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in vivo facilitated diffusion

Suheyla Cetin Karayumak, Evren Özarslan, Gozde Unal
Characterization of anisotropy via diffusion MRI reveals fiber crossings in a substantial portion of voxels within the white-matter (WM) regions of the human brain. A considerable number of such voxels could exhibit asymmetric features such as bends and junctions. However, widely employed reconstruction methods yield symmetric Orientation Distribution Functions (ODFs) even when the underlying geometry is asymmetric. In this paper, we employ inter-voxel directional filtering approaches through a cone model to reveal more information regarding the cytoarchitectural organization within the voxel...
March 14, 2018: Magnetic Resonance Imaging
Amandine Jullienne, Andrew M Fukuda, Aleksandra Ichkova, Nina Nishiyama, Justine Aussudre, André Obenaus, Jérôme Badaut
Aquaporins (AQPs) facilitate water diffusion through the plasma membrane. Brain aquaporin-4 (AQP4) is present in astrocytes and has critical roles in normal and disease physiology. We previously showed that a 24.9% decrease in AQP4 expression after in vivo silencing resulted in a 45.8% decrease in tissue water mobility as interpreted from magnetic resonance imaging apparent diffusion coefficients (ADC). Similar to previous in vitro studies we show decreased expression of the gap junction protein connexin 43 (Cx43) in vivo after intracortical injection of siAQP4 in the rat...
March 8, 2018: Scientific Reports
Zhigao Niu, Eleni Samaridou, Emilie Jaumain, Julie Coëne, Gabriela Ullio, Neha Shrestha, Josep Garcia, Matilde Durán-Lobato, Sulay Tovar, Manuel J Santander-Ortega, M Victoria Lozano, M Mar Arroyo-Jiménez, Rocío Ramos-Membrive, Iván Peñuelas, Aloïse Mabondzo, Véronique Préat, Meritxell Teixidó, Ernest Giralt, María José Alonso
The objective of this work was the development of a new drug nanocarrier intended to overcome the barriers associated to the oral modality of administration and to assess its value for the systemic or local delivery of peptides. The nanocarrier was rationally designed taking into account the nature of the intestinal barriers and was loaded with insulin, which was selected as a model peptide. The nanocarrier consisted of a nanocomplex between insulin and a hydrophobically-modified cell penetrating peptide (CPP), enveloped by a protecting polymer...
March 5, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Maria Tsoli, Jie Liu, Laura Franshaw, Han Shen, Cecilia Cheng, MoonSun Jung, Swapna Joshi, Anahid Ehteda, Aaminah Khan, Angel Montero-Carcabosso, Pierre J Dilda, Philip Hogg, David S Ziegler
Diffuse Intrinsic Pontine Gliomas (DIPG) are the most devastating of all pediatric brain tumors. They mostly affect young children and, as there are no effective treatments, almost all patients with DIPG will die of their tumor within 12 months of diagnosis. A key feature of this devastating tumor is its intrinsic resistance to all clinically available therapies. It has been shown that glioma development is associated with metabolic reprogramming, redox state disruption and resistance to apoptotic pathways...
January 26, 2018: Oncotarget
Kenneth J O'Riordan, Neng-Wei Hu, Michael J Rowan
Promotion of long-term depression (LTD) mechanisms by synaptotoxic soluble oligomers of amyloid-β (Aß) has been proposed to underlie synaptic dysfunction in Alzheimer's disease (AD). Previously, LTD was induced by relatively non-specific electrical stimulation. Exploiting optogenetics, we studied LTD using a more physiologically diffuse spatial pattern of selective pathway activation in the rat hippocampus in vivo. This relatively sparse synaptic LTD requires both the ion channel function and GluN2B subunit of the NMDA receptor but, in contrast to electrically induced LTD, is not facilitated by boosting endogenous muscarinic acetylcholine or metabotropic glutamate 5 receptor activation...
February 20, 2018: Cell Reports
Aleem Mohammad, Srinidhi V Ballullaya, Jayaprakash Thumu, Sohani Maroli, Pushpa Shankarappa
Aim: The aim of this study is to evaluate the effectiveness of ultrasonic activation of photosensitizer (PS) drug Foscan in the elimination of endodontic pathogen from root canal system. Materials and Methods: The minimal bactericidal concentration of "Foscan" was determined using disc diffusion and broth dilution method. Forty-eight extracted single-rooted premolars with periapical pathology were used for the study. After access opening, the first microbial sample was taken...
November 2017: Journal of Conservative Dentistry: JCD
Heidi I L Jacobs, Trey Hedden, Aaron P Schultz, Jorge Sepulcre, Rodrigo D Perea, Rebecca E Amariglio, Kathryn V Papp, Dorene M Rentz, Reisa A Sperling, Keith A Johnson
Animal models of Alzheimer's disease have suggested that tau pathology propagation, facilitated by amyloid pathology, may occur along connected pathways. To investigate these ideas in humans, we combined amyloid scans with longitudinal data on white matter connectivity, hippocampal volume, tau positron emission tomography and memory performance in 256 cognitively healthy older individuals. Lower baseline hippocampal volume was associated with increased mean diffusivity of the connecting hippocampal cingulum bundle (HCB)...
February 5, 2018: Nature Neuroscience
Sarah Treit, Trevor Steve, Donald W Gross, Christian Beaulieu
The human hippocampus is a key target of many imaging studies given its capacity for neurogenesis, role in long term potentiation and memory, and nearly ubiquitous involvement in neurological and psychiatric conditions. Diffusion tensor imaging (DTI) has detected microstructural abnormalities of the human hippocampus associated with various disorders, but acquisitions have typically been limited to low spatial resolution protocols designed for whole brain (e.g. > 2 mm isotropic, >8 mm3 voxels), limiting regional specificity and worsening partial volume effects...
January 30, 2018: NeuroImage
Mainak Mustafi, James C Weisshaar
In bacteria, elongation factor Tu is a translational cofactor that forms ternary complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close proximity to the ribosomal A site. Two sequential tests for a match between the aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are not cognate with the current mRNA codon, this testing must occur rapidly...
January 16, 2018: MBio
Cirong Liu, Frank Q Ye, Cecil Chern-Chyi Yen, John D Newman, Daniel Glen, David A Leopold, Afonso C Silva
The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI...
December 5, 2017: NeuroImage
Manuela Chiper, Karen Niederreither, Guy Zuber
The human organism and its constituting cells rely on interplay between multiple proteins exerting specific functions. Progress in molecular biotechnologies has facilitated the production of recombinant proteins. When administrated to patients, recombinant proteins can provide important healthcare benefits. To date, most therapeutic proteins must act from the extracellular environment, with their targets being secreted modulators or extracellular receptors. This is because proteins cannot passively diffuse across the plasma membrane into the cytosol...
December 5, 2017: Advanced Healthcare Materials
Michiel W Pot, Laurie M G de Kroon, Peter M van der Kraan, Toin H van Kuppevelt, Willeke F Daamen
Microfracture surgery may be improved by the implantation of unidirectional collagen scaffolds that provide a template for mesenchymal stem cells to regenerate cartilage. Incorporation of growth factors in unidirectional scaffolds may further enhance cartilage regeneration. In scaffolds, immobilization of growth factors is required to prolong in vivo activity, to limit diffusion and to reduce the amount of growth factor needed for safe clinical application. We investigated the immobilization of bone morphogenetic protein 2 (BMP2) to unidirectional collagen scaffolds and the effect on in vitro chondrogenesis...
November 22, 2017: Biomedical Materials
Gerrit C Langhout, Torre M Bydlon, Marjolein van der Voort, Manfred Müller, Jeroen Kortsmit, Gerald Lucassen, Andrea J R Balthasar, Geert-Jan van Geffen, Thorsten Steinfeldt, Henricus J C M Sterenborg, Benno H W Hendriks, Theo J M Ruers
OBJECTIVE: Identification of peripheral nerve tissue is crucial in both surgery and regional anesthesia. Recently, optical tissue identification methods are presented to facilitate nerve identification in transcutaneous procedures and surgery. Optimization and validation of such techniques require large datasets. The use of alternative models to human in vivo, like human post mortem, or swine may be suitable to test, optimize and validate new optical techniques. However, differences in tissue characteristics and thus optical properties, like oxygen saturation and tissue perfusion are to be expected...
November 21, 2017: Lasers in Surgery and Medicine
Minghui Cao, Jiaji Mao, Xiaohui Duan, Liejing Lu, Fang Zhang, Bingling Lin, Meiwei Chen, Chushan Zheng, Xiang Zhang, Jun Shen
Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell-based gene therapies for tumors. In this study, we used ferritin gene-based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma...
October 19, 2017: International Journal of Cancer. Journal International du Cancer
Joseph Kuchling, Alexander U Brandt, Friedemann Paul, Michael Scheel
The afferent visual pathway represents the most frequently affected white matter pathway in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Diffusion tensor imaging (DTI) can reveal microstructural or non-overt brain tissue damage and quantify pathological processes. DTI facilitates the reconstruction of major white matter fiber tracts allowing for the assessment of structure-function and damage-dysfunction relationships . In this review, we outline DTI studies investigating the afferent visual pathway in idiopathic optic neuritis (ON), NMOSD, and MS...
September 2017: EPMA Journal
Sophie Mavrogeni, Roser Pons, Ioannis Nikas, George Papadopoulos, Dimitrios A Verganelakis, Genovefa Kolovou, George P Chrousos
Duchenne muscular dystrophy (DMD) is an X-linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well-described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement (LGE), using cardiovascular magnetic resonance imaging (CMR), is an early marker of heart involvement in both DMD patients and female carriers...
December 2017: European Journal of Clinical Investigation
Lóránd Kiss, Alexandra Bocsik, Fruzsina R Walter, James Ross, Denise Brown, Brooke A Mendenhall, Sarah R Crews, Jana Lowry, Valerie Coronado, David E Thompson, Peter Sipos, Piroska Szabó-Révész, Mária A Deli, Ilona Petrikovics
Recent in vitro and in vivo studies highlight the strong potential of dimethyl trisulfide (DMTS) as an antidote for cyanide (CN) intoxication. Due to its high oxygen demand, the brain is one of the main target organs of CN. The blood-brain barrier (BBB) regulates the uptake of molecules into the brain. In the literature, there is no data about the ability of DMTS to penetrate the BBB. Therefore, our aim was to test the in vitro BBB penetration of DMTS and its in vivo pharmacokinetics in blood and brain. The in vitro BBB penetration of DMTS was measured by using a parallel artificial membrane permeability assay (BBB-PAMPA), and a triple BBB co-culture model...
December 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Diana Alcantara, Andrew E Timms, Karen Gripp, Laura Baker, Kaylee Park, Sarah Collins, Chi Cheng, Fiona Stewart, Sarju G Mehta, Anand Saggar, László Sztriha, Melinda Zombor, Oana Caluseriu, Ronit Mesterman, Margot I Van Allen, Adeline Jacquinet, Sofia Ygberg, Jonathan A Bernstein, Aaron M Wenger, Harendra Guturu, Gill Bejerano, Natalia Gomez-Ospina, Anna Lehman, Enrico Alfei, Chiara Pantaleoni, Valerio Conti, Renzo Guerrini, Ute Moog, John M Graham, Robert Hevner, William B Dobyns, Mark O'Driscoll, Ghayda M Mirzaa
Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations...
October 1, 2017: Brain: a Journal of Neurology
Marco Bertleff, Sebastian Domsch, Sebastian Weingärtner, Jascha Zapp, Kieran O'Brien, Markus Barth, Lothar R Schad
Artificial neural networks (ANNs) were used for voxel-wise parameter estimation with the combined intravoxel incoherent motion (IVIM) and kurtosis model facilitating robust diffusion parameter mapping in the human brain. The proposed ANN approach was compared with conventional least-squares regression (LSR) and state-of-the-art multi-step fitting (LSR-MS) in Monte-Carlo simulations and in vivo in terms of estimation accuracy and precision, number of outliers and sensitivity in the distinction between grey (GM) and white (WM) matter...
December 2017: NMR in Biomedicine
Laura Tiozzo Fasiolo, Michele Dario Manniello, Elena Tratta, Francesca Buttini, Alessandra Rossi, Fabio Sonvico, Fabrizio Bortolotti, Paola Russo, Gaia Colombo
In the field of nasal drug delivery, among the preparations defined by the European Pharmacopoeia, nasal powders facilitate the formulation of poorly water-soluble active compounds. They often display a simple composition in excipients (if any), allow for the administration of larger drug doses and enhance drug diffusion and absorption across the mucosa, improving bioavailability compared to nasal liquids. Despite the positive features, however, nasal products in this form still struggle to enter the market: the few available on the market are Onzetra Xsail® (sumatriptan) for migraine relief and, for the treatment of rhinitis, Rhinocort® Turbuhaler® (budesonide), Teijin Rhinocort® (beclomethasone dipropionate) and Erizas® (dexamethasone cipecilate)...
September 20, 2017: European Journal of Pharmaceutical Sciences
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