Abstract:
:The risk assessment of environmental chemicals and drugs is undergoing a paradigm shift in approach which seeks the full replacement of animal testing with high throughput, mechanistic, in vitro systems. This new approach will be reliant on the measurement in vitro, of concentration-dependent responses where prolonged excessive perturbations of specific biochemical pathways are likely to lead to adverse health effects in an intact organism. Such an approach requires a framework, into which disparate data generated by in vitro, in silico, and in chemico systems can be integrated and utilized for quantitative in vitro-to-in vivo extrapolation (QIVIVE), ultimately to the human population level. Physiologically based pharmacokinetic (PBPK) models are ideally suited to this and are needed to translate in vitro concentration- response relationships to an exposure or dose, route and duration regime in human populations. Thus, a realistic description of the variation in the physiology of the human population being modeled is critical. Whilst various studies in the past decade have made progress in describing human variability, the algorithms are typically coded in computer programs and as such are unsuitable for reverse dosimetry. In this report we overcome this limitation by developing a hierarchical statistical model using standard probability distributions for the specification of a virtual US and UK human population. The work draws on information from both population databases and cadaver studies.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
McNally K,Loizou GDdoi
10.3389/fphar.2015.00213subject
Has Abstractpub_date
2015-10-12 00:00:00pages
213issn
1663-9812journal_volume
6pub_type
杂志文章abstract::Why antidepressants vary in terms of efficacy is currently unclear. Despite the leadership of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression, the precise neurobiological mechanisms involved in their therapeutic action are poorly understood. A better knowledge of molecular interactions b...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00098
更新日期:2013-08-08 00:00:00
abstract::Previous data showed that neuropathic pain induced by mechanical lesion of peripheral nerves has specific characteristics and responds differently to alleviating drugs at cephalic versus extracephalic level. This is especially true for tricyclic antidepressants currently used for alleviating neuropathic pain in humans...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00587
更新日期:2018-06-07 00:00:00
abstract::Atherosclerotic cardiovascular disease (CVD) is a lipid-driven chronic inflammatory disease, in which macrophages are responsible for taking up these lipids and driving disease progression. Over the years, we and others have uncovered key pathways that regulate macrophage number/function and identified how metabolic d...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00666
更新日期:2019-06-13 00:00:00
abstract::[This corrects the article DOI: 10.3389/fphar.2019.01370.]. ...
journal_title:Frontiers in pharmacology
pub_type: 已发布勘误
doi:10.3389/fphar.2019.01697
更新日期:2020-02-21 00:00:00
abstract:Background:Acetylcholinesterase inhibitors (AChE-I) are recommended for the treatment of cognitive symptoms but also of behavioral and psychological symptoms in dementia. They are widely used not only in Alzheimer's disease, but also in other forms of dementia. Efficacy of treatment might depend on serum concentration ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00691
更新日期:2020-05-21 00:00:00
abstract::Neutrophil killing of bacteria is mediated by oxidative and non-oxidative mechanisms. Oxidants are generated through the NADPH oxidase complex, whereas antimicrobial proteins and peptides rank amongst non-oxidative host defenses. Mucus hypersecretion, deficient hydration and poor clearance from the airways are promine...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.554353
更新日期:2020-09-30 00:00:00
abstract::Background: This study aimed to explore the intellectual landscape of the studies investigating the clinical application of enteral nutrition (EN) in patients with ventilator associated pneumonia (VAP), and to identify thematic development trends and research frontiers in this area. Methods: Scientometric research was...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00246
更新日期:2019-03-20 00:00:00
abstract::Background: Satisfaction of patients for pharmaceutical services reflects their preferences and expectations, and the realities of care. It is critical to understand the extent of dissatisfaction for pharmaceutical services and its associated factors in order to optimize the required quality of the services provided. ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01132
更新日期:2018-10-12 00:00:00
abstract::The scaffold protein syntenin abounds during fetal life where it is important for developmental movements. In human adulthood, syntenin gain-of-function is increasingly associated with various cancers and poor prognosis. Depending on the cancer model analyzed, syntenin affects various signaling pathways. We previously...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2015.00241
更新日期:2015-10-21 00:00:00
abstract::Inflammation-related intestinal diseases are a set of various conditions presenting an overactive enteric immune system. A continuous overproduction of pro-inflammatory cytokines and a decreased production of anti-inflammatory modulators are generally observed, while morpho-functional alterations of the enteric nervou...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00212
更新日期:2018-03-14 00:00:00
abstract::Localized neuropathic pain can be relieved following the topical application of high-concentration capsaicin. This clinical effect is thought to be related to the temporary desensitization of capsaicin- and heat-sensitive epidermal nociceptors. The objective of the present study was to examine whether the changes in t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00615
更新日期:2020-05-19 00:00:00
abstract::Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the pre...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00906
更新日期:2017-12-12 00:00:00
abstract::The mTOR signaling pathway is abnormally activated in pancreatic cancer and is related to tumor glucose metabolism. However, its specific regulation mechanism is still unclear. Therefore, this study aims to investigate whether Sestrin2 affects the glucose metabolism of pancreatic cancer by modulating mTOR signal and t...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.580407
更新日期:2020-11-11 00:00:00
abstract::Background: No risk model for predicting thrombocytopenia associated with periprocedural tirofiban exposure is available. The purpose of this study was to develop a simple clinical pre-procedure risk model based on pre-procedural characteristics for early prediction of thrombocytopenia before patients were exposed to ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01456
更新日期:2018-12-10 00:00:00
abstract::Polyunsaturated fatty acids (PUFAs) are bioactive lipids which modulate inflammation and immunity. They gained recognition in nutritional therapy and are recommended dietary supplements. There is a growing body of evidence suggesting the usefulness of PUFAs in active therapy of various gastrointestinal (GI) diseases. ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2016.00459
更新日期:2016-12-01 00:00:00
abstract::Gamithromycin is approved for the treatment and prevention of bovine respiratory disease (BRD), which is caused mainly by Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma species. In this study, multiple dosage regimens were administered to the neutropenic mouse lung infection model in ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01090
更新日期:2019-09-24 00:00:00
abstract::Trichloroethylene (TCE) is a common volatile organic solvent which is considered as an ubiquitous environmental pollutant. It is claimed to be a developmental neurotoxicant. Our group evaluated previously its impact on three-dimensional neurospheres in vitro. The current work aims to investigate the neurotoxic effects...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00741
更新日期:2018-07-10 00:00:00
abstract::Inborn cardiac diseases are among the most frequent congenital anomalies and are the main cause of death in infants within the first year of age in industrialized countries when not adequately treated. They can be divided into simple and complex cardiac malformations. The former ones, for instance atrial and ventricul...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00070
更新日期:2013-06-03 00:00:00
abstract::6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present in Wasabia japonica rhizome. Several scientific studies have shown that 6-MITC possesses interesting antimicrobial, anti-inflammatory, antiplatelet and antioxidant properties which therefore suggested us it could have an interesti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.01242
更新日期:2020-08-18 00:00:00
abstract::The radioresistance of tumors affect the outcome of radiotherapy. Accumulating data suggest that 1α,25(OH)2D3 is a potential anti-oncogenic molecule in various cancers. In the present study, we investigated the radiosensitive effects and underlying mechanisms of 1α,25(OH)2D3in vitro and in vivo. We found that 1α,25(OH...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2020.00945
更新日期:2020-08-07 00:00:00
abstract::Fasudil, a Rho-kinase inhibitor, has shown outstanding therapeutic effects against cerebral vasospasm after subarachnoid hemorrhage (SAH) in humans. Studies show various biological effects of fasudil in the cardiovascular system. We conducted a preclinical systematic review to determine the efficacy and possible mecha...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01083
更新日期:2018-10-01 00:00:00
abstract:Objective:Drawing a growth curve of multidrug-resistant Pseudomonas aeruginosa (MDR-PA) provides a foundation for susceptibility testing. By observing in vitro antibacterial activity and ultrastructure cthanges on MDR-PA of the effective components in the drug-containing serum of rats after the administration of Fuzhen...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01682
更新日期:2020-02-12 00:00:00
abstract::The growing interest in testosterone's effects on men's social behaviors, in particular aggressive, risk-taking, or status maintenance behaviors, is accompanied by a paucity of dose-dependent pharmacokinetic data. Examining the neurophysiological effects of transdermal testosterone typically includes a 4h delay before...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.01397
更新日期:2019-11-21 00:00:00
abstract::The effect of parecoxib sodium on the duration and severity of acute postoperative pain after laparoscopic-assisted vaginal hysterectomy has been inadequately studied. This randomized, controlled trial compared the effects of parecoxib, methylprednisolone, and placebo on the duration of acute postoperative pain after ...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00689
更新日期:2019-06-18 00:00:00
abstract::Orientin is a flavonoid extracted from Chinese traditional herb, Polygonum orientale L. Previous study has reported that orientin protected myocardial from ischemia reperfusion injury. However, whether orientin could protect against cardiac remodeling after myocardial injury remains unclear. The aim of our study is to...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00926
更新日期:2017-12-21 00:00:00
abstract::Background and purpose: We have shown that in vitro treatment with cannabidiol (CBD, 2 h) enhances endothelial function in arteries from Zucker diabetic fatty (ZDF) rats, partly due to a cyclooxygenase (COX)-mediated mechanism. The aim of the present study was to determine whether treatment with CBD in vivo would also...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2017.00248
更新日期:2017-05-18 00:00:00
abstract::The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over acti...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2017.00022
更新日期:2017-01-30 00:00:00
abstract::15-F2t-Isoprostane, a reliable biomarker of oxidative stress, has been found elevated in exhaled breath condensate (EBC), a non-invasive technique for sampling of airway secretions, in patients with cystic fibrosis (CF). Azithromycin has antioxidant properties in experimental models of CF, but its effects on oxidative...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00595
更新日期:2018-06-18 00:00:00
abstract::β2-adrenoceptor agonists are commonly used as bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, they induce severe side effects. Therefore, developing new bronchodilators is essential. Herbal plants were extracted and the extracts' effect on ai...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01389
更新日期:2018-12-04 00:00:00
abstract::Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhib...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2020.578091
更新日期:2020-10-07 00:00:00