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https://www.readbyqxmd.com/read/28636951/structure-of-cc-chemokine-receptor-5-with-a-potent-chemokine-antagonist-reveals-mechanisms-of-chemokine-recognition-and-molecular-mimicry-by-hiv
#1
Yi Zheng, Gye Won Han, Ruben Abagyan, Beili Wu, Raymond C Stevens, Vadim Cherezov, Irina Kufareva, Tracy M Handel
CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636828/pharmacokinetic-drug-evaluation-of-extended-release-lorcaserin-for-the-treatment-of-obesity
#2
Kathryn Hurren, Marissa W Dunham
Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3% and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively...
June 21, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28636771/is-transvaginal-contained-tissue-extraction-for-everyone
#3
Charles Miller
Professor Ghezzi, et al. should be congratulated for their excellent manuscript "Transvaginal Contained Tissue Extraction After Laparoscopic Myomectomy: A Cohort Study". This is a well-conceived, well-written retrospective cohort study describing operative and peri-operative outcomes for patients who have undergone transvaginal morcellation via a posterior colpotomy. Given the continued controversy regarding electronic power morcellation leading to restriction of use in certain areas, this study is not only impactful, in that it describes an alternative technique with data accumulated over a decade of experience, but it describes a technique of contained morcellation that is neither based on the controversial power morcellation, nor the mini-laparotomy (https://www...
June 21, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28636484/bezlotoxumab-anti-toxin-b-monoclonal-antibody-to-prevent-recurrence-of-clostridium-difficile-infection
#4
Javier A Villafuerte Gálvez, Ciarán P Kelly
Clostridium difficile infection (CDI) is the most common nosocomial infection in the U.S. 25% of CDI patients go on to develop recurrent CDI (rCDI) following current standard of care (SOC) therapy, leading to morbidity, mortality and economic loss. The first passive immunotherapy drug targeting C.difficile toxin B (bezlotoxumab) has been approved recently by the FDA and EMA for prevention of rCDI. Areas covered: A body of key studies was selected and reviewed by the authors. The unmet needs in CDI care were ascertained with emphasis in rCDI, including the epidemiology, pathophysiology and current management...
June 21, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#5
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28636191/-fast-track-development-and-approval-process-for-heart-failure-therapeutics
#6
L Papadimitriou, J Butler
Heart failure (HF) is a global epidemic, with a high mortality and morbidity burden. In such diseases, earlier access to lifesaving therapeutic regimens is imperative, and could be accomplished by improving the drug development and approval process, without jeopardizing patient safety. The US Food and Drug Administration (FDA) has already established mechanisms facilitating the latter, but further guidance to enhance and expedite the process holds promise to further improve patient outcomes.
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28635679/the-role-of-angiogenesis-in-cancer-treatment
#7
REVIEW
Mehdi Rajabi, Shaker A Mousa
A number of anti-angiogenesis drugs have been FDA-approved and are being used in cancer treatment, and a number of other agents are in different stages of clinical development or in preclinical evaluation. However, pharmacologic anti-angiogenesis strategies that arrest tumor progression might not be enough to eradicate tumors. Decreased anti-angiogenesis activity in single mechanism-based anti-angiogenic strategies is due to the redundancy, multiplicity, and development of compensatory mechanism by which blood vessels are remodeled...
June 21, 2017: Biomedicines
https://www.readbyqxmd.com/read/28635650/the-application-of-heptamethine-cyanine-dye-dz-1-and-indocyanine-green-for-imaging-and-targeting-in-xenograft-models-of-hepatocellular-carcinoma
#8
Caiqin Zhang, Yong Zhao, He Zhang, Xue Chen, Ningning Zhao, Dengxu Tan, Hai Zhang, Changhong Shi
Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634770/medical-negligence-determinations-the-right-to-try-and-expanded-access-to-innovative-treatments
#9
Denise Meyerson
This article considers the issue of expanded access to innovative treatments in the context of recent legislative initiatives in the United Kingdom and the United States. In the United Kingdom, the supporters of legislative change argued that the common law principles governing medical negligence are a barrier to innovation. In an attempt to remove this perceived impediment, two bills proposed that innovating doctors sued for negligence should be able to rely in their defence on the fact that their decision to innovate was "responsible...
June 20, 2017: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#10
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28634163/reducing-tobacco-related-harm-fda-s-proposed-product-standard-for-smokeless-tobacco
#11
Micah L Berman, Dorothy K Hatsukami
This Special Communication discusses the Food and Drug Administration's (FDA's) proposed rule that would limit N-nitrosonornicotine (NNN) levels in smokeless tobacco products. It argues that finalising and implementing this first 'product standard' would mark a significant step forward in the FDA's efforts to reduce tobacco-related harms.
June 20, 2017: Tobacco Control
https://www.readbyqxmd.com/read/28633806/il-17-for-therapy
#12
REVIEW
Florian C Kurschus, Sonja Moos
The cytokine IL-17 is now a target for an array of therapeutic monoclonal antibodies supposed to treat a variety of inflammatory diseases. The forerunner Secukinumab, an IL-17A neutralizing antibody, is meanwhile approved as first-line treatments for moderate-to-severe plaque psoriasis, and as second-line treatment for psoriatic arthritis and ankylosing spondylitis. Ixekizumab and Brodalumab, both also targeting the IL-17 pathway, were also recently approved by the FDA for plaque psoriasis. Using mice overexpressing IL-17A in a tissue of choice, we showed that the ectopic expression of this cytokine in keratinocytes resulted in a spontaneous and very strong form of psoriasis-like dermatitis...
June 15, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28633320/discussion-is-fda-in-need-of-a-major-change-in-the-way-it-regulates
#13
Janet Wittes
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633317/discussion-is-the-fda-in-need-of-a-major-change-in-the-way-it-regulates
#14
Alex Tabarrok
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633316/discussion-is-the-fda-in-need-of-a-major-change-in-the-way-it-regulates
#15
Geert Molenberghs
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633313/discussion-new-directions-for-the-fda-in-the-21st-century
#16
Andrew W Lo
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633307/discussion-the-role-position-and-function-of-the-fda-the-past-present-and-future
#17
Thomas R Fleming, David L Demets, Lisa M McShane
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633289/discussion-is-the-fda-in-need-of-a-major-change-in-the-way-it-regulates
#18
Susan S Ellenberg
No abstract text is available yet for this article.
June 12, 2017: Biostatistics
https://www.readbyqxmd.com/read/28633191/-urothelial-cancer-update-on-systemic-treatment-options
#19
Günter Niegisch
Perioperative chemotherapy is likely to improve survival in both the neoadjuvant and the adjuvant setting. Therefore, it is an integral part of the modern treatment of patients with muscle-invasive urothelial bladder cancer. All patients who are suitable for cisplatin-based chemotherapy should be involved in a corresponding concept.Cisplatin-based combinations are standard regimens in the perioperative and palliative systemic treatment of urothelial cancer. Carboplatin is only an inferior substitute for "unfit" patients in the palliative treatment situation...
June 20, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28632953/updates-to-the-us-food-and-drug-administration-regulations-for-mifepristone-implications-for-clinical-practice-and-access-to-abortion
#20
Katherine E Simmonds, Margaret W Beal, Meghan K Eagen-Torkko
This article provides information on recent changes in the US Food and Drug Administration (FDA) labeling and safety regulations for mifepristone (Mifeprex). The revised label now permits midwives, advanced practice nurses, and physician assistants to order and prescribe mifepristone, eliminating the requirement for physician supervision. The updated label also extends eligibility for use from 49 to 70 days' gestation and decreases the number of required visits from 3 to 2. The recommended dose of mifepristone has been reduced, and the dosage, timing, and route of administration for misoprostol have also been changed to reflect current research...
May 2017: Journal of Midwifery & Women's Health
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