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Frontiers in Pharmacology

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https://www.readbyqxmd.com/read/28101058/genetic-variation-in-the-histamine-production-response-and-degradation-pathway-is-associated-with-histamine-pharmacodynamic-response-in-children-with-asthma
#1
Bridgette L Jones, Catherine M T Sherwin, Xiaoxi Liu, Hongying Dai, Carrie A Vyhlidal
Introduction: There is growing knowledge of the wide ranging effects of histamine throughout the body therefore it is important to better understand the effects of this amine in patients with asthma. We aimed to explore the association between histamine pharmacodynamic (PD) response and genetic variation in the histamine pathway in children with asthma. Methods: Histamine Iontophoresis with Laser Doppler Monitoring (HILD) was performed in children with asthma and estimates for area under the effect curve (AUEC), maximal response over baseline (Emax), and time of Emax (Tmax) were calculated using non-compartmental analysis and non-linear mixed-effects model with a linked effect PK/PD model...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28101057/pomegranate-extract-enhances-endothelium-dependent-coronary-relaxation-in-isolated-perfused-hearts-from-spontaneously-hypertensive-ovariectomized-rats
#2
Nathalie T B Delgado, Wender do N Rouver, Leandro C Freitas-Lima, Tiago D-C de Paula, Andressa Duarte, Josiane F Silva, Virgínia S Lemos, Alexandre M C Santos, Helder Mauad, Roger L Santos, Margareth R Moysés
Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28101056/cerebral-gluconeogenesis-and-diseases
#3
REVIEW
James Yip, Xiaokun Geng, Jiamei Shen, Yuchuan Ding
The gluconeogenesis pathway, which has been known to normally present in the liver, kidney, intestine, or muscle, has four irreversible steps catalyzed by the enzymes: pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase, and glucose 6-phosphatase. Studies have also demonstrated evidence that gluconeogenesis exists in brain astrocytes but no convincing data have yet been found in neurons. Astrocytes exhibit significant 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity, a key mechanism for regulating glycolysis and gluconeogenesis...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28101055/inferring-the-impact-of-regulatory-mechanisms-that-underpin-cd8-t-cell-control-of-b16-tumor-growth-in-vivo-using-mechanistic-models-and-simulation
#4
David J Klinke, Qing Wang
A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28101054/protease-activated-receptor-2-promotes-pro-atherogenic-effects-through-transactivation-of-the-vegf-receptor-2-in-human-vascular-smooth-muscle-cells
#5
Ira Indrakusuma, Tania Romacho, Jürgen Eckel
Background: Obesity is associated with impaired vascular function. In the cardiovascular system, protease-activated receptor 2 (PAR2) exerts multiple functions such as the control of the vascular tone. In pathological conditions, PAR2 is related to vascular inflammation. However, little is known about the impact of obesity on PAR2 in the vasculature. Therefore, we explored the role of PAR2 as a potential link between obesity and cardiovascular diseases. Methods: C57BL/6 mice were fed with either a chow or a 60% high fat diet for 24 weeks prior to isolation of aortas...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28096795/editorial-in-vivo-imaging-in-pharmacological-research
#6
EDITORIAL
Nicolau Beckmann, Igor A Kaltashov, Albert D Windhorst
No abstract text is available yet for this article.
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082903/identification-of-febuxostat-as-a-new-strong-abcg2-inhibitor-potential-applications-and-risks-in-clinical-situations
#7
Hiroshi Miyata, Tappei Takada, Yu Toyoda, Hirotaka Matsuo, Kimiyoshi Ichida, Hiroshi Suzuki
ATP-binding cassette transporter G2 (ABCG2) is a plasma membrane protein that regulates the pharmacokinetics of a variety of drugs and serum uric acid (SUA) levels in humans. Despite the pharmacological and physiological importance of this transporter, there is no clinically available drug that modulates ABCG2 function. Therefore, to identify such drugs, we investigated the effect of drugs that affect SUA levels on ABCG2 function. This strategy was based on the hypothesis that the changes of SUA levels might caused by interaction with ABCG2 since it is a physiologically important urate transporter...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082902/optimized-cocktail-phenotyping-study-protocol-using-physiological-based-pharmacokinetic-modeling-and-in-silico-assessment-of-metabolic-drug-drug-interactions-involving-modafinil
#8
Angela Rowland, Arduino A Mangoni, Ashley Hopkins, Michael J Sorich, Andrew Rowland
In vivo cocktail pathway phenotyping (ICPP) is routinely used to assess the metabolic drug-drug interaction (mDDI) potential of new drug candidates (NDC) during drug development. However, there are a number of potential limitations to this approach and the use of validated drug cocktails and study protocols is essential. Typically ICPP mDDI studies assess only the impact of interactions following multiple postulated perpetrator doses and hence the emphasis in terms of validation of these studies has been ensuring that there are no interactions between probe substrates...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082901/sustained-contraction-in-vascular-smooth-muscle-by-activation-of-l-type-ca-2-channels-does-not-involve-ca-2-sensitization-or-caldesmon
#9
Hillevi K Ets, Chun Y Seow, Robert S Moreland
Vascular smooth muscle (VSM) is unique in its ability to maintain an intrinsic level of contractile force, known as tone. Vascular tone is believed to arise from the constitutive activity of membrane-bound L-type Ca(2+) channels (LTCC). This study used a pharmacological agonist of LTCC, Bay K8644, to elicit a sustained, sub-maximal contraction in VSM that mimics tone. Downstream signaling was investigated in order to determine what molecules are responsible for tone. Medial strips of swine carotid artery were stimulated with 100 nM Bay K8644 to induce a sustained level of force...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082900/blockade-of-serotonin-5-ht2a-receptors-suppresses-behavioral-sensitization-and-naloxone-precipitated-withdrawal-symptoms-in-morphine-treated-mice
#10
Gang Pang, Xian Wu, Xinrong Tao, Ruoying Mao, Xueke Liu, Yong-Mei Zhang, Guangwu Li, Robert W Stackman, Liuyi Dong, Gongliang Zhang
: The increasing prescription of opioids is fueling an epidemic of addiction and overdose deaths. Morphine is a highly addictive drug characterized by a high relapse rate - even after a long period of abstinence. Serotonin (5-HT) neurotransmission participates in the development of morphine dependence, as well as the expression of morphine withdrawal. In this study, we examined the effect of blockade of 5-HT2A receptors (5-HT2ARs) on morphine-induced behavioral sensitization and withdrawal in male mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082899/bnn27-a-17-spiroepoxy-steroid-derivative-interacts-with-and-activates-p75-neurotrophin-receptor-rescuing-cerebellar-granule-neurons-from-apoptosis
#11
Iosif Pediaditakis, Alexandra Kourgiantaki, Kyriakos C Prousis, Constantinos Potamitis, Kleanthis P Xanthopoulos, Maria Zervou, Theodora Calogeropoulou, Ioannis Charalampopoulos, Achille Gravanis
Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75(NTR) receptor...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28082898/comparison-of-different-risk-classification-systems-in-558-patients-with-gastrointestinal-stromal-tumors-after-r0-resection
#12
Michael Schmieder, Doris Henne-Bruns, Benjamin Mayer, Uwe Knippschild, Claudia Rolke, Matthias Schwab, Klaus Kramer
Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066255/cardioprotective-effect-of-ulmus-wallichiana-planchon-in-%C3%AE-adrenergic-agonist-induced-cardiac-hypertrophy
#13
Anees A Syed, Shibani Lahiri, Divya Mohan, Guru R Valicherla, Anand P Gupta, Sudhir Kumar, Rakesh Maurya, Himanshu K Bora, Kashif Hanif, Jiaur R Gayen
Ulmus wallichiana Planchon (Family: Ulmaceae), a traditional medicinal plant, was used in fracture healing in the folk tradition of Uttarakhand, Himalaya, India. The present study investigated the cardioprotective effect of ethanolic extract (EE) and butanolic fraction (BF) of U. wallichiana in isoprenaline (ISO) induced cardiac hypertrophy in Wistar rats. Cardiac hypertrophy was induced by ISO (5 mg/kg/day, subcutaneously) in rats. Treatment was performed by oral administration of EE and BF of U. wallichiana (500 and 50 mg/kg/day)...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066254/peptides-derived-from-a-phage-display-library-inhibit-adhesion-and-protect-the-host-against-infection-by-paracoccidioides-brasiliensis-and-paracoccidioides-lutzii
#14
Haroldo C de Oliveira, Jussara S Michaloski, Julhiany F da Silva, Liliana Scorzoni, Ana C A de Paula E Silva, Caroline M Marcos, Patrícia A Assato, Daniella S Yamazaki, Ana M Fusco-Almeida, Ricardo J Giordano, Maria J S Mendes-Giannini
Paracoccidioides brasiliensis and Paracoccidioides lutzii are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with Paracoccidioides and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by Paracoccidioides, thus inhibiting infection and preventing the disease...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066253/unnecessary-hysterectomy-due-to-menorrhagia-and-disorders-of-hemostasis-an-example-of-overuse-and-excessive-demand-for-medical-services
#15
Svetlana M Djukic, Danijela Lekovic, Nikola Jovic, Mirjana Varjacic
No abstract text is available yet for this article.
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066252/the-blood-flow-shutdown-induced-by-combretastatin-a4-impairs-gemcitabine-delivery-in-a-mouse-hepatocarcinoma
#16
Anne-Catherine Fruytier, Cecile S Le Duff, Chrystelle Po, Julie Magat, Caroline Bouzin, Marie-Aline Neveu, Olivier Feron, Benedicte F Jordan, Bernard Gallez
In recent clinical studies, vascular disrupting agents (VDAs) are mainly used in combination with chemotherapy. However, an often overlooked concern in treatment combination is the VDA-induced impairment of chemotherapy distribution in the tumor. The work presented here investigated the impact of blood flow shutdown induced by Combretastatin A4 (CA4) on gemcitabine uptake into mouse hepatocarcinoma. At 2 h after CA4 treatment, using DCE-MRI, a significant decrease in the perfusion-relevant parameters K(trans) and Vp were observed in treated group compared with the control group...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066251/geroprotective-and-radioprotective-activity-of-quercetin-epicatechin-and-ibuprofen-in-drosophila-melanogaster
#17
Ekaterina Proshkina, Ekaterina Lashmanova, Eugenia Dobrovolskaya, Nadezhda Zemskaya, Anna Kudryavtseva, Mikhail Shaposhnikov, Alexey Moskalev
The modulation of longevity genes and aging-associated signaling pathways using pharmacological agents is one of the potential ways to prolong the lifespan and increase the vitality of an organism. Phytochemicals flavonoids and non-steroidal anti-inflammatory drugs have a large potential as geroprotectors. The goal of the present study was to investigate the effects of long-term and short-term consumption of quercetin, (-)-epicatechin, and ibuprofen on the lifespan, resistance to stress factors (paraquat, hyperthermia, γ-radiation, and starvation), as well as age-dependent physiological parameters (locomotor activity and fecundity) of Drosophila melanogaster...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066250/selective-estrogen-receptor-modulators-cannabinoid-receptor-inverse-agonists-with-differential-cb1-and-cb2-selectivity
#18
Lirit N Franks, Benjamin M Ford, Paul L Prather
Selective estrogen receptor modulators (SERMs) are used to treat estrogen receptor (ER)-positive breast cancer and osteoporosis. Interestingly, tamoxifen and newer classes of SERMs also exhibit cytotoxic effects in cancers devoid of ERs, indicating a non-estrogenic mechanism of action. Indicative of a potential ER-independent target, reports demonstrate that tamoxifen binds to cannabinoid receptors (CBRs) with affinity in the low μM range and acts as an inverse agonist. To identify cannabinoids with improved pharmacological properties relative to tamoxifen, and further investigate the use of different SERM scaffolds for future cannabinoid drug development, this study characterized the affinity and activity of SERMs in newer structural classes at CBRs...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066249/development-of-an-igy-antibody-based-immunoassay-for-the-screening-of-the-cyp2e1-inhibitor-enhancer-from-herbal-medicines
#19
Zhihui Jiang, Xuemei Jiang, Cui Li, Huiting Xue, Xiaoying Zhang
Cytochrome P450 (CYP) 2E1 is an important enzyme involved in the metabolism of many endogenous and exogenous compounds. It is essential to evaluate the expression of CYP2E1 in the studies of drug-drug interactions and the screening of drugs, natural products, and foodstuffs. The present work is a feasibility study on the development of immunoassays using a specific and sensitive chicken-sourced anti-CYP2E1 IgY antibody. Cloning, expression, and purification of a recombinant CYP2E1 (mice origin) protein were carried out...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28066248/a-novel-sensitive-method-to-measure-catechol-o-methyltransferase-activity-unravels-the-presence-of-this-activity-in-extracellular-vesicles-released-by-rat-hepatocytes
#20
Enriqueta Casal, Laura Palomo, Diana Cabrera, Juan M Falcon-Perez
There is a clear need for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. One of the main enzymes to take into account in pharmacogenomics is catechol O-methyltransferase (COMT), which catalyzes the transfer of a methyl group from S-adenosylmethionine to catechols and catecholamines, like the neurotransmitters dopamine, epinephrine, and norepinephrine. Although, most of this enzyme is associated to intracellular vesicles, recently it has also been detected in extracellular vesicles secreted by hepatocytes and in serum circulating vesicles...
2016: Frontiers in Pharmacology
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