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https://www.readbyqxmd.com/read/28442899/approaches-to-drug-therapy-for-copd-in-russia-a-proposed-therapeutic-algorithm
#1
Kirill A Zykov, Svetlana I Ovcharenko
Until recently, there have been few clinical algorithms for the management of patients with COPD. Current evidence-based clinical management guidelines can appear to be complex, and they lack clear step-by-step instructions. For these reasons, we chose to create a simple and practical clinical algorithm for the management of patients with COPD, which would be applicable to real-world clinical practice, and which was based on clinical symptoms and spirometric parameters that would take into account the pathophysiological heterogeneity of COPD...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28441276/augs-consensus-statement-association-of-anticholinergic-medication-use-and-cognition-in-women-with-overactive-bladder
#2
(no author information available yet)
Overactive bladder affects a significant portion of the overall population and has substantial impact on daily activities and quality-of-life. When considering treatment, behavioral therapies should be instituted first, followed by medical therapies. Anticholinergic medications and beta-3 agonists are often used as initial pharmacologic therapy, but caution should be taken in prescribing anticholinergic medications in frail or cognitively impaired patients. Recently, concerns have developed regarding anticholinergic medications and the associated risk of cognitive impairment, dementia, and Alzheimer disease in the general population...
May 2017: Female Pelvic Medicine & Reconstructive Surgery
https://www.readbyqxmd.com/read/28438778/the-dual-amylin-and-calcitonin-receptor-agonist-kbp-042-works-as-adjunct-to-metformin-on-fasting-hyperglycaemia-and-hba1c-in-a-rat-model-of-type-2-diabetes
#3
Sara Toftegaard Hjuler, Sofie Gydesen, Kim Vietz Andreassen, Morten Asser Karsdal, Kim Henriksen
KBP-042 is a dual amylin and calcitonin receptor agonist which increases glucose tolerance and insulin action, and reduces body weight in rat models of obesity and pre-diabetes. The objective of the present study was to 1) Evaluate KBP-042 as a treatment of late stage type 2 diabetes in a rat model and 2) Assess the value of adding KBP-042 to the standard of care, metformin, in order to consider KBP-042 as a relevant drug for treating patients with type 2 diabetes. Two studies were included: an intervention and a prevention study...
April 24, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28437032/autonomic-receptor-mediated-regulation-of-production-and-release-of-nitric-oxide-in-normal-and-malignant-human-urothelial-cells
#4
Michael Winder, Renata Vesela, Patrik Aronsson, Bhavik Patel, Thomas Carlsson
In the urinary bladder, the main source of NO seems to be the urothelium and the underlying suburothelium. In this study, we aimed to characterize how receptors in the human urothelium regulate the production and release of NO. For this, we cultured two human urothelial cell lines - the normal immortalized cell line UROtsa and the malignant cell line T24. These were treated with an array of agonists and antagonists with affinity for adrenergic, muscarinic and purinergic receptors. The production of NO and expression of nitric oxide synthase (NOS) was studied by immunocytochemistry and western blotting...
April 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28434969/translational-science-approach-for-assessment-of-cardiovascular-effects-and-proarrhythmogenic-potential-of-the-beta-3-adrenergic-agonist-mirabegron
#5
Cees Korstanje, Masanori Suzuki, Koichiro Yuno, Shuichi Sato, Masashi Ukai, Marlowe J Schneidkraut, Gan X Yan
INTRODUCTION: Translational assessment of cardiac safety parameters is a challenge in clinical development of beta-3 adrenoceptor agonists. The preclinical tools are presented that were used for assessing human safety for mirabegron. METHODS: Studies were performed on electrical conductance at ion channels responsible for cardiac repolarization (IKr, IKs, Ito, INa, and ICa,L), on QT-interval, subendocardial APD90, Tpeak-end interval, and arrhythmia's in ventricular dog wedge tissue in vitro and on cardiovascular function (BP, HR, and QTc) in conscious dogs...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28432748/future-challenges-and-therapeutic-opportunities-in-type-2-diabetes-changing-the-paradigm-of-current-therapy
#6
REVIEW
D R Owens, L Monnier, A H Barnett
Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen ('treat to failure'). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti-diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431781/clenbuterol-hydrochloride
#7
Abdulrahman A Al-Majed, Nasr Y Khalil, Ibraheem Khbrani, Hatem A Abdel-Aziz
Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28426939/high-throughput-agonist-shift-assay-development-for-the-analysis-of-m1-positive-allosteric-modulators
#8
Michelle F Homsher, Douglas C Beshore, Jason Cassaday, Brian Squadroni, Elizabeth Mohammed, Michelle Hartnett, Stephen Day, Lei Ma, David Pechter, Michelle D Smith, Fredrick Monsma, Paul Zuck, Michael F Finley, Victor N Uebele, Jeffrey D Hermes
Agonist shift assays feature cross-titrations of allosteric modulators and orthosteric ligands. Information generated in agonist shift assays can include a modulator's effect on the orthosteric agonist's potency (alpha) and efficacy (beta), as well as direct agonist activity of the allosteric ligand (tauB) and the intrinsic binding affinity of the modulator to the unoccupied receptor (KB). Because of the heavy resource demand and complex data handling, these allosteric parameters are determined infrequently during the course of a drug discovery program and on a relatively small subset of compounds...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28415051/cross-interference-of-two-model-peroxisome-proliferators-in-peroxisomal-and-estrogenic-pathways-in-brown-trout-hepatocytes
#9
Tânia Vieira Madureira, Ivone Pinheiro, Fernanda Malhão, Célia Lopes, Ralph Urbatzka, L Filipe C Castro, Eduardo Rocha
Peroxisome proliferators cause species-specific effects, which seem to be primarily transduced by peroxisome proliferator-activated receptor alpha (PPARα). Interestingly, PPARα has a close interrelationship with estrogenic signaling, and this latter has already been promptly activated in brown trout primary hepatocytes. Thus, and further exploring this model, we assess here the reactivity of two PPARα agonists in direct peroxisomal routes and, in parallel the cross-interferences in estrogen receptor (ER) mediated paths...
April 6, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28411128/the-effects-of-experimental-gestational-hypertension-on-maternal-blood-pressure-and-fluid-intake-and-pre-weanling-hypothalamic-neuronal-activity
#10
Juan Arguelles, Carmen Perillan, Terry G Beltz, Baojian Xue, Daniel Badaue-Passos, Jose A Vega, Alan Kim Johnson
To examine the fetal programming effects of maternal hypertension, natriophilia and hyperreninemia [experimentally induced in rats by partial inter-renal aortic ligature (PAL) prior to mating] fos immunoreactivity was studied in 6-day-old offspring of PAL and control mothers. The purposes of the present set of experiments were twofold. The first was to characterize the effects of PAL on the mother's arterial blood pressure and intake of salt (1.8% NaCl solution) and water over the course of gestation. Second, was to study the pattern of neuronal activation in key brain areas of 6-day-old offspring treated with the dipsogen isoproterenol that were from PAL and control mothers...
April 11, 2017: Appetite
https://www.readbyqxmd.com/read/28410944/-asthma-control-in-patients-attending-primary-care-in-spain-actis-study
#11
Eduardo Calvo, Juan A Trigueros, Araceli López, Guadalupe Sánchez
OBJECTIVE: To assess prevalence of non controlled (ACT- Asthma Control Test<20) asthma in real world clinical practice in Spain. DESIGN: Observational, cross-sectional study. LOCATION: 58 primary care centers from 13 Autonomous Communities. PARTICIPANTS: Asthma patients attending physicians office to collect repeat prescriptions for continuous treatment (Group A), or due to symptoms worsening (Group B). MAIN MEASUREMENTS: Socio-demographic characteristics (age, gender, education, smoking history), physician's assessment of asthma severity, current treatment for asthma, co-morbidities, healthcare-related resources utilization (primary care or emergency visits, hospitalizations), labour or school absenteeism, ACT score and treatment adherence...
April 12, 2017: Atencion Primaria
https://www.readbyqxmd.com/read/28410560/role-of-long-acting-muscarinic-antagonist-long-acting-%C3%AE-2-agonist-therapy-in-chronic-obstructive-pulmonary-disease
#12
Sarah E Petite
OBJECTIVE: To compare the available literature regarding the use of long-acting muscarinic antagonist (LAMA)/long-acting β2 agonists (LABA) and inhaled corticosteroid (ICS)/LABA combination inhaler therapy in chronic obstructive pulmonary disease (COPD) maintenance therapy management. DATA SOURCES: A MEDLINE literature search from database inception to February 2017 was conducted using the search terms chronic obstructive pulmonary disease, adrenergic beta-agonist, muscarinic antagonist, and inhaled corticosteroid...
April 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28404638/kidney-triglyceride-accumulation-in-the-fasted-mouse-is-dependent-upon-serum-free-fatty-acids
#13
Diego Scerbo, Ni-Huiping Son, Alaa Sirwi, Lixia Zeng, Kelli M Sas, Vincenza Cifarelli, Gabriele Schoiswohl, Lesley-Ann Huggins, Namrata Gumaste, Yunying Hu, Subramaniam Pennathur, Nada A Abumrad, Erin E Kershaw, M Mahmood Hussain, Katalin Susztak, Ira J Goldberg
Lipid accumulation is a pathological feature of every type of kidney injury. Despite this striking histological feature, physiological accumulation of lipids in the kidney is poorly understood. We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or non-esterified fatty acids (NEFAs). With overnight fasting, kidneys accumulated triglyceride but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28398147/salmeterol-a-long-acting-%C3%AE-2-aderenergic-receptor-agonist-inhibits-macrophage-activation-by-lipopolysaccharide-from-porphyromonas-gingivalis
#14
Monika Sharma, Lindsay Patterson, Elisha Chapman, Patrick M Flood
BACKGROUND: Salmeterol is a long-acting beta-2 adrenergic receptor (β2AR) agonist that is used to treat chronic obstructive pulmonary disease (COPD). Previously we had shown that pre-incubation of primary microglial enriched cells with Salmeterol could inhibit the inflammatory response induced by E. Coli LPS, a TLR-4 (toll-like receptor-4) agonist. In this study, we sought to determine if Salmeterol had a similar inhibitory effect on the inflammatory response of the murine macrophage cell line RAW264...
March 3, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28397719/toll-like-receptor-4-signaling-pathway-in-the-protective-effect-of-pioglitazone-on-experimental-immunoglobulin-a-nephropathy
#15
Jia-Nan Zou, Jing Xiao, Sha-Sha Hu, Chen-Sheng Fu, Xiao-Li Zhang, Zhen-Xing Zhang, Yi-Jun Lu, Wei-Jun Chen, Zhi-Bin Ye
BACKGROUND: In vitro experiments have revealed that toll-like receptor 4 (TLR4) pathway is involved in the progression of immunoglobulin A nephropathy (IgAN) by induction of proinflammatory cytokines. Evidence showed that, in other disease models, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been shown to exert anti-inflammatory effects through suppression of the expression and activity of TLR4. However, the interaction between PPAR-γ and TLR4 in IgAN has not been fully studied both in vitro and in vivo...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28396116/beta-2-adrenergic-receptor-agonists-are-novel-regulators-of-macrophage-activation-in-diabetic-renal-and-cardiovascular-complications
#16
Hyunjin Noh, Mi Ra Yu, Hyun Joo Kim, Ji Hye Lee, Byoung-Won Park, I-Hsien Wu, Motonobu Matsumoto, George L King
Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (β2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-α production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, β2AR agonists inhibited diabetes-induced tumor necrosis factor-α production, which was prevented by co-treatment with a selective β2AR blocker...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28383836/-study-of-the-month-flame-study-in-chronic-obstructive-pulmonary-disease
#17
REVIEW
J-L Corhay
The place of combinations of bronchodilators (longacting beta-agonist / muscarinic agonist or LABA / LAMA) in the prevention of the exacerbations of the chronic obstructive pulmonary disease (COPD) is not still clearly established, and need a comparison with combination of LABA/ inhaled steroids. FLAME was a randomized non-inferiority phase 3 study comparing indacaterol/glycopyrronium 110/50 μg (IND/GLY) once daily with salmeterol/proprionate of fluticasone 50/500 μg (SAL/FC) twice daily. The primary objective of the study was to demonstrate that IND/GLY was non-inferior to SAL/FC in terms of reduction of all COPD exacerbations (mild/moderate/severe) during 52 weeks of treatment in patients having had at least 1 exacerbation in previous 12 months...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28382543/the-role-of-beta-arrestin2-in-shaping-fmri-bold-responses-to-dopaminergic-stimulation
#18
Kristoffer Sahlholm, Giovanna D Ielacqua, Jinbin Xu, Lynne A Jones, Felix Schlegel, Robert H Mach, Markus Rudin, Aileen Schroeter
RATIONALE: The dopamine D2 receptor (D2R) couples to inhibitory Gi/o proteins and is targeted by antipsychotic and antiparkinsonian drugs. Beta-arrestin2 binds to the intracellular regions of the agonist-occupied D2R to terminate G protein activation and promote internalization, but also to initiate downstream signaling cascades which have been implicated in psychosis. Functional magnetic resonance imaging (fMRI) has proven valuable for measuring dopamine receptor-mediated changes in neuronal activity, and might enable beta-arrestin2 function to be studied in vivo...
April 5, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28374135/oxabicycloheptene-sulfonate-protects-against-%C3%AE-amyloid-induced-toxicity-by-activation-of-pi3k-akt-and-erk-signaling-pathways-via-gper1-in-c6-cells
#19
Li-Juan Deng, Chen Cheng, Jun Wu, Cai-Hua Wang, Hai-Bing Zhou, Jian Huang
Oxabicycloheptene sulfonate (OBHS) is a novel bicyclic core selective estrogen receptor modulator (SERM) with estrogen receptor (ER) antagonistic-activity and anti-inflammatory activity. However, little is known about protective action of OBHS on neurodegenerative disorders. In the present study, OBHS demonstrated a remarkably protective effect against amyloid beta (Aβ) induced cytotoxicity via G-protein-coupled estrogen receptor 1 (GPER1) in rat astroglial cell line (C6). The C6 cell death induced by Aβ was decreased by OBHS (1 μM) treatment for 45 min...
April 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28373136/decreased-vasorelaxation-induced-by-iloprost-during-acute-inflammation-in-human-internal-mammary-artery
#20
Nabil Foudi, Gulsev Ozen, Yasmine Amgoud, Liliane Louedec, Christine Choqueux, Aouatef Badi, Larissa Kotelevets, Eric Chastre, Dan Longrois, Xavier Norel
Cyclooxygenase-2 (COX-2) induction in human internal mammary arteries (IMA) under inflammatory conditions has been associated with attenuated norepinephrine (NE)-induced vasoconstriction. This effect was associated with increased prostaglandin (PG) E2 and prostacyclin (PGI2) releases. The present study was designed to assess the role of these PG and their receptors (EP and IP, respectively) on the vascular reactivity during acute inflammation. Isolated IMA were cultured in the absence (Control conditions) or presence (Inflammatory conditions) of both interleukin-1 beta (IL-1β) and lipopolysaccharide (LPS)...
June 5, 2017: European Journal of Pharmacology
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