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https://www.readbyqxmd.com/read/28102287/crotalus-atrox-venom-preconditioning-increases-plasma-fibrinogen-and-reduces-perioperative-hemorrhage-in-a-rat-model-of-surgical-brain-injury
#1
Cherine H Kim, Devin W McBride, Ronak Raval, Prativa Sherchan, Karen L Hay, Eric C K Gren, Wayne Kelln, Tim Lekic, William K Hayes, Brian S Bull, Richard Applegate, Jiping Tang, John H Zhang
Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101863/lessons-from-animal-models-of-cytoplasmic-intermediate-filament-proteins
#2
Jamal-Eddine Bouameur, Thomas M Magin
Cytoplasmic intermediate filaments (IFs) represent a major cytoskeletal network contributing to cell shape, adhesion and migration as well as to tissue resilience and renewal in numerous bilaterians, including mammals. The observation that IFs are dispensable in cultured mammalian cells, but cause tissue-specific, life-threatening disorders, has pushed the need to investigate their function in vivo. In keeping with human disease, the deletion or mutation of murine IF genes resulted in highly specific pathologies...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101724/drug-drug-multicomponent-solid-forms-cocrystal-coamorphous-and-eutectic-of-three-poorly-soluble-antihypertensive-drugs-using-mechanochemical-approach
#3
Jamshed Haneef, Renu Chadha
The present study deals with the application of mechanochemical approach for the preparation of drug-drug multicomponent solid forms of three poorly soluble antihypertensive drugs (telmisartan, irbesartan and hydrochlorothiazide) using atenolol as a coformer. The resultant solid forms comprise of cocrystal (telmisartan-atenolol), coamorphous (irbesartan-atenolol) and eutectic (hydrochlorothiazide-atenolol). The study emphasizes that solid-state transformation of drug molecules into new forms is a result of the change in structural patterns, diminishing of dimers and creating new facile hydrogen bonding network based on structural resemblance...
January 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28101520/an-observational-study-of-alemtuzumab-following-fingolimod-for-multiple-sclerosis
#4
Mark Willis, Owen Pearson, Zsolt Illes, Tobias Sejbaek, Christian Nielsen, Martin Duddy, Kate Petheram, Caspar van Munster, Joep Killestein, Clas Malmeström, Emma Tallantyre, Neil Robertson
OBJECTIVE: To describe a series of patients with relapsing multiple sclerosis (MS) who experienced significant and unexpected disease activity within the first 12 months after switching from fingolimod to alemtuzumab. METHODS: Patients with relapsing MS treated sequentially with fingolimod then alemtuzumab who experienced significant subsequent disease activity were identified by personal communication with 6 different European neuroscience centers. RESULTS: Nine patients were identified...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#5
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#6
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28099785/a-dual-topoisomerase-inhibitor-of-intense-pro-apoptotic-and-antileukemic-nature-for-cancer-treatment
#7
Christopher Meier, Tamara N Steinhauer, Fabian Koczian, Birte Plitzko, Katharina Jarolim, Ulrich Girreser, Simone Braig, Doris Marko, Angelika M Vollmar, Bernd Clement
Classic cytotoxic drugs constantly remain an indispensable instrument in antitumor therapy due to their effectiveness and a more prevalent insensibility against tumor resistance mechanisms. We describe the favorable properties of P8-D6, a powerful inductor of apoptosis caused by an equipotent inhibition of human topoisomerase I and II activities. A broad spectrum effect against human tumor cell lines in nanomolar concentrations as well as strong anti-leukemic effects were shown and proven to be superior to marketed topo-targeting drugs and dual topoisomerase inhibitors in clinical trials...
January 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28099423/high-dose-erythropoietin-population-pharmacokinetics-in-neonates-with-hypoxic-ischemic-encephalopathy-receiving-hypothermia
#8
Adam Frymoyer, Sandra E Juul, An N Massaro, Theo K Bammler, Yvonne W Wu
BACKGROUND: High-dose erythropoietin (Epo) is a promising neuroprotective treatment in neonates with hypoxic ischemic encephalopathy (HIE) receiving hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of high-dose Epo in this population to inform future dosing strategies. METHODS: We performed a population pharmacokinetic analysis of 47 neonates with HIE treated with hypothermia who received up to 6 doses of Epo in two previous clinical trials...
January 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28098886/novel-zinc-phthalocyanine-as-a-promising-photosensitizer-for-photodynamic-treatment-of-esophageal-cancer
#9
Weronika Kuzyniak, Jacob Schmidt, Wojciech Glac, Janine Berkholz, Gustav Steinemann, Björn Hoffmann, Eugeny A Ermilov, Ayşe Gül Gürek, Vefa Ahsen, Bianca Nitzsche, Michael Höpfner
Photodynamic therapy (PDT) has gathered much attention in the field of cancer treatment and is increasingly used as an alternative solution for esophageal cancer therapy. However, there is a constant need for improving the effectiveness and tolerability of the applied photosensitizers (PS). Here, we propose tetra-triethyleneoxysulfonyl substituted zinc phthalocyanine (ZnPc) as a promising PS for photodynamic treatment of esophageal cancer. ZnPc-induced phototoxicity was studied in two human esophageal cancer cell lines: OE-33 (adenocarcinoma) and Kyse-140 (squamous cell carcinoma)...
January 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098415/intracranial-aav-ifn-%C3%AE-gene-therapy-eliminates-invasive-xenograft-glioblastoma-and-improves-survival-in-orthotopic-syngeneic-murine-model
#10
Dwijit GuhaSarkar, James Neiswender, Qin Su, Guangping Gao, Miguel Sena-Esteves
The highly invasive property of glioblastoma (GBM) cells and genetic heterogeneity are largely responsible for tumor recurrence after the current standard-of-care treatment and thus a direct cause of death. Previously, we have shown that intracranial interferon-beta (IFN-β) gene therapy by locally administered adeno-associated viral vectors (AAV) successfully treats noninvasive orthotopic glioblastoma models. Here, we extend these findings by testing this approach in invasive human GBM xenograft and syngeneic mouse models...
November 9, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28097286/-pain-therapy-in-small-pets
#11
Sabine Tacke, Andrea Gollwitzer, Lukas Grammel, Julia Henke
Although many advances in pain therapy have been made in recent years, pain therapy is more difficult in the small domestic animal than in cats and dogs. However, there is the ethical obligation that these animals also receive adequate pain therapy. An analgesic is rarely authorized for use in small pets, with pharmacological investigations often lacking and dosages frequently only determined empirically. The small size of the animals often requires a higher dose per kilogram bodyweight compared to cats and dogs...
January 17, 2017: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/28097007/safety-assessment-in-rats-and-dogs-of-acoustic-cluster-therapy-a-novel-concept-for-ultrasound-mediated-targeted-drug-delivery
#12
Oddvar Myhre, Marie Bjørgan, Derek Grant, Svein-Olaf Hustvedt, Per C Sontum, Hubert Dirven
Acoustic Cluster Therapy (ACT) represents a novel concept for targeted drug delivery. Ultrasound is applied to activate intravenously administered free-flowing clusters of microbubbles and microdroplets within the target pathology, depositing 20-30 μm large bubbles in the microvasculature for 5-10 min. Further application of ultrasound induces biomechanical effects which increase vascular permeability and enhance localized extravasation of coadministered drugs. Herein we report investigations done to assess the preclinical safety of ACT, using doses up to 1 mL/kg (3 μL perfluoromethyl-cyclopentane/kg)...
December 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#13
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28095907/the-targeted-smac-mimetic-sw-iv-134-is-a-strong-enhancer-of-standard-chemotherapy-in-pancreatic-cancer
#14
Yassar M Hashim, Suwanna Vangveravong, Narendra V Sankpal, Pratibha S Binder, Jingxia Liu, S Peter Goedegebuure, Robert H Mach, Dirk Spitzer, William G Hawkins
BACKGROUND: Pancreatic cancer is a lethal malignancy that frequently acquires resistance to conventional chemotherapies often associated with overexpression of inhibitors of apoptosis proteins (IAPs). We have recently described a novel means to deliver second mitochondria-derived activator of caspases (SMAC) mimetics selectively to cancer cells employing the sigma-2 ligand/receptor interaction. The intrinsic death pathway agonist SMAC offers an excellent opportunity to counteract the anti-apoptotic activity of IAPs...
January 17, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28095860/mouse-models-of-atherosclerosis-a-historical-perspective-and-recent-advances
#15
REVIEW
Yee Ting Lee, Hiu Yu Lin, Yin Wah Fiona Chan, Ka Hou Christien Li, Olivia Tsz Ling To, Bryan P Yan, Tong Liu, Guangping Li, Wing Tak Wong, Wendy Keung, Gary Tse
Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors...
January 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28095731/n-palmitoylethanolamine-oxazoline-pea-oxa-as-a-new-therapeutic-strategy-to-control-neuroinflammation-neuroprotective-effects-in-experimental-models-of-spinal-cord-and-brain-injury
#16
Daniela Impellizzeri, Marika Cordaro, Giuseppe Bruschetta, Rosalba Siracusa, Rosalia Crupi, Emanuela Esposito, Salvatore Cuzzocrea
Modulation of N-acylethanolamine-hydrolyzing acid amidase (NAAA) represents a potential alternative strategy in the treatment of neuroinflammation. Recent studies showed that pharmacological modulation of NAAA could be achieved with the oxazoline of palmitoylethanolamide (PEA) (PEA-OXA). The aim of this study was to evaluate the neuroprotective effects of PEA-OXA in the secondary neuro-inflammatory events induced by spinal and brain trauma in mice. Animals were subjected to spinal cord and brain injury models and PEA-OXA (10 mg/kg) administered both intraperitoneally and orally 1 h and 6 h after trauma...
January 17, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28095637/gene-therapy-for-achromatopsia
#17
REVIEW
Stylianos Michalakis, Christian Schön, Elvir Becirovic, Martin Biel
AIM: This review summarizes the current status of Achromatopsia (ACHM) gene therapy-related research activities and provides an outlook for their clinical application. DISCUSSION: ACHM is an inherited eye disease characterized by congenital absence of cone photoreceptor function. As a consequence, ACHM is associated with strongly impaired daylight vision, photophobia, nystagmus, and lack of color discrimination. Currently, six genes have been linked to ACHM. Up to 80% of the patients carry mutations in the genes CNGA3 and CNGB3 encoding the two subunits of the cone cyclic nucleotide-gated (CNG) channel...
January 17, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/28095260/differential-expression-and-roles-of-secreted-frizzled-related-protein-5-and-the-wingless-homolog-wnt5a-in-periodontitis
#18
T Maekawa, P Kulwattanaporn, K Hosur, H Domon, M Oda, Y Terao, T Maeda, G Hajishengallis
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28094579/expression-profile-of-the-integrin-receptor-subunits-in-the-guinea-pig-sclera
#19
Kevin K Wang, Ravikanth Metlapally, Christine F Wildsoet
PURPOSE: The ocular dimensional changes in myopia reflect increased scleral remodeling, and in high myopia, loss of scleral integrity leads to biomechanical weakening and continued scleral creep. As integrins, a type of cell surface receptors, have been linked to scleral remodeling, they represent potential targets for myopia therapies. As a first step, this study aimed to characterize the integrin subunits at the messenger RNA level in the sclera of the guinea pig, a more recently added but increasingly used animal model for myopia research...
January 17, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28094536/the-novel-induction-of-retinal-ganglion-cell-apoptosis-in-porcine-organ-culture-by-nmda-an-opportunity-for-the-replacement-of-animals-in-experiments
#20
Sandra Kuehn, Jose Hurst, Adelina Jashari, Kathrin Ahrens, Teresa Tsai, Ilan M Wunderlich, H Burkhard Dick, Stephanie C Joachim, Sven Schnichels
Some of the advantages of retina organ culture models include their efficient and easy handling and the ability to standardise relevant parameters. Additionally, when porcine eyes are obtained from the food industry, no animals are killed solely for research purposes. To induce retinal degeneration, a commonly used toxic substance, N-methyl-D-aspartate (NMDA), was applied to the cultures. To this end, organotypic cultures of porcine retinas were cultured and treated with different doses of NMDA (0 [control], 50, 100 and 200μM) on day 2 for 48 hours...
December 2016: Alternatives to Laboratory Animals: ATLA
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