Wilson, Tyler A* Dotaz Zobrazit nápovědu
Selective agonism of the estrogen receptor (ER) subtypes, ERα and ERβ, has historically been difficult to achieve due to the high degree of ligand-binding domain structural similarity. Multiple efforts have focused on the use of classical organic scaffolds to model 17β-estradiol geometry in the design of ERβ selective agonists, with several proceeding to various stages of clinical development. Carborane scaffolds offer many unique advantages including the potential for novel ligand/receptor interactions but remain relatively unexplored. We synthesized a series of para-carborane estrogen receptor agonists revealing an ERβ selective structure-activity relationship. We report ERβ agonists with low nanomolar potency, greater than 200-fold selectivity for ERβ over ERα, limited off-target activity against other nuclear receptors, and only sparse CYP450 inhibition at very high micromolar concentrations. The pharmacological properties of our para-carborane ERβ selective agonists measure favorably against clinically developed ERβ agonists and support further evaluation of carborane-based selective estrogen receptor modulators.
- MeSH
- beta receptor estrogenů agonisté MeSH
- estrogeny chemická syntéza chemie farmakologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- molekulární struktura MeSH
- sloučeniny boru chemická syntéza chemie farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.
- MeSH
- COVID-19 * MeSH
- dexamethason škodlivé účinky MeSH
- dospělí MeSH
- farmakoterapie COVID-19 MeSH
- hypoxie MeSH
- lidé MeSH
- pacienti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Avison and Peter M. Chandler 121 -- PART II THERAPEUTIC AGENTS AND VACCINES 145 -- 7 Antifungal agents and antifungal susceptibility Tyler -- 14 The immune response to viral infections Anthony A. Nash and Bernadette M. Tyler -- The immune response to viral infections Anthony A. Nash and Bernadette M. Aurrand-Lions and Beat A.
10th ed. 8 sv. : il. ; 28 cm + 1 CD-ROM
- MeSH
- alergologie a imunologie MeSH
- bakteriologie MeSH
- mikrobiologie MeSH
- mykologie MeSH
- parazitologie MeSH
- virologie MeSH
- Publikační typ
- monografie MeSH
Aminoff / Arthur K. Asbury -- 26 Confusion and Delirium . . 158 -- S. Andrew Josephson / Bruce L. Awtry / Wilson S. Colucci -- 234 Cardiac Manifestations of Systemic Disease 1498 -- Eric H. Awtry / Wilson S. Tyler -- 377 Chronic and Recurrent Meningitis . -- Walter J. Koroshetz / Morton N. Reus -- ^ ALCOHOLISM AND DRUG DEPENDENCY -- 387 Alcohol and Alcoholism . 2724 -- Marc A.
17th ed. 1 nebo 2 sv. (xxxvii, 2754, A-16, I-149) : il., portrét ; 29 cm + 1 DVD-ROM
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- vnitřní lékařství
- NLK Publikační typ
- kolektivní monografie
1825-1829 -- Andrew Jackson 1829-1837 -- Martin Van Buren 1837-1841 -- William H. Harrison 1841 -- John Tyler 1841-1845 -- James K. Lincoln 1861-1865 -- Andrew Johnson 1865-1869 -- Ulysses S. Hayes 1877-1881 -- James A. Garfield 1881 -- Chester A. po Alberta („Ala“) Gora First Ladies Spojených států od Marthy Washingtonové po Hillary Clintonovou
1. vyd. 538 s. : obr., fotogr. ; 22 cm
- MeSH
- dějiny MeSH
- významné osobnosti MeSH
- Publikační typ
- biografie MeSH
- monografie MeSH
- Geografické názvy
- Spojené státy americké MeSH
- Konspekt
- Dějiny Spojených států amerických
- NLK Obory
- humanitní vědy a umění
Baddour, and Walter R. Wilson -- 84 Infections of Nonvalvular Cardiovascular Devices 1041 -- M. Wilson, and Larry M. Baddour -- 85 Prophylaxis of Infective Endocarditis 1057 -- David T. David Beckham and Kenneth L. Tyler -- 92 Brain Abscess 1164 -- Allan R. DeBiasi and Kenneth L. Tyler -- 151 Coltiviruses and Seadornaviruses 1851 -- Roberta L. DeBiasi and Kenneth L. Tyler -- 152 Rotaviruses 1854 -- Philip R. Dormitzer -- b.
8th ed. 2 sv. : il., tab. ; 28 cm
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- infekční lékařství
- NLK Publikační typ
- kolektivní monografie
- učebnice vysokých škol
Wilson, Michael A. Marchetti -- 23. Wilson -- 28. The Para-Athlete, 315 -- Daniel Herman, Mary E Caldwell, Arthur Jason De Luigi -- 29. Tyler Huish, Erik Mitchell, Sean McMillan -- 79. Hip Arthroscopy, 947 -- Joshua D. Harris -- 80. Leg, Ankle, and Foot Diagnosis and Decision-Making, 1370 -- Anish ft. Kadakia, Amiethab A. Aiyer -- 112. Imaging of the Foot and Ankle, 1380 -- Anish ft. Kadakia, Amiethab A. Aiyer -- 113.
Fifth edition 2 svazky (xxvii, 1764, 45 stran) : ilustrace ; 29 cm
The publication focuses on sports medicine and treatment of athletic injuries. Intended for professionals.
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- ortopedie
- tělovýchovné lékařství
- NLK Publikační typ
- kolektivní monografie
Melton and Chad Cowan Stem Cells 91 -- Fiona A. Mack and M. Cell Fusion and the Differentiated State .111 -- Penny A. Johnson and Peter W. Andrews -- 10. Potten and James W. Wilson -- 2. “Adult” Stem Cells: Tissue Specific or Not? 13 -- Catherine M. Multipotent Adult Progenitor Cells 293 -- Alaa Adassi and Catherine M. Verfaillie -- 28. and Maeve A.
2 sv. : il., tab. ; 30 cm + 1 CD-ROM
- MeSH
- kmenové buňky MeSH
- tkáňové inženýrství MeSH
- výzkum embrya etika MeSH
- výzkum plodu etika MeSH
- Publikační typ
- příručky MeSH
MR1 and 5-ALA) 25 -- Kimon Bekelis and David W. Wilson and Peter Nakaji -- 17 Evidence-Based Management of Central Neurocytoma (Gross Total Resection Coon -- 30 Adjuvant Therapies (Chemotherapy and Radiation Therapy) for Atypical and Anaplastic Meningiomas A. Karim, Anand Veeravagu, and Steven D. David Beahm, Tyler J. Kenning, Christopher J. Farrell, Marc R. Rosen, and James J.
xxiii, 495 s. : il. ; 29 cm
- MeSH
- medicína založená na důkazech MeSH
- nádory mozku chirurgie radioterapie MeSH
- radiochirurgie metody MeSH
- Publikační typ
- příručky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurochirurgie
- onkologie
- NLK Publikační typ
- kolektivní monografie
- učebnice vysokých škol
Gifford -- O 8 Global Developmental Delay and Regression, 67 -- Rachel Goode, Alice Lawrence, Tyler Reimschisel Wilson -- 14 Dysarthria and Apraxia of Speech, 149 -- Howard S. Tyler -- 79 Bacterial, Fungal, and Parasitic Diseases of the Nervous -- System, 1214 -- Nicolaas C. Anderson, Anita A. Koshy, Karen L. Doughty, Anthony A.
Eighth edition 2 svazky : ilustrace, tabulky ; 28 cm
The textbook focuses on diseases of the nervous system and on practical approach to their diagnosis and treatment.
- MeSH
- neurologie MeSH
- Konspekt
- Patologie. Klinická medicína
- Učební osnovy. Vyučovací předměty. Učebnice
- NLK Obory
- neurologie
- NLK Publikační typ
- kolektivní monografie
- učebnice vysokých škol
