pharmacology
D Czock, V Schwenger, D Kindgen-Milles, M Joannidis, S John, M Schmitz, A Jörres, A Zarbock, M Oppert, J T Kielstein, C Willam
BACKGROUND: Many anti-infective drugs require dose adjustments in critically ill patients with acute kidney injury (AKI) and renal replacement therapy, in order to achieve adequate therapeutic drug concentrations. OBJECTIVES: The fundamental pharmacokinetic and pharmacodynamic principles of drug dose adjustment are presented. Recommendations on anti-infective drug dosage in intensive care are provided. MATERIALS AND METHODS: We established dose recommendations of selected anti-infective drugs based on information in the summary of product characteristics, published studies and recommendations, pharmacokinetic and pharmacodynamic considerations, and the experience and expert opinion of the authors...
March 15, 2018: Medizinische Klinik, Intensivmedizin und Notfallmedizin
Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
Selcuk Kayir, Hulya Ulusoy, Guvenc Dogan
Background/aims Sedation is one of the most important components of intensive care unit (ICU) in patients who are mechanically ventilated at intensive care conditions. As a result of sedation and analgesia in the intensive care unit, the patient is to be awakened a comfortable and easy process. The aim of the study is to demonstrate the effects of day-time sedation interruptions in intensive care patients. Material and methods We made a retrospective review of 100 patients who were monitored, mechanically ventilated and treated at our intensive care unit between January 2008 and January 2013...
January 13, 2018: Curēus
Stephen Caltabiano, Kelly M Mahar, Karyn Lister, David Tenero, Ramiya Ravindranath, Borut Cizman, Alexander R Cobitz
This study was conducted to evaluate the likelihood of daprodustat to act as a perpetrator in drug-drug interactions (DDI) with the CYP2C8 enzyme and OATP1B1 transporter using the probe substrates pioglitazone and rosuvastatin as potential victims, respectively. Additionally, this study assessed the effect of a weak CYP2C8 inhibitor, trimethoprim, as a perpetrator of a DDI with daprodustat. This was a two-part study: Part A assessed the effect of coadministration of daprodustat on the pharmacokinetics of pioglitazone and rosuvastatin in 20 subjects; Part B assessed the coadministration of trimethoprim on the pharmacokinetics of daprodustat in 20 subjects...
April 2018: Pharmacology Research & Perspectives
Katarzyna Morawska, Françoise Goirand, Laurine Marceau, Madeline Devaux, Adèle Cueff, Aurélie Bertaut, Julie Vincent, Leila Bengrine-Lefevre, François Ghiringhelli, Antonin Schmitt
Aims: 5-FU is used as the main backbone of chemotherapy regimens for patients with colorectal and other gastrointestinal cancers. Despite development of new strategies that allowed enhancing clinical effectiveness and tolerability of 5-FU, 10-30% of patients treated with 5-FU-based regimens experience severe treatment-related toxicity. In our study, we evaluated the 5-FU exposure-toxicity relationship and investigated the efficacy of PK-guided dosing in increasing tolerability of 5-FU-based chemotherapy...
February 20, 2018: Oncotarget
Lu Xie, Wei Guo, Yi Yang, Tao Ji, Jie Xu
5,10-Methylenetrahydrofolate reductase (MTHFR), a key enzyme for folate metabolism, catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is located at the end of the short arm (1p36.3). Two common non-synonymous variants, the C677T (Ala222Val) and A1298C (Glu429Ala), were mainly described with decreased enzymatic activity and an alteration of intracellular folate distribution. Osteosarcomas are currently treated with high dose of methotrexate (MTX). The decreased enzyme activity of MTHFR theoretically could increase the drug action of MTX and at the same time increase toxic and side effect...
February 20, 2018: Oncotarget
Yaming Xi, Zhuanzhen Ma, Hao Zhang, Maowen Yuan, Lina Wang
The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle-apoptosis was analyzed by flow cytometry, P-glycoprotein (P-gp) expression was determined by western blot analysis and caspase-3 activity was measured using a caspase-3 activity kit...
April 2018: Oncology Letters
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