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Quantitative systems pharmacology

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https://www.readbyqxmd.com/read/29762314/effectiveness-of-dexmedetomidine-versus-propofol-on-extubation-times-length-of-stay-and-mortality-rates-in-adult-cardiac-surgery-patients-a-systematic-review-and-meta-analysis
#1
John Nguyen, Noel Nacpil
OBJECTIVE: To determine the effects of dexmedetomidine versus propofol on extubation time, intensive care unit (ICU) length of stay, total hospital length of stay and in-hospital mortality rates in cardiac surgery patients. INTRODUCTION: Recovery from cardiovascular surgery involves weaning from mechanical ventilation. Mechanical ventilation decreases the work of breathing for patients by inhaling oxygen and exhaling carbon dioxide via a ventilator or breathing machine...
May 2018: JBI Database of Systematic Reviews and Implementation Reports
https://www.readbyqxmd.com/read/29762011/strategies-toward-organic-carbon-monoxide-prodrugs
#2
Xingyue Ji, Binghe Wang
Carbon monoxide is widely acknowledged as an important gasotransmitter in the mammalian system with importance on par with that of nitric oxide. It has also been firmly established as a potential therapeutic agent with a wide range of indications including organ transplantation, cancer, bacterial infection, and inflammation-related conditions such as colitis and sepsis. One major issue in developing CO based therapeutics is its delivery in a pharmaceutically acceptable form. Currently, there are generally five forms of deliveries: inhaled CO, photosensitive CO-releasing molecules, encapsulated CO, CO dissolved in drinks, and molecules that would release CO under physiological conditions without the need for light...
May 15, 2018: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29757687/a-review-of-analytical-methods-for-p-coumaric-acid-in-plant-based-products-beverages-and-biological-matrices
#3
Paula Scanavez Ferreira, Francesca Damiani Victorelli, Bruno Fonseca-Santos, Marlus Chorilli
p-Coumaric acid (p-CA), also known as 4-hydroxycinnamic acid, is a phenolic acid, which has been widely studied due to its beneficial effects against several diseases and its wide distribution in the plant kingdom. This phenolic compound can be found in the free form or conjugated with other molecules; therefore, its bioavailability and the pathways via which it is metabolized change according to its chemical structure. p-CA has potential pharmacological effects because it has high free radical scavenging, anti-inflammatory, antineoplastic, and antimicrobial activities, among other biological properties...
May 14, 2018: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/29753005/a-transcriptome-comparison-of-time-matched-developing-human-mouse-and-rat-neural-progenitor-cells-reveals-human-uniqueness
#4
Stefan Masjosthusmann, Daniel Becker, Barbara Petzuch, Jördis Klose, Clara Siebert, Rene Deenen, Marta Barenys, Jenny Baumann, Katharina Dach, Julia Tigges, Ulrike Hübenthal, Karl Köhrer, Ellen Fritsche
It is widely accepted that human brain development has unique features that cannot be represented by rodents. Obvious reasons are the evolutionary distance and divergent physiology. This might lead to false predictions when rodents are used for safety or pharmacological efficacy studies. For a better translation of animal-based research to the human situation, human in vitro systems might be useful. In this study, we characterize developing neural progenitor cells from prenatal human and time-matched rat and mouse brains by analyzing the changes in their transcriptome profile during neural differentiation...
May 9, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29750250/analysis-of-fentanyl-and-18-novel-fentanyl-analogs-and-metabolites-by-lc-ms-ms-and-report-of-fatalities-associated-with-methoxyacetylfentanyl-and-cyclopropylfentanyl
#5
Melissa F Fogarty, Donna M Papsun, Barry K Logan
Methoxyacetylfentanyl and cyclopropylfentanyl are two of the newest illicit opioids that are infiltrating the heroin market. Methoxyacetylfentanyl and cyclopropylfentanyl were reported by the Drug Enforcement Administration (DEA) in their third quarter report of 2017 to have been chemically identified seven and five times, respectively, from drug evidence analyzed by the DEA's lab system; Q3 was the first time cyclopropylfentanyl was identified by the DEA's lab system, while methoxyacetylfentanyl was reported one time in Q2 2017...
May 10, 2018: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/29746491/emergence-and-selection-of-isoniazid-and-rifampin-resistance-in-tuberculosis-granulomas
#6
Elsje Pienaar, Jennifer J Linderman, Denise E Kirschner
Drug resistant tuberculosis is increasing world-wide. Resistance against isoniazid (INH), rifampicin (RIF), or both (multi-drug resistant TB, MDR-TB) is of particular concern, since INH and RIF form part of the standard regimen for TB disease. While it is known that suboptimal treatment can lead to resistance, it remains unclear how host immune responses and antibiotic dynamics within granulomas (sites of infection) affect emergence and selection of drug-resistant bacteria. We take a systems pharmacology approach to explore resistance dynamics within granulomas...
2018: PloS One
https://www.readbyqxmd.com/read/29739484/outpatient-pharmacologic-weaning-for-neonatal-abstinence-syndrome-a-systematic-review
#7
Jodie Murphy-Oikonen, Karen McQueen
AimThe purpose of this systematic review was to assess the literature regarding the effectiveness and safety of outpatient pharmacologic weaning for infants with neonatal abstinence syndrome (NAS). BACKGROUND: NAS is a multi-system disorder observed in infants experiencing withdrawal from opioid exposure in utero. Infants requiring pharmacologic treatment to manage withdrawal, traditionally receive treatment as a hospital inpatient resulting in lengthy hospitalization periods. However, there is evidence to suggest that some healthcare institutions are continuing outpatient pharmacologic weaning for select infants in a home environment...
May 9, 2018: Primary Health Care Research & Development
https://www.readbyqxmd.com/read/29739358/implementation-of-an-evidence-based-intervention-to-improve-the-wellbeing-of-people-with-dementia-and-their-carers-study-protocol-for-care-of-people-with-dementia-in-their-environments-cope-in-the-australian-context
#8
Lindy Clemson, Kate Laver, Yun-Hee Jeon, Tracy A Comans, Justin Scanlan, Miia Rahja, Jennifer Culph, Lee-Fay Low, Sally Day, Monica Cations, Maria Crotty, Susan Kurrle, Catherine Piersol, Laura N Gitlin
BACKGROUND: There are effective non-pharmacological treatment programs that reduce functional disability and changed behaviours in people with dementia. However, these programs (such as the Care of People with dementia in their Environments (COPE) program) are not widely available. The primary aim of this study is to determine the strategies and processes that enable the COPE program to be implemented into existing dementia care services in Australia. METHODS: This study uses a mixed methods approach to test an implementation strategy...
May 9, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/29738261/the-significance-of-the-stromal-response-in-breast-cancer-an-immunohistochemical-study-of-myofibroblasts-in-primary-and-metastatic-breast-cancer
#9
Alale Roozdar, Malcolm M Hayes, Bahram Pourseyedei, Hamid Zeinalinejad, Manzumeh Shamsi Meymandi, Bahram Dabiri, Shahriar Dabiri
BACKGROUND: Gene expression profiling of breast cancer has demonstrated the importance of stromal response in determining the prognosis of invasive breast cancer. The host response to breast cancer is of increasing interest to pathologists and may be a future focus for novel pharmacological treatments. METHODS: This study describes the pattern of distribution of stromal myofibroblasts using immunostains for CD10 and smooth muscle actin (SMA) in 50 primary breast cancers and their matched nodal metastases (68...
May 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/29736721/a-quantitative-systems-pharmacology-approach-to-infer-pathways-involved-in-complex-disease-phenotypes
#10
Mark E Schurdak, Fen Pei, Timothy R Lezon, Diane Carlisle, Robert Friedlander, D Lansing Taylor, Andrew M Stern
Designing effective therapeutic strategies for complex diseases such as cancer and neurodegeneration that involve tissue context-specific interactions among multiple gene products presents a major challenge for precision medicine. Safe and selective pharmacological modulation of individual molecular entities associated with a disease often fails to provide efficacy in the clinic. Thus, development of optimized therapeutic strategies for individual patients with complex diseases requires a more comprehensive, systems-level understanding of disease progression...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29734020/ultrastructural-and-mechanical-changes-in-tubular-epithelial-cells-by-angiotensin-ii-and-aldosterone-as-observed-with-atomic-force-microscopy
#11
Fu-Shi Quan, Kyung Hwan Jeong, Gi-Ja Lee
Tubular epithelial cells (TECs) play an important pathophysiological role in the promotion of renal fibrosis. Quantitative analysis of the mechanical changes in TECs may be helpful in evaluating novel pharmacological strategies. Atomic force microscopy (AFM) is a common nanotechnology tool used for imaging and measuring interaction forces in biological systems. In this study, we used AFM to study ultrastructural and mechanical changes in TECs mediated by the renin-angiotensin-aldosterone system. We quantitatively analyzed changes in the mechanical properties of TECs using three extrinsic factors, namely, chemical fixation, angiotensin II (AT II), and aldosterone (AD)...
May 2, 2018: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/29725796/multiscale-systems-pharmacological-analysis-of-everolimus-action-in-hepatocellular-carcinoma
#12
Anusha Ande, Maher Chaar, Sihem Ait-Oudhia
Dysregulation of mTOR pathway is common in hepatocellular carcinoma (HCC). A translational quantitative systems pharmacology (QSP), pharmacokinetic (PK), and pharmacodynamic (PD) model dissecting the circuitry of this pathway was developed to predict HCC patients' response to everolimus, an mTOR inhibitor. The time course of key signaling proteins in the mTOR pathway, HCC cells viability, tumor volume (TV) and everolimus plasma and tumor concentrations in xenograft mice, clinical PK of everolimus and progression free survival (PFS) in placebo and everolimus-treated patients were extracted from literature...
May 3, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29689586/enhanced-solubility-and-permeability-of-salicis-cortex-extract-by-formulating-as-a-microemulsion
#13
Vieri Piazzini, Elisabetta Bigagli, Cristina Luceri, Anna Rita Bilia, Maria Camilla Bergonzi
A microemulsion system was developed and investigated as a novel oral formulation to increase the solubility and absorption of Salicis cortex extract. This extract possesses many pharmacological activities, in particular, it is beneficial for back pain and osteoarthritic and rheumatic complaints. In this work, after qualitative and quantitative characterization of the extract and the validation of an HPLC/diode array detector analytical method, solubility studies were performed to choose the best components for microemulsion formulation...
April 24, 2018: Planta Medica
https://www.readbyqxmd.com/read/29669397/direct-detection-of-the-psychoactive-substance-mt-45-in-human-tissue-samples-by-probe-electrospray-ionization-tandem-mass-spectrometry
#14
Kiyotaka Usui, Tasuku Murata, Yuji Fujita, Yoshito Kamijo, Tomoki Hanazawa, Tomohiro Yoshizawa, Masato Funayama
Analyses of drugs and poisons in tissue samples are essential in forensic toxicology and pharmacology. However, current procedures for tissue analysis are laborious and time-consuming. Therefore, we assessed the utility of a newly devised probe electrospray ionization (PESI) technique with tandem mass spectrometry (MS/MS) for easy, ultra-rapid drug detection in human tissue samples. Using this system, typical pre-treatment procedures, such as solid-phase extraction, liquid-liquid extraction, deproteinization, or homogenization, can be avoided...
April 18, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/29663628/exenatide-effects-on-gastric-emptying-and-oral-glucose-appearance-in-plasma-a-quantitative-assessment-using-an-integrative-systems-pharmacology-model
#15
Veronika Voronova, Kirill Zhudenkov, Robert C Penland, David W Boulton, Gabriel Helmlinger, Kirill Peskov
Glucagon-like peptide (GLP)-1 and synthetic GLP-1 receptor agonists (GLP-1RA) slow gastric emptying rate (GER), thereby decreasing the Glucose Rate of Appearance (GluRA) in plasma, which may contribute to postprandial plasma glucose (PPG) stabilization under GLP-1RA treatment. A quantitative systems pharmacology (QSP) approach was used to evaluate the effect of exenatide immediate release (IR), a short-acting GLP-1RA, on GER and GluRA. The proposed model is based on the data from multiple published sources including: (1) GLP-1 and exenatide plasma concentration-time profiles; (2) GER estimates under placebo, GLP-1 or exenatide IR dosing; (3) GluRA measurements upon food intake...
April 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29659246/membrane-nanotubes-increase-the-robustness-of-giant-vesicles
#16
Tripta Bhatia, Jaime Agudo-Canalejo, Rumiana Dimova, Reinhard Lipowsky
Giant unilamellar vesicles (GUVs) provide a direct connection between the nano- and the microregime. On the one hand, these vesicles represent biomimetic compartments with linear dimensions of many micrometers. On the other hand, the vesicle walls are provided by single molecular bilayers that have a thickness of a few nanometers and respond sensitively to molecular interactions with small solutes, biopolymers, and nanoparticles. These nanoscopic responses are amplified by the GUVs and can then be studied on much larger scales...
April 16, 2018: ACS Nano
https://www.readbyqxmd.com/read/29648838/binding-of-small-molecule-drugs-to-porcine-vitreous-humor
#17
Anna-Kaisa Rimpelä, Saku Reunanen, Marja Hagström, Heidi Kidron, Arto Urtti
Pharmacokinetics in the posterior eye segment has therapeutic implications due to the importance of retinal diseases in ophthalmology. In principle, drug binding to the components of the vitreous, such as proteins, collagen or glycosaminoglycans, could prolong ocular drug retention and modify levels of pharmacologically active free drug in the posterior eye segment. Since drug binding in the vitreous has been investigated only sparsely, we studied vitreal drug binding of 35 clinical small molecular drugs. Isolated homogenized porcine vitreous and the drugs were placed in a two-compartmental dialysis system that was used to separate the bound and unbound drug...
April 12, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29628291/citri-reticulatae-pericarpium-chenpi-botany-ethnopharmacology-phytochemistry-and-pharmacology-of-a-frequently-used-traditional-chinese-medicine
#18
REVIEW
Xin Yu, Shuang Sun, Yuyan Guo, Yan Liu, Dayu Yang, Guoyu Li, Shaowa Lü
ETHNOPHARMACOLOGICAL RELEVANCE: Citri Reticulatae Pericarpium (Rutaceae, CRP), commonly called as Chenpi () in Chinese, is most frequently used as a qi-regulating drug in thousands of Chinese medicine prescriptions. CRP is found mainly in major citrus-producing areas such as the Guangdong, Guangxi, Sichuan, Fujian, and Zhejiang Provinces of China. Since thousands of years in China, CRP has been used widely in clinical practice to treat nausea, vomiting, indigestion, anepithymia, diarrhea, cough, expectoration, and so on...
April 5, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29615704/virtual-screening-docking-admet-and-system-pharmacology-studies-on-garcinia-caged-xanthone-derivatives-for-anticancer-activity
#19
Sarfaraz Alam, Feroz Khan
Caged xanthones are bioactive compounds mainly derived from the Garcinia genus. In this study, a structure-activity relationship (SAR) of caged xanthones and their derivatives for anticancer activity against different cancer cell lines such as A549, HepG2 and U251 were developed through quantitative (Q)-SAR modeling approach. The regression coefficient (r2 ), internal cross-validation regression coefficient (q2 ) and external cross-validation regression coefficient (pred_r2 ) of derived QSAR models were 0.87, 0...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29604616/a-porous-graphitized-carbon-lc-esi-ms-method-for-the-quantitation-of-metronidazole-and-fluconazole-in-breast-milk-and-human-plasma
#20
Ariadni Geballa-Koukoula, Irene Panderi, Konstantinos Zervas, Khalil Geballa-Koukoulas, Eirini Kavvalou, Eirini Panteri-Petratou, Panagiota Vourna, Dimitra Gennimata
Information on drug transfer into the breast milk is essential to protect the infant from undesirable adverse effects of maternal consumption of drugs and to allow effective pharmacological treatment of breastfeeding mothers. Metronidazole and fluconazole are two drugs frequently used in nursing women to treat various infections, thus questioning infant's safety due to drug exposure through breast milk. In this article a porous graphitized carbon LC/ESI-MS assay was developed for the quantitation of metronidazole and fluconazole in breast milk and human plasma...
March 22, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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