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https://www.readbyqxmd.com/read/28645995/mepolizumab-for-the-treatment-of-severe-eosinophilic-asthma
#1
REVIEW
Mara N Poulakos, Shawna M Cargill, Melissa F Waineo, Allen L Wolford
PURPOSE: Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed. SUMMARY: Asthma of the eosinophilic phenotype is characterized by persistent eosinophilic airway inflammation promoted primarily by T-helper type 2 cytokines, the key regulator of eosinophils. Patients with severe eosinophilic asthma are burdened by the need to administer high doses of corticosteroids to help manage their symptoms...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28639542/fluticasone-propionate-and-fluticasone-propionate-salmeterol-multidose-dry-powder-inhalers-compared-with-placebo-for-persistent-asthma
#2
L D Sher, G Yiu, A Sakov, S Liu, C F Caracta
BACKGROUND: A novel, inhalation-driven, multidose dry powder inhaler (MDPI) has been developed, which allows for lowerdoses of fluticasone propionate (Fp) and Fp/salmeterol (FS) for the treatment of patients with asthma. OBJECTIVE: This phase III, multicenter, double-blind, parallel-group study (NCT02141854) evaluated the efficacy and safetyof Fp MDPI and FS MDPI versus placebo MDPI. METHODS: Patients aged greater than or equal to 12 years with persistent asthma who previously took an inhaled corticosteroid with or without a long-acting beta-agonist entered a 14- to 21-day run-in period, during which they received single-blind, low-dose Fp MDPI 50 microgram (1 inhalation twice daily [b...
June 21, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28631599/efficacy-and-safety-of-omalizumab-in-children-and-adolescents-with-moderate-to-severe-asthma-a-systematic-literature-review
#3
J Corren, A Kavati, B Ortiz, J A Colby, K Ruiz, B A Maiese, S M Cadarette, R A Panettieri
BACKGROUND: There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety ofomalizumab in the real-world management of allergic asthma. OBJECTIVE: The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinicaltrials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. METHODS: Studies that evaluated omalizumab use in patients < 18 years old and with asthma, published between January2003 and October 2016, were retrieved from medical literature data bases...
June 19, 2017: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/28625688/electrically-atomised-formulations-of-timolol-maleate-for-direct-and-on-demand-ocular-lens-coatings
#4
Prina Mehta, Ali Al-Kinani, Rita Haj-Ahmad, Muhammad Sohail Arshad, Ming-Wei Chang, G Raid Alany, Zeeshan Ahmad
Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface...
June 15, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28622905/discovery-of-novel-somatostatin-receptor-subtype-5-sstr5-antagonists-pharmacological-studies-and-design-to-improve-pharmacokinetic-profiles-and-human-ether-a-go-go-related-gene-herg-inhibition
#5
Takeshi Yamasaki, Hideki Hirose, Tohru Yamashita, Nobuyuki Takakura, Sachie Morimoto, Takashi Nakahata, Asato Kina, Yoshihide Nakano, Yumiko Okano Tamura, Jun Sugama, Tomoyuki Odani, Yuji Shimizu, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin (SST) is a peptide hormone comprising 14 or 28 amino acids that inhibits endocrine and exocrine secretion via five distinct G-protein-coupled receptors (SSTR1-5). SSTR5 has an important role in inhibiting the secretion of pancreatic and gastrointestinal hormones (e.g., insulin, GLP-1, PYY) through the binding of SSTs; hence, SSTR5 antagonists are expected to be novel anti-diabetic drugs. In the course of our lead generation program of SSTR5 antagonists, we have discovered a novel spiroazetidine derivative 3a...
June 13, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28611949/pseudomalabsorption-of-levothyroxine-a-challenge-for-the-endocrinologist-in-the-treatment-of-hypothyroidism
#6
Nancy Van Wilder, Bert Bravenboer, Sarah Herremans, Nathalie Vanderbruggen, Brigitte Velkeniers
BACKGROUND: Hypothyroidism due to non-compliance with levothyroxine therapy (pseudomalabsorption) is rare. The diagnosis is considered in patients with persistent severe hypothyroidism despite treatment with large doses of levothyroxine. Intestinal malabsorption, drug and dietary interference with levothyroxine absorption and nephrotic syndrome should be excluded. The diagnosis of pseudomalabsorption can be demonstrated by using "an oral 1,000 µg of levothyroxine test" showing a rapid decrease in thyroid-stimulating hormone and increase in thyroxine...
February 2017: European Thyroid Journal
https://www.readbyqxmd.com/read/28599683/pain-sensitivity-and-analgesic-use-among-10-486-adults-the-troms%C3%A3-study
#7
Per-Jostein Samuelsen, Christopher Sivert Nielsen, Tom Wilsgaard, Audun Stubhaug, Kristian Svendsen, Anne Elise Eggen
BACKGROUND: Increased pain sensitivity is a putative risk factor for chronic pain and consequently for analgesic use. Conversely, analgesic use may be a cause of increased pain sensitivity, e.g., through opioid-induced hyperalgesia. We aimed to study the association between pain sensitivity and analgesic use in a general population, and to test the hypothesis that increased baseline pain sensitivity is a risk factor for future persistent analgesic use. METHODS: The Tromsø Study (2007-08), a population-based health study, was linked with eight years of prescription data from the Norwegian Prescription Database...
June 9, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28596760/in-depth-profiling-of-mvfr-regulated-small-molecules-in-pseudomonas-aeruginosa-after-quorum-sensing-inhibitor-treatment
#8
Giuseppe Allegretta, Christine K Maurer, Jens Eberhard, Damien Maura, Rolf W Hartmann, Laurence Rahme, Martin Empting
Pseudomonas aeruginosa is a Gram-negative bacterium, which causes opportunistic infections in immuno-compromised individuals. Due to its multiple resistances toward antibiotics, the development of new drugs is required. Interfering with Quorum Sensing (QS), a cell-to-cell communication system, has shown to be highly efficient in reducing P. aeruginosa pathogenicity. One of its QS systems employs Pseudomonas Quinolone Signal (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signal molecules. Both activate the transcriptional regulator MvfR (Multiple Virulence Factor Regulator), also called PqsR, driving the production of QS molecules as well as toxins and biofilm formation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28589493/a-randomized-placebo-controlled-trial-evaluating-the-safety-and-efficacy-of-adding-omarigliptin-to-antihyperglycemic-therapies-in-japanese-patients-with-type-2-diabetes-and-inadequate-glycemic-control
#9
Ira Gantz, Taro Okamoto, Yuka Ito, Asako Sato, Kotoba Okuyama, Edward A O'Neill, Samuel S Engel, Eseng Lai
INTRODUCTION: Daily dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used with other orally administered antihyperglycemic agents (AHA), as combination therapy, to treat Japanese patients with type 2 diabetes. When combination therapy is indicated, use of a once-weekly (q.w.) orally administered DPP-4 inhibitor might be an appropriate therapeutic option for some patients. METHODS: A 52-week trial was conducted to assess the safety and tolerability (primary objectives) and glycemic efficacy (secondary objectives) of the q...
June 6, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28570482/targeting-the-s1p-s1pr1-axis-mitigates-cancer-induced-bone-pain-and-neuroinflammation
#10
Shaness A Grenald, Timothy M Doyle, Hong Zhang, Lauren M Slosky, Zhoumou Chen, Tally M Largent-Milnes, Sarah Spiegel, Todd W Vanderah, Daniela Salvemini
Metastatic bone pain is the single most common form of cancer pain, and persists as a result of peripheral and central inflammatory, as well as, neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P)...
May 31, 2017: Pain
https://www.readbyqxmd.com/read/28529326/persistent-bacterial-infections-and-persister-cells
#11
REVIEW
Robert A Fisher, Bridget Gollan, Sophie Helaine
Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. The formation of persister cells establishes phenotypic heterogeneity within a bacterial population and has been hypothesized to be important for increasing the chances of successfully adapting to environmental change...
May 22, 2017: Nature Reviews. Microbiology
https://www.readbyqxmd.com/read/28518128/an-in-vitro-caseum-binding-assay-that-predicts-drug-penetration-in-tuberculosis-lesions
#12
Jansy P Sarathy, Hsin-Pin Ho Liang, Danielle Weiner, Jacqueline Gonzales, Laura E Via, Véronique Dartois
The eradication of tuberculosis disease requires drug regimens that can penetrate the multiple layers of complex pulmonary lesions. Drug distribution in the caseous cores of cavities and lesions is especially crucial because they harbor subpopulations of drug-tolerant bacteria also commonly referred to as persisters. Existing methods for the measurement of drug penetration in tuberculosis lesions involve costly and time-consuming in vivo pharmacokinetic studies coupled to bioanalytical or imaging techniques...
May 8, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28513455/glucose-tolerance-disorders-during-treatment-with-glucocorticoids-in-patients-with-inflammatory-diseases-of-the-musculoskeletal-system-based-on-the-analysis-of-data-from-the-literature-and-own-research-results
#13
Piotr Dąbrowski, Maria Majdan
Glucocorticoids are among the most frequently used anti-inflammatory and immunosuppressive drugs. They are widely used in the treatment of numerous autoimmune disorders. However, the treatment with glucocorticoids is connected with the risk of a number of side effects. Among them, glucose tolerance disorders play an important role. The results of meta-analyses show that the risk of diabetes is from 1.4 to 2.5 times higher in the case of treated patients in comparison to the general population. Glucocorticoids can directly impair pancreatic β-cell secretion...
May 4, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28510695/effects-of-an-autoinducer-analogue-on-antibiotic-tolerance-in-pseudomonas-aeruginosa
#14
Takashi Amoh, Keiji Murakami, Reiko Kariyama, Kenji Hori, Darija Viducic, Katsuhiko Hirota, Jun Igarashi, Hiroaki Suga, Matthew R Parsek, Hiromi Kumon, Yoichiro Miyake
Objectives: Antibiotic tolerance causes chronic, refractory and persistent infections. In order to advance the development of a new type of drug for the treatment of infectious diseases, we herein investigated the effects of a newly synthesized analogue of the Pseudomonas aeruginosa quorum-sensing autoinducer named AIA-1 ( a uto i nducer a nalogue) on antibiotic tolerance in P. aeruginosa . Methods: A P. aeruginosa luminescent strain derived from PAO1 was injected into neutropenic ICR mice and bioluminescence images were acquired for a period of time after treatments with antibiotics and AIA-1...
May 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28495642/feasibility-of-lenalidomide-therapy-for-persistent-chronic-lymphocytic-leukemia-after-allogeneic-transplantation
#15
Maria R Khouri, Elias J Jabbour, Alison M Gulbis, Francesco Turturro, Celina Ledesma, Martin Korbling, Barry I Samuels, Sairah Ahmed, Amin M Alousi, Stefan O Ciurea, David Marin, Krina K Patel, Uday R Popat, Carlos E Bueso-Ramos, Roland L Bassett, Issa F Khouri
In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28484041/transcriptional-repressor-ptvr-regulates-phenotypic-tolerance-to-vancomycin-in-streptococcus-pneumoniae
#16
Xue Liu, Jing-Wen Li, Zhixing Feng, Youfu Luo, Jan-Willem Veening, Jing-Ren Zhang
Reversible or phenotypic tolerance to antibiotics within microbial populations has been implicated in treatment failure of chronic infections and development of persister cells. However, the molecular mechanisms regulating phenotypic drug tolerance are largely unknown. In this study, we identified a four-gene operon in Streptococcus pneumoniae that contributes to phenotypic tolerance to vancomycin (ptv). RNA-Seq, qRT-PCR, and transcriptional luciferase reporter experiments revealed that transcription of the ptv operon (consisting of ptvR, ptvA, ptvB and ptvC) is induced by exposure to vancomycin...
May 8, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28473458/effects-of-acute-and-chronic-treatments-with-dopamine-d2-and-d3-receptor-ligands-on-cocaine-versus-food-choice-in-rats
#17
Morgane Thomsen, Andrew C Barrett, Paul Butler, S Stevens Negus, S Barak Caine
Dopamine D3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D2- and D3-preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28461784/retrospective-evaluation-of-the-effectiveness-of-radiotherapy-in-patients-with-plantar-fascitis-heel-spurs
#18
Piotr Kędzierawski, Rafał Stando, Paweł Macek
AIM: The aim of the study was the evaluation of the effectiveness of radiotherapy in patients with the feet pain caused by heel spurs. BACKGROUND: Treatment options for patients reporting these symptoms include use of suitable orthopedic footwear, the use of general or topical non-steroidal anti-inflammatory drugs or steroids, physiotherapy, manual therapy, shock wave or appropriate surgical procedures. Radiotherapy is one of the method used in patients with chronic pain syndrome...
May 2017: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/28458514/riociguat-a-soluble-guanylate-cyclase-stimulator-for-the-treatment-of-pulmonary-hypertension
#19
REVIEW
Tian-Yu Lian, Xin Jiang, Zhi-Cheng Jing
Despite advances in treatments and improved survival, patients with pulmonary hypertension still experience poor exercise and functional capacity, which has a significant detrimental impact on their quality of life. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine 3',5'-monophosphate (cGMP) pathway has been shown to play an important role in cardiovascular physiology, especially in vasodilation and pulmonary vascular tone. The oral sGC stimulator riociguat has a dual mode of action on the NO-sGC-cGMP pathway: direct stimulation of sGC independent of NO and indirect simulation via sensitization of sGC to endogenous NO...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28450388/clinical-relevance-of-detecting-anti-infliximab-antibodies-with-a-drug-tolerant-assay-post-hoc-analysis-of-the-taxit-trial
#20
Thomas Van Stappen, Niels Vande Casteele, Gert Van Assche, Marc Ferrante, Séverine Vermeire, Ann Gils
OBJECTIVE: To evaluate the clinical relevance of antidrug antibodies (ADAs) measured using a drug-tolerant assay in a post hoc analysis of the Trough Concentration (TC) Adapted Infliximab Treatment (TAXIT) randomised controlled trial. DESIGN: ADA in serum samples (n=221) of 76 patients enrolled in TAXIT, who presented with an infliximab TC <3 µg/mL at screening, were reanalysed after optimisation and at the end of the study using a drug-tolerant ADA assay...
April 27, 2017: Gut
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