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Clinical Case Report of a Novel Immunotherapeutic Approach to Autism Spectrum Disorders based on an emulsion of Chondroitin Sulfate, Vitamin D 3 and Oleic Acid 基于硫酸软骨素、维生素D3和油酸乳液的自闭症谱系障碍新免疫治疗方法的临床病例报告
Pub Date : 2017-08-10 DOI: 10.3844/AJISP.2017.180.185
Nicola Antonucci, S. Pacini, M. Ruggiero
In this clinical case report we describe the effects associated with the administration of a supplement constituted by chondroitin sulfate, vitamin D3 and oleic acid (Rerum®) on the symptoms of Autism Spectrum Disorders (ASD). 44 patients (11 females and 33 males) were administered this supplement for a period of two months and variations of symptomatology were evaluated by the Clinical Global Impression of Improvement (CGI-I). 32 out of 44 subjects (73%), showed improvements in the two months of observation. In the group of female subjects, 9 out of 11 (81%) showed improvements and, among these, 6 out of 9 (66%) showed moderate to very considerable improvements. In the group of male subjects, 24 out of 33 (73%) showed improvements and, among these, 22 out of 24 (91%) showed moderate to very considerable improvements. We attribute these remarkable results to the effects of the supplement on the endocannabinoid system as it relates to neuro-inflammation and neuro-immune alterations.
在这个临床病例报告中,我们描述了一种由硫酸软骨素、维生素D3和油酸(Rerum®)组成的补充剂对自闭症谱系障碍(ASD)症状的影响。44名患者(11名女性和33名男性)服用这种补充剂两个月,并通过临床总体改善印象(CGI-I)评估症状的变化。44名受试者中有32名(73%)在两个月的观察中表现出改善。在女性受试者组中,11人中有9人(81%)表现出改善,其中9人中有6人(66%)表现出中度到非常显著的改善。在男性受试者组中,33人中有24人(73%)表现出改善,其中24人中有22人(91%)表现出中度至非常显著的改善。我们将这些显著的结果归因于补充剂对内源性大麻素系统的影响,因为它与神经炎症和神经免疫改变有关。
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引用次数: 3
Initiatives to Improve the Quality of Life of HIV Positive Diagnosed Subjects: A Review of Diagnosis, Prognosis and Therapeutics under the Light of Science and Ethics 提高HIV阳性患者生活质量的举措:科学与伦理视野下的诊断、预后和治疗学综述
Pub Date : 2017-08-03 DOI: 10.3844/ajisp.2017.173.179
M. Molina, Jeremías Abou Medelej, Jorgelina Zucchi, C. Manassero
The first cases of AIDS occurred about 1981. There are not fully appropriate therapeutic interventions for treating this medical condition. People who are diagnosed HIV-positive or with AIDS suffer a poor quality of life and receive medication that produces severe adverse reactions. We have analyzed a significant number of papers published in several countries on these topics, and we have found various inconsistencies: - HIV risk behaviors: According to the Centers for Disease Control and Prevention, in the United States, the Estimated Per-Act Probability of Acquiring HIV from an Infected Source, by Exposure Act (heterosexual) is about one in one thousand for women and about one in two thousand for men. Nevertheless, in an investigation conducted through the University of San Francisco, California, on 442 discordant heterosexual couples no seroconversions were observed throughout the ten years the research lasted. (1985-1995). No other study of similar characteristics has been conducted ever since. - Diagnostics methods: In Argentina, we employ the ELISA screening method, subsequently confirmed by a Western Blot test, but in the United Stated this last is discouraged since 2014. - Medication: Many of the drugs that are used to treat HIV are DNA chain terminators which interfere with the normal functioning and replication of normal cells. As a result, damage in the immune system and the mitochondrial DNA are reported very frequently. We ask the scientific community what we should inform the patients about all these. We urge the experts´ opinion on the ethical management aspects. Since the diagnostic tests employed may result in false positives and the fact that the medication is highly toxic, we recommend that patients with HIV positive diagnosis fully re-test their condition at least once a year to minimize eventual diagnostic errors, suspending specific medications in case of discrepancies on the testing results.
第一例艾滋病发生在1981年左右。目前还没有完全适当的治疗干预措施来治疗这种疾病。被诊断为艾滋病毒阳性或艾滋病患者的生活质量很差,接受的药物会产生严重的不良反应。我们分析了几个国家发表的关于这些主题的大量论文,我们发现了各种不一致之处:-艾滋病毒风险行为:根据疾病控制和预防中心的数据,在美国,通过暴露法(异性恋)从感染源感染艾滋病毒的估计每次行为概率约为女性的千分之一,男性的千分之一。然而,在加州旧金山大学进行的一项调查中,对442对不和谐的异性恋夫妇进行了调查,在研究持续的十年中,没有观察到任何性关系转变。(1985 - 1995)。从那以后,再没有其他类似特征的研究。-诊断方法:在阿根廷,我们采用ELISA筛选方法,随后通过Western Blot测试确认,但在美国,自2014年以来,最后一种方法不被鼓励。-药物治疗:许多用于治疗HIV的药物是DNA链终止剂,会干扰正常细胞的正常功能和复制。因此,免疫系统和线粒体DNA的损伤被报道得非常频繁。我们询问科学界关于这些我们应该告诉病人什么。我们敦促专家就道德管理方面发表意见。由于所采用的诊断测试可能导致假阳性,而且药物具有高毒性,因此我们建议诊断为艾滋病毒阳性的患者每年至少对其病情进行一次全面重新测试,以尽量减少最终的诊断错误,如果测试结果不一致,则暂停使用特定药物。
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引用次数: 0
"Ebola Ça Suffit!" is not enough to Prove Efficacy of an Ebola Vaccine “埃博拉Ça Suffit!”不足以证明埃博拉疫苗的有效性
Pub Date : 2017-07-08 DOI: 10.3844/AJISP.2017.165.172
D. Crowe
A recently published Ebola vaccine trial claimed an almost perfect result with no cases of Ebola after the vaccine had time to take effect - a vaccine efficacy of 100%. This article is a detailed review of the information published about the trial and, particularly, this claim. The trial design was sub-optimal because randomization was only partial (and one treatment arm was unrandomized), it was unblinded and did not use a placebo. Less information on the comparison arm that substituted for a placebo was provided, such as adverse events, compared to the active treatment arms. There was little baseline information on the trial participants, which is particularly important to ensure equivalence of the arms of a trial that was not fully randomized. In particular, Ebola tests were not performed at baseline, so the possibility of false positive test results or pre-existing asymptomatic cases exists. Ebola symptoms and adverse reactions following vaccination seen during the trial were very similar, allowing diagnostic bias. The exclusion of Ebola cases among the vaccinated during the 10 days after randomization is an arbitrary decision for an infection with an incubation period of 2 to 21 days and not a substitute for comparing vaccine to placebo. Considering the entire 31-day reporting period, two subgroups of unvaccinated participants had significantly fewer cases of Ebola than the two vaccinated groups. The problems with this trial are so grave that it cannot be taken as even weak evidence that the vaccine trialed is effective at preventing Ebola Virus Disease (EVD).
最近发表的一项埃博拉疫苗试验声称,在疫苗有时间生效后,结果几乎完美,没有埃博拉病例——疫苗有效性为100%。这篇文章详细回顾了有关审判的信息,尤其是这一指控。试验设计是次优的,因为随机化只是部分的(一个治疗组是非随机化的),它是非盲的,没有使用安慰剂。与积极治疗组相比,提供的关于替代安慰剂的比较组的信息较少,如不良事件。几乎没有关于试验参与者的基线信息,这对于确保未完全随机化的试验的臂的等效性尤为重要。特别是,埃博拉病毒检测没有在基线进行,因此存在假阳性检测结果或先前存在的无症状病例的可能性。试验期间发现的埃博拉症状和接种疫苗后的不良反应非常相似,允许存在诊断偏差。对于潜伏期为2至21天的感染,在随机化后的10天内排除接种疫苗的人中的埃博拉病例是一个任意的决定,不能代替将疫苗与安慰剂进行比较。考虑到整个31天的报告期,两个未接种疫苗的参与者亚组的埃博拉病例明显少于两个接种疫苗的组。这项试验的问题非常严重,甚至不能作为试验疫苗有效预防埃博拉病毒病(EVD)的薄弱证据。
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引用次数: 1
The Etiological Role of Microglia in Autism Spectrum Disorder: A Possible Route for Early Intervention 小胶质细胞在自闭症谱系障碍中的病因学作用:早期干预的可能途径
Pub Date : 2017-06-24 DOI: 10.3844/AJISP.2017.99.106
R. Slovak, N. Chakraborty
Autism Spectrum Disorder (ASD) is a dreaded diagnosis. The treatment options are sparse and our knowledge of its etiology is woefully lacking. The purpose of this review is to outline a unifying pathway for the pathogenesis of Autism Spectrum Disorder and to describe how this sequence could be exploited to offer early intervention to patients at high risk of developing ASD. Specifically, we will describe how gestational insults can alter the lifelong functioning of fetal microglia. Those aberrant microglia are unable to properly fulfill their roles in cortical differentiation as well as synaptogenesis and the resulting cortical disorganization plus dendritic overgrowth may be responsible for the characteristic Autistic phenotype. This pathogenic pathway presents several opportunities for intervention. If applied early enough, it is possible that these therapies could alleviate some of the symptoms of ASD.
自闭症谱系障碍(ASD)是一种可怕的诊断。治疗选择很少,我们对其病因的了解也少得可怜。这篇综述的目的是概述自闭症谱系障碍发病机制的统一途径,并描述如何利用这一序列为患有ASD的高危患者提供早期干预。具体来说,我们将描述妊娠期损伤如何改变胎儿小胶质细胞的终身功能。这些异常的小胶质细胞无法正确发挥其在皮质分化和突触发生中的作用,由此产生的皮质紊乱加上树突过度生长可能是自闭症特征表型的原因。这种致病途径提供了多种干预机会。如果及早应用,这些疗法有可能缓解ASD的一些症状。
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引用次数: 1
Is Rerum ® the New Coley's Vaccine? Rerum®是新型科利疫苗吗?
Pub Date : 2017-05-31 DOI: 10.3844/AJISP.2017.91.98
M. Ruggiero
Email: marco.drruggiero@gmail.com Abstract: In this article I describe the development of an alternative type of immunotherapy that traces its origins to the nineteenth century when Dr. William B. Coley successfully treated inoperable cancer patients with his vaccine. Despite the well-documented successes, the vaccine did not survive Coley's times and was forgotten and neglected for decades in favor of radioand chemotherapy. In the mid-fifties of the last century, the concept of a therapy based on stimulation of the immune system re-emerged from oblivion even though with a profoundly diverse connotation; the interest in this approach to cancer has grown exponentially ever since, up to the point of appointing immunotherapy of cancer the" breakthrough of the year" in 2013. Most cancer immunotherapies are based on proteins that either empower the immune system or attempt to selectively kill cancer cells. There are, however, some exceptions to this protein-based approach; the pioneering work of Dr. Prudden in New York and our research work in Florence, Italy. Thus, independently of each other, we pursued an alternative concept of immunotherapy that is based on glycosaminoglycans rather than proteins. From this research, a novel, tridimensional supramolecular structure constituted by chondroitin sulfate, vitamin D3 and oleic acid, designated Rerum ® , was developed with the intent of reviving the historical approach of Dr. Coley at the light of today's knowledge. Here, I describe the rationale for the development of Rerum ® as well as some preliminary results that were presented at the Fourth International Congress of Integrative Medicine held in Fulda, Germany, in April 2017.
电子邮件:marco.drruggiero@gmail.com摘要:在这篇文章中,我描述了一种替代类型的免疫疗法的发展,其起源可以追溯到19世纪,当时威廉·B·科利博士成功地用他的疫苗治疗了无法手术的癌症患者。尽管取得了有据可查的成功,但该疫苗并没有在科利时代幸存下来,几十年来一直被遗忘和忽视,取而代之的是放疗和化疗。在上个世纪五十年代中期,基于免疫系统刺激的治疗概念从遗忘中重新出现,尽管其内涵极其多样;自那以来,人们对这种治疗癌症的方法的兴趣呈指数级增长,直到2013年任命癌症免疫疗法为“年度突破”。大多数癌症免疫疗法都是基于增强免疫系统能力或试图选择性杀死癌症细胞的蛋白质。然而,这种基于蛋白质的方法也有一些例外;普鲁登博士在纽约的开创性工作以及我们在意大利佛罗伦萨的研究工作。因此,我们相互独立地追求了一种基于糖胺聚糖而非蛋白质的免疫疗法的替代概念。通过这项研究,开发了一种由硫酸软骨素、维生素D3和油酸组成的新型三维超分子结构,命名为Rerum®,旨在根据当今的知识复兴Coley博士的历史方法。在这里,我描述了Rerum®开发的基本原理,以及2017年4月在德国富尔达举行的第四届国际综合医学大会上发表的一些初步结果。
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引用次数: 6
Chasing the Fat Demon: Fat Chance, Buddy? 追逐胖恶魔:机会渺茫,伙计?
Pub Date : 2017-05-29 DOI: 10.3844/AJISP.2017.86.88
D. Katz, J. Storsberg, C. Schmidt
Yale University Prevention Research Center; Griffin Hospital; Derby, CT, USA Fraunhofer-Institute for Applied Polymer Research (IAP), Division of Life Science and Bioprocesses, Department of Biomaterials and Healthcare, Potsdam-Golm, Germany Editorial Office, The American Journal of Immunology, S-207, 244, 5th Avenue, New York, NY, 10001 USA and S-71, 1A, 400, King William St, Adelaide, SA 5000, Australia
耶鲁大学预防研究中心;格里芬医院;弗劳恩霍夫应用聚合物研究所(IAP),生命科学和生物过程分部,生物材料和医疗保健系,波茨坦戈姆,德国编辑部,美国免疫学杂志,美国纽约,纽约州,10001第五大道S-207号244号,澳大利亚阿德莱德,SA 5000,国王威廉街S-71号1A, 400号
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引用次数: 1
Choice Meaning and Context: Two Sides of the Same Coin? 选择意义和语境:同一枚硬币的两面?
Pub Date : 2017-05-24 DOI: 10.3844/AJISP.2017.89.90
S. Sel, J. Storsberg, Mark A. Brown, C. Schmidt
Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany Department of Biomaterials and Healthcare, Division of Life Science and Bioprocesses, Fraunhofer Institute for Applied Polymer Research (IAP), Potsdam-Golm, Germany Department of Clinical Sciences and Colorado School of Public Health, Colorado State University, Fort Collins, CO, USA Editorial Office, Am. J. Immunol., New York, NY, USA and Adelaide, SA, Australia
海德堡大学眼科系,海德堡,德国生物材料与医疗保健系,生命科学与生物工艺部,弗劳恩霍夫应用聚合物研究所(IAP),波茨坦戈尔姆,德国临床科学系和科罗拉多州立大学科罗拉多公共卫生学院,科罗拉多州科林斯堡,美国编辑部,Am.J.Immunol。,美国纽约州纽约市和澳大利亚南部阿德莱德
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引用次数: 1
Functionalization Strategies for Antibodies: Lessons Learned 抗体功能化策略:经验教训
Pub Date : 2017-05-04 DOI: 10.3844/AJISP.2017.144.154
C. Schmidt, M. Geyer, J. Bohrisch, Verena Jentzen, Alexander Gorczyza, Karim Khalil, Marina Volkert, Mark A. Brown, S. Sel, J. Storsberg
Precious little is known about useful functionalization strategies of antibodies that will not impair either reactivity or specificity of this valuable reagent. We used an experimental approach to demonstrate our own experience with published protocols. The conjugates obtained were then tested with regard to their performance against commercially available detection kits. Our results are then viewed in light of published precedence to highlight areas where future effort is needed to refine such versatile tools.
对于不会损害这种有价值试剂的反应性或特异性的抗体的有用功能化策略,我们知之甚少。我们使用了一种实验方法来展示我们自己对已发布协议的经验。然后对获得的缀合物相对于市售检测试剂盒的性能进行测试。然后,我们根据公布的优先顺序来看待我们的结果,以突出未来需要努力完善这种多功能工具的领域。
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引用次数: 0
Humoral and Cellular Effects of Stress-An Extensive Model System 应激的幽默和细胞效应——一个可扩展的模型系统
Pub Date : 2017-04-18 DOI: 10.3844/ajisp.2017.131.143
M. Shimon-Hophy, R. Avtalion
The influence of stress on the immune system of the common carp (Cyprinus carpio) was studied by measuring leukocytes levels using flow cytometry and mRNA immune components by real time qPCR. Acute and chronic oxidative stresses were generated by different regimes of exposure of carp to environmental air. In acute stress, induced by single air exposure, the pro-inflammatory cytokines (IL1β, IL6 and TNFα) and the down-regulatory ones (IL10 and TGFβ) showed significant simultaneous elevations (515, 147, 373, 300 and 198% respectively). Following chronic stress (multiple air exposures) however, a drastic decline of 80%, in macrophages/monocytes, B-cells likes and plasma-cells like, occurred in peripheral blood. No statistical changes in IL6 and TNFα, as well as in IgM and C3s mRNA levels could be shown during this experiment. CD4 mRNA decreased up to 6% in the 2nd week of chronic stress and elevated only to 55% at the 3rd week Vs a temporal decline of up to 22% in CD8a mRNA at the 2nd week. The regulatory cytokines (IL10, FoxP3 and TGFβ) as well as the pro-inflammatory ones (IL1β and IL17) decreased significantly up to 0.06, 0.2, 5, 6 and 4% respectively, at the second week before being restored to normal at the 3rd week. Moreover, a persistent decrease, up to null levels, in the cytokines IFNγ2b, IL12b and IL8 was also revealed. These downregulations were suggested as a result of the impaired Th1 and/or cytotoxic cell function and, to a certain degree, the leukocytes mobilization. The above findings show that in contrast to the detrimental effects of chronic stress, in which cells and functions of acquired immunity were partially or completely impaired, the acute stress was found rather beneficial and in line with the known ephemeral “fight and flight” response.
通过流式细胞仪检测白细胞水平,实时qPCR检测信使核糖核酸免疫组分,研究了应激对鲤鱼免疫系统的影响。鲤鱼暴露于环境空气的不同方式会产生急性和慢性氧化应激。在单次空气暴露诱导的急性应激中,促炎细胞因子(IL1β、IL6和TNFα)和下调因子(IL10和TGFβ)同时显著升高(分别为515、147、373、300和198%)。然而,在慢性应激(多次暴露于空气中)后,外周血中的巨噬细胞/单核细胞、B细胞样和浆细胞样急剧下降80%。在本实验中,IL6和TNFα以及IgM和C3s mRNA水平没有显示出统计学变化。CD4 mRNA在慢性应激的第2周下降了6%,在第3周仅上升到55%,而CD8a mRNA在第2周暂时下降了22%。调节性细胞因子(IL10、FoxP3和TGFβ)和促炎细胞因子(IL-1β和IL17)在第二周显著下降,分别降至0.06%、0.2%、5%、6%和4%,第三周恢复正常。此外,细胞因子IFNγ2b、IL12b和IL8也持续下降,直至零水平。这些下调被认为是Th1和/或细胞毒性细胞功能受损的结果,并且在一定程度上是白细胞动员的结果。上述发现表明,与慢性应激的有害影响(其中获得性免疫的细胞和功能部分或完全受损)相反,急性应激被发现是有益的,并且符合已知的短暂的“战斗和逃跑”反应。
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引用次数: 5
Glucans and the Poultry Immune System 葡聚糖和家禽免疫系统
Pub Date : 2017-04-12 DOI: 10.3844/AJISP.2017.45.49
J. Jacob, A. Pescatore
With the reduced availability of antibiotics, poultry producers are looking for feed additives to stimulate the immune system of their birds. Some beta-glucans have been shown to improve gut health in poultry subjected to a bacterial challenge, to increase the flow of new immunocytes into the various lymphoid organs, to increase macrophage function, to increase antibody titers after a vaccination and to function as an anti-inflammatory immunomodulator. As a result, beta-glucans may provide a tool for producers trying to reduce or eliminate the use of antibiotics in poultry diets.
随着抗生素供应的减少,家禽生产商正在寻找饲料添加剂来刺激家禽的免疫系统。一些β-葡聚糖已被证明可以改善受到细菌攻击的家禽的肠道健康,增加新免疫细胞进入各种淋巴器官的流量,增加巨噬细胞功能,增加疫苗接种后的抗体滴度,并起到抗炎免疫调节剂的作用。因此,β-葡聚糖可能为生产商提供一种工具,试图减少或消除家禽饮食中抗生素的使用。
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引用次数: 21
期刊
American journal of immunology
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