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https://www.readbyqxmd.com/read/28731838/neuroprotection-in-glaucoma-animal-models-and-clinical-trials
#1
Mohammadali Almasieh, Leonard A Levin
Glaucoma is a progressive neurodegenerative disease that frequently results in irreversible blindness. Glaucoma causes death of retinal ganglion cells (RGCs) and their axons in the optic nerve, resulting in visual field deficits and eventual loss of visual acuity. Glaucoma is a complex optic neuropathy, and a successful strategy for its treatment requires not only better management of known risk factors such as elevated intraocular pressure and the development of improved tools for detecting RGC injury but also treatments that address this injury (i...
July 21, 2017: Annual Review of Vision Science
https://www.readbyqxmd.com/read/28731692/quinolinyl-nitrone-rp19-induces-neuroprotection-after-transient-brain-ischemia
#2
Maria Irene Ayuso, Emma Martinez-Alonso, Mourad Chioua, Alejandro Escobar-Peso, Rafael Gonzalo-Gobernado, Joan Montaner, José Marco-Contelles, Alberto Alcazar
There is a need to develop additional effective therapies for ischemic stroke. Nitrones, which were first developed as reactive oxygen species (ROS)-trapping compounds, have been proposed as neuroprotective agents for ischemic stroke, a ROS-related disorder. The previous reported ROS-trapping compound, quinolyl nitrone RP19, is here being assayed to induce neuroprotection to ischemia-reperfusion injury in three experimental ischemia models: (i), oxygen-glucose deprivation (OGD) on primary neuronal cultures; (ii), transient global cerebral ischemia in four-vessel occlusion model; and (iii), transient focal cerebral ischemia in middle cerebral artery occlusion (tMCAO) model...
July 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#3
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28730968/modulation-of-the-immune-system-for-the-treatment-of-glaucoma
#4
Katharina Bell, Nadine von Thun Und Hohenstein-Blaul, Julia Teister, Franz H Grus
At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730967/microglia-and-astrocytes-in-alzheimer-s-disease-implications-for-therapy
#5
Marc Fakhoury
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptide and the formation of neurofibrillary tangles (NFTs) in the brain. Over the past few years, mounting evidence has implicated sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28730707/establishment-and-characterization-of-a-novel-murine-model-of-pancreatic-cancer-cachexia
#6
Katherine A Michaelis, Xinxia Zhu, Kevin G Burfeind, Stephanie M Krasnow, Peter R Levasseur, Terry K Morgan, Daniel L Marks
BACKGROUND: Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC-associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS(G12D) P53(R172H) Pdx-Cre(+/+) (KPC) mouse...
July 20, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28730408/evolution-of-the-hiv-1-transgenic-rat-utility-in-assessing-the-progression-of-hiv-1-associated-neurocognitive-disorders
#7
Kristen A McLaurin, Rosemarie M Booze, Charles F Mactutus
Understanding the progression of HIV-1-associated neurocognitive disorders (HAND) is a critical need as the prevalence of HIV-1 in older individuals (>50 years) is markedly increasing due to the great success of combination antiretroviral therapy (cART). Longitudinal experimental designs, in comparison to cross-sectional studies, provide an opportunity to establish age-related disease progression in HAND. The HIV-1 transgenic (Tg) rat, which has been promoted for investigating the effect of long-term HIV-1 viral protein exposure, was used to examine two interrelated goals...
July 20, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28730387/dynamics-of-the-pro-oxidant-antioxidant-system-parameters-in-wound-discharge-and-plasma-in-experimental-purulent-wound-during-its-technological-liquid-phase-treatment
#8
I M Bykov, A A Basov, V V Malyshko, S S Dzhimak, S R Fedosov, A V Moiseev
The dynamics of the pro-oxidant/antioxidant system of rabbits was studied at the local (in exudate) and systemic (blood) levels during therapy of purulent wounds in liquid medium with the use of a programmed device and the efficiency of the proposed technological method was compared with that of classical methods for the treatment of these wounds. More rapid recovery of the indicators of the pro-oxidant/antioxidant system to physiological values in the postoperative period was observed after treatment by the proposed method (7 days vs...
July 18, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28729967/tesevatinib-ameliorates-progression-of-polycystic-kidney-disease-in-rodent-models-of-autosomal-recessive-polycystic-kidney-disease
#9
William E Sweeney, Philip Frost, Ellis D Avner
AIM: To investigate the therapeutic potential of tesevatinib (TSV), a unique multi-kinase inhibitor currently in Phase II clinical trials for autosomal dominant polycystic kidney disease (ADPKD), in well-defined rodent models of autosomal recessive polycystic kidney disease (ARPKD). METHODS: We administered TSV in daily doses of 7.5 and 15 mg/kg per day by I.P. to the well characterized bpk model of polycystic kidney disease starting at postnatal day (PN) 4 through PN21 to assess efficacy and toxicity in neonatal mice during postnatal development and still undergoing renal maturation...
July 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28729680/the-use-of-radiocobalt-as-a-label-improves-imaging-of-egfr-using-dota-conjugated-affibody-molecule
#10
Javad Garousi, Ken G Andersson, Johan H Dam, Birgitte B Olsen, Bogdan Mitran, Anna Orlova, Jos Buijs, Stefan Ståhl, John Löfblom, Helge Thisgaard, Vladimir Tolmachev
Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729640/radiation-induced-liver-disease-current-understanding-and-future-perspectives
#11
REVIEW
Jieun Kim, Youngmi Jung
Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD...
July 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28729634/novel-intraperitoneal-treatment-with-non-thermal-plasma-activated-medium-inhibits-metastatic-potential-of-ovarian-cancer-cells
#12
Kae Nakamura, Yang Peng, Fumi Utsumi, Hiromasa Tanaka, Masaaki Mizuno, Shinya Toyokuni, Masaru Hori, Fumitaka Kikkawa, Hiroaki Kajiyama
Non-thermal atmospheric pressure plasma has been proposed as a new therapeutic tool for cancer treatment. Recently, plasma-activated medium (PAM) has been widely studied in various cancer types. However, there are only few reports demonstrating the anti-tumour effects of PAM in an animal model reflecting pathological conditions and the accompanying mechanism. Here we investigated the inhibitory effect of PAM on the metastasis of ovarian cancer ES2 cells in vitro and in vivo. We demonstrated that ES2 cell migration, invasion and adhesion were suppressed by PAM at a certain PAM dilution ratio, whereas cell viability remained unaffected...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#13
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28728415/-177-lu-labelled-cyclic-minigastrin-analogues-with-therapeutic-activity-in-cck2r-expressing-tumours-preclinical-evaluation-of-a-kit-formulation
#14
Christine Rangger, Maximilian Klingler, Lajos Balogh, Zita Pöstényi, Andras Polyak, Dariusz Pawlak, Renata Mikołajczak, Elisabeth von Guggenberg
Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumours and enable targeted radiotherapy of advanced and disseminated disease when radiolabelled with a beta emitter such as (177)Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [D-Glu1,desGlu2-6]MG (MG11) we have designed the two cyclic MG analogues cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9]MG (cyclo-MG1) and cyclo1,9[γ-D-Glu1,desGlu2-6,D-Lys9,Nle11]MG (cyclo-MG2)...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28727797/prophylactic-supplementation-of-resveratrol-is-more-effective-than-its-therapeutic-use-against-doxorubicin-induced-cardiotoxicity
#15
Heba Samy Shoukry, Hania Ibrahim Ammar, Laila Ahmed Rashed, Maha Balegh Zikri, Ashraf Ali Shamaa, Sahar Gamal Abou Elfadl, Ejlal Abu-Al Rub, Sekaran Saravanan, Sanjiv Dhingra
Resveratrol (RSV), a polyphenolic compound and naturally occurring phytoalexin, has been reported to exert cardio-protective effects in several animal studies. However, the outcome of initial clinical trials with RSV was less effective compared to pre-clinical studies. Therefore, RSV treatment protocols need to be optimized. In this study we evaluated prophylactic versus therapeutic effect of resveratrol (RSV) in mitigating doxorubicin (Dox)-induced cardiac toxicity in rats. To investigate prophylactic effects, RSV was supplemented for 2 weeks along with Dox administration...
2017: PloS One
https://www.readbyqxmd.com/read/28727712/intervertebral-foramen-injection-of-ozone-relieves-mechanical-allodynia-and-enhances-analgesic-effect-of-gabapentin-in-animal-model-of-neuropathic-pain
#16
Wen-Jun Luo, Fan Yang, Fei Yang, Wei Sun, Wei Zheng, Xiao-Liang Wang, Fang-Fang Wu, Jiang-Lin Wang, Jia-Shuang Wang, Su-Min Guan, Jun Chen
BACKGROUND: In a 5-year follow-up study in a hospital in southern China, it was shown that intervertebral foramen (IVF) injection of ozone at the involved segmental levels could significantly alleviate paroxysmal spontaneous pain and mechanical allodynia in patients with chronic, intractable postherpetic neuralgia (PHN) and improve the quality of life. However, so far no proof-of-concept studies in animals have been available. OBJECTIVE: This study was designed to investigate whether IVF ozone has an analgesic effect on animal models of neuropathic and inflammatory pain...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727705/activation-of-the-rage-stat3-pathway-in-the-dorsal-root-ganglion-contributes-to-the-persistent-pain-hypersensitivity-induced-by-lumbar-disc-herniation
#17
Xin-Sheng Zhang, Xiao Li, Hai-Jie Luo, Zhu-Xi Huang, Cui-Cui Liu, Qing Wan, Shu-Wei Xu, Shao-Ling Wu, Song-Jian Ke, Chao Ma
BACKGROUND: Clinically, chronic low back pain and sciatica associated with lumbar disc herniation (LDH) is a common musculoskeletal disorder. Due to the unawareness of detailed mechanisms, it is difficult to get an effective therapy. OBJECTIVE: The aim of the present study was to identify the role of the RAGE/STAT3 pathway in the dorsal root ganglion (DRG) on the formation and development of persistent pain hypersensitivity induced by LDH. STUDY DESIGN: Controlled animal study...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727221/scar-formation-following-excisional-and-burn-injuries-in-a-red-duroc-pig-model
#18
Britani N Blackstone, Jayne Y Kim, Kevin L McFarland, Chandan K Sen, Dorothy M Supp, J Kevin Bailey, Heather M Powell
Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn-induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome...
July 20, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28726577/will-optogenetics-be-used-to-treat-chronic-pain-patients
#19
Hélène Beaudry, Ihab Daou, Alfredo Ribeiro-da-Silva, Philippe Séguéla
Chronic pain affects a third of the population and current treatments produce limited relief and severe side effects. An alternative strategy to decrease pain would be to directly modulate somatosensory pathways using optogenetics. Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits. In preclinical animal models, optical silencing of peripheral nociceptors has been shown to alleviate both inflammatory and neuropathic pain. An opsin-based gene therapy to treat chronic pain patients is not ready yet, but encouraging advances have been made in optical and viral technology...
July 20, 2017: Pain Management
https://www.readbyqxmd.com/read/28726495/use-of-adeno-associated-virus-vector-for-cardiac-gene-delivery-in-large-animal-surgical-models-of-heart-failure
#20
Michael G Katz, Anthony S Fargnoli, Thomas Weber, Roger Hajjar, Charles Bridges
The advancement of gene-therapy-based approaches to treat heart disease represents a need for clinically-relevant animal models with characteristics equivalent to human pathologies. Rodent models of cardiac disease do not precisely reproduce heart failure phenotype and molecular defects. This has motivated researchers to use large animals whose heart size and physiological processes more similar and comparable to those of humans. Today, adeno-associated viruses (AAV)-based vectors are undoubtedly among the most promising DNA delivery vehicles...
July 20, 2017: Human Gene Therapy. Clinical Development
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