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Immunopathology in Lungs after Intranasal Challenge with Live Virus in EHV-1 Recovered Murine Model of EHV-1 Infection: Lessons Learned From Unexpected Findings ehev -1感染小鼠鼻内活病毒攻击后肺部的免疫病理学:从意外发现中吸取的教训
Pub Date : 1900-01-01 DOI: 10.13188/2325-4645.1000058
A. Awan
Equine herpes virus (EHV-1) causes wide-spread infection among horses worldwide. Virus causes respiratory disease, abortion, neonatal death, paresis, retinopathy, viramea and becomes latent. Horses show transient immunity after EHV-1 infection, where immune responses have been observed to decline after a few months of infection and recovered horses are prone to EHV-1 reinfection. Due to transient immune responses, effective and lasting vaccination to EHV-1 remains a challenge. In an HSV murine model, mice provides solid protection and recovered mice could not be re-infected. In this study we infected mice with EHV-1 intra nasally and after five months, mice were re-infected with EHV-1 along with the previously placebo control. It was expected that mice that had recovered would show some level of protection, but in fact they showed unexpectedly severe clinical signs and more deaths on reinfection. Reinfected mice showed severe breathing difficulties, abdominal breathing, weight loss and death compared to mice infected for the first time. The answers to the worst clinical signs came from post-mortem and histopathological findings. Lungs of challenged mice showed severe consolidation and profound infiltration of inflammatory cells such that the normal parenchyma and architecture of lungs were completely lost. The results of this study suggest that immunoreactive pathological mechanisms exists and should be considered in designing intranasal vaccine preparation for EHV-1 and possibly for other respiratory infections.
马疱疹病毒(EHV-1)在全世界的马中引起广泛的感染。病毒可引起呼吸系统疾病、流产、新生儿死亡、麻痹、视网膜病变、病毒病,并具有潜伏性。马在感染EHV-1后表现出短暂的免疫,在感染几个月后观察到免疫反应下降,康复的马容易再次感染EHV-1。由于短暂的免疫反应,有效和持久的EHV-1疫苗接种仍然是一个挑战。在HSV小鼠模型中,小鼠提供了坚实的保护,恢复后的小鼠不能再次感染。在这项研究中,我们通过鼻内感染EHV-1小鼠,五个月后,小鼠与先前的安慰剂对照组一起再次感染EHV-1。人们预计,恢复后的老鼠会表现出一定程度的保护作用,但事实上,它们表现出了出乎意料的严重临床症状,并且在再次感染时死亡人数更多。与首次感染的小鼠相比,再次感染的小鼠表现出严重的呼吸困难、腹式呼吸、体重减轻和死亡。最糟糕的临床症状的答案来自于尸检和组织病理学结果。攻击小鼠的肺显示严重的实变和炎症细胞的深度浸润,使正常的肺实质和结构完全丧失。本研究结果提示存在免疫反应性病理机制,在设计EHV-1和其他呼吸道感染的鼻内疫苗制剂时应考虑这一机制。
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引用次数: 0
Carnitine Enigma: From Antioxidant Action to Vitagene Regulation. Part 1. Absorption, Metabolism, and Antioxidant Activities 肉毒碱之谜:从抗氧化作用到维生素调节。第1部分。吸收、代谢和抗氧化活性
Pub Date : 1900-01-01 DOI: 10.13188/2325-4645.1000017
Peter F Surai
L-carnitine (LC) is a small water-soluble molecule playing an important role in fat metabolism and there is a growing interest in the potential uses of LC as a medicinal agent and as a nutritional/dietary supplement. In addition to a great interest from medical sciences, carnitine received a substantial attention from pig and poultry industry. In particular, poultry and pig diets are formulated mainly with plant feed ingredients which are poor sources of carnitine. Furthermore, internal carnitine synthesis depends on many factors and in some cases could be inadequate. Therefore, it seems likely that carnitine dietary supplementation of highly productive and/or stressed animals/ birds is of great importance. The molecular mechanisms accounting for the positive effects of LC on farm animals and poultry are not yet determined but many protective effects of LC reported in literature have been related to its antioxidant action. Based on literature review it is concluded that there are several important mechanisms of antioxidant action of carnitine. Firstly, carnitine is shown to directly scavenge free radicals. However, this activity is most likely related to the gut antioxidant defences and has limited relevance to target tissues with relatively low carnitine concentrations. Secondly, carnitine can chelate transition metals (Fe 2+ and Cu + ), preventing their participation in ROS formation via Fenton reaction. However, detailed mechanisms of this process should be further elucidated using modern techniques applied to various biological systems. Again, this carnitine action is very much related to the gut. Thirdly, and more importantly, LC is found to decrease free radical formation by inhibiting specific enzymes (e.g. xanthine oxidase and NADPH oxidase) responsible for free radical production. This carnitine action has a high biological relevance in various stress conditions. Fourthly, and most importantly, carnitine is shown to participate in maintaining the integrity of mitochondria, including electron-transport chain of mitochondria, in stress conditions. Indeed, carnitine can be considered as a mitochondria-specific antioxidant, responsible for mitochondria integrity maintenance and regulation of ROS production and ROS signalling. Fifthly, carnitine can affect vitamin E absorption and metabolism improving the total antioxidant systems. There are important additional mechanisms of carnitine AO activity, including activation/inhibition of various transcription factors and vitagene networks. Antioxidant activities of carnitine in physiologically relevant concentrations have been well demonstrated in various in vitro systems including cell cultures or isolated cells or organelles. Protective effect of LC and its derivatives on the antioxidant systems of the body are also shown in various models of oxidative stress/toxicity caused by a variety of toxicants and neurotoxic agents. Several lines of evidence from animal experiments and clinical studies in
左旋肉碱(LC)是一种在脂肪代谢中起重要作用的小水溶性分子,作为一种药物制剂和营养/膳食补充剂的潜在用途越来越受到人们的关注。除了医学界的极大兴趣外,肉毒碱也受到养猪业和家禽业的极大关注。特别是,家禽和猪的日粮主要由植物性饲料成分组成,它们是肉碱的不良来源。此外,内部肉碱合成取决于许多因素,在某些情况下可能不足。因此,在高产和/或应激动物/鸟类中添加肉碱似乎是非常重要的。LC对农场动物和家禽的积极作用的分子机制尚未确定,但文献报道的许多LC的保护作用都与其抗氧化作用有关。通过文献综述,认为肉碱的抗氧化作用有几个重要的机制。首先,肉碱被证明可以直接清除自由基。然而,这种活性很可能与肠道抗氧化防御有关,与肉毒碱浓度相对较低的靶组织的相关性有限。其次,肉碱可以螯合过渡金属(Fe 2+和Cu +),阻止它们通过Fenton反应参与ROS的形成。然而,这一过程的详细机制应该利用应用于各种生物系统的现代技术进一步阐明。肉毒碱的作用与肠道密切相关。第三,更重要的是,人们发现LC通过抑制负责自由基产生的特定酶(如黄嘌呤氧化酶和NADPH氧化酶)来减少自由基的形成。这种肉碱作用在各种应激条件下具有很高的生物学相关性。第四,也是最重要的一点,在应激条件下,肉碱参与维持线粒体的完整性,包括线粒体的电子传递链。事实上,肉碱可以被认为是线粒体特异性抗氧化剂,负责线粒体完整性维护和ROS产生和ROS信号的调节。第五,肉碱可以影响维生素E的吸收和代谢,改善总抗氧化系统。肉毒碱AO活性还有重要的其他机制,包括各种转录因子和维生素网络的激活/抑制。在各种体外系统中,包括细胞培养或分离的细胞或细胞器中,生理相关浓度的肉碱的抗氧化活性已经得到了很好的证明。LC及其衍生物对机体抗氧化系统的保护作用也显示在各种由各种毒物和神经毒性物质引起的氧化应激/毒性模型中。来自动物实验和临床研究的几条证据表明,在各种病理条件下(缺氧、缺血-再灌注、电离辐射、高血压、肾功能衰竭和药物性肾毒性、过度运动和衰老)和各种疾病患者中,补充LC可有效预防氧化应激。经应用表明其具有抗氧化保护作用
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引用次数: 17
Stable Isotope Ratios of Carbon, Nitrogen, Oxygen, and Mercury Concentrations in North Pacific Baleen Whales and the Comparison of Their Calves with Toothed Whale Calves 北太平洋须鲸体内碳、氮、氧和汞浓度的稳定同位素比率及其幼鲸与齿鲸幼鲸的比较
Pub Date : 1900-01-01 DOI: 10.13188/2325-4645.1000059
Invi t ing Innova t ions
, and
,
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引用次数: 1
Investigation of Antiviral Effect of Far-UVC Microplasma Lamp against Influenza A Virus (H9N2) 远紫外微等离子体灯对甲型流感病毒(H9N2)的抗病毒作用研究
Pub Date : 1900-01-01 DOI: 10.13188/2325-4645.1000060
WK Jung
Influenza A virus is one of the most serious diseases in the world. Therefore, it is necessary to find an effective and safe method to prevent the spread of the disease. A far-UVC at 222nm is considered safe and effective for viral and bacterial treatment. In this study, virucidal effects and the safety status of far-UVC microplasma were evaluated in vitro against influenza A virus H9N2 0130 strain. The results (from TCID 50 and real-time PCR) indicated that a far-UVC inhibited influenza A virus depending on dosage. A far-UVC eliminated 99.99% of the virus at doses of 44 and 56 mJ/cm 2 in clarified and un-clarified solutions, respectively. Moreover, a far-UVC 222 nm did not have any harmful effects in MDCK cell at dose 78 mJ/cm 2 . Our study provided useful information in a far-UVC application against influenza A virus.
甲型流感病毒是世界上最严重的疾病之一。因此,有必要找到一种有效而安全的方法来防止疾病的传播。222nm的远紫外线被认为对病毒和细菌治疗是安全有效的。本研究对远紫外微血浆体外对甲型流感病毒H9N2 0130株的毒力及安全性进行了评价。结果(从TCID 50和实时PCR)表明,远紫外线抑制甲型流感病毒取决于剂量。在澄清溶液和未澄清溶液中,远紫外线分别以44和56 mJ/ cm2的剂量杀灭了99.99%的病毒。此外,远紫外线222 nm在78 mJ/ cm2剂量下对MDCK细胞没有任何有害影响。我们的研究为远紫外线抗甲型流感病毒的应用提供了有用的信息。
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引用次数: 0
Changes in Lactate Levels and Blood Cell Composition in Hokkaido Native Horses after exercise Simulating Yabusame (Traditional Japanese Mounted Archery) 北海道本土马模拟矢箭运动后乳酸水平和血细胞组成的变化
Pub Date : 1900-01-01 DOI: 10.13188/2325-4645.1000057
TJ Acosta
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引用次数: 0
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