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https://www.readbyqxmd.com/read/28324909/an-extrapericardial-minimally-invasive-approach-for-implantable-cardioverter-defibrillator
#1
Jeko M Madjarov, Michael G Katz, Brad Poole, Svetozar Madzharov, John M Fedor, Francis Robicsek
The indications for placement of an implantable cardioverter defibrillators (ICDs) have greatly expanded over the last years. However, standard transvenous approach is not suitable for a subset of patients who cannot benefit from ICD therapy. Here, we have demonstrated the feasibility and efficacy of extrapericardial ICD placement through a minimally invasive access in intact hearts as well as in postmyocardial infarction large animal models. Based on our data, we conclude that extrapericardial ICD placement is a feasible approach that may be a valuable alternative or adjunct to current defibrillator lead systems...
March 21, 2017: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/28324751/the-rationale-of-indoleamine-2-3-dioxygenase-inhibition-for-cancer-therapy
#2
REVIEW
Lieve Brochez, Ines Chevolet, Vibeke Kruse
Indoleamine 2,3-dioxygenase (IDO, also referred to as IDO1) has been demonstrated to be a normal endogenous mechanism of acquired peripheral immune tolerance in vivo. In the field of oncology, IDO expression and/or activity has been observed in several cancer types and has usually been associated with negative prognostic factors and worse outcome measures. This manuscript reviews current available data on the role of IDO in cancer and the current results obtained with IDO inhibition, both in animal models and in phase 1 and 2 clinical trials in humans...
March 18, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324653/evaluation-of-brain-pharmacokinetic-and-neuropharmacodynamic-attributes-of-antiepileptic-drug-lacosamide-in-hepatic-and-renal-impairment-preclinical-evidence
#3
Baldeep Kumar, Manish Modi, Biman Saikia, Bikash Medhi
The knowledge of pharmacokinetic and pharmacodynamic properties of antiepileptic drugs is helpful in optimizing drug therapy for epilepsy. This study was designed to evaluate the pharmacokinetic and pharmacodynamic properties of lacosamide in experimentally induced hepatic and renal impairment in seizure animals. Hepatic or renal impairment was induced by injection of carbon tetrachloride or diclofenac sodium, respectively. After induction, the animals were administered with a single dose of lacosamide. At different time points, MES seizure recordings were done followed by isolation of plasma and brain samples for drug quantification and pharmacodynamic measurements...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28324244/animal-models-and-antifungal-agents-in-paracoccidioidomycosis-an-overview
#4
REVIEW
Luciano Z Goldani, Fernanda Wirth
Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis...
March 21, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28320131/epigenetic-and-gene-expression-alterations-of-foxp3-in-the-t-cells-of-eae-mouse-model-of-multiple-sclerosis
#5
Ali Noori-Zadeh, Seyed Alireza Mesbah-Namin, Ali Akbar Saboor-Yaraghi
Multiple sclerosis (MS) is a chronic autoimmune disease with demyelination and neurodegeneration of the central nervous system. It has been shown that the regulatory T (Treg) cells are responsible for maintaining tolerance to self-antigens and can suppress the autoimmune process in several animal models such as experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Recent basic studies have demonstrated that forkhead box P (FOXP3) and BTB domain and CNC homolog 2 (BACH2) are the master transcription factors of these cells playing a pivotal role in the polarization of naïve T cells into Treg cells...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320105/anti-fibrotic-potential-of-human-umbilical-cord-mononuclear-cells-and-mouse-bone-marrow-cells-in-ccl4-induced-liver-fibrosis-in-mice
#6
Nageh Ahmed Elmahdy, Samia Salem Sokar, Mohamed Labib Salem, Naglaa Ibrahim Sarhan, Sherin Hamed Abou-Elela
Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl4) induced liver fibrosis in mice and compare it with that of silymarin...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28320043/effects-of-ranolazine-in-a-model-of-doxorubicin-induced-left-ventricle-diastolic-dysfunction
#7
Donato Cappetta, Grazia Esposito, Raffaele Coppini, Elena Piegari, Rosa Russo, Loreta Pia Ciuffreda, Alessia Rivellino, Lorenzo Santini, Concetta Rafaniello, Cristina Scavone, Francesco Rossi, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
BACKGROUND AND PURPOSE: Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319449/non-clinical-study-examining-aav8-tbg-hldlr-vector-associated-toxicity-in-chow-fed-wild-type-and-ldlr-rhesus-macaques
#8
Jenny A Greig, Maria P Limberis, Peter Bell, Shu-Jen Chen, Roberto Calcedo, Daniel J Rader, James M Wilson
Vectors based on adeno-associated virus serotype 8 (AAV8) have been evaluated in several clinical trials of gene therapy for hemophilia B with encouraging results. In preparation for a Phase 1 clinical trial of AAV8 gene therapy for the treatment of homozygous familial hypercholesterolemia (HoFH), the safety of the clinical candidate vector, AAV8.TBG.hLDLR, was evaluated in wild-type rhesus macaques and macaques heterozygous for a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene (LDLR(+/-))...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319446/good-laboratory-practice-preclinical-safety-studies-for-gsk2696273-mlv-vector-based-ex-vivo-gene-therapy-for-adenosine-deaminase-deficiency-severe-combined-immunodeficiency-in-nsg-mice
#9
Nicola Carriglio, Jan Klapwijk, Raisa Jofra Hernandez, Michela Vezzoli, Franck Chanut, Rhiannon Lowe, Draghici Elena, Melanie Nord, Paola Albertini, Patrizia Cristofori, Jane Richards, Hazel Staton, Jonathan Appleby, Alessandro Aiuti, Aisha V Sauer
GSK2696273 (autologous CD34+ cells transduced with retroviral vector that encodes for the human adenosine deaminase [ADA] enzyme) is a gamma-retroviral ex vivo gene therapy of bone marrow-derived CD34+ cells for the treatment of adenosine deaminase deficiency severe combined immunodeficiency (ADA-SCID). ADA-SCID is a severe monogenic disease characterized by immunologic and nonimmunologic symptoms. Bone-marrow transplant from a matched related donor is the treatment of choice, but it is available for only a small proportion of patients...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28319174/simultaneous-induction-of-graves-hyperthyroidism-and-graves-ophthalmopathy-by-tshr-genetic-immunization-in-balb-c-mice
#10
Nan Xia, Xiaozhen Ye, Xiaohao Hu, Shiyu Song, Hui Xu, Mengyuan Niu, Hongwei Wang, Jian Wang
BACKGROUND: Graves' disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves' disease (GD) in concert with Graves' Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized...
2017: PloS One
https://www.readbyqxmd.com/read/28318924/aged-rats-under-zoledronic-acid-therapy-and-oral-surgery
#11
Mariza Akemi Matsumoto, Elisa Mara de Abreu Furquim, Alaíde Gonçalves, Joel Ferreira Santiago-Júnior, Patrícia Pinto Saraiva, Camila Lopes Cardoso, Marcelo Salles Munerato, Roberta Okamoto
INTRODUCTION: Aging brings a number of health conditions that can compromise the healing process in elderly individuals, significantly when it comes to bone tissue. The aim of the present study was to analyze the effects of zoledronic acid (ZL) therapy on socket healing of aged male rats. MATERIALS AND METHODS: Twenty-four Wistar male rats, 20 months old, underwent surgical procedures for the extraction of the upper right incisor and were divided into two groups according to the treatment: Control (C) - intravenous (IV) 0...
February 17, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28318037/deoxycytidine-and-deoxythymidine-treatment-for-thymidine-kinase-2-deficiency
#12
Carlos Lopez-Gomez, Rebecca J Levy, Maria J Sanchez-Quintero, Marti Juanola-Falgarona, Emanuele Barca, Beatriz Garcia-Diaz, Saba Tadesse, Caterina Garone, Michio Hirano
OBJECTIVE: Thymidine kinase 2 (TK2), a critical enzyme in the mitochondrial pyrimidine salvage pathway, is essential for mitochondrial DNA (mtDNA) maintenance. Mutations in the nuclear gene TK2 cause TK2 deficiency, which manifests predominantly in children as myopathy with mtDNA depletion. Molecular bypass therapy with the TK2 products, dCMP and dTMP, prolongs the lifespan of Tk2-deficient (Tk2(-/-) ) mice by 2-3 fold. Because we observed rapid catabolism of the deoxynucleoside monophosphates to deoxythymidine (dT) and deoxycytidine (dC), we hypothesized that: 1) deoxynucleosides might be the major active agents and 2) inhibition of deoxycytidine deamination might enhance dTMP+dCMP therapy...
March 20, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28317878/kidney-specific-transposon-mediated-gene-transfer-in-vivo
#13
Lauren E Woodard, Jizhong Cheng, Richard C Welch, Felisha M Williams, Wentian Luo, Leslie S Gewin, Matthew H Wilson
Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317026/toxoplasma-gondii-ap2ix-4-regulates-gene-expression-during-bradyzoite-development
#14
Sherri Huang, Michael J Holmes, Joshua B Radke, Dong-Pyo Hong, Ting-Kai Liu, Michael W White, William J Sullivan
Toxoplasma gondii is a protozoan parasite of great importance to human and animal health. In the host, this obligate intracellular parasite persists as a tissue cyst that is imperceptible to the immune response and unaffected by current therapies. The tissue cysts facilitate transmission through predation and give rise to chronic cycles of toxoplasmosis in immunocompromised patients. Transcriptional changes accompany conversion of the rapidly replicating tachyzoites into the encysted bradyzoites, and yet the mechanisms underlying these alterations in gene expression are not well defined...
March 2017: MSphere
https://www.readbyqxmd.com/read/28316999/does-the-gut-microbiota-influence-immunity-and-inflammation-in-multiple-sclerosis-pathophysiology
#15
Monika Adamczyk-Sowa, Aldona Medrek, Paulina Madej, Wirginia Michlicka, Pawel Dobrakowski
Aim. Evaluation of the impact of gut microflora on the pathophysiology of MS. Results. The etiopathogenesis of MS is not fully known. Gut microbiota may be of a great importance in the pathogenesis of MS, since recent findings suggest that substitutions of certain microbial population in the gut can lead to proinflammatory state, which can lead to MS in humans. In contrast, other commensal bacteria and their antigenic products may protect against inflammation within the central nervous system. The type of intestinal flora is affected by antibiotics, stress, or diet...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28316386/successful-therapeutic-management-of-canine-isosporosis-in-puppies
#16
Nishiswapna Garanayak, A R Gupta, R C Patra
Four labrador male puppies were confirmed for the Isospora spp infection by direct smear and flotation method following complains of anorexia, haematemesis and haematochezia. The puppies were treated with trimethoprime and sulphamethoxazole @ 40 mg/kg body weight in combination with metronidazole @ 10 mg/kg body weight twice daily for 5 days which was supported with fluid therapy, aniemetics and plasma expanders. All the animals showed completed clinical recovery along with clearing of faecal oocyst.
March 2017: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
https://www.readbyqxmd.com/read/28316335/complement-in-anca-associated-vasculitis-mechanisms-and-implications-for-management
#17
REVIEW
Min Chen, David R W Jayne, Ming-Hui Zhao
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. The main histological feature in the kidneys of patients with AAV is pauci-immune necrotizing crescentic glomerulonephritis with little immunoglobulin and complement deposition in the glomerular capillary walls. The complement system was not, therefore, initially thought to be associated with the development of AAV. Accumulating evidence from animal models and clinical observations indicate, however, that activation of the complement system - and the alternative pathway in particular - is crucial for the development of AAV, and that the complement activation product C5a has a central role...
March 20, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28315465/early-preclinical-evaluation-of-dihydropyrimidin-thi-ones-as-potential-anticonvulsant-drug-candidates
#18
Mariana Matias, Gonçalo Campos, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
Although significant advances are occurring in epilepsy research, about 30% of epileptic patients are still inadequately controlled by standard drug therapy. For this reason, it continues to be important to develop new chemical entities through which epilepsy could be effectively controlled. In this study, the anticonvulsant activity of forty-two dihydropyrimidin(thi)ones was explored and their efficacy was evaluated in rodents against the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole tests...
March 14, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28315269/sigma-1-receptors-and-neurodegenerative-diseases-towards-a-hypothesis-of-sigma-1-receptors-as-amplifiers-of-neurodegeneration-and-neuroprotection
#19
Linda Nguyen, Brandon P Lucke-Wold, Shona Mookerjee, Nidhi Kaushal, Rae R Matsumoto
Sigma-1 receptors are molecular chaperones that may act as pathological mediators and targets for novel therapeutic applications in neurodegenerative diseases. Accumulating evidence indicates that sigma-1 ligands can either directly or indirectly modulate multiple neurodegenerative processes, including excitotoxicity, calcium dysregulation, mitochondrial and endoplasmic reticulum dysfunction, inflammation, and astrogliosis. In addition, sigma-1 ligands may act as disease-modifying agents in the treatment for central nervous system (CNS) diseases by promoting the activity of neurotrophic factors and neural plasticity...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315202/validation-of-bevacizumab-therapy-effect-on-colon-cancer-subtypes-by-using-whole-body-imaging-in-mice
#20
Ivan Vuletic, Kedi Zhou, Hui Li, Huichen Bai, Xiangxi Meng, Sihao Zhu, Yichen Ding, Jun Li, Hongfang Sun, Qiushi Ren
PURPOSE: Preclinical imaging offers a useful tool for monitoring cancer biological behavior and therapy in vivo without the necessity of animal surgery. The following paper describes our examination of tumor progress and anti-angiogenic therapy with Bevacizumab on colon cancer subtypes (SW480 and SW620) by using different non-invasive real-time in vivo imaging techniques. PROCEDURES: Color Doppler ultrasound imaging (CDUI) was used to observe the formation of new blood vessels; a homemade fluorescence reflectance imaging (FRI) apparatus was mainly used to test the difference in VEGFR2 expression between the tumor subtypes...
March 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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