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https://www.readbyqxmd.com/read/27905067/mathematical-model-of-bone-remodeling-captures-the-antiresorptive-and-anabolic-actions-of-various-therapies
#1
David S Ross, Khamir Mehta, Antonio Cabal
A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27891289/nor-bni-antagonism-of-kappa-opioid-agonist-induced-reinstatement-of-ethanol-seeking-behavior
#2
Erin Harshberger, Emily A Gilson, Kelli Gillett, Jasmine H Stone, Laila El Amrani, Glenn R Valdez
Recent work suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system may be a key mediator in the behavioral effects of alcohol. The objective of the present study was to examine the ability of the KOR antagonist norbinaltorphimine (nor-BNI) to attenuate relapse to ethanol seeking due to priming injections of the KOR agonist U50,488 at time points consistent with KOR selectivity. Male Wistar rats were trained to self-administer a 10% ethanol solution, and then responding was extinguished. Following extinction, rats were injected with U50,488 (0...
2016: Journal of Addiction
https://www.readbyqxmd.com/read/27887774/rationale-and-study-design-of-respite-an-open-label-phase-3b-study-of-riociguat-in-patients-with-pulmonary-arterial-hypertension-who-demonstrate-an-insufficient-response-to-treatment-with-phosphodiesterase-5-inhibitors
#3
Marius M Hoeper, James R Klinger, Raymond L Benza, Gerald Simonneau, David Langleben, Robert Naeije, Paul A Corris
Patients with pulmonary arterial hypertension (PAH) who do not have an adequate response to therapy with phosphodiesterase-5 inhibitors (PDE-5i) may have insufficient synthesis of cyclic guanosine monophosphate (cGMP). These patients may respond to a direct soluble guanylate cyclase (sGC) stimulator such as riociguat. RESPITE (NCT02007629) was an open-label, multicenter, uncontrolled, single-arm phase 3b study of riociguat in patients with PAH who demonstrated an insufficient response to treatment with PDE-5i...
November 5, 2016: Respiratory Medicine
https://www.readbyqxmd.com/read/27884008/left-ventricular-plication-reduces-wall-stress-and-cardiomyocyte-hypertrophy-in-a-rat-model-of-ischemic-cardiomyopathy
#4
Hidetsugu Asai, Yasushige Shingu, Tomoji Yamakawa, Haruki Niwano, Satoru Wakasa, Tomonori Ooka, Hiroki Kato, Tsuyoshi Tachibana, Yoshiro Matsui
BACKGROUND: The indications of left-ventricular plication (LVP) are controversial, although several studies have reported favorable outcomes in heart failure patients. The aim of this study was to assess left-ventricular (LV) wall stress and myocardial remodeling after LVP in a rat model of myocardial infarction (MI). METHODS: Sixteen rats underwent LVP by excluding the LV anterior wall scar 4 weeks after ligation of the left anterior descending artery. After 4 weeks, LV wall stress was assessed using transthoracic echocardiography and an LV catheter...
November 25, 2016: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/27872912/chirality-sensing-and-discrimination-of-lysine-derivatives-in-water-with-a-dyn-4-arene
#5
Laurent Vial, Melissa Dumartin, Marion Donnier-Maréchal, Florent Perret, Jean-Patrick Francoia, Julien Leclaire
The asymmetric deformation of a dyn[4]arene upon the binding of various lysine derivatives leads to distinct induced circular dichroism outputs in buffered water, which can be exploited not only for the determination of their enantiomeric excesses, but also for their classification by linear discriminant analysis.
November 22, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27847162/patient-specific-computational-fluid-dynamics-assessment-of-aortic-hemodynamics-in-a-spectrum-of-aortic-valve-pathologies
#6
Pouya Youssefi, Alberto Gomez, Taigang He, Lisa Anderson, Nick Bunce, Rajan Sharma, C Alberto Figueroa, Marjan Jahangiri
OBJECTIVES: The complexity of aortic disease is not fully exposed by aortic dimensions alone, and morbidity or mortality can occur before intervention thresholds are met. Patient-specific computational fluid dynamics (CFD) were used to assess the effect of different aortic valve morphologies on velocity profiles, flow patterns, helicity, wall shear stress (WSS), and oscillatory shear index (OSI) in the thoracic aorta. METHODS: A total of 45 subjects were divided into 5 groups: volunteers, aortic regurgitation-tricuspid aortic valve (AR-TAV), aortic stenosis-tricuspid aortic valve (AS-TAV), aortic stenosis-bicuspid aortic valve right-left cusp fusion (BAV[RL]), and aortic stenosis-right-non cusp fusion (AS-BAV[RN])...
September 23, 2016: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/27845924/temperature-dependent-heterogeneous-rotational-correlation-in-lipids
#7
Neda Dadashvand, Christina M Othon
Lipid structures exhibit complex and highly dynamic lateral structure; and changes in lipid density and fluidity are believed to play an essential role in membrane targeting and function. The dynamic structure of liquids on the molecular scale can exhibit complex transient density fluctuations. Here the lateral heterogeneity of lipid dynamics is explored in free standing lipid monolayers. As the temperature is lowered the probes exhibit increasingly broad and heterogeneous rotational correlation. This increase in heterogeneity appears to exhibit a critical onset, similar to those observed for glass forming fluids...
November 15, 2016: Physical Biology
https://www.readbyqxmd.com/read/27836440/reticulocyte-hemoglobin-content-mchr-in-the-detection-of-iron-deficiency
#8
Eloísa Urrechaga Igartua, Johannes J M L Hoffmann, Silvia Izquierdo-Álvarez, Jesús F Escanero
BACKGROUND: Blood hemoglobin (Hb) concentration within the reference interval does not exclude iron deficiency (ID): individuals with normal stores lose iron during a long period before their Hb falls below of the level that is defined as anemia. The process entails a decrease of storage iron, shown by serum ferritin below reference range, followed by iron depletion, eventually leading to iron restricted erythropoiesis; consequence of an imbalance between erythropoietic iron requirements and too low supply is a reduction of Hb synthesis in reticulocytes...
November 4, 2016: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27822327/modulating-wall-shear-stress-gradient-via-equilateral-triangular-channel-for-in-situ-cellular-adhesion-assay
#9
Hyung Woo Kim, Seonjin Han, Wonkyoung Kim, Jiwon Lim, Dong Sung Kim
This study introduces an equilateral triangular channel (ETRIC), a novel microfluidic channel with an equilateral triangular cross-section, for cell adhesion assay by modulating the wall shear stress (WSS) gradient. The channel can generate a parabolic WSS gradient perpendicular to the flow direction at a single flow rate, and cell detachment can be in situ screened in response to spatially different levels of WSS. The existence of a simple form of exact solution for the velocity field inside the entire ETRIC region enables the easy design and modulation of the WSS levels at the bottom surface; therefore, the detachment of the cells can be investigated at the pre-defined observation window in real time...
September 2016: Biomicrofluidics
https://www.readbyqxmd.com/read/27806729/hematological-reference-intervals-determination-in-adults-at-gondar-university-hospital-northwest-ethiopia
#10
Aregawi Yalew, Betelihem Terefe, Meseret Alem, Bamlaku Enawgaw
BACKGROUND: Hematological reference values are important for the clinical decisions in laboratory diagnosis and monitoring of patients. The correct interpretation of laboratory results depends entirely on the reference intervals that have been established for the locality. But, in sub-Saharan African countries particularly in Ethiopia, locally derived reference intervals were not established and they are forced to use intervals established from western population. Thus this study aimed to establish locally derived hematological reference values that could be used in Northwest Ethiopia...
November 2, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27797517/structure-activity-relationships-of-des-arg-7-dynorphin-a-analogues-at-the-kappa-opioid-receptor
#11
Cyf N Ramos-Colon, Yeon Sun Lee, Michael Vincent Remesic, Sara M Hall, Justin LaVigne, Peg Davis, Alexander J Sandweiss, Mary I McIntosh, Jessica Hanson, Tally M Largent-Milnes, Todd W Vanderah, John M Streicher, Frank Porreca, Victor J Hruby
Dynorphin A (Dyn A) is an endogenous ligand for the opioid receptors with preference for the kappa opioid receptor (KOR), and its structure-activity relationship (SAR) has been extensively studied at the KOR to develop selective potent agonists and antagonists. Numerous SAR studies have revealed that the Arg(7) residue is essential for KOR activity. In contrast, our systematic SAR studies on [des-Arg(7)]-Dyn A analogues found that Arg(7) is not a key residue and even deletion of the residue does not affect biological activities at the KOR...
October 31, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27796753/promotion-of-the-unfolding-protein-response-in-orexin-dynorphin-neurons-in-sudden-infant-death-syndrome-sids-elevated-pperk-and-atf4-expression
#12
Nicholas J Hunt, Karen A Waters, Rita Machaalani
We previously demonstrated that sudden infant death syndrome (SIDS) infants have decreased orexin immunoreactivity within the hypothalamus and pons compared to non-SIDS infants. In this study, we examined multiple mechanisms that may promote loss of orexin expression including programmed cell death, impaired maturation/structural stability, neuroinflammation and impaired unfolding protein response (UPR). Immunofluorescent and immunohistochemical staining for a number of markers was performed in the tuberal hypothalamus and pons of infants (1-10 months) who died from SIDS (n = 27) compared to age- and sex-matched non-SIDS infants (n = 19)...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27765843/the-blood-pressure-reduction-after-gastric-bypass-surgery-is-explained-by-a-decrease-in-cardiac-output
#13
Peter Mathijs van Brussel, Bas van den Bogaard, Barbara A de Weijer, Jasper Truijen, Paul Ct Krediet, Ignace M Janssen, Arnold van de Laar, Karin A Kaasjager, Eric Fliers, Johannes J Van Lieshout, Mireille Johanna Serlie, Bert-Jan H van den Born
BACKGROUND: Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet, the pathophysiology of the BP lowering effects observed after gastric bypass surgery are incompletely understood. METHODS: We evaluated BP, systemic hemodynamics and baroreflex sensitivity in 15 obese women (mean age 42±7 yrs, body mass index 45±6 kg/m(2)) two weeks before and six weeks following Roux-and-Y gastric bypass surgery. RESULTS: Six weeks after gastric bypass surgery mean body weight decreased by 13±5 kg (10%, p<0...
October 20, 2016: Journal of Applied Physiology
https://www.readbyqxmd.com/read/27763913/the-open-lung-approach-improves-pulmonary-vascular-mechanics-in-an-experimental-model-of-acute-respiratory-distress-syndrome
#14
Arnoldo Santos, Luca Lucchetta, M Ignacio Monge-Garcia, Joao Batista Borges, Gerardo Tusman, Goran Hedenstierna, Anders Larsson, Fernando Suarez-Sipmann
OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome. DESIGN: Experimental study. SETTING: Animal research laboratory. SUBJECTS: Ten pigs, 35 ± 5.2 kg. INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation...
October 19, 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27756562/cyclic-non-opioid-dynorphin-a-analogues-for-the-bradykinin-receptors
#15
Yeon Sun Lee, Michael Remesic, Cyf Ramos-Colon, Sara M Hall, Alexander Kuzmin, David Rankin, Frank Porreca, Josephine Lai, Victor J Hruby
Nerve injury and inflammation cause up-regulation of an endogenous opioid ligand, dynorphin A (Dyn A), in the spinal cord resulting in hyperalgesia via the interaction with bradykinin receptors (BRs). This is a non-opioid neuroexcitatory effect that cannot be blocked by opioid antagonists. Our systematic structure-activity relationships study on Dyn A identified lead ligands 1 and 4, along with the key structural feature (i.e. amphipathicity) for the BRs. However, the ligands showed very low metabolic stability in plasma (t1/2 <1h) and therefore, in order to improve their metabolic stabilities with retained biological activities, various modifications were performed...
October 6, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27731497/low-shear-stress-attenuates-cox-2-expression-induced-by-resistin-in-human-osteoarthritic-chondrocytes
#16
Yu-Ping Su, Cheng-Nan Chen, Hsin-I Chang, Kuo-Chin Huang, Chin-Chang Cheng, Fang-Yao Chiu, Ko-Chao Lee, Chun-Min Lo, Shun-Fu Chang
Low shear stress has been proposed to play a reparative role in modulating cartilage homeostasis. Recently, epidemiological studies have found a positive correlation between the resistin level in serum and synovial fluid and osteoarthritis (OA) severity in patients. However, the effect of moderate shear stress on the catabolic stimulation of resistin in OA chondrocytes remains unclear. Hence, this study was to investigate whether low shear stress could regulate resistin-induced catabolic cyclooxygenase (COX)-2 expression in human OA chondrocytes and the underlying mechanism...
October 12, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27723319/protein-dynamics-and-contact-topology-reveal-protein-dna-binding-orientation
#17
Aravind Chandrasekaran, Justin Chan, Carmay Lim, Lee-Wei Yang
Structure-encoded conformational dynamics are crucial for biomolecular functions. However, there is insufficient evidence to support the notion that dynamics plays a role in guiding protein-nucleic acid interactions. Here, we show that protein-DNA docking orientation is a function of protein intrinsic dynamics but the binding site itself does not display unique patterns in the examined spectrum of motions. This revelation is made possible by a novel technique that locates 'dynamics interfaces' in proteins across which protein parts are anti-correlated in their slowest dynamics...
October 10, 2016: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/27702879/pulsatility-and-high-shear-stress-deteriorate-barrier-phenotype-in-brain-microvascular-endothelium
#18
Fernando Garcia-Polite, Jordi Martorell, Paula Del Rey-Puech, Pedro Melgar-Lesmes, Caroline C O'Brien, Jaume Roquer, Angel Ois, Alessandro Principe, Elazer R Edelman, Mercedes Balcells
Microvascular endothelial cells at the blood-brain barrier exhibit a protective phenotype, which is highly induced by biochemical and biomechanical stimuli. Amongst them, shear stress enhances junctional tightness and limits transport at capillary-like levels. Abnormal flow patterns can reduce functional features of macrovascular endothelium. We now examine if this is true in brain microvascular endothelial cells. We suggest in this paper a complex response of endothelial cells to aberrant forces under different flow domains...
October 4, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27698065/fluid-shear-stress-promotes-placental-growth-factor-upregulation-in-human-syncytiotrophoblast-through-the-camp-pka-signaling-pathway
#19
Edouard Lecarpentier, Anthony Atallah, Jean Guibourdenche, Marylise Hebert-Schuster, Sarah Vieillefosse, Audrey Chissey, Bassam Haddad, Guillaume Pidoux, Daniele Evain-Brion, Abdul Barakat, Thierry Fournier, Vassilis Tsatsaris
The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture...
October 3, 2016: Hypertension
https://www.readbyqxmd.com/read/27693512/cutaneous-microvascular-reactivity-and-aortic-elasticity-in-coronary-artery-disease-comparison-of-the-laser-doppler-flowmetry-and-echocardiography
#20
Edip Güvenç Çekiç, Özcan Başaran, Nesrin Filiz Başaran, Onur Elmas, Volkan Doğan, Gurbet Özge Mert, Kadir Uğur Mert, Ibrahim Altun, Fatih Akın, Murat Biteker
BACKGROUND AND AIM: Decreased vascular reactivity in atherosclerosis was previously shown. In our study, it was aimed to demonstrate the decreased vascular functions in both microvascular and macrovascular tissues and to estimate any correlation between them. METHODS: Twenty-five control outpatients with no coronary artery disease (CAD) history and 26 outpatients with CAD history were enrolled in the study. Local cutaneous post-occlusive reactive hyperemia (PORH) responses after three minutes of brachial occlusion with a pneumatic cuff were recorded noninvasively by a Perimed Periflux 5010 laser Doppler flow system...
September 28, 2016: Microvascular Research
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