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https://www.readbyqxmd.com/read/29042321/multimodal-imaging-approach-to-examine-biodistribution-kinetics-of-cabotegravir-gsk1265744-long-acting-parenteral-formulation-in-rat
#1
Beat M Jucker, Hasan Alsaid, Mary Rambo, Stephen C Lenhard, Bao Hoang, Fang Xie, M Reid Groseclose, Stephen Castellino, Valeriu Damian, Gary Bowers, Manish Gupta
Long-Acting Parenterals (LAPs) have been used in the clinic to provide sustained therapeutic drug levels at a target site, and thereby reducing the frequency of dosing required. In an effort to understand the factors associated with long-acting cabotegravir (GSK1265744 LAP) pharmacokinetic variability, the current study was designed to investigate the temporal relationship between intramuscular (IM) or subcutaneous (SC) drug depot morphology and distribution kinetics with plasma pharmacokinetics. Therefore, a multi-modal molecular imaging (MRI & MALDI IMS) approach was employed to examine the temporal GSK1265744 LAP biodistribution in rat following either IM or SC administration...
October 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29040230/serum-concentrations-of-paliperidone-after-administration-of-the-long-acting-injectable-formulation
#2
Arne Helland, Olav Spigset
BACKGROUND: The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring (TDM) service. METHODS: Serum concentration measurements in 310 samples from 110 male and 75 female patients receiving depot injections of paliperidone were retrospectively retrieved from the TDM database...
October 14, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29039241/aripiprazole-long-acting-injection-a-mirror-image-study-of-its-effects-on-hospitalisation-at-one-year
#3
David M Taylor, Anna Sparshatt, Fahima Amin, Ian Osborne, Olubanke Dzahini, Gwenllian Hughes, Catrin Fischetti
Second generation antipsychotic long-acting injections have a greater cost than older depots. Their cost-effectiveness has yet to be established. We conducted a non-interventional, observational, follow-up of patients prescribed aripiprazole long-acting injection in two centres using a mirror image method. Data were available for 160 patients consecutively prescribed aripiprazole long-acting injection, of whom 30 were not included in the analysis (21 forensic patients, five incomplete data and four lost to follow-up)...
October 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29038978/panuveitis-like-reaction-following-encircling-laser-retinopexy-cerclage-in-a-21-year-old-male
#4
David Francis Fullon Chan, Milagros Herrera-Arroyo, Darby E Santiago, Teresita R Castillo, Ma Florentina Q Fajardo-Gomez
BACKGROUND: Severe vision-impairing ocular inflammation is rarely reported following extensive laser. Previous cases have involved retinal photocoagulation for diabetic retinopathy resolving over days. This report documents a rare instance of this where encircling retinopexy/cerclage was done as fellow eye retinal detachment prophylaxis in a patient with no overt comorbidities. RESULTS: A panuveitis-like reaction with severe, near-total visual impairment was documented 1 day following single-sitting encircling laser retinopexy/cerclage done as fellow eye prophylaxis for a 21-year-old male presenting with total retinal detachment in the other eye...
October 16, 2017: Journal of Ophthalmic Inflammation and Infection
https://www.readbyqxmd.com/read/29038352/differential-relationships-of-hepatic-and-epicardial-fat-to-body-composition-in-hiv
#5
Lindsay T Fourman, Michael T Lu, Hang Lee, Kathleen V Fitch, Travis R Hallett, Jakob Park, Natalia Czerwonka, Julian Weiss, Takara L Stanley, Janet Lo, Steven K Grinspoon
HIV-infected patients commonly experience changes in central and peripheral fat content as well as ectopic fat accumulation. However, whether hepatic and epicardial fat stores relate differentially to body composition or how these associations are modified by HIV status has not been well explored. A previously recruited sample of 124 HIV-infected patients and 58 healthy controls had undergone dual energy X-ray absorptiometry (DEXA) and computed tomography (CT) from which body composition measures, liver-spleen ratio, and epicardial fat volume were obtained...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29038234/patient-reported-symptom-control-of-diarrhea-and-flushing-in-patients-with-neuroendocrine-tumors-treated-with-lanreotide-depot-autogel-results-from-a-randomized-placebo-controlled-double-blind-and-32-week-open-label-study
#6
George A Fisher, Edward M Wolin, Nilani Liyanage, Susan Pitman Lowenthal, Beloo Mirakhur, Rodney F Pommier, Montaser Shaheen, Aaron Vinik
BACKGROUND: In the double-blind (DB) ELECT study, lanreotide depot/autogel significantly reduced versus placebo the need for short-acting octreotide for symptomatic carcinoid syndrome (CS) control in neuroendocrine tumor (NET) patients. Here we present patient-reported symptom data during DB and initial open-label (IOL) treatment. MATERIALS AND METHODS: Adults with NETs and CS history, with/without prior somatostatin analog use, were randomized to 16 weeks' DB lanreotide 120 mg subcutaneous or placebo every 4 weeks, followed by 32 weeks' IOL lanreotide...
October 16, 2017: Oncologist
https://www.readbyqxmd.com/read/29037895/title-in-situ-depot-formation-of-anti-hiv-fusion-inhibitor-peptide-in-recombinant-protein-polymer-hydrogel
#7
Daisuke Asai, Taisei Kanamoto, Mitsuko Takenaga, Hideki Nakashima
Most peptide drugs have short half-lives, necessitating frequent injections that may induce skin sensitivity reactions; therefore, versatile prolonged-release delivery platforms are urgently needed. Here, we focused on an oxidatively and thermally responsive recombinant elastin-like polypeptide with periodic cysteine residues (cELP), which can rapidly and reversibly form a disulfide cross-linked network in which peptide can be physically incorporated. As a model for proof of concept, we used enfuvirtide, an antiretroviral fusion-inhibitor peptide approved for treatment of human immunodeficiency virus (HIV) infection...
October 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29035280/adipocyte-cannabinoid-receptor-cb1-regulates-energy-homeostasis-and-alternatively-activated-macrophages
#8
Inigo Ruiz de Azua, Giacomo Mancini, Raj Kamal Srivastava, Alejandro Aparisi Rey, Pierre Cardinal, Laura Tedesco, Cristina Maria Zingaretti, Antonia Sassmann, Carmelo Quarta, Claudia Schwitter, Andrea Conrad, Nina Wettschureck, V Kiran Vemuri, Alexandros Makriyannis, Jens Hartwig, Maria Mendez-Lago, Laura Bindila, Krisztina Monory, Antonio Giordano, Saverio Cinti, Giovanni Marsicano, Stefan Offermanns, Enzo Nisoli, Uberto Pagotto, Daniela Cota, Beat Lutz
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29029184/low-plasma-adiponectin-concentrations-predict-increases-in-visceral-adiposity-and-insulin-resistance
#9
Seung Jin Han, Edward J Boyko, Wilfred Y Fujimoto, Steven E Kahn, Donna L Leonetti
Context: Plasma adiponectin concentration has been shown to be inversely associated with body mass index (BMI) and insulin resistance in cross-sectional research. However, it is unclear whether adiponectin predicts future body composition and insulin resistance. Objective: To investigate the potential relationship between adiponectin concentration and future regional body fat distribution and insulin resistance. Design and Setting: Community-based prospective cohort study with 5 years of follow-up...
September 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29029113/estrogen-metabolism-in-abdominal-subcutaneous-and-visceral-adipose-tissue-in-postmenopausal-women
#10
Natalia Hetemäki, Hanna Savolainen-Peltonen, Matti J Tikkanen, Feng Wang, Hanna Paatela, Esa Hämäläinen, Ursula Turpeinen, Mikko Haanpää, Veera Vihma, Tomi S Mikkola
CONTEXT: In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. While increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. OBJECTIVE: We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for non-malignant gynecological reasons...
September 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29027120/elucidating-the-preadipocyte-and-its-role-in-adipocyte-formation-a-comprehensive-review
#11
REVIEW
Christos N Sarantopoulos, Derek A Banyard, Mary E Ziegler, Beatrice Sun, Ashkaun Shaterian, Alan D Widgerow
Adipogenesis is a complex process whereby the multipotent adipose-derived stem cell is converted to a preadipocyte before terminal differentiation into the mature adipocyte. Preadipocytes are present throughout adult life, exhibit adipose fat depot specificity, and differentiate and proliferate from distinct progenitor cells. The mechanisms that promote preadipocyte commitment and maturation involve numerous protein factor regulators, epigenetic factors, and miRNAs. Detailed characterization of this process is currently an area of intense research and understanding the roles of preadipocytes in tissue plasticity may provide insight into novel approaches for tissue engineering, regenerative medicine and treating a host of obesity-related conditions...
October 13, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/29025708/intermuscular-adipose-tissue-and-subclinical-coronary-artery-calcification-in-midlife-the-cardia-study-coronary-artery-risk-development-in-young-adults
#12
James G Terry, Christina M Shay, Pamela J Schreiner, David R Jacobs, Otto A Sanchez, Jared P Reis, David C Goff, Samuel S Gidding, Lyn M Steffen, John Jeffrey Carr
OBJECTIVE: Excess deposition of fat within and around vital organs and nonadipose tissues is hypothesized to contribute to cardiovascular disease (CVD) risk. We evaluated the association of abdominal intermuscular adipose tissue (IMAT) volume with coronary artery calcification in CARDIA study (Coronary Artery Risk Development in Young Adults) participants. APPROACH AND RESULTS: We measured IMAT in the abdominal muscles, visceral adipose tissue and pericardial adipose tissue, and coronary artery calcification using computed tomography in 3051 CARDIA participants (56% women) at the CARDIA year 25 examination (2010-2011)...
October 12, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29024495/differences-in-the-neovascular-potential-of-thymus-versus-subcutaneous-adipose-derived-stem-cells-from-patients-with-myocardial-ischemia
#13
Wilfredo Oliva-Olivera, Leticia Coín-Aragüez, Said Lhamyani, Julián Salas, Adiana-Mariel Gentile, Silvana-Yanina Romero-Zerbo, Hatem Zayed, J F Valderrama, Francisco José Tinahones, Rajaa E L Bekay
Adipose tissue-derived multipotent mesenchymal cells (ASCs) participate in the formation of blood vessels under hypoxic conditions. It is probable that the susceptibility of ASCs to the influence of age and aging-associated pathologies compromises their therapeutic effectiveness depending on the adipose tissue (AT) depot. Our aim was to examine the neovascular potential under hypoxic conditions of ASCs-derived from thymic (thymASCs) and subcutaneous (subASCs) AT from 39 subjects with and without type 2 diabetes mellitus (T2DM) and of different ages who were undergoing coronary bypass surgery (CBS)...
October 11, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29020342/lack-of-ovarian-secretions-reverts-the-anabolic-action-of-olanzapine-in-female-rats
#14
Silje Skrede, Ismael González-García, Luís Martins, Rolf Kristian Berge, Ruben Nogueiras, Manuel Tena-Sempere, Gunnar Mellgren, Vidar Martin Steen, Miguel López, Johan Fernø
Background: Olanzapine (OLZ) is an orexigenic antipsychotic drug associated with serious metabolic adverse effects in humans. Development of valid rodent models for antipsychotic-induced metabolic adverse effects is hampered by the fact that such effects occur in females only. Estradiol (E2) is a predominant female hormone that regulates energy balance. We hypothesized that the female-specific hyperphagia and weight gain induced by OLZ in the rat are dependent on the presence of estrogens...
August 14, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29017592/omentin-1-effects-on-mesenchymal-stem-cells-proliferation-apoptosis-and-angiogenesis-in-vitro
#15
Li Yin, Dan Huang, Xinxin Liu, Yongshun Wang, Jingjin Liu, Fang Liu, Bo Yu
BACKGROUND: Mesenchymal stem cells (MSCs) are emerging as an extremely promising therapeutic agent for tissue repair. However, limitations exist such as the low numbers of MSCs obtained from donors, and the poor survival and function of donor cells. Omentin-1, a new fat depot-specific secretory adipokine, exerts proproliferation, prosurvival, and proangiogenic functions in certain cells via an Akt-dependent mechanism; however, little is known about the influence of omentin-1 on MSCs. METHODS: MSCs were isolated from 60-80 g donor rats...
October 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28994775/assessment-of-human-adipose-tissue-microvascular-function-using-videomicroscopy
#16
Melissa G Farb, Song-Young Park, Shakun Karki, Noyan Gokce
While obesity is closely linked to the development of metabolic and cardiovascular disease, little is known about mechanisms that govern these processes. It is hypothesized that pro-atherogenic mediators released from fat tissues particularly in association with central/visceral adiposity may promote pathogenic vascular changes locally and systemically, and the notion that cardiovascular disease may be the consequence of adipose tissue dysfunction continues to evolve. Here, we describe a unique method of videomicroscopy that involves analysis of vasodilator and vasoconstrictor responses of intact small human arterioles removed from the adipose depot of living human subjects...
September 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28992034/the-effect-of-energy-restriction-on-fatty-acid-profiles-of-longissimus-dorsi-and-tissue-adipose-depots-in-sheep
#17
S Z Song, J P Wu, S G Zhao, D P Casper, B He, T Liu, X Lang, X Y Gong, L S Liu
Sheep production systems in northwest China depend mostly on natural grasslands. Seasonal growth and maturity fluctuations can cause periodical restrictions in food quality and quantity. These fluctuations, in turn, result in variability in fat deposition and fatty acid profiles in different fat depots. Consequently, the study objective was to compare fat deposition, intramuscular fat (IMF) percentage and fatty acid profiles of the longissimus dorsi (LD), kidney fat (KF), tail fat (TF), and subcutaneous fat (SF) in lambs under ME restrictions similar to seasonal changes observed in the natural grasslands of northwest China...
September 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28989976/hematopoietic-stem-cell-derived-adipocytes-promote-tumor-growth-and-cancer-cell-migration
#18
Y Xiong, D L Russell, L T McDonald, L A Cowart, A C LaRue
Adipocytes, apart from their critical role as the energy storage depots, contribute to the composition of the tumor microenvironment. Our previous studies based on a single hematopoietic stem cell (HSC) transplantation model, have revealed a novel source of adipocytes from HSCs via monocyte/macrophage progenitors. Herein, we extend these studies to examine the role of HSC-derived adipocytes (HSC-Ad) in tumor progression. When cultured under adipogenic conditions, bone marrow-derived monocytic progenitors differentiated into adipocytes that accumulated oil droplets containing triglyceride...
2017: International Journal of Cancer Research and Molecular Mechanisms
https://www.readbyqxmd.com/read/28987880/heparin-functionalized-polymer-graft-surface-eluting-mk2-inhibitory-peptide-to-improve-hemocompatibility-and-anti-neointimal-activity
#19
Yunki Lee, Phuong Le Thi, Gyeung Mi Seon, Seung Bae Ryu, Colleen M Brophy, YongTae Kim, Jong-Chul Park, Ki Dong Park, Joyce Cheung-Flynn, Hak-Joon Sung
The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64...
October 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28985509/untangling-p-bodies-dissecting-the-complex-web-of-interactions-that-enable-tiered-control-of-gene-expression
#20
Christopher J Kershaw, Mark P Ashe
In this issue of Molecular Cell, Hubstenberger et al. (2017) define the molecular composition of P-bodies isolated from human epithelial cells to propose that these foci act as mRNA storage depots rather than mRNA decay facilities.
October 5, 2017: Molecular Cell
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