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https://www.readbyqxmd.com/read/29236223/transit-and-lifespan-in-neutrophil-production-implications-for-drug-intervention
#1
Daniel Câmara De Souza, Morgan Craig, Tyler Cassidy, Jun Li, Fahima Nekka, Jacques Bélair, Antony R Humphries
A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells...
December 13, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29236090/novel-hydrogel-advanced-modified-clay-nanocomposites-as-possible-vehicles-for-drug-delivery-and-controlled-release
#2
Raluca Ianchis, Claudia M Ninciuleanu, Ioana C Gifu, Elvira Alexandrescu, Raluca Somoghi, Augusta R Gabor, Silviu Preda, Cristina L Nistor, Sabina Nitu, Cristian Petcu, Madalina Icriverzi, Paula E Florian, Anca M Roseanu
Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid) (PMAA) with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N,N'-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel...
December 13, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#3
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29235903/brain-targeted-intranasal-zaleplon-solid-dispersion-in-hydrophilic-carrier-system-23-full-factorial-design-and-in-vivo-determination-of-gaba-neurotransmitter
#4
Eman Abd-Elrasheed, Sara Nageeb El-Helaly, Manal M El-Ashmoony, Salwa Salah
Intranasal Zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 23full factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied...
December 13, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29235532/investigation-of-the-effects-of-the-cftr-potentiator-ivacaftor-on-human-p-glycoprotein-abcb1
#5
Swathi Lingam, Nopnithi Thonghin, Robert C Ford
Ivacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use for the chronic treatment of cystic fibrosis in patients. There is evidence that the bioavailability of ivacaftor in the body may be influenced by the multi-drug exporter P-glycoprotein. Here we have employed purified and reconstituted P-glycoprotein to study its interaction with ivacaftor as well as the ability of the drug to compete with a known transported substrate of the protein. We find that ivacaftor stimulates the ATPase activity of the purified protein and can compete with the transport of the fluorescent substrate Hoechst 33342...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29235430/prevalence-and-risk-factors-for-delirium-diagnosis-in-patients-followed-in-general-practices-in-germany
#6
Jens Bohlken, Karel Kostev
BACKGROUND: The aim of this study is to identify the prevalence and risk factors of documented delirium in general practices in Germany. METHODS: The present study includes 2,194 patients over the age of 65 years with delirium and 2,194 controls without delirium from a sample of 6,180,042 patients from 1,262 general practices. Multivariate logistic regression models were fitted with delirium as a dependent variable and other disorders and drugs as potential predictors...
December 13, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/29235378/the-hexane-fraction-of-bursera-microphylla-a-gray-induces-p21-mediated-anti-proliferative-and-pro-apoptotic-effects-in-human-cancer-derived-cell-lines
#7
Sabrina Adorisio, Alessandra Fierabracci, Giulia Gigliarelli, Isabella Muscari, Lorenza Cannarile, Anna Marina Liberati, Maria Carla Marcotullio, Carlo Riccardi, Massimo Curini, Ramon Enrique Robles Zepeda, Domenico V Delfino
Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran Desert in Mexico. The Seri ethnic group in the Sonoran Desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29235095/immune-cells-regulate-vegf-signaling-via-release-of-vegf-and-antagonistic-soluble-vegf-receptor-1
#8
Timm Hoeres, Martin Wilhelm, Manfred Smetak, Elisabeth Holzmann, Gundula Schulze-Tanzil, Josef Birkmann
Vascular endothelial growth factor (VEGF) is an important regulator of physiological and pathological angiogenesis. Beside malignant and stromal cells, local immune cells shape VEGF signaling in the tumor microenvironment. Aminobisphosphonates like zoledronic acid (Zol) are drugs known to inhibit osteoclast activity and bone resorption, but also have immunomodulatory and anti-tumor effects. These properties have previously been linked to the downregulation of VEGF and interference with tumor neo-angiogenesis...
December 13, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29234968/a-cross-national-analysis-of-the-association-between-years-of-implementation-of-opioid-substitution-treatments-and-drug-related-deaths-in-europe-from-1995-to-2013
#9
Phillip L Marotta, Charlotte A McCullagh
Data at the individual-level provide evidence that opioid substitution treatment (OST) programs protect against mortality for opioid dependent populations. Prior research has not examined the merits of national implementation of opioid substitution programs for reducing mortality at the country-level. This study elucidates longitudinal associations between country-level implementation of opioid substitution treatment programs on mortality rates of drug related deaths (DRD) from 1995 to 2013 in 30 European nations...
December 12, 2017: European Journal of Epidemiology
https://www.readbyqxmd.com/read/29234674/microrna-in-glioblastoma-an-overview
#10
REVIEW
Barbara Banelli, Alessandra Forlani, Giorgio Allemanni, Anna Morabito, Maria Pia Pistillo, Massimo Romani
Glioblastoma is the most aggressive brain tumor and, even with the current multimodal therapy, is an invariably lethal cancer with a life expectancy that depends on the tumor subtype but, even in the most favorable cases, rarely exceeds 2 years. Epigenetic factors play an important role in gliomagenesis, are strong predictors of outcome, and are important determinants for the resistance to radio- and chemotherapy. The latest addition to the epigenetic machinery is the noncoding RNA (ncRNA), that is, RNA molecules that are not translated into a protein and that exert their function by base pairing with other nucleic acids in a reversible and nonmutational mode...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/29234439/herbal-medicine-for-the-treatment-of-obesity-an-overview-of-scientific-evidence-from-2007-to-2017
#11
REVIEW
Yanfei Liu, Mingyue Sun, Hezhi Yao, Yue Liu, Rui Gao
Obesity is a very common global health problem, and it is known to be linked to cardiovascular and cerebrovascular diseases. Western medical treatments for obesity have many drawbacks, including effects on monoamine neurotransmitters and the potential for drug abuse and dependency. The safety of these medications requires improvement. Herbal medicine has been used for treatment of disease for more than 2000 years, and it has proven efficacy. Many studies have confirmed that herbal medicine is effective in the treatment of obesity, but the mechanisms are not clear...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234429/effects-of-jiawei-shaoyao-gancao-decoction-and-its-drug-containing-serum-on-proliferation-apoptosis-and-ultrastructure-of-human-adenomyosis-foci-cells
#12
Yu-Yan Zeng, Kun-Yin Li
Objective: The present study aimed to investigate the effects of Jiawei Shaoyao-Gancao Decoction (JSGD) and its drug-containing serum (CDS) on the proliferation, apoptosis, and ultrastructure of human adenomyosis foci cells. Methods: Primary cultures of human adenomyosis foci cells were prepared from hard uterine lesions of adenomyosis patients. The cells were treated with JSGD (10 and 20 mg/ml), CDS, and mifepristone (MIF) for 24 or 48 h. Cell proliferation was detected using CCK-8 assay, cell apoptosis was measured by flow cytometry, and the cell ultrastructure was observed by transmission electron microscopy (TEM)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234376/roles-of-nitric-oxide-and-prostaglandins-in-the-sustained-antihypertensive-effects-of-acanthospermum-hispidum-dc-on-ovariectomized-rats-with-renovascular-hypertension
#13
Rhanany Alan Calloi Palozi, Maysa Isernhagen Schaedler, Cleide Adriane Signor Tirloni, Aniely Oliveira Silva, Francislaine Aparecida Dos Reis Lívero, Roosevelt Isaias Carvalho Souza, Ariany Carvalho Dos Santos, Thiago Bruno Lima Prando, Lauro Mera de Souza, Arquimedes Gasparotto Junior
Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29234248/incorporating-cdk4-6-inhibitors-in-the-treatment-of-advanced-luminal-breast-cancer
#14
REVIEW
Isabel Echavarria, Yolanda Jerez, Miguel Martin, Sara López-Tarruella
After optimizing endocrine monotherapy modalities in the setting of advanced luminal breast cancer (BC), dual endocrine/targeted therapy combinations have been tested with positive results, and are transforming this BC subtype treatment landscape. Cell cycle deregulation is a hallmark of cancer that has become a key druggable target in hormone receptor (HR)-positive BC due to its role in endocrine resistance mechanisms. Cyclin dependent kinase (CDK)4/6 inhibitors have experienced a fast development in combination with endocrine therapy and have already been commercialized in some countries...
October 2017: Breast Care
https://www.readbyqxmd.com/read/29234062/development-of-erasin-a-chromone-based-stat3-inhibitor-which-induces-apoptosis-in-erlotinib-resistant-lung-cancer-cells
#15
Christian Lis, Stefan Rubner, Martin Roatsch, Angela Berg, Tyler Gilcrest, Darwin Fu, Elizabeth Nguyen, Anne-Marie Schmidt, Harald Krautscheid, Jens Meiler, Thorsten Berg
Inhibition of protein-protein interactions by small molecules offers tremendous opportunities for basic research and drug development. One of the fundamental challenges of this research field is the broad lack of available lead structures from nature. Here, we demonstrate that modifications of a chromone-based inhibitor of the Src homology 2 (SH2) domain of the transcription factor STAT5 confer inhibitory activity against STAT3. The binding mode of the most potent STAT3 inhibitor Erasin was analyzed by the investigation of structure-activity relationships, which was facilitated by chemical synthesis and biochemical activity analysis, in combination with molecular docking studies...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233910/targeting-cdk1-and-mek-erk-overcomes-apoptotic-resistance-in-braf-mutated-human-colorectal-cancer
#16
Peng Zhang, Hisato Kawakami, Weizhen Liu, Xiangyu Zeng, Klaus Strebhardt, Kaixiong Tao, Shengbing Huang, Frank A Sinicrope
The BRAFV600E mutation occurs in ~8% of human colorectal cancers (CRCs) and is associated with therapeutic resistance that is due, in part, to re-activation of MEK/ERK signaling cascade. Recently, pathway analysis identified cyclin-dependent kinase 1 (CDK1) upregulation in a subset of human BRAFV600E CRCs. Therefore, it was determined whether CDK1 antagonism enhances the efficacy of MEK inhibition in BRAFV600E CRC cells. BRAFV600E CRC cell lines expressing CDK1 were sensitized to apoptosis upon siRNA knockdown or small-molecule inhibition with RO-3306 (CDK1 inhibitor) or dinaciclib (CDK1,2,5,9 inhibitor)...
December 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29233818/importance-of-the-unstirred-water-layer-and-hepatocyte-membrane-integrity-in-vitro-for-quantification-of-intrinsic-metabolic-clearance
#17
Francesca Leanne Wood, James Brian Houston, David Hallifax
Prediction of clearance - a vital component of drug discovery - remains in need of improvement and, in particular, requires more incisive assessment of mechanistic methodology in vitro, according to a number of recent reports. Although isolated hepatocytes have become an irreplaceable standard system for measurement of intrinsic hepatic clearance mediated by active uptake transport and metabolism, lack of prediction reliability appears to reflect a lack of methodological validation, especially for highly cleared drugs, as we have previously shown...
December 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29233683/caspase-mediated-cleavage-of-x-ray-repair-cross-complementing-group-4-promotes-apoptosis-by-enhancing-nuclear-translocation-of-caspase-activated-dnase
#18
Yumi Sunatani, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, Tadashi Matsui, Ryo Sakasai, Mitsumasa Hashimoto, Yasuhito Ishigaki, Yoshihisa Matsumoto, Kuniyoshi Iwabuchi
X-ray repair cross-complementing group 4 (XRCC4), a repair protein for DNA double-strand breaks, is cleaved by caspases during apoptosis. In this study, we examined the role of XRCC4 in apoptosis. Cell lines, derived from XRCC4-deficient M10 mouse lymphoma cells and stably expressing wild-type XRCC4 or caspase-resistant XRCC4, were established and treated with staurosporine (STS) to induce apoptosis. In STS-induced apoptosis, expression of wild-type, but not caspase-resistant, XRCC4 in XRCC4-deficient cells enhanced oligonucleosomal DNA fragmentation and the appearance of TUNEL-positive cells by promoting nuclear translocation of caspase-activated DNase (CAD), a major nuclease for oligonucleosomal DNA fragmentation...
December 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29233672/time-latencies-of-helicobacter-pylori-eradication-after-peptic-ulcer-and-risk-of-recurrent-ulcer-ulcer-adverse-events-and-gastric-cancer-a-population-based-cohort-study
#19
Emma Sverdén, Nele Brusselaers, Karl Wahlin, Jesper Lagergren
BACKGROUND: Helicobacter pylori (H pylori) is associated with peptic ulcer disease and gastric cancer. AIM: To test how various lengths of delays in H pylori eradication therapy influence the risk of recurrent peptic ulcer, ulcer adverse events and gastric cancer. METHODS: This population-based nationwide Swedish cohort study included 29,032 patients receiving H pylori eradication therapy after peptic ulcer disease in 2005-2013. Pre-defined time intervals between date of peptic ulcer diagnosis and date of eradication therapy were analysed in relation to study outcomes...
December 9, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29233603/individual-susceptibility-analysis-using-patient-derived-slice-cultures-of-colorectal-carcinoma
#20
Rasmus Sönnichsen, Laura Hennig, Vera Blaschke, Karsten Winter, Justus Körfer, Susann Hähnel, Astrid Monecke, Christian Wittekind, Boris Jansen-Winkeln, René Thieme, Ines Gockel, Kerstin Grosser, Arved Weimann, Christoph Kubick, Volker Wiechmann, Achim Aigner, Ingo Bechmann, Florian Lordick, Sonja Kallendrusch
BACKGROUND: Nonresponse to chemotherapy in colorectal carcinoma (CRC) is still a clinical problem. For most established treatment regimens, no predictive biomarkers are available. Patient-derived tumor slice culture may be a promising ex vivo technology to assess the drug susceptibility in individual tumors. METHODS: Patient-derived slice cultures of CRC specimens were prepared according to a standardized protocol and treated with different concentrations of 5-fluorouracil (5-FU) and an adapted FOLFOX regimen (5-FU and oxaliplatin) to investigate histologic response...
November 21, 2017: Clinical Colorectal Cancer
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