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Quantitative systems pharmacology

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https://www.readbyqxmd.com/read/28930822/five-years-experience-on-3-4-diaminopyridine-phosphate-in-lambert-eaton-syndrome-case-reports
#1
Simona Portaro, Teresa Brizzi, Stefano Sinicropi, Alberto Cacciola, Maria Cristina De Cola, Alessia Bramanti, Demetrio Milardi, Antonino Lupica, Placido Bramanti, Antonio Toscano, Carmelo Rodolico
RATIONALE: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28930267/%C3%AE-selinene-rich-essential-oils-from-the-parts-of-callicarpa-macrophylla-and-their-antioxidant-and-pharmacological-activities
#2
Mahesh Chandra, Om Prakash, Ravendra Kumar, Rakesh Kumar Bachheti, Brij Bhushan, Mahesh Kumar, Anil Kumar Pant
Background:Callicarpa macrophylla (Varbenaceae) is a medicinal shrub and is traditionally used in India, China, and South Asia. Methods: The plant material was collected from lower Himalayan region of Uttarakhand in India. The essential oils from three different aerial parts were analyzed by GC-MS. Antioxidant activity, phenolic assay, and various pharmacological activities were determined by using existing methods which are generally practiced widely. Results: Over 51, 53, and 40 compounds were identified in C...
July 10, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/28924075/edoxaban-enhances-thromboprophylaxis-by-physiotherapy-after-total-knee-arthroplasty%C3%A3-the-randomized-controlled-escort-tka-trial
#3
Daisuke Sueta, Koichi Kaikita, Nobukazu Okamoto, Soichiro Yamabe, Masanobu Ishii, Yuichiro Arima, Miwa Ito, Yu Oimatsu, Tatsuro Mitsuse, Satomi Iwashita, Eiichi Nakamura, Seiji Hokimoto, Hiroshi Mizuta, Hisao Ogawa, Kenichi Tsujita
BACKGROUND: The pharmacological advantage of combining physiotherapy with anticoagulants for the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA) is not fully known. Herein we investigated the potential benefit of this combination therapy in patients undergoing TKA.Methods and Results:The 38 patients were randomly assigned to a physiotherapy group (n=19) or a physiotherapy plus 30 mg/day edoxaban group (n=19). The occurrence of VTE was evaluated, as were serial changes in parameters measured by the Total Thrombus-formation Analysis System, a novel system for quantitatively analyzing thrombus formation using microchips with thrombogenic surfaces (collagen plus tissue factor, atheroma [AR]-chip)...
September 16, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28921644/clinical-pharmacology-considerations-for-the-development-of-immune-checkpoint-inhibitors
#4
Jennifer Sheng, Shivani Srivastava, Kinjal Sanghavi, Zheng Lu, Brian J Schmidt, Akintunde Bello, Manish Gupta
Immuno-oncology works through activation of the patient's immune system against cancer, with several advantages over other treatment approaches, including cytotoxic agents and molecular-targeted therapies. The most notable feature of immuno-oncology treatments is the nature of the patient responses achieved, which can be more durable and sustained than with other modalities. Increased understanding of immune system complexity has provided a number of opportunities to advance several strategies for the development of immuno-oncology therapies...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28918570/mathematical-description-of-drug-target-interactions-application-to-biologics-that-bind-to-targets-with-two-binding-sites
#5
Leonid Gibiansky, Ekaterina Gibiansky
The emerging discipline of mathematical pharmacology occupies the space between advanced pharmacometrics and systems biology. A characteristic feature of the approach is application of advance mathematical methods to study the behavior of biological systems as described by mathematical (most often differential) equations. One of the early application of mathematical pharmacology (that was not called this name at the time) was formulation and investigation of the target-mediated drug disposition (TMDD) model and its approximations...
September 16, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28917974/cross-cultural-analysis-of-medicinal-plants-commonly-used-in-ethnoveterinary-practices-at-south-waziristan-agency-and-bajaur-agency-federally-administrated-tribal-areas-fata-pakistan
#6
Muhammad Abdul Aziz, Muhammad Adnan, Amir Hasan Khan, Muhammad Sufyan, Shahid Niaz Khan
ETHNOPHARMACOLOGICAL RELEVANCE: In remote areas, medicinal plants have an imperative role in curing various livestock's ailments. In Pakistan, people residing in remote areas including South Waziristan Agency and Bajaur Agency depend on traditional herbal remedies for treating their domestic animals. Medicinal plants are an important part of the medical system in these Agencies. The prime goal of the current study is to explore the ethnoveterinary practices in the two regions and discuss cross-cultural consensus on the use of medicinal plants...
September 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28917669/knowledge-driven-computational-modeling-in-alzheimer-s-research-current-state-and-future-trends
#7
Hugo Geerts, Martin Hofmann-Apitius, Thomas J Anastasio
Neurodegenerative diseases such as Alzheimer's disease (AD) follow a slowly progressing dysfunctional trajectory, with a large presymptomatic component and many comorbidities. Using preclinical models and large-scale omics studies ranging from genetics to imaging, a large number of processes that might be involved in AD pathology at different stages and levels have been identified. The sheer number of putative hypotheses makes it almost impossible to estimate their contribution to the clinical outcome and to develop a comprehensive view on the pathological processes driving the clinical phenotype...
September 14, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28911689/effect-of-oleuropein-against-chemotherapy-drug-induced-histological-changes-oxidative-stress-and-dna-damages-in-rat-kidney-injury
#8
Fatime Geyikoglu, Murat Emir, Suat Colak, Kubra Koc, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Salim Cerig, Osman Nuri Keles, Nihal Simsek Ozek
Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28910306/a-quantitative-systems-pharmacology-approach-incorporating-a-novel-liver-model-for-predicting-pharmacokinetic-drug-drug-interactions
#9
Mohammed H Cherkaoui-Rbati, Stuart W Paine, Peter Littlewood, Cyril Rauch
All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ...
2017: PloS One
https://www.readbyqxmd.com/read/28895653/clinical-interventions-for-takayasu-arteritis-a-systematic-review
#10
REVIEW
Rafael L Pacheco, Carolina de Oliveira Cruz Latorraca, Alexandre Wagner Silva de Souza, Daniela V Pachito, Rachel Riera
INTRODUCTION: Takayasu arteritis (TA) is a rare systemic vasculitis that affects large vessels often resistant to treatment and associated with high morbidity and mortality. Treatment is defied by the relapsing nature of the disease and frequent adverse effects of corticosteroids and immunosuppressors, rendering failure of treatment in a significant portion of patients. Considering the low quantity and quality of published studies focusing on treatment of TA, synthesis and critical assessment of the available evidence is fundamental to establish recommendations for clinical practice...
September 12, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28882304/assessing-the-degradation-of-tau-in-primary-neurons-the-role-of-autophagy
#11
Changyi Ji, Maoping Tang, Gail V W Johnson
Tau is a neuronal cytosolic, highly regulated protein. Although first identified as a protein that binds and stabilizes microtubules, it is now clear that tau plays numerous other roles in neurons. In addition to its key physiological roles in neuronal structure and function, tau is also involved in the pathogenesis of Alzheimer's disease and numerous other neurodegenerative disorders. In all tauopathies, there are pathogenic accumulations of tau. Given that tau homeostasis requires a balance of synthesis and degradation, understanding the pathways that mediate tau clearance and regulate this process in the disease state is of fundamental importance...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28879893/a-novel-swine-model-of-subarachnoid-hemorrhage-induced-cerebral-vasospasm
#12
Zion Zibly, Lory Fein, Mayur Sharma, Yaron Assaf, Anton Wohl, Sagi Harnof
OBJECTIVE: One of the most serious complications following subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI) secondary to symptomatic vasospasm. An animal model mimicking post SAH vasospasm is essential for enabling the translation of newer technologies from the conceptual phase to animal studies, and eventually to clinical trials. Various animal models of DCI following SAH have been reported, with canine models being the most common. Due to the similarity of the swine cardiovascular system and its dimensions to the human's system, the main objective of this study was to establish a consistent and quantitatively representative model of SAH-induced vasospasm in swine...
September 2017: Neurology India
https://www.readbyqxmd.com/read/28878692/optimization-of-an-in-silico-cardiac-cell-model-for-proarrhythmia-risk-assessment
#13
Sara Dutta, Kelly C Chang, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Wendy W Wu, Min Wu, David G Strauss, Thomas Colatsky, Zhihua Li
Drug-induced Torsade-de-Pointes (TdP) has been responsible for the withdrawal of many drugs from the market and is therefore of major concern to global regulatory agencies and the pharmaceutical industry. The Comprehensive in vitro Proarrhythmia Assay (CiPA) was proposed to improve prediction of TdP risk, using in silico models and in vitro multi-channel pharmacology data as integral parts of this initiative. Previously, we reported that combining dynamic interactions between drugs and the rapid delayed rectifier potassium current (IKr) with multi-channel pharmacology is important for TdP risk classification, and we modified the original O'Hara Rudy ventricular cell mathematical model to include a Markov model of IKr to represent dynamic drug-IKr interactions (IKr-dynamic ORd model)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28846728/carbon-nanotubes-exhibit-fibrillar-pharmacology-in-primates
#14
Simone Alidori, Daniel L J Thorek, Bradley J Beattie, David Ulmert, Bryan Aristega Almeida, Sebastien Monette, David A Scheinberg, Michael R McDevitt
Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation...
2017: PloS One
https://www.readbyqxmd.com/read/28843937/determination-of-protein-unbound-active-rifampicin-in-serum-by-ultrafiltration-and-ultra-performance-liquid-chromatography-with-uv-detection-a-method-suitable-for-standard-and-high-doses-of-rifampicin
#15
Eleonora W J van Ewijk-Beneken Kolmer, Marga J A Teulen, Erik C A van den Hombergh, Nielka E van Erp, Lindsey H M Te Brake, Rob E Aarnoutse
Rifampicin is the most important antibiotic in use for the treatment of tuberculosis (TB). Preclinical and clinical data suggest that higher doses of rifampicin, resulting in disproportionally higher systemic exposures to the drug, are more effective. Serum concentrations of rifampicin are the intermediary link between the dose administered and eventual response and only protein-unbound (free) rifampicin is pharmacologically active. The objective of this work was to develop an ultra performance liquid chromatography assay for protein-unbound rifampicin in serum with ultrafiltration, carried out at a sample temperature of 37°C, suitable for measurement of concentrations achieved after currently used and higher doses of rifampicin...
August 4, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28836571/pharmacological-inhibition-of-macrophage-toll-like-receptor-4-nuclear-factor-kappa-b-alleviates-rhabdomyolysis-induced-acute-kidney-injury
#16
Rong-Shuang Huang, Jiao-Jiao Zhou, Yu-Ying Feng, Min Shi, Fan Guo, Shen-Ju Gou, Stephen Salerno, Liang Ma, Ping Fu
Background: Acute kidney injury (AKI) is the most common and life-threatening systemic complication of rhabdomyolysis. Inflammation plays an important role in the development of rhabdomyolysis-induced AKI. This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role of macrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Methods: C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis, and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0...
September 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28831019/multiplex-quantitative-assays-indicate-a-need-for-reevaluating-reported-small-molecule-trkb-agonists
#17
Umed Boltaev, Yves Meyer, Farangis Tolibzoda, Teresa Jacques, Madalee Gassaway, Qihong Xu, Florence Wagner, Yan-Ling Zhang, Michelle Palmer, Edward Holson, Dalibor Sames
Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), have emerged as key regulators of brain plasticity and represent disease-modifying targets for several brain disorders, including Alzheimer's disease and major depressive disorder. Because of poor pharmacokinetic properties of BDNF, the interest in small-molecule TrkB agonists and modulators is high. Several compounds have been reported to act as TrkB agonists, and their increasing use in various nervous system disorder models creates the perception that these are reliable probes...
August 22, 2017: Science Signaling
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#18
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816073/overactive-bladder-treatment-application-of-methylene-blue-to-improve-the-injection-technique-of-onabotulinum-toxin-a
#19
Michał Szczypior, Wojciech Połom, Marcin Markuszewski, Krzesimir Ciura, Magdalena Buszewska-Forajta, Julia Jacyna, Michał Markuszewski, Marcin Matuszewski
OBJECTIVE: The aim of this study was to test the addition of methylene blue (MB) to onabotulinum toxin A (BTX-A) solution in overactive bladder (OAB) treatment, as a means of facilitating observation of the injection site and assessing the distribution of the drug under the bladder mucosa during injection. Pharmacological interactions between BTX-A and MB were also evaluated. MATERIALS AND METHODS: The study was conducted between December 2014 and April 2016 on 30 patients: six males and 24 females (median age 57...
August 17, 2017: Scandinavian Journal of Urology
https://www.readbyqxmd.com/read/28815872/a-multimethod-computational-simulation-approach-for-investigating-mitochondrial-dynamics-and-dysfunction-in-degenerative-aging
#20
Timothy E Hoffman, Katherine J Barnett, Lyle Wallis, William H Hanneman
Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans...
August 16, 2017: Aging Cell
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