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Clinic pharmacology

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https://www.readbyqxmd.com/read/28346882/determination-of-prodrug-treosulfan-and-its-biologically-active-monoepoxide-in-rat-plasma-liver-lungs-kidneys-muscle-and-brain-by-hplc-esi-ms-ms-method
#1
Michał Romański, Anna Kasprzyk, Artur Teżyk, Agnieszka Widerowska, Czesław Żaba, Franciszek Główka
A prodrug treosulfan (TREO) is currently investigated in clinical trials for conditioning prior to hematopoietic stem cell transplantation. Bioanalysis of TREO and its active derivatives, monoepoxide (S,S-EBDM) and diepoxide, in plasma and urine underlay the pharmacokinetic studies of these compounds but cannot explain an organ pharmacological action or toxicity. Recently, distribution of TREO and S,S-EBDM into brain, cerebrospinal fluid, and aqueous humor of the eye has been investigated in animal models and the obtained results presented clinical relevance...
March 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#2
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346121/can-memories-of-traumatic-experiences-or-addiction-be-erased-or-modified-a-critical-review-of-research-on-the-disruption-of-memory-reconsolidation-and-its-applications
#3
Michael Treanor, Lily A Brown, Jesse Rissman, Michelle G Craske
Recent research suggests that the mere act of retrieving a memory can temporarily make that memory vulnerable to disruption. This process of "reconsolidation" will typically restabilize the neural representation of the memory and foster its long-term storage. However, the process of reconsolidating the memory takes time to complete, and during this limited time window, the original memory may be modified either by the presentation of new information or with pharmacological agents. Such findings have prompted rising interest in using disruption during reconsolidation as a clinical intervention for anxiety, posttraumatic stress, and substance use disorders...
March 2017: Perspectives on Psychological Science: a Journal of the Association for Psychological Science
https://www.readbyqxmd.com/read/28345745/in-vitro-and-in-vivo-assessment-of-the-abuse-potential-of-pf614-a-novel-bio-md%C3%A2-prodrug-of-oxycodone
#4
D Lynn Kirkpatrick, William K Schmidt, Ricardo Morales, John Cremin, Julie Seroogy, Craig Husfeld, Thomas Jenkins
OBJECTIVE: The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential...
January 2017: Journal of Opioid Management
https://www.readbyqxmd.com/read/28345483/spinal-epidural-stimulation-strategies
#5
Prithvi K Shah, Igor Lavrov
Significant advancements in spinal epidural stimulation (ES) strategies to enable volitional motor control in persons with a complete spinal cord injury (SCI) have generated much excitement in the field of neurorehabilitation. Still, an obvious gap lies in the ability of ES to effectively generate a robust locomotor stepping response after a complete SCI in rodents, but not in humans. In order to reveal potential discrepancies between rodent and human studies that account for this void, in this review, we summarize the findings of studies that have utilized ES strategies to enable successful hindlimb stepping in spinal rats...
March 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/28345369/pulmonary-fibrosis-part-ii-state-of-the-art-patient-management
#6
Keith C Meyer
While many pharmacologic therapies for the treatment of idiopathic pulmonary fibrosis (IPF) have been evaluated via randomized, placebo-controlled clinical trials (RCTs) conducted over the past two decades, most therapies have been shown to be ineffective or even potentially harmful. However, a number of recently completed RCTs have shown significant efficacy for pirfenidone and nintedanib for the treatment of IPF. Areas Covered: This manuscript reviews recent advances in the management of IPF and other forms of fibrosing interstitial lung disease (ILD) with an emphasis on IPF...
March 26, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28345333/assessment-of-anxiety-and-depression-status-in-turkish-cutaneous-melanoma-patients
#7
Faruk Tas, Senem Karabulut, Hulya Guveli, Sidika Kurul, Kayhan Erturk, Murat Guveli, Hasibe Kinik
Background: Even though anxiety and depression are two mood disorders encountered commonly in cancer patients only few trials have been carried out so far in melanoma patients. The aim of the study was to determine the clinical prevalence of these disorders in Turkish cutaneous melanoma patients and to clarify possible clinicopathological factors influencing them. Material and methods: A total of 100 consecutive outpatient melanoma patients were enrolled and asked to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire immediately after scheduled visits...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28345177/pharmacogenomics-of-off-target-adrs
#8
REVIEW
Sarah L Garon, Rebecca K Pavlos, Katie D White, Nancy J Brown, Cosby A Stone, Elizabeth J Phillips
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention...
March 26, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28344466/an-overview-of-pharmacodynamic-modelling-ligand-binding-approach-and-its-application-in-clinical-practice
#9
REVIEW
Mohammed Saji Salahudeen, Prasad S Nishtala
The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344125/capadenoson-a-clinically-trialed-partial-adenosine-a1-receptor-agonist-can-stimulate-adenosine-a2b-receptor-biased-agonism
#10
Jo-Anne Baltos, Elizabeth A Vecchio, Matthew A Harris, Cheng Xue Qin, Rebecca H Ritchie, Arthur Christopoulos, Paul J White, Lauren T May
The adenosine A2B receptor (A2BAR) has been identified as an important therapeutic target in cardiovascular disease, however in vitro and in vivo targeting has been limited by the paucity of pharmacological tools, particularly potent agonists. Interestingly, 2-((6-amino-3,5-dicyano-4-(4-(cyclopropylmethoxy)phenyl)-2-pyridinyl)thio)acetamide (BAY60-6583), a potent and subtype-selective A2BAR agonist, has the same core structure as 2-amino-6-[[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methylsulfanyl]-4-[4-(2-hydroxyethoxy)phenyl]pyridine-3,5-dicarbonitril (capadenoson)...
March 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#11
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
March 23, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28344031/culture-bound-syndromes-of-a-brazilian-amazon-riverine-population-tentative-correspondence-between-traditional-and-western-medicine-terms-and-possible-ethnopharmacological-implications
#12
E Pagani, J de F L Santos, E Rodrigues
ETHNOPHARMACOLOGICAL RELEVANCE: It is not always possible to correlate the "emic" terms to the "etic" ones during ethnopharmacological surveys, especially regarding those related to Culture-Bound Syndromes (CBS). Nevertheless, it is the role of ethnopharmacology to address these correlations, since they are the basis for the understanding of potential bioactives. AIM AND OBJECTIVES: This study reports the clinical manifestations and therapeutic resources used for the treatment of CBS among some riverine inhabitants of Brazilian Amazonia...
March 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28344029/herbasl-remedies-for-urinary-stones-used-in-india-and-china-a-review
#13
REVIEW
Deepak M Kasote, Suresh D Jagtap, Dinesh Thapa, Mahendra S Khyade, Wendy R Russell
ETHANOPHARMACOLOGICAL RELEVANCE: The process of formation or appearance of a urinary stone anywhere in the renal tract is known as urolithiasis. It is a longstanding health problem, known to exist since early age of civilization. Records about symptoms, signs and treatment strategies of urinary stones diseases are found in the several ancient texts of traditional medicines such as Ayurveda, Traditional Chinese Medicine (TCM), Siddha and Unani. In Ayurveda, urolithiasis has been considered as one of the eight most troublesome diseases...
March 23, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28343425/ppar-%C3%AE-agonists-are-still-on-the-rise-an-update-on-clinical-and-experimental-findings
#14
Nicola Ferri, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica
Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e...
March 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28343073/breviscapine-confers-a-neuroprotective-efficacy-against-transient-focal-cerebral-ischemia-by-attenuating-neuronal-and-astrocytic-autophagy-in-the-penumbra
#15
Zhang Pengyue, Guo Tao, He Hongyun, Yang Liqiang, Deng Yihao
Breviscapine is a flavonoid derived from a traditional Chinese herb Erigerin breviscapus (Vant.) Hand-Mazz, and has been extensively used in clinical treatment for cerebral stroke in China, but the underlying pharmacological mechanisms are still unclear. In present study, we investigated whether breviscapine could confer a neuroprotection against cerebral ischemia injury by targeting autophagy mechanisms. A cerebral stroke model in Sprague-Dawley rats was prepared by middle cerebral artery occlusion (MCAO), rats were then randomly divided into 5 groups: MCAO+Bre group, rats were treated with breviscapine; MCAO+Tat-Beclin-1 group, animals were administrated with specific autophagy inducer Tat-Beclin-1; MCAO+Bre+Tat-Beclin-1 group, rats were treated with both breviscapine and Tat-Beclin-1, MCAO+saline group, rats received the same volume of physiological saline, and Sham surgery group...
March 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28342943/would-i-take-antipsychotics-if-i-had-psychotic-symptoms-examining-determinants-of-the-decision-to-take-antipsychotics
#16
Fabrice Berna, Anja S Göritz, Pierre-Michel Llorca, Pierre Vidailhet, Guillaume Fond, Steffen Moritz
Poor adherence to treatment in schizophrenia is mainly associated to patients-related factors. However, social negative representations of schizophrenia and its treatment may also contribute to patients' decision to take or not to take antipsychotics. A web-based study on 1807 participants was conducted during which participants imagined that they had a particular chronic illness based on clinical vignettes (mental illnesses: schizophrenia, depression; somatic illnesses: multiple sclerosis, rheumatoid arthritis)...
March 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28342907/active-placebo-control-groups-of-pharmacological-interventions-were-rarely-used-but-merited-serious-consideration-a-methodological-overview
#17
Jakob Solgaard Jensen, Andreas Ørsted Bielefeldt, Asbjørn Hróbjartsson
OBJECTIVES: Active placebos are control interventions that mimic the side-effects of the experimental interventions in randomised trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomised clinical drug trials implement active placebo control groups; to provide a catalogue, and a characterisation, of such trials; and to analyse methodological arguments for and against use of active placebo. STUDY DESIGN: An overview consisting of three thematically linked sub-studies...
March 22, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28342891/cost-utility-of-group-acceptance-and-commitment-therapy-for-fibromyalgia-versus-recommended-drugs-an-economic-analysis-alongside-a-6-month-randomised-controlled-trial-conducted-in-spain-effigact-study
#18
Juan V Luciano, Francesco D'Amico, Albert Feliu-Soler, Lance M McCracken, Jaume Aguado, María T Peñarrubia-María, Martin Knapp, Antoni Serrano-Blanco, Javier García-Campayo
The aim of this study was to analyse the cost-utility of a group-based form of Acceptance and Commitment Therapy (GACT) in patients with fibromyalgia (FM) compared to patients receiving recommended pharmacological treatment (RPT) or on a waiting list (WL). The data were derived from a previously published study, an RCT that focused on clinical outcomes. Health economic outcomes included health-related quality of life and healthcare use at baseline and at 6-month follow-up using the EuroQol (EQ-5D-3L) and the Client Service Receipt Inventory (CSRI), respectively...
March 22, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28342292/ultra-fast-liquid-chromatography-with-tandem-mass-spectrometry-determination-of-eight-bioactive-components-of-kai-xin-san-in-rat-plasma-and-its-application-to-a-comparative-pharmacokinetic-study-in-normal-and-alzheimer-s-disease-rats
#19
Xiaotong Wang, Yue Zhang, Huibin Niu, Yajing Geng, Bing Wang, Xiaomei Yang, Pengyu Yan, Qing Li, Kaishun Bi
A method of ultra-fast liquid chromatography with tandem mass spectrometry was developed and validated for the simultaneous quantitation of eight bioactive components, including polygalaxanthone III, sibiricaxanthone B, tenuifolin, sibiricose A5, sibiricose A6, tenuifoliside A, ginsenoside Re and ginsenoside Rb1 in rat plasma after oral administration of Kai-Xin-San. The plasma samples were extracted by liquid-liquid extraction using digoxin as internal standard. Chromatographic separation was performed on a Venusil MP C18 column (100 mm × 2...
March 25, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28342064/hdl-cholesterol-reappraisal-of-its-clinical-relevance
#20
REVIEW
Winfried März, Marcus E Kleber, Hubert Scharnagl, Timotheus Speer, Stephen Zewinger, Andreas Ritsch, Klaus G Parhofer, Arnold von Eckardstein, Ulf Landmesser, Ulrich Laufs
BACKGROUND: While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted...
March 24, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
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