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https://www.readbyqxmd.com/read/28213743/development-of-cer-001-preclinical-dose-selection-through-to-phase-i-clinical-findings
#1
Constance H Keyserling, Ronald Barbaras, Renee Benghozi, Jean-Louis Dasseux
BACKGROUND: CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day...
February 17, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28213406/mitochondria-regulated-formation-of-endothelial-extracellular-vesicles-shifts-the-mediator-of-flow-induced-vasodilation
#2
Julie K Freed, Matthew J Durand, Brian Robert Hoffmann, John C Densmore, Andrew S Greene, David D Gutterman
In order to examine the effect of endothelial-derived extracellular vesicles (eEVs) on the mechanism of flow-induced dilation (FID) composition, formation, and functional effects on the mechanism of FID were examined from two different eEV subtypes, one produced from ceramide, the other from plasminogen-activator inhibitor 1 (PAI-1). Using videomicroscopy, internal diameter changes in response to increases in flow were measured in human adipose resistance arteries acutely exposed (30min) to eEVs derived from cultured endothelial cells exposed to ceramide or PAI-1...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28210705/gastric-esd-may-be-useful-as-accurate-staging-and-decision-of-future-therapeutic-strategy
#3
Ai Fujimoto, Osamu Goto, Toshihiro Nishizawa, Yasutoshi Ochiai, Joichiro Horii, Tadateru Maehata, Teppei Akimoto, Satoshi Kinoshita, Seiji Sagara, Motoki Sasaki, Toshio Uraoka, Naohisa Yahagi
Background and study aims We sometimes perform gastric endoscopic submucosal dissection (ESD) for total pathologic diagnosis when preoperative diagnosis is difficult. In the present study we analyzed the treatment outcomes and adverse events of diagnostic ESD for early gastric cancer (EGC). Patients and methods We conducted a retrospective analysis of 18 consecutive cases of EGC in 18 patients with a suspected out-of-indication diagnosis who underwent diagnostic ESD, between June 2010 and November 2014...
February 2017: Endoscopy International Open
https://www.readbyqxmd.com/read/28202334/synthesis-of-specifically-deuterated-ceramide-ap-c18-and-its-biophysical-characterization-using-neutron-diffraction
#4
Stefan Sonnenberger, Adina Eichner, Thomas Hauß, Annett Schroeter, Reinhard H H Neubert, Bodo Dobner
The very heterogeneous group of ceramides is known to be mandatory for proper barrier functions of the outermost layer of mammalian skin, referred to as stratum corneum (SC). The synthesis of a specifically deuterated ceramide [AP]-C18 variant is described. The synthesized ceramide contains the racemic forms of the α hydroxy fatty acid. For the biophysical implementation, the received diastereomeric ceramide was applied in a neutron diffraction experiment. Therefore, a SC lipid model membrane was prepared containing the described ceramide (CER), cholesterol (CHOL), stearic acid (SA), and cholesterol sulfate (ChS) in a ratio of 55/25/15/5wt%...
February 12, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28196533/assessment-of-complementary-feeding-of-canadian-infants-effects-on-microbiome-oxidative-stress-a-randomized-controlled-trial
#5
Wafaa Qasem, Meghan B Azad, Zakir Hossain, Elnaz Azad, Sarah Jorgensen, Sandra Castillo San Juan, Chenxi Cai, Ehsan Khafipour, Trust Beta, L Jackson Roberts, James Friel
BACKGROUND: The World Health Organization recommends exclusive breastfeeding until 6 months followed by introduction of iron-rich complementary foods (CFs). The aim of this study was to determine the impact of different iron-rich CFs on infant gut inflammation and microbiota. METHODS: Eighty-seven exclusively breastfed infants were randomly assigned to receive one of the following as their first CF: iron-fortified cereal (Cer), iron-fortified cereal with fruit (Cer + Fr), or meat (M)...
February 14, 2017: BMC Pediatrics
https://www.readbyqxmd.com/read/28190803/characterization-of-a-novel-rhamnose-containing-acidic-glycosphingolipid-from-the-ascidian-halocynthia-aurantium
#6
Hisao Kojima, Ryota Shinohara, Saki Itonori, Masahiro Ito
Halocynthia aurantium, an edible ascidian species belonging to Urochordata, was subjected to structural characterization of acidic glycosphingolipids to investigate these molecules in ascidians: sulfatide from Ciona intestinalis and the glucuronic acid-containing acidic glycosphingolipid from H. roretzi. Acidic glycosphingolipids containing three or five sugars were isolated from soft parts of the ascidian H. aurantium by chloroform-methanol extraction, mild-alkaline hydrolysis, precipitation with cold acetone, and subsequent column chromatography using a DEAE-Sephadex A-25 column, a Florisil column, and an Iatrobead column...
February 10, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28188720/the-effect-of-non-deuterated-and-deuterated-isopropyl-myristate-on-the-thermodynamical-and-structural-behavior-of-a-2d-stratum-corneum-model-with-ceramide-ap
#7
J S L Oliveira, S Lange, B Dobner, G Brezesinski
Isopropyl myristate (IPM) is a widely used penetration enhancer in pharmaceutical formulations, however, its mechanism of action on a molecular scale is still not completely understood. Previous work using a quaternary Stratum Corneum (SC) lipid model in bulk suggested the incorporation of isopropyl myristate into the SC lipid matrix, phase separation, and perturbation of the multilamellar lipid assembly. Here, we used 2D Langmuir monolayers of a ternary SC lipid model, containing ceramide AP C18:18, stearic acid and cholesterol in a molar ratio of [1:1:0...
February 7, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28188148/analysis-of-sphingolipids-in-human-corneal-fibroblasts-from-normal-and-keratoconus-patients
#8
Hui Qi, Shrestha Priyadarsini, Sarah E Nicholas, Akhee Sarker-Nag, Jeremy Allegood, Charles E Chalfant, Nawajes A Mandal, Dimitrios Karamichos
The pathophysiology of human keratoconus (KC), a bilateral progressive corneal disease, leading to protrusion of the cornea, stromal thinning, and scarring is not well understood. In this study we investigated a novel Sphingolipid (SPL) signaling pathway through which KC may be regulated. Using human corneal fibroblasts (HCF) and human keratoconus cells (HKC) we examined the SPL pathway modulation. Both cell types were stimulated by the three TGF-β isoforms: TGF-B1 (T1), B2 (T2), and B3 (T3). All samples were analyzed using lipidomics, and real time-PCR...
February 10, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28183032/manganese-neurotoxicity-and-protective-effects-of-resveratrol-and-quercetin-in-preclinical-research
#9
Maciej Gawlik, Małgorzata B Gawlik, Irena Smaga, Małgorzata Filip
BACKGROUND: Exposure to Mn results in a neurological syndrome known as manganism. METHODS: We examined how 4-week Mn exposure (20mg/kg MnCl2po, 5days/week) induces neurotoxic effects in rats. Oxidized-to-reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, catalase (CAT) activity, vitamin E content and caspase-3 activity were measured in several rat brain structures. Further, we examined protective effects of the polyphenols: resveratrol (R) or quercetin (QCT) against Mn-induced neurotoxicity...
December 14, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28177564/involving-latina-o-parents-in-patient-centered-outcomes-research-contributions-to-research-study-design-implementation-and-outcomes
#10
Mónica Pérez Jolles, Maria Martinez, San Juanita Garcia, Gabriela L Stein, Kathleen C Thomas
BACKGROUND: Comparative effectiveness research (CER) is supported by policymakers as a way to provide service providers and patients with evidence-based information to make better health-care decisions and ultimately improve services for patients. However, Latina/o patients are rarely involved as study advisors, and there is a lack of documentation on how their voices contribute to the research process when they are included as collaborators. OBJECTIVES: The purpose of this article was to contribute to the literature by presenting concrete contributions of Latina/o parent involvement to study design, implementation and outcomes in the context of a CER study called Padres Efectivos (Parent Activation)...
February 8, 2017: Health Expectations: An International Journal of Public Participation in Health Care and Health Policy
https://www.readbyqxmd.com/read/28173724/patient-caregiver-and-clinician-use-of-comparative-effectiveness-research-findings-in-care-decisions-results-from-a-national-study
#11
Lori B Frank, Laura P Forsythe, Thomas A Workman, Tandrea Hilliard, Mary Lavelle, Daniel Harwell, Lauren Fayish
AIM: To assess awareness, use and attitudes concerning comparative effectiveness research (CER) findings. MATERIALS & METHODS: Online surveys of patients and caregivers managing rare (n = 560 patients, n = 609 caregivers) or chronic conditions (n = 762 patients, n = 776 caregivers), and practicing clinicians (n = 638). RESULTS: Less than half of patients and caregivers reported exposure to any type of CER findings in the past 12 months. Of those, over half identify healthcare professionals as the information source, yet only 10% of clinicians indicated they were 'very familiar' with CER...
February 8, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28173710/health-researcher-views-on-comparative-effectiveness-research-and-research-engagement
#12
Laura P Forsythe, Lori B Frank, Thomas A Workman, Amanda Borsky, Tandrea Hilliard, Daniel Harwell, Lauren Fayish
AIM: To understand researcher capability for and interest in patient-centered comparative effectiveness research (PC-CER), particularly related to engaging with patients/caregivers. MATERIALS & METHODS: Web-based survey of 508 health researchers recruited via professional health research organizations. RESULTS: Most respondents (94%) were familiar with CER and many (69%) reported having previously conducting some form of CER. Most respondents were familiar with (81%) and interested in (87%) partnering with patients and/or caregivers in research...
February 8, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/28170002/regulation-of-dopaminergic-function-an-18-f-dopa-pet-apomorphine-challenge-study-in-humans
#13
S Jauhar, M Veronese, M Rogdaki, M Bloomfield, S Natesan, F Turkheimer, S Kapur, O D Howes
Dopaminergic function has a key role in normal brain function, dopaminergic dysfunction being implicated in numerous neuropsychiatric disorders. Animal studies show that dopaminergic stimulation regulates dopaminergic function, but it is not known whether this exists in humans. In the first study (study 1), we measured dopamine synthesis capacity (indexed as Ki(cer)) to identify the relationship between baseline and change in Ki(cer) under resting conditions for comparison with effects of dopaminergic stimulation...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28164012/effect-of-serial-infusions-of-reconstituted-high-density-lipoprotein-cer-001-on-coronary-atherosclerosis-rationale-and-design-of-the-carat-study
#14
Jordan Andrews, Alex Janssan, Tracy Nguyen, Anthony D Pisaniello, Daniel J Scherer, John J P Kastelein, Bela Merkely, Steven E Nissen, Kausik Ray, Gregory G Schwartz, Stephen G Worthley, Connie Keyserling, Jean-Louis Dasseux, Julie Butters, Jacinta Girardi, Rosemary Miller, Stephen J Nicholls
BACKGROUND: High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS)...
February 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28163861/cost-effectiveness-of-zoledronic-acid-to-prevent-and-treat-postmenopausal-osteoporosis-in-comparison-with-routine-medical-treatment
#15
Fateme Rostami Golmohamdi, Mahnaz Abbasi, Ali Kazemi Karyani, Ali Akbari Sari
INTRODUCTION: Fractures caused by osteoporosis are prevalent among elderly females, which reduce quality of life significantly. This study aimed at comparing cost-effectiveness of Zoledronic acid in preventing and treating post-menopause osteoporosis as compared with routine medical treatment. METHODS: This cost-effectiveness study was carried out retrospectively from the Ministry of Health and insurance organizations perspective. Costs were evaluated based on the cost estimation of a sample of patients...
December 2016: Electronic Physician
https://www.readbyqxmd.com/read/28159270/lipidomics-profiling-of-goat-milk-soymilk-and-bovine-milk-by-uplc-q-exactive-orbitrap-mass-spectrometry
#16
Qiangqiang Li, Yan Zhao, Dan Zhu, Xiumei Pang, Yue Liu, Russell Frew, Gang Chen
Lipids are very important for human health and milk is a rich dietary source of lipids. In this study, the lipid content in three types of milk (goat, soy and bovine) were determined by using UPLC-Q-Exactive Orbitrap Mass Spectrometry. A total of 13 classes of lipids (including Cer, SM, LPC, PC, PE, DG, TG, PA, PG, PI, PS, LPE, FA) were measured. Moreover, lipid profiles differed significantly between the different milk types. Soymilk is rich in phospholipids including PC, PE, PS, PG, while goat milk is rich in medium chain triglycerides (MCT), USFA, ω-6 FA and ω-3 FA, especially EPA and DHA...
June 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28157411/novel-lipidomic-biomarkers-in-hyperlipidemia-and-cardiovascular-diseases-an-integrative-biology-analysis
#17
Sneha Rai, Sonika Bhatnagar
Lipidomics is a new frontier of omics research and offers much promise for new-generation biomarkers for common complex phenotypes such as hyperlipidemia (HL) and cardiovascular diseases (CVDs). HL is a disorder characterized by increased levels of blood lipids and is a well-established risk factor for CVD. Traditional clinical markers for prognosis of hyperlipidemic individuals are inadequate to forecast or diagnose cardiac events. In this expert review, lipidomic profiles from recent HL and CVD studies were compared with the normolipidemic profile prepared from the Standard Reference Material...
February 3, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28154307/molecular-interaction-between-intercellular-lipids-in-the-stratum-corneum-and-l-menthol-as-analyzed-by-synchrotron-x-ray-diffraction
#18
Shinya Yoshida, Yasuko Obata, Yoshinori Onuki, Shunichi Utsumi, Noboru Ohta, Hiroshi Takahashi, Kozo Takayama
l-Menthol increases drug partitioning on the surface of skin, diffusion of drugs in the skin, and lipid fluidity in the stratum corneum and alters the rigidly arranged lipid structure of intercellular lipids. However, l-menthol is a solid at room temperature, and it is difficult to determine the effects of l-menthol alone. In this study, we vaporized l-menthol in order to avoid the effects of solvents. The vaporized l-menthol was applied to the stratum corneum or lipid models comprising composed of ceramides (CER) [EOS], the longest lipid acyl chain of the ceramides in the stratum corneum lipids that is associated with the barrier function of the skin; CER [NS], the shorter lipid acyl chain of the ceramides, and the most components in the stratum corneum of the intercellular lipids that is associated with water retention in the intercellular lipid structure of the stratum corneum; cholesterol; and palmitic acid...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28153667/quantitative-analysis-of-gadoxetic-acid-enhanced-magnetic-resonance-imaging-predicts-histological-grade-of-hepatocellular-carcinoma
#19
Hong-Fei Tong, Hong-Bo Liang, Zhi-Kang Mo, Tian-Pei Guan, Jian Yang, Chi-Hua Fang
OBJECTIVE: To confirm the histological grade of hepatocellular carcinoma (HCC) by gadoxetic acid-enhanced MRI. METHODS: Ninety-five HCC patients underwent gadoxetic acid-enhanced MRI before surgical intervention. The correlations among the signal absolute enhancement, contrast enhancement ratio (CER) and tumor histological grade were analyzed. RESULTS: The correlation between CER of tumor-to-liver and the grades of tumor differentiation is the most significant negative...
January 11, 2017: Clinical Imaging
https://www.readbyqxmd.com/read/28153310/high-precision-direct-analysis-of-magnesium-isotope-ratio-by-ion-chromatography-multicollector-icpms-using-wet-and-dry-plasma-conditions
#20
Jakub Karasinski, Ewa Bulska, Marcin Wojciechowski, Ludwik Halicz, Agnieszka Anna Krata
In this work the applicability of Ion Chromatography (IC) coupled to Multicollector Inductively Coupled Plasma Mass Spectrometry (MC-ICPMS) for on-line magnesium isotope ratio analysis was explored. Various instrumental setups were employed to enable continuous magnesium separation from the sample matrix by IC followed by MC-ICPMS. The performance of two separation columns IonPac CS16 (ID 5mm or ID 3mm) connected with appropriate CERS 500 suppressors (4mm or 2mm) using dry and wet plasma conditions was compared...
April 1, 2017: Talanta
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