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Clinical pharmacology

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https://www.readbyqxmd.com/read/27911116/finding-the-right-route-for-insulin-delivery-an-overview-of-implantable-pump-therapy
#1
Lia Bally, Hood Thabit, Roman Hovorka
Implantable pump therapy adopting the intraperitoneal route of insulin delivery has been available for the past three decades. The key rationale for implantable pump therapy is the restoration of the portal-peripheral insulin gradient of the normal physiology. Uptake in clinical practice is limited to specialized centers and selected patient populations. Areas covered: Implantable pump therapy is discussed, including technical aspects, rationale for its use, and glycemic and non-glycemic effects. Target populations, summaries of clinical studies and issues related to implantable pump therapy are highlighted...
December 2, 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27910963/daratumumab-monoclonal-antibody-therapy-to-treat-multiple-myeloma
#2
C Xia, M Ribeiro, S Scott, S Lonial
Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed...
October 2016: Drugs of Today
https://www.readbyqxmd.com/read/27910877/a-comprehensive-map-of-molecular-drug-targets
#3
Rita Santos, Oleg Ursu, Anna Gaulton, A Patrícia Bento, Ramesh S Donadi, Cristian G Bologa, Anneli Karlsson, Bissan Al-Lazikani, Anne Hersey, Tudor I Oprea, John P Overington
The success of mechanism-based drug discovery depends on the definition of the drug target. This definition becomes even more important as we try to link drug response to genetic variation, understand stratified clinical efficacy and safety, rationalize the differences between drugs in the same therapeutic class and predict drug utility in patient subgroups. However, drug targets are often poorly defined in the literature, both for launched drugs and for potential therapeutic agents in discovery and development...
December 2, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27910751/recent-advances-in-pharmacotherapeutic-paradigm-of-mild-to-recalcitrant-atopic-dermatitis
#4
Zahid Hussain, Shariza Sahudin, Hnin Ei Thu, Ahmad Nazrun Shuid, Syed Nasir Abbas Bukhari, Endang Kumolosasi
Atopic dermatitis (AD) is a common, chronic skin inflammatory disorder characterized by perivascular infiltration of immunoglobulin E (IgE), T lymphocytes, and mast cells. The key factors responsible for the pathophysiology of this disease are immunological disorders and defects in epidermal barrier properties. Pruritus, intense itching, psychological stress, deprived physical and mental performance, and sleep disturbance are the hallmark features of this dermatological disorder. Preventive interventions such as educational programs, avoidance of allergens, and exclusive care toward the skin could play a partial role in suppressing the symptoms...
2016: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/27910097/chronic-migraine-an-update-on-physiology-imaging-and-the-mechanism-of-action-of-two-available-pharmacologic-therapies
#5
Sheena K Aurora, Mitchell F Brin
Several lines of research support the hypothesis that migraine is a spectrum of illness, with clinical symptoms that vary along a continuum from episodic migraine to chronic migraine. Physiologic changes may result in episodic migraine evolving into chronic migraine over months to years in susceptible individuals. With chronification, headache frequency increases, becoming more disabling and less responsive to therapy. Neurophysiologic and functional imaging research has reported that chronic migraine may be associated with severity-specific metabolic, functional, and structural abnormalities in the brainstem...
December 2, 2016: Headache
https://www.readbyqxmd.com/read/27909986/toxicity-and-pharmacokinetic-profile-for-single-dose-injection-of-aby-029-a-fluorescent-anti-egfr-synthetic-affibody-molecule-for-human-use
#6
Kimberley S Samkoe, Jason R Gunn, Kayla Marra, Sally M Hull, Karen L Moodie, Joachim Feldwisch, Theresa V Strong, Daniel R Draney, P Jack Hoopes, David W Roberts, Keith Paulsen, Brian W Pogue
PURPOSE: ABY-029, a synthetic Affibody peptide, Z03115-Cys, labeled with a near-infrared fluorophore, IRDye® 800CW, targeting epidermal growth factor receptor (EGFR) has been produced under good manufacturing practices for a US Food and Drug Administration-approved first-in-use human study during surgical resection of glioma, as well as other tumors. Here, the pharmacology, phototoxicity, receptor activity, and biodistribution studies of ABY-029 were completed in rats, prior to the intended human use...
December 1, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27909508/arguments-to-apply-epinephrine-for-pocket-hematoma-reduction-the-maitre-study
#7
REVIEW
Nikolay Ilov Md, Nikolay Ilov Md, Anatoly Nechepurenko Md, Albert Abdulkadyrov, Damir Paskeev, Elena Damrina, Elena Kulikova, Marina Terent'eva, Dinara Stompel, Dmitry Tarasov Md
Pocket hematoma (PH) is a common complication of implantations of cardiac electrophysiological devices with occurring at a particularly high rate in patients on oral anticoagulation or antiplatelet treatment. Different pharmacological agents with hemostatic effect are used to avoid PH. We supposed that the vasoconstrictor effects of epinephrine may reduce bleeding extent and be effective in prevention of PH. Maitre is the first clinical trial conducted with an aim to show the safety and efficacy of epinephrine in PH prophylaxis...
June 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#8
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is major unmet medical need. Most patients have poor long-term survival and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T-cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacological activity, pharmacokinetics, and safety of a CD3 T-cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
December 1, 2016: Blood
https://www.readbyqxmd.com/read/27908822/how-admission-to-a-vascular-surgery-department-improves-medical-treatment-in-patients-with-lower-extremity-peripheral-arterial-disease
#9
M Thiney, N Della Schiava, P Feugier, P Lermusiaux, J Ninet, A Millon, A Long
OBJECTIVES: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin converting enzyme (ACE) inhibitors or Angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department...
November 28, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27908257/ginkgo-biloba-as-an-alternative-medicine-in-the-treatment-of-anxiety-in-dementia-and-other-psychiatric-disorders
#10
Sandeep Kumar Singh, George E Barreto, Gjumrakch Aliev, Valentina Echeverria
BACKGROUND: Mental disorders are the most common health problems in the worldwide population. Current medicines against these conditions have undesired side effects or limited effectiveness. These disadvantageous pharmacological and therapeutic characteristics provoke a low adherence to treatment in an important percentage of patients with mental disorders. Since ancient times, ethnically different groups have been using plants extracts as medicines for the treatment of mental conditions including dementia, depression and anxiety disorders...
December 1, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27907971/-interpretation-of-bacterial-susceptibility-resistance-to-antibiotics
#11
Milan Kolář
Bacterial resistance may be defined from a microbiological, clinical and pharmacological perspective. Microbiological resistance refers to the presence of genetic information coding for the relevant mechanism of resistance of a bacterium to a particular antibiotic. In case of clinical interpretation, breakpoints are of key importance as their role is to distinguish bacterial pathogens in which successful therapy is highly probable from isolates with a high likelihood of failure. However, it is questionable whether this approach is suitable for all patients, particularly those receiving intensive care for life-threatening infections...
September 2016: Klinická Mikrobiologie a Infekc̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27907963/optimizing-medication-outcomes-in-neurocritical-care-focus-on-clinical-pharmacology
#12
Denise H Rhoney, Kathryn Morbitzer, Jimmi Hatton-Kolpek
Drug dosing in neurocritically ill patients presents enormous challenges for clinicians due to the complex pathophysiological alterations. These alterations are dynamic both between and within patients. Unpredictable exposure from standard dosing regimens, which were extrapolated to intensive care unit patients from healthy volunteer studies, may influence medication outcomes. Knowledge of potential alterations in pharmacokinetics/pharmacodynamics in these patients could be applied to maximize the clinical response and minimize adverse effects...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27907931/-koronararterienanomalien-diagnostik-und-klassifikation-auf-basis-der-ct-und-mrt-des-herzens-von-alcapa-bis-terminationsanomaliecoronary-artery-anomalies-diagnosis-and-classification-based-on-cardiac-ct-and-mri-cmr-from-alcapa-to-anomalies-of-termination
#13
Philipp Heermann, Walter Heindel, Christoph Schülke
Background Coronary artery anomalies encompass a clinically and anatomically variable spectrum including physiological variants and pathophysiologically relevant anomalies. The majority of the variants has no hemodynamic relevance and is often detected accidentally. The recognition of the rare and relevant anomalies that cause either relevant shunt volumes leading to myocardial ischemia or ventricular tachyarrhythmias with the risk of sudden cardiac death is of major importance. Methods This review is based on a literature search in PubMed conducted using the key words "coronary artery" and/or "anomaly" and/or "anomalous origin" and/or "myocardial bridging" and/or "coronary artery fistula" and/or "Bland-White-Garland" and/or "ALCAPA"...
December 1, 2016: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
https://www.readbyqxmd.com/read/27907000/whole-body-vibration-treatments-in-postmenopausal-women-can-improve-bone-mineral-density-results-of-a-stimulus-focussed-meta-analysis
#14
Antonio Fratini, Tecla Bonci, Anthony M J Bull
Whole body vibration treatment is a non-pharmacological intervention intended to stimulate muscular response and increase bone mineral density, particularly for postmenopausal women. The literature related to this topic is controversial, heterogeneous, and unclear despite the prospect of a major clinical effect.The aim of this study was to identify and systematically review the literature to assess the effect of whole body vibration treatments on bone mineral density (BMD) in postmenopausal women with a specific focus on the experimental factors that influence the stimulus...
2016: PloS One
https://www.readbyqxmd.com/read/27906863/bartter-s-and-gitelman-s-syndrome
#15
Hannsjörg W Seyberth, Stefanie Weber, Martin Kömhoff
PURPOSE OF REVIEW: The clinical presentations of Bartter's syndrome and Gitelman's syndrome will be reviewed including two most recently described hypokalemic salt-losing tubulopathies. By taking the quite heterogeneous presentations and the apparently different pathophysiologies as the basis, the applicability of the physiologic classification has been tested. RECENT FINDINGS: According to the physiologic approach, salt-losing tubulopathies can be divided into two major groups (with completely different tubular defects): first, disorders of the thick ascending limb of Henle's loop (loop disorders); second, disorders of the distal convolute tubule (DCT disorders)...
November 30, 2016: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/27906778/the-role-of-prostatic-inflammation-in-the-development-and-progression-of-benign-and-malignant-diseases
#16
Giorgio Gandaglia, Emanuele Zaffuto, Nicola Fossati, Vito Cucchiara, Vincenzo Mirone, Francesco Montorsi, Alberto Briganti
PURPOSE OF REVIEW: To evaluate the role of prostatic inflammation in the development and progression of benign and malignant prostatic diseases. RECENT FINDINGS: Preclinical studies demonstrate that the activation of a chronic inflammatory prostatic response plays an important role in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Approximately 40-70% of patients with BPH-related lower urinary tract symptoms harbour chronic inflammation at pathologic evaluation...
November 30, 2016: Current Opinion in Urology
https://www.readbyqxmd.com/read/27906464/methodological-considerations-for-optimizing-and-validating-behavioral-assays
#17
Stacey J Sukoff Rizzo, Jill L Silverman
Preclinical animal models are indispensable tools for translational research for which behavioral characterization and phenotyping are essential to testing hypotheses and for evaluating the potential of novel therapeutic agents to treat diseases. The methods employed for comprehensive behavioral phenotyping and pharmacological experiments are complex and should be conducted exclusively by trained technicians with demonstrated proficiency. The ultimate goal is to identify disease-relevant and translational behavioral endpoints that are robust, reliable, and reproducible, and that can be employed to evaluate potential of novel therapeutic agents to treat disease...
December 1, 2016: Current Protocols in Mouse Biology
https://www.readbyqxmd.com/read/27906452/primary-prophylaxis-for-venous-thromboembolism-in-ambulatory-cancer-patients-receiving-chemotherapy
#18
REVIEW
Marcello Di Nisio, Ettore Porreca, Matteo Candeloro, Michele De Tursi, Ilaria Russi, Anne Ws Rutjes
BACKGROUND: Venous thromboembolism (VTE) often complicates the clinical course of cancer. The risk is further increased by chemotherapy, but the trade-off between safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain. This is the second update of a review first published in February 2012. OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis for VTE in ambulatory cancer patients receiving chemotherapy compared with placebo or no thromboprophylaxis...
December 1, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27906188/large-scale-pharmacological-profiling-of-3d-tumor-models-of-cancer-cells
#19
Lesley A Mathews Griner, Xiaohu Zhang, Rajarshi Guha, Crystal McKnight, Ian S Goldlust, Madhu Lal-Nag, Kelli Wilson, Sam Michael, Steve Titus, Paul Shinn, Craig J Thomas, Marc Ferrer
The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#20
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
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