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Clinical pharmacology

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https://www.readbyqxmd.com/read/28215029/an-introduction-to-the-pathophysiology-of-aneurysmal-subarachnoid-hemorrhage
#1
REVIEW
Jasper H van Lieshout, Maxine Dibué-Adjei, Jan F Cornelius, Philipp J Slotty, Toni Schneider, Tanja Restin, Hieronymus D Boogaarts, Hans-Jakob Steiger, Athanasios K Petridis, Marcel A Kamp
Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH...
February 18, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28215027/economic-burden-of-patients-affected-by-non-small-cell-lung-cancer-nsclc-the-life-study
#2
Maria Rita Migliorino, Antonio Santo, Giampiero Romano, Diego Cortinovis, Domenico Galetta, Oscar Alabiso, Giacomo Cartenì, Sabrina Vari, Gianpiero Fasola, Antonio Pazzola, Dario Giuffrida, Alberto Zaniboni, Alberto Caprioli, Flavia Longo, Valentina Acciai, Filippo de Marinis
PURPOSE: Non-small cell lung cancer (NSCLC) is a condition with significant clinical burden for patients and relevant economic impact. Limited evidence exists on the management costs of NSCLC patients, especially in the late phases of the disease. The main objective of this analysis was to evaluate the economic impact of clinical management of NSCLC patients in the Italian population. METHODS: This evaluation was an economic analysis of the observational and multicentre study LIFE, which described the therapeutic approach in routine clinical practice for NSCLC patients, progressing after first-line treatment...
February 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#3
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#4
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28214841/drug-dosing-and-estimated-renal-function-any-step-forward-from-effersoe
#5
Mads Hornum, Bo Feldt-Rasmussen
Drug dosing in accordance with the renal function is a long-standing challenge to clinicians. For many years it has been evident that in many clinical situations there is no easy way to correctly dose any drug that is mainly cleared by the kidneys. Despite the development of many formulas for estimating the glomerular filtration rate, they all have serious shortcomings. Much effort has been put in to develop estimation formulas to evaluate the renal function as an alternative to direct methods with the aim of safely dosing drugs that are mainly cleared by the kidneys...
February 18, 2017: Nephron
https://www.readbyqxmd.com/read/28214078/the-optimize-heart-failure-care-program-initial-lessons-from-global-implementation
#6
Martin R Cowie, Yuri M Lopatin, Clara Saldarriaga, Cândida Fonseca, David Sim, Jose Antonio Magaña, Denilson Albuquerque, Marcelo Trivi, Gustavo Moncada, Baldomero A González Castillo, Mario Osvaldo Speranza Sánchez, Edward Chung
Hospitalization for heart failure (HF) places a major burden on healthcare services worldwide, and is a strong predictor of increased mortality especially in the first three months after discharge. Though undesirable, hospitalization is an opportunity to optimize HF therapy and advise clinicians and patients about the importance of continued adherence to HF medication and regular monitoring. The Optimize Heart Failure Care Program (www.optimize-hf.com), which has been implemented in 45 countries, is designed to improve outcomes following HF hospitalization through inexpensive initiatives to improve prescription of appropriate drug therapies, patient education and engagement, and post-discharge planning...
February 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28214075/asymmetric-total-synthesis-of-tetrahydroprotoberberine-derivatives-and-evaluation-of-their-binding-affinities-at-dopamine-receptors
#7
David Y W Lee, Jing Liu, Shuzhen Zhang, Peng Huang, Lee-Yuan Liu-Chen
Cocaine addiction remains a serious challenge for clinical and medical research because there is no effective pharmacological treatment. l-THP, a natural product isolated from Corydalis yanhusuo W.T. Wang, is one of the most frequently used traditional herbs to treat drug addiction in China. Our laboratory first reported that its demethylated metabolites l-ICP, l-CD, and l-CP had high affinity at dopamine D1, D2, and D5 receptors. Here we report the chemical synthesis of these metabolites and other derivatives and their binding affinities at dopamine receptors...
January 31, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28213937/targeting-phosphodiesterase-5-as-a-therapeutic-option-against-myocardial-ischemia-reperfusion-injury-and-in-treating-heart-failure
#8
REVIEW
Sevil Korkmaz-Icöz, Tamás Radovits, Gábor Szabó
Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cyclic 3´-5´guanosine monophosphate (cGMP) into 5'-GMP, thereby regulating its intracellular concentrations. Dysregulation of the cGMP-dependent pathway plays a significant role in various cardiovascular diseases. Therefore, its modulation by drugs, such as PDE5 inhibitors, may represent an effective therapeutic approach. There are currently four PDE5 inhibitors available for the treatment of erectile dysfunction: sildenafil, vardenafil, tadalafil, and avanafil...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213805/an-overview-of-autism-spectrum-disorder-heterogeneity-and-treatment-options
#9
REVIEW
Anne Masi, Marilena M DeMayo, Nicholas Glozier, Adam J Guastella
Since the documented observations of Kanner in 1943, there has been great debate about the diagnoses, the sub-types, and the diagnostic threshold that relates to what is now known as autism spectrum disorder (ASD). Reflecting this complicated history, there has been continual refinement from DSM-III with 'Infantile Autism' to the current DSM-V diagnosis. The disorder is now widely accepted as a complex, pervasive, heterogeneous condition with multiple etiologies, sub-types, and developmental trajectories. Diagnosis remains based on observation of atypical behaviors, with criteria of persistent deficits in social communication and restricted and repetitive patterns of behavior...
February 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28213480/a-common-genetic-variant-risk-score-is-associated-with-drug-induced-qt-prolongation-and-torsade-de-pointes-risk-a-pilot-study
#10
David G Strauss, Jose Vicente, Lars Johannesen, Ksenia Blinova, Jay W Mason, Peter Weeke, Elijah R Behr, Dan M Roden, Raymond Woosley, Gulum Kosova, Michael A Rosenberg, Christopher Newton-Cheh
Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs...
February 17, 2017: Circulation
https://www.readbyqxmd.com/read/28213190/n-acetylcysteine-for-treating-cocaine-addiction-a-systematic-review
#11
REVIEW
Marco Antonio Nocito Echevarria, Tassio Andrade Reis, Giulianno Ruffo Capatti, Victor Siciliano Soares, Dartiu Xavier da Silveira, Thiago Marques Fidalgo
The aim of this paper is to extensively review the current literature available on N-acetylcysteine (NAC) treatment for cocaine dependence (clinical and experimental studies). We screened all articles published before February 2016 reporting on the use of NAC as a pharmacological intervention for cocaine dependence or discussed its potential as a therapeutic approach for cocaine dependence. We described our results qualitatively. 21 studies matched our search criteria: 6 clinical trials and 15 animal studies...
February 11, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28212889/inhibition-of-proliferation-and-invasion-in-2d-and-3d-models-by-2-methoxyestradiol-in-human-melanoma-cells
#12
R R Massaro, F Faião-Flores, V W Rebecca, S Sandri, D K Alves-Fernandes, P C Pennacchi, K S M Smalley, S S Maria-Engler
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and CyclinB1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assays, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors...
February 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28212592/novel-insights-into-gonadotropin-releasing-hormone-action-in-the-pituitary-gonadotrope
#13
Jessica L Brown, Mark Roberson
The hypothalamic-pituitary-gonadal axis controls reproduction via a series of hormones regulating gonadal function through interconnected feedback loops. Secretion of hypothalamic-derived gonadotropin-releasing hormone (GnRH) integrates inputs from higher brain centers to coordinate the activity of the pituitary gonadotrope and the biosynthesis and secretion of the gonadotropins which ultimately regulate gonadal function. Failure of GnRH to serve as the central integrator of this system has been associated with hypogonadotropic-hypogonadism and clinical infertility, while pharmacological application of GnRH analogs and gonadotropins have important implications of the treatment of such infertility...
February 17, 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28212580/network-pharmacology-based-and-clinically-relevant-prediction-of-the-active-ingredients-and-potential-targets-of-chinese-herbs-in-metastatic-breast-cancer-patients
#14
Yu Mao, Jian Hao, Zi-Qi Jin, Yang-Yang Niu, Xue Yang, Dan Liu, Rui Cao, Xiong-Zhi Wu
Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#15
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#16
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210939/deep-phenotyping-of-systemic-arterial-hemodynamics-in-hfpef-part-1-physiologic-and-technical-considerations
#17
REVIEW
Julio A Chirinos
A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population...
February 16, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28210904/acute-and-neuropathic-orofacial-antinociceptive-effect-of-eucalyptol
#18
José de Maria de Albuquerque de Melo Júnior, Marina de Barros Mamede Vidal Damasceno, Sacha Aubrey Alves Rodrigues Santos, Talita Matias Barbosa, João Ronielly Campêlo Araújo, Antonio Eufrásio Vieira-Neto, Deysi Viviana Tenazoa Wong, Roberto César Pereira Lima-Júnior, Adriana Rolim Campos
Terpenes have a wide range of pharmacological properties, including antinociceptive action. The anti-inflammatory and antinociceptive effects of eucalyptol are well established. The purpose of this study was to evaluate the antinociceptive effect of eucalyptol on acute and neuropathic orofacial pain in rodent models. Acute orofacial and corneal nociception was induced with formalin, capsaicin, glutamate and hypertonic saline in mice. In another series, animals were pretreated with capsazepine or ruthenium red to evaluate the involvement of TRPV1 receptors in the effect of eucalyptol...
February 16, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28210513/seizure-following-the-use-of-the-cox-2-inhibitor-etoricoxib
#19
Valentina Arnao, Marianna Riolo, Brigida Fierro, Paolo Aridon
We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/28210454/managing-patients-taking-edoxaban-in-dentistry
#20
REVIEW
Adrian Curto, Daniel Curto, Jorge Sanchez
BACKGROUND: Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life...
February 2017: Journal of Clinical and Experimental Dentistry
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