Read by QxMD icon Read

Conn fractionation

Andrew S Felts, Alice L Rodriguez, Ryan D Morrison, Anna L Blobaum, Frank W Byers, J Scott Daniels, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte
Based on previous work that established fused heterocycles as viable alternatives for the picolinamide core of our lead series of mGlu5 negative allosteric modulators (NAMs), we designed a novel series of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide mGlu5 NAMs. These new quinoline derivatives also contained carbon linkers as replacements for the diaryl ether oxygen atom common to our previously published chemotypes. Compounds were evaluated in a cell-based functional mGlu5 assay, and an exemplar analog 27 was >60-fold selective versus the other seven mGlu receptors...
April 22, 2018: Bioorganic & Medicinal Chemistry Letters
Rafael Barreto, Yukiko Kitase, Tsutomu Matsumoto, Fabrizio Pin, Kyra C Colston, Katherine E Couch, Thomas M O'Connell, Marion E Couch, Lynda F Bonewald, Andrea Bonetto
Chemotherapy promotes the development of cachexia, a debilitating condition characterized by muscle and fat loss. ACVR2B/Fc, an inhibitor of the Activin Receptor 2B signaling, has been shown to preserve muscle mass and prolong survival in tumor hosts, and to increase bone mass in models of osteogenesis imperfecta and muscular dystrophy. We compared the effects of ACVR2B/Fc on muscle and bone mass in mice exposed to Folfiri. In addition to impairing muscle mass and function, Folfiri had severe negative effects on bone, as shown by reduced trabecular bone volume fraction (BV/TV), thickness (Tb...
October 31, 2017: Scientific Reports
G Y Liu, G L Cao, F M Tian, H P Song, L L Yuan, L D Geng, Z Y Zheng, L Zhang
Ovariectomized (OVX) rats with type 2 diabetes mellitus (T2DM) with femur fracture received vehicle, insulin, or insulin plus parathyroid hormone (PTH) treatment for 2 and 3 weeks. Radiography, histomorphometry, histology, and immunohistochemistry in callus were evaluated. INTRODUCTION: Reports about effects of PTH plus insulin on callus formation of osteoporotic fracture with T2DM were limited. This study was designed to investigate the effects of the combination of PTH and insulin on fracture healing in OVX rats with T2DM...
October 2017: Osteoporosis International
Bong-Jae Jun, Amit Vasanji, Eric T Ricchetti, Eric Rodriguez, Naveen Subhas, Zong-Ming Li, Joseph P Iannotti
The purpose of this study was to demonstrate feasibility of a clinical CT imaging and analysis technique to quantify regional variations in trabecular bone architecture and mineralization of glenoid bones. Specifically, our objective was to determine to what extent clinical CT imaging of intact upper extremities can describe variations of trabecular bone architectures at anatomic and peri-implant regions by comparing trabecular bone architectures as measured by high-resolution, micro CT imaging of same excised glenoid bones...
January 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
Nadia Mohd Effendy, Mohd Fadhli Khamis, Ahmad Nazrun Shuid
BACKGOUND: Labisia pumila (LP) is a popular herb used by women over the past few decades. This herb has shown potentials as an alternative agent for treatment and prevention of postmenopausal osteoporosis. It was observed in previous studies that supplementation to ovariectomized rats were associated with increased bone antioxidative enzymes and reduced lipid peroxidation activity. It had also improved bone formation markers in ovariectomized rats. This study aimed to evaluate the effects of giving different forms of LP extracts on the trabecular bone microarchitecture of ovariectomised rats...
2017: Journal of X-ray Science and Technology
A Minematsu, Y Nishii, H Imagita, D Takeshita, S Sakata
STUDY DESIGN: Experimental, controlled study. OBJECTIVE: To examine the effects of whole-body vibration (WBV) on bone mass and trabecular bone microstructure (TBMS) during the early stage in juvenile rats with spinal cord injury (SCI). SETTING: Studied at the Kio University in Japan. METHODS: Thirty-four 8-week-old male Wistar rats were divided into 3 groups: the SCI group, the sham-operation group (SHAM) and the SCI+WBV group...
August 2016: Spinal Cord
Rohan Mandaliya, Jason Korenblit, Brendan O'Hare, Anastasia Shnitser, Ramalinga Kedika, Rebecca Matro, Dina Halegoua-De Marzio, Anthony Infantolino, Mitchell Conn
Background and Aim. Spiral enteroscopy (SE) is a new small bowel endoscopic technique. Our aim is to review the diagnostic and therapeutic yield, safety of SE, and the predictive role of prior capsule endoscopy (CE) at an academic center. Methods. A retrospective review of patients undergoing SE after prior CE between 2008 and 2013 was performed. Capsule location index (CLI) was defined as the fraction of total small bowel transit time when the lesion was seen on CE. Results. A total of 174 SEs were performed: antegrade (147) and retrograde (27)...
2015: Diagnostic and Therapeutic Endoscopy
Roei Levy, Richard F Mott, Fuad A Iraqi, Yankel Gabet
BACKGROUND: The microstructure of trabecular bone is a composite trait governed by a complex interaction of multiple genetic determinants. Identifying these genetic factors should significantly improve our ability to predict of osteoporosis and its associated risks. Genetic mapping using collaborative cross mice (CC), a genetically diverse recombinant inbred mouse reference panel, offers a powerful tool to identify causal loci at a resolution under one mega base-pairs, with a relatively small cohort size...
November 26, 2015: BMC Genomics
Loai Alsofi, Eileen Daley, Ian Hornstra, Elise F Morgan, Zachary D Mason, Jesus F Acevedo, R Ann Word, Louis C Gerstenfeld, Philip C Trackman
Lysyl oxidases are required for collagen and elastin cross-linking and extracellular matrix maturation including in bone. The lysyl oxidase family consists of lysyl oxidase (LOX) and 4 isoforms (LOXL1-4). Here we investigate whether deletion of LOXL1, which has been linked primarily to elastin maturation, leads to skeletal abnormalities. Left femurs (n = 8), L5 vertebrae (n = 8), and tibiae (n = 8) were analyzed by micro-computed tomography in 13-week-old wild-type (WT) and LOXL1-/- male and female mice. Right femurs (n = 8) were subjected to immunohistochemistry for LOXL1, and histochemical/histology analyses of osteoclasts and growth plates...
February 2016: Calcified Tissue International
Jin-Woo Kim, Jacquiline Czar I Tatad, Maria Erika A Landayan, Sun-Jong Kim, Myung-Rae Kim
Despite the fact that the medications used to treat abnormal bone conditions often induce osteonecrosis of the jaw (ONJ), previous attempts to establish an animal model for ONJ have shown insufficient consideration for this important prerequisite for the development of the disease. The purpose of this study was to establish an animal model with the most common metabolic bone disease, osteoporosis. Ninty-six rats were randomly divided into ovariectomy (Ov) group (n=48) and sham-operated group (n=48). Six weeks after Ov or sham surgery, rats in each group were subdivided into bisphosphonate group (n=36 each) and control group (n=12 each) and injected with zoledronic acid and normal saline, respectively, once a week...
December 2015: Bone
Shlomo Barak, Moshe Neuman, Giovanna Iezzi, Adriano Piattelli, Vittoria Perrotti, Yankel Gabet
OBJECTIVE: In the present study, a new healing cap that could generate a pulsed electromagnetic field (PEMF) around titanium implants to stimulate peri-implant osteogenesis was tested in the rabbit model. MATERIALS AND METHODS: A total of 22 implants were inserted in the proximal tibial metaphysis of 22 rabbits. A healing cap containing the active device was inserted in half of the implants (11 test implants); an "empty" healing cap was inserted in the other ones (11 control implants)...
August 2016: Clinical Oral Implants Research
Zhibin Du, Roland Steck, Nghiem Doan, Maria Ann Woodruff, Saso Ivanovski, Yin Xiao
The effects of estrogen deficiency on bone characteristics are site-dependent, with the most commonly studied sites being appendicular long bones (proximal femur and tibia) and axial bones (vertebra). The effect on the maxillary and mandibular bones is still inconsistent and requires further investigation. This study was designed to evaluate bone quality in the posterior maxilla of ovariectomized rats to validate this site as an appropriate model to study the effect of osteoporotic changes. Forty-eight 3-month-old female Sprague-Dawley rats were randomly divided into two groups: an ovariectomized (OVX) group (n=24) and Sham-operated (SHAM) group (n=24)...
May 2015: Tissue Engineering. Part C, Methods
Liang Fang, Xi Ding, Hui-ming Wang, Xing-Hao Zhu
Our objectives were to examine the titanium-bone interfaces chronologically and to clarify the process of osseointegration using microcomputed tomography (microCT). The mandibular premolars of 3 dogs were extracted and 12 weeks later 2 Straumann dental implants were installed in each quadrant. The microstructural changes at the bone-implant interface at the first, fourth, and eighth weeks after installation were evaluated by microCT and a 3-dimensional image was constructed. The microstructural measurements at the bone-implant interface, including the trabecular number (Tb...
November 2014: British Journal of Oral & Maxillofacial Surgery
Jing Peng, Yong Zhou, Li Min, Wenli Zhang, Yi Luo, Xuelei Zhang, Chang Zou, Rui Shi, Chongqi Tu
OBJECTIVE: To analyze the correlation between the trabecular microstructure and the clinical imaging parameters in the fracture region of osteoporotic hip so as to provide a simple method to evaluate the trabecular microstructure by a non-invasive way. METHODS: Between June 2012 and January 2013, 16 elderly patients with femoral neck fracture underwent hip arthroplasty were selected as the trial group; 5 young patients with pelvic fracture were selected as the control group...
May 2014: Chinese Journal of Reparative and Reconstructive Surgery
Andreas Lahm, Richard Kasch, Heiko Spank, Christoph Erggelet, Jan Esser, Harry Merk, Eike Mrosek
Cartilage degeneration of the knee joint is considered to be a largely mechanically driven process. We conducted a microstructural and histomorphometric analysis of subchondral bone samples of intact cartilage and in samples with early and higher- grade arthritic degeneration to compare the different states and correlate the findings with the condition of hyaline cartilage. These findings will enable us to evaluate changes in biomechanical properties of subchondral bone during the evolution of arthritic degeneration, for which bone density alone is an insufficient parameter...
November 2014: Histology and Histopathology
Feng Yang, Pu-wei Yuan, Yang-Quan Hao, Zheng-Mao Lu
BACKGROUND: It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and the balance between osteogenesis and adipogenesis differentiation of MSCs (mesenchymal stem cells) is disrupted in osteoporosis. In order to improve the treatment of osteoporosis, available agents with roles of regulating the balance is highly desirable. Emodin is a natural anthraquinone derivative extracted from Chinese herbs, which have been used to treat bone diseases for thousands of years...
2014: BMC Complementary and Alternative Medicine
Douglas J Sheffler, Michael T Nedelcovych, Richard Williams, Stephen C Turner, Brittany B Duerk, Megan R Robbins, Sataya B Jadhav, Colleen M Niswender, Carrie K Jones, P Jeffrey Conn, R Nathan Daniels, Craig W Lindsley
This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores.
February 15, 2014: Bioorganic & Medicinal Chemistry Letters
Carrie K Jones, Douglas J Sheffler, Richard Williams, Sataya B Jadhav, Andrew S Felts, Ryan D Morrison, Colleen M Niswender, J Scott Daniels, P Jeffrey Conn, Craig W Lindsley
This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach that provided a robust intellectual property position, in lieu of a traditional, expensive HTS campaign. Members within this new [3.1.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, CNS penetration and efficacy in a preclinical model of schizophrenia (prepulse inhibition).
February 15, 2014: Bioorganic & Medicinal Chemistry Letters
Yingcai Wang, Ming Yu, Jiang Zhu, Jian Ken Zhang, Frank Kayser, Julio C Medina, Karen Siegler, Marion Conn, Bei Shan, Mark P Grillo, Jiwen Jim Liu, Peter Coward
We describe the discovery and optimization of 5-(2-((1-(phenylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-yl)oxy)pyridin-4-yl)-1,2,4-oxadiazoles as novel agonists of GPR119. Previously described aniline 2 had suboptimal efficacy in signaling assays using cynomolgus monkey (cyno) GPR119 making evaluation of the target in preclinical models difficult. Replacement of the aniline ring with a tetrahydroquinoline ring constrained the rotation of the aniline C-N bond and gave compounds with increased efficacy on human and cyno receptors...
February 15, 2014: Bioorganic & Medicinal Chemistry Letters
W Hösel, J Berlin, T N Hanzlik, E E Conn
Cell suspension cultures of Eschscholtzia californica produce one or more cyanogenic compounds when placed under osmotic stress. The nature of the compound(s) has not yet been established but they are not identical with the cyanogenic glucosides triglochinin and dhurrin, which occur in the intact plant. Microsomal fractions isolated from stressed cell cultures catalyze the synthesis of 1-(4'-hydroxyphenyl)-2-nitroethane from L-tyrosine. Both NADPH and molecular oxygen are required as cosubstrates, and 4-hydroxyphenylacetaldoxime is an intermediate in the synthesis of the nitrocompound...
October 1985: Planta
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"