Streptomycin Sulfate

来源：搜狐网、央视新闻   整理：wangxinglai2004近日，日本国立医药品食品卫生研究所在日本小林制药公司销售的含红曲成分的保健品中，检测出除“软毛青霉酸”外，还有至少两种“未预料到的物质”，截至4月19日，服用该公司涉事保健品的消费者中已有5人死亡、240人住院。围绕小林制药公司含红曲保健品致服用者健康受损问题，日本厚生劳动省及国立医药品食品卫生研究所对该公司2023年6月至8月生产的问题原料样本进行分析，分析结果显示，除发现的软毛青霉酸【1】外，还检测出了其他几种通常情况下不会出现在红曲原料里的化合物。目前，厚生劳动省和国立医药品食品卫生研究所正在调查这些化合物是否由霉菌产生、在哪个阶段混入原料。厚生劳动省表示，新物质有可能使人健康受损，但没有透露检测到的物质数量，也没有说明这些物质的名称和特性。报道称，目前暂不清楚这些新物质对人体带来的影响，厚生劳动省正在推进相关研究工作，软毛青霉酸是由青霉菌产生的一种天然化合物。【1】“软毛青霉酸”到底是个啥？为什么会出现在红曲保健品中？说到青霉菌，相信很多人都不陌生。青霉菌产生的多种抗生素，如青霉素、红霉素、链霉素等，拯救了亿万人的生命，但是并非所有的青霉菌都能救人。有一部分青霉菌会产生其他毒素，甚至会夺走人性命。比如此次涉事的软毛青霉酸，就是一种由青霉菌产生的毒素。青霉菌毒素通常具有耐高温，加热烹调也很难让其毒性减弱，主要侵害实质器官的特性。研究发现，长期饲喂含青霉酸类毒素的饲料，能使动物肝脏肿大、肝细胞变性并能抑制动物细胞DNA合成，严重的可使动物细胞DNA断裂。而目前，软毛青霉酸导致的肾脏毒性，报道较少，仍需确认相关性。那么，软毛青霉酸为何会出现在红曲保健品中呢？原因是，青霉酸类毒素非常容易在如高粱、大麦、燕麦、小麦、玉米和大米上产生，且产量较高，是霉变饲料中的主要真菌毒素。红曲，是由红曲霉菌发酵而成的一种红色物质，而大米正是生产红曲的主要原材料。尽管日本厚生劳动省称，目前尚不清楚青霉菌是如何混入的，但可以预估，本次红曲事件是大米原料受到了青霉菌的污染导致。除了软毛青霉酸，红曲在发酵过程中可能产生黄曲霉素和桔青霉素，黄曲霉素摄入过量会导致肝损害、中毒、致癌等，桔青霉素有很强的肾脏毒性，摄入过量会导致肾损害。截至4月19日，服用该公司涉事保健品的消费者中已有5人死亡、240人住院。01 案件回顾：2024年1月起，据报道陆续有13名消费者因服用小林制药保健品出现身体不适，其中有6人住院治疗，有的患者甚至需要进行透析。2024年03月22日，据小林制药（中国）有限公司官网讯，小林制药株式会社在日本制造、销售的保健食品“红麹胆固醇颗粒”，我们收到了一些食用后可能导致肾脏疾病等问题的报告，小林制药（中国）有限公司官网显示，小林公司自主召回红麹原料相关产品；2024年03月22日，涉事产品已在通知中提到的电商平台小林制药官方店铺内下架，多个电商平台已搜索不到该产品。2024年03月26日，据央视援引日本广播协会（NHK）报道，日本厚生劳动省公布了因摄取含有“小林制药”公司“红曲”成分的保健品后发生的第二例死亡案例，入院人数已增至106人。小林制药呼吁消费者停用受影响的产品。2024年03月29日，中国消费者协会就服用日本小林制药公司生产的红曲胆固醇颗粒等产品导致消费者死亡一事发布消费提示，服用日本小林制药公司生产的红曲胆固醇颗粒、纳豆激酶颗粒以及降胆固醇健康辅助颗粒等产品可能导致肾脏疾病，截至3月29日，上述产品已导致5名日本消费者死亡。2024年04月05日,日本厚生劳动省发布消息，据小林制药公司报告，截至当地时间4日，服用小林制药含红曲成分问题保健品的消费者已有5人死亡，该公司含红曲原料保健品相关的住院人数住院人数增至196人。2024年04月05日，日本小林制药公司发布消息称，将从6日开始开通针对所有购买了该公司含红曲成分保健品的网上退货渠道。小林制药公司于1日开设了退货接待中心，但只有通过网上或书信等方式购买产品的消费者才能够提交在线退货申请。2024年4月12日，据日本小林制药公司报告，截至4月11日，服用小林制药公司含红曲成分涉事保健品的消费者已有5人死亡、住院人数增至226人。日本肾脏学会9日公布调查结果，称对服用日本小林制药公司问题保健品的部分消费者开展的调查显示，多半出现了范科尼综合征的症状，大部分患者在停止服用后症状出现改善。通俗来讲，范科尼综合征就是肾脏受损后，体内的酸碱平衡和电解质平衡被打破，导致体内的一些营养物质被排出，而应该排出体内的酸性物质等体内垃圾，却排出减少。据日本广播协会电视台报道，已于去年12月关闭的小林制药公司大阪工厂在去年4月曾因生产过程中的疏忽，导致33公斤红曲生产原料在混合搅拌过程中，散落在地，其中部分原料随后被收集，并与其他红曲原料混合后出货。小林制药公司方面称，发生这一问题的红曲原料是用于食品着色用途，与含红曲成分问题保健品事件无直接关联。02 质量问题原因：根据小林药业的回复，其在对问题产品原料红麹原料（自社制造）进行了成分分析，结果发现部分红麹原料中可能含有非预期的成分，目前尚未确定该成分的具体性质，以及与肾脏疾病等问题之间的关联性，但出于保护消费者健康的目的，小林制药（中国）有限公司受日本小林制药的委托，呼吁停止销售和使用含有日本小林制药生产的红麹原料的产品。如果最终确认红麹原料中非预期成分存在着明确的人体伤害性，或是已知的控制物质，那对于小林药业、及其下游企业都是致命的打击，同时也警醒其他生产企业是否存在同类问题，可以遇见本次事件将成为食品、药品危害事件的典型案例被收录。同时，对于含有日本小林制药生产的红麹原料的产品，也属于日本小林制药要求的自主召回对象，因此，小林制药中国公司也恳请各位协助该类产品的召回。小林制药中国公司表示，如消费者需要确认手中的产品是否含有日本小林制药生产的红麹原料，以及有关自主召回和退款的具体方式等，请与该产品的生产或销售企业进行确认。如经确认后手中持有的是含日本小林制药红麹原料的产品，请立即停止食用。如曾食用过该产品，并感觉身体不适，也请立即与该产品的生产或者销售企业进行咨询。据报道小林制药公司生产的问题红曲原料最多恐波及日本国内3.3万家企业，其中包括超过5000家食品和饮料零售商。这些企业中，食品和饮料零售企业最多，达5582家，占比16.6%；其他零售企业5171家，占比15.4%；医疗企业3884家，占比11.5%；餐饮店3115家，占比9.3%。购买上述问题红曲原料的企业所加工食品包括纳豆、面包、盒饭、咸鱼、腌菜和发酵食品等，由于红曲用途广泛，要追溯使用问题原料的产品并非易事，这得注意的是，部分受影响产品通过跨境渠道销往中国大陆。

Researchers have discovered toxic protein particles, shaped like umbrellas, that soil bacteria known as Streptomyces secrete to squelch competitors in their crowded microbial communities, especially others of their own species. What makes these newly detected antibacterial toxins different is that, unlike the Streptomyces' small-molecule antibiotics, umbrella toxins are large complexes composed of multiple proteins. They are also far more specific in the bacteria they target. They tend to go after bacteria that form branching filaments, an usual growth pattern among bacteria. The scientists are intrigued by the potential clinical clinical applications of this discovery, because they suspect the pathogens that cause tuberculosis and diphtheria might be sensitive to umbrella toxins. Researchers have discovered toxic protein particles, shaped like umbrellas, that soil bacteria known as Streptomyces secrete to squelch competitors, especially others of their own species. The discovery of the umbrella toxin particles and related information about their structures, composition and mode of action were published April 17 in Nature. The umbrella toxin proteins are the latest example of these bacteria's varied, combative strikes on their microscopic rivals. The crowded, diverse bacteria communities in which they live are a melee of antimicrobial attacks, counterattacks and defenses. Ironically, many clinically used antibiotics are derived directly from, or are inspired by, molecules that bacteria use against each other in their natural habitat. Streptomyces' chemical weaponry against their competitors is one of the richest sources of such molecules. Among them is the common, broad-spectrum drug streptomycin. What makes these newly detected antibacterial toxins different is that, unlike the Streptomyces' small-molecule antibiotics, umbrella toxins are large complexes composed of multiple proteins. They are also far more specific in the bacteria they target. The authors of the Nature paper speculate that these properties of umbrella toxins explain why they escaped discovery for more than 100 years of research on toxins produced by Streptomyces. Genes encoding umbrella toxins were originally uncovered through a bioinformatics search for new bacterial toxins. In biochemical and genetic experiments led by Qinqin Zhao in Joseph Mougous' microbiology lab at the University of Washington School of Medicine, the scientists learned that these toxins associate with other proteins in a large complex. Cryo-electron microscopy of these protein complexes was performed by Young Park in the laboratory of David Veesler, professor of biochemistry at the UW School of Medicine and an investigator of the Howard Hughes Medical Institute. These studies revealed that the toxin complexes Qinqin isolated adopt a striking appearance befitting their discovery in Seattle. They look like umbrellas. "The shape of these particles is quite peculiar, and it will be interesting in future work to learn how their unusual morphology helps them eliminate target bacteria," noted Mougous, a professor of microbiology at the UW School of Medicine and a Howard Hughes Medical Institute investigator. The scientists then sought to determine the targets of these toxins by screening their effects on every organism they could conceivably target, from fungi to 140 different bacteria, including some taken from sorghum plants in the lab of study author Devin Coleman at the University of California-Berkeley and the U.S. Department of Agriculture Agricultural Research Service. . Among these potential adversaries, the toxins specifically targeted their own brethren: other Streptomyces species. "We think this exquisite specificity may be due to the proteins that make up the spokes of the umbrella, which vary across the particles. These include proteins that might latch onto specific sugars found on the surface of competitor bacteria," commented study author S. Brook Peterson, a senior scientist in the Mougous lab. By analyzing the thousands of publicly available bacterial genomes, study authors Dapeng Zhang of St. Louis University and his graduate student Youngjun Tan found that many other species of bacteria also have the genes to manufacture umbrella particle toxins. Interestingly, these species all form branching filaments, an unusual mode of growth among bacteria. In addition to the many questions remaining to be answered about the basic biology of umbrella toxin particles, Mougous and his colleagues are intrigued by their potential clinical applications. They suspect that the bacteria that cause tuberculosis and diphtheria may be sensitive to umbrella toxins. They note these same bacteria have become resistant to traditional antibiotics. Umbrella toxin particles might be worth exploring, the scientists suggested, for their potential to subdue these serious disease-causing bacteria.