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https://www.readbyqxmd.com/read/30093793/imaging-mass-spectrometry-for-toxicity-assessment-a-useful-technique-to-confirm-drug-distribution-in-histologically-confirmed-lesions
#1
Akane Kashimura, Kouji Tanaka, Hiroko Sato, Hidefumi Kaji, Masaharu Tanaka
To evaluate the usefulness of imaging mass spectrometry (IMS) technology for assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)-induced phospholipidosis model by IMS and confirmed the relationship between the distribution of AMD, its metabolites, and representative phospholipids (phosphatidylcholine, PC) and histological changes. AMD was administered to rats for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were histologically examined and analyzed using IMS. The detection intensities of AMD, its metabolites, and typical PCs were higher in regions infiltrated by foamy macrophages compared with normal areas...
July 2018: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/30075775/astragalus-membranaceus-fisch-bunge-repairs-intestinal-mucosal-injury-induced-by-lps-in-mice
#2
Yizhe Cui, Qiuju Wang, Rui Sun, Li Guo, Mengzhu Wang, Junfeng Jia, Chuang Xu, Rui Wu
BACKGROUND: Astragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The purpose of the study was to investigate the curative effects of the decoction obtained from Astragalus membranaceus root in intestinal mucosal injury induced by LPS in mice. An LPS-induced intestinal mucosal injury mice model was applied in the study...
August 3, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/30025105/a-perspective-of-amd-through-the-eyes-of-immunology
#3
David A Copland, Sofia Theodoropoulou, Jian Liu, Andrew D Dick
Despite strong genetic associations, compelling human histological data and numerous hypotheses generated with supportive animal data, the mechanisms of inflammation or inflammatory control of cell health during progression of age-related macular degeneration arguably remain elusive. This perspective delivers a view that maintaining tissue health requires active immune cellular and tissue pathways, but when responses are perturbed or exaggerated, chronic inflammation is destructive. There are potential pathways and processes to enable understanding and determine how potential causative factors including altered cellular metabolism, senescence, oxidative stress disrupt tissue homeostasis are engaged...
March 20, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29927057/role-of-diet-and-food-intake-in-age-related-macular-degeneration-a-systematic-review
#4
REVIEW
Naoko A Chapman, Robert J Jacobs, Andrea J Braakhuis
A systematic literature review was conducted to evaluate the role of diet and food intake in age-related macular degeneration (AMD). Eighteen high-quality studies were identified. Adherence to a Mediterranean diet had decreased risk of AMD progression. An Oriental diet pattern had decreased association with AMD prevalence, whereas a Western diet pattern had increased association with AMD prevalence. High consumption of vegetables rich in carotenoids and fatty fish containing omega-3 fatty acids was beneficial for those at risk of AMD...
June 21, 2018: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/29883119/4-hydroxy-7-oxo-5-heptenoic-acid-lactone-is-a-potent-inducer-of-the-complement-pathway-in-human-retinal-pigmented-epithelial-cells
#5
Mikhail Linetsky, Karina S Bondelid, Sofiya Losovskiy, Vadym Gabyak, Mario J Rullo, Thomas I Stiadle, Vasu Munjapara, Priyali Saxena, Duoming Ma, Yu-Shiuan Cheng, Andrew M Howes, Emeka Udeigwe, Robert G Salomon
We previously discovered that oxidative cleavage of docosahexaenoate (DHA), which is especially abundant in the retinal photoreceptor rod outer segments and retinal pigmented endothelial (RPE) cells, generates 4-hydroxy-7-oxo-5-heptenoate (HOHA) lactone, and that HOHA lactone can enter RPE cells that metabolize it through conjugation with glutathione (GSH). The consequent depletion of GSH results in oxidative stress. We now find that HOHA lactone induces upregulation of the antioxidant transcription factor Nrf2 in ARPE-19 cells...
July 9, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29872758/kus121-an-atp-regulator-mitigates-chorioretinal-pathologies-in-animal-models-of-age-related-macular-degeneration
#6
Yuki Muraoka, Yuto Iida, Hanako O Ikeda, Sachiko Iwai, Masayuki Hata, Takeshi Iwata, Mao Nakayama, Nobuhiro Shimozawa, Yuko Katakai, Akira Kakizuka, Nagahisa Yoshimura, Akitaka Tsujikawa
Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD...
May 2018: Heliyon
https://www.readbyqxmd.com/read/29862169/effect-of-integrin-%C3%AE-5%C3%AE-1-inhibition-on-sdf-l-cxcr4-mediated-choroidal-neovascularization
#7
Yang Lyu, Wen-Qin Xu, Li-Juan Sun, Xiao-Yan Pan, Jian Zhang, Yu-Sheng Wang
AIM: To investigate the roles of integrins in choroidal neovascularization (CNV) and their associations with the stromal cell-derived factor-1 (SDF-1)/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD) 3100 (CXCR4 inhibitor), and SDF-1+ATN161 (integrin α5β1 inhibitor) groups; their effects on CNV progression were observed using hematoxylin eosin (HE) staining, fundus fluorescein angiography (FFA) grading and optical coherence tomography (OCT), and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining...
2018: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/29860455/anti-cd160-alone-or-in-combination-with-bevacizumab-is-a-potent-inhibitor-of-ocular-neovascularization-in-rabbit-and-monkey-models
#8
Thierry Menguy, Anne Briaux, Elisabeth Jeunesse, Jérôme Giustiniani, Alexandre Calcei, Thierry Guyon, Jacques Mizrahi, Hélène Haegel, Vanessa Duong, Vincent Soler, Pierre Brousset, Armand Bensussan, Isabelle Raymond Letron, Philippe Le Bouteiller
Purpose: To assess the efficacy of the murine first-in-class CL1-R2 monoclonal antibody (mAb) targeting human CD160 (alone or in combination with bevacizumab) by using the rabbit corneal neovascularization (CNV) model, and determine the safety and efficacy of ELB01101, a novel CL1-R2-derived humanized IgG4 mAb, in a monkey model of choroidal neovascularization (ChNV). Methods: Comparison of effect of CL1-R2, bevacizumab, or aflibercept or IgG1 (control) injections in early and late treatment schemes on evolution of VEGF- or FGF2-induced rabbit CNV was performed...
June 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29800005/association-of-anticholinergic-drug-use-with-risk-for-late-age-related-macular-degeneration
#9
Gauthier Aldebert, Jean-Luc Faillie, Dominique Hillaire-Buys, Thibault Mura, Isabelle Carrière, Cécile Delcourt, Catherine Creuzot-Garcher, Max Villain, Vincent Daien
Importance: Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. Objective: To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). Design, Setting and Participants: A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017...
July 1, 2018: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29786830/blue-light-filtering-intraocular-lenses-iols-for-protecting-macular-health
#10
REVIEW
Laura E Downie, Ljoudmila Busija, Peter R Keller
BACKGROUND: An intraocular lens (IOL) is a synthetic lens that is surgically implanted within the eye following removal of the crystalline lens, during cataract surgery. While all modern IOLs attenuate the transmission of ultra-violet (UV) light, some IOLs, called blue-blocking or blue-light filtering IOLs, also reduce short-wavelength visible light transmission. The rationale for blue-light filtering IOLs derives primarily from cell culture and animal studies, which suggest that short-wavelength visible light can induce retinal photoxicity...
May 22, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29728379/effects-of-ceftiofur-and-chlortetracycline-on-the-resistomes-of-feedlot-cattle
#11
Margaret D Weinroth, H Morgan Scott, Bo Norby, Guy H Loneragan, Noelle R Noyes, Pablo Rovira, Enrique Doster, Xiang Yang, Dale R Woerner, Paul S Morley, Keith E Belk
Treatment of food-producing animals with antimicrobial drugs (AMD) is controversial because of concerns regarding promotion of antimicrobial resistance (AMR). To investigate this concern, resistance genes in metagenomic bovine fecal samples during a clinical trial were analyzed to assess the impacts of treatment on beef feedlot cattle resistomes. Four groups of cattle were exposed, using a 2-by-2 factorial design, to different regimens of antimicrobial treatment. Injections of ceftiofur crystalline-free acid (a third-generation cephalosporin) were used to treat all cattle in treatment pens or only a single animal, and either chlortetracycline was included in the feed of all cattle in a pen or the feed was untreated...
July 1, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29721997/validation-of-ips-cell-derived-rpe-tissue-in-animal-models
#12
Vladimir Khristov, Arvydas Maminishkis, Juan Amaral, Aaron Rising, Kapil Bharti, Sheldon Miller
Previous work suggests that replacing diseased Retinal Pigment Epithelium (RPE) with a healthy autologous RPE sheet can provide vision rescue for AMD patients. We differentiated iPSCs into RPE using a directed differentiation protocol. RPE cells at the immature RPE stage were purified and seeded onto either electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds or non-biodegradable polyester cell culture inserts and compared the two tissues. In vitro, PLGA and polyester substrates produced functionally similar results...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721963/the-role-of-c-jun-n-terminal-kinase-jnk-in-retinal-degeneration-and-vision-loss
#13
Byung-Jin Kim, Donald J Zack
c-Jun N-terminal kinase (JNK), a member of stress-induced mitogen-activated protein (MAP) kinase family, has been shown to modulate a variety of biological processes associated with neurodegenerative pathology of the retina. In particular, various retinal cell culture and animal models related to glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa indicate that JNK signaling may contribute to disease pathogenesis. This mini-review discusses the impact of JNK signaling in retinal disease, with a focus on retinal ganglion cells (RGCs), photoreceptor cells, retinal pigment epithelial (RPE) cells, and animal studies, with particular attention to modulation of JNK signaling as a potential therapeutic target for the treatment of retinal disease...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29720843/modulatory-effect-of-carotenoid-supplement-constituting-lutein-and-zeaxanthin-10-1-on-anti-oxidant-enzymes-and-macular-pigments-level-in-rats
#14
Jayashree Madhavan, Sundaram Chandrasekharan, M K Priya, Ashok Godavarthi
Background: Human eye is constantly exposed to different wavelengths and intensities of light. Oxidative stress results in distinct changes to retinal organs and tissues. Macular pigments (lutein and zeaxanthin), present in the central macular region, provide protection from photodamages by absorption of high energy blue light and also by virtue of their anti-oxidant activity. Ocular phototoxicity is thus prevented by our efficient anti-oxidant system, in both young and old. One of the best commercial sources of pure lutein and zeaxanthin is Marigold flowers...
April 2018: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29708536/culturing-of-retinal-pigment-epithelial-cells-on-an-ex-vivo-model-of-aged-human-bruch-s-membrane
#15
Hui Cai, Jie Gong, Lucian V Del Priore, Tongalp H Tezel, Mark A Fields
Aside from vitamins and antioxidants recommended by the Age-Related Eye Disease Study, there is no effective therapy for "dry," or atrophic age-related macular degeneration (AMD) which represents 90% of the cases. Therapies are needed to slow or retard the development of geographic atrophy (GA), and understanding Bruch's membrane pathology is part of this process. Alterations in human Bruch's membrane precede the progression of AMD by contributing to the damage of retinal pigment epithelial (RPE) cells...
April 12, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29666051/female-drosophila-melanogaster-respond-to-song-amplitude-modulations
#16
Birgit Brüggemeier, Mason A Porter, Jim O Vigoreaux, Stephen F Goodwin
Males in numerous animal species use mating songs to attract females and intimidate competitors. We demonstrate that modulations in song amplitude are behaviourally relevant in the fruit fly Drosophila We show that D rosophila melanogaster females prefer amplitude modulations that are typical of melanogaster song over other modulations, which suggests that amplitude modulations are processed auditorily by D. melanogaster Our work demonstrates that receivers can decode messages in amplitude modulations, complementing the recent finding that male flies actively control song amplitude...
June 11, 2018: Biology Open
https://www.readbyqxmd.com/read/29664944/ccl2-single-nucleotide-polymorphism-of-rs1024611-implicates-prominence-of-inflammatory-cascade-by-univariate-modeling-in-indian-amd
#17
Neel Kamal Sharma, Kaushal Sharma, Ramandeep Singh, Suresh Kumar Sharma, Akshay Anand
BACKGROUND: The role of chemotactic protein CCL2/MCP-1 has been widely explored in age related macular degeneration (AMD) patients as well as animal models through our previous studies. AIM: Aim of the study was to examine the association of another variance of CCL2, rs1024611 in pathophysiology of AMD. METHODS: This particular SNP has been found to be involved in inflammatory processes in various diseases. Total 171 subjects were recruited in the study with all demographic details by administering a standard questionnaire...
2018: PloS One
https://www.readbyqxmd.com/read/29651346/choriocapillaris-loss-in-advanced-age-related-macular-degeneration
#18
REVIEW
Carlos A Moreira-Neto, Eric M Moult, James G Fujimoto, Nadia K Waheed, Daniela Ferrara
The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy...
2018: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29625463/taurine-depletion-causes-iprgc-loss-and-increases-light-induced-photoreceptor-degeneration
#19
Diego García-Ayuso, Johnny Di Pierdomenico, Wahiba Hadj-Said, Mélanie Marie, Marta Agudo-Barriuso, Manuel Vidal-Sanz, Serge Picaud, María P Villegas-Pérez
Purpose: To examine if light exposure exacerbates retinal neuronal loss induced by taurine depletion. Methods: Albino rats received β-alanine in the drinking water to induce taurine depletion. One month later, half of the animals were exposed to white light (3000 lux) continuously for 48 hours and the rest remained in normal environmental conditions. A control group of animals nontreated with β-alanine also was prepared, and half of them were exposed to light using the same protocol...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29602770/lipocalin-2-plays-an-important-role-in-regulating-inflammation-in-retinal-degeneration
#20
Tanu Parmar, Vipul M Parmar, Lindsay Perusek, Anouk Georges, Masayo Takahashi, John W Crabb, Akiko Maeda
It has become increasingly important to understand how retinal inflammation is regulated because inflammation plays a role in retinal degenerative diseases. Lipocalin 2 (LCN2), an acute stress response protein with multiple innate immune functions, is increased in ATP-binding cassette subfamily A member 4 ( Abca4 ) -/- retinol dehydrogenase 8 ( Rdh8 ) -/- double-knockout mice, an animal model for Stargardt disease and age-related macular degeneration (AMD). To examine roles of LCN2 in retinal inflammation and degeneration, Lcn2-/- Abca4-/- Rdh8-/- triple-knockout mice were generated...
May 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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