Therapeutic application of NO scavenger and NO donor for endotoxin shock

这现在是可以理解的，因为硝酸氧化物过度生产（不）与各种疾病的病理学有关。在内毒性冲击中，例如，具有去分解的Peripheral Vascular Resistance的hypotension现在是众所周知的，通过NO的exessive production进行介导的。在这种情况下，它似乎是合理的，因为它抑制了NO的生产或清除将导致PTIO的治疗效应，我们以前开发的一个NO清除者，反对内毒性冲击。在事实上， PTIO可以在病理条件下拯救这样的模型动物。是的，不管怎样，我发现PTIO在生物系统中并不一定是稳定的，特别是当管理员对动物有害的时候。在目前的研究中，由于克服了PTIO的这一挫折，我们第一个成功地准备好了脂质体封装的PTIO，因此可以作为一种特定的无清除剂来治疗与NO相关的疾病，包括内毒素休克。在对比之下，它现在已经被确认为不在器官功能中的作用是 ... More 10种具有保护性和不愉快影响的双重效果这些相反的功能也被报道为内毒素冲击。我们进一步发明了一本小说，也可能是一个“不”的捐赠者，以看到“不”在休克病理学中的细胞保护效应对于this purpose，α-D21-protease inhibitor （α-D21-PI），谁是人类等离子体已知的最先进的丝氨酸蛋白质抑制剂，即一个重要的defense-oriented acute phase protein， is S-nitrosylated under physiological conditions， yielding 100% S-nitrosylated α-D21-PI（S-NO-α-D21-D2 PI）。S-NO-α-D-21 E-D-2 PI具有多种药理学功能，包括细胞凋亡的潜力抗菌活性和抑制，以及维持血流和器官功能。此外，它是S-NO-α-D21-D2 PI显示在大鼠活体中的潜在抗中性和抗氧化剂活性物质中的化学再灌注引起的潜在影响。目前的证据，讨论S-NO-α-D21 YED 2 PI的独特生物活动，可能导致S-NO-α-D21 YED 2 PI的进一步临床应用，用于治疗各种炎症和传染病，包括内毒素休克。Less（低）

It is now well conceivable that overproduction of nitric oxide (NO) contributes to the pathogenesis of various diseases. In endotoxic shock, for example, hypotension with decreased peripheral vascular resistance is now known to be mediated through excessive production of NO. In this context, it seems reasonable that inhibition of NO production or scavenging of NO will result in therapeutic effect of PTIO, an NO scavenger we developed previously, against endotoxin shock. In fact, PTIO can rescue such model animals in pathological condition. It is, however, found that PTIO was not necessarily stable in biological systems particularly when administered intravenously to the animals. In the present study, to overcome this drawback of PTIO, we first successfully prepared liposome-encapsulated PTIO, which can be applicable as a specific NO scavenger for the treatment of NO-related diseases including endotoxin shock. In contrast, it is now recognized that the role of NO in organ function is of … More ten dual with protective and injurious effects. These opposing functions of NO are also reported for endotoxin shock. We thus further invented a novel and potent NO donor to see the cytoprotective effect of NO in shock pathogenesis. For this purpose, αィイD21ィエD2-protease inhibitor (αィイD21ィエD2-PI), which is the most abundant serine protease inhibitor in human plasma known as an important defense-oriented acute phase protein, is S-nitrosylated under physiological conditions, yielding 100% S-nitrosylatedαィイD21ィエD2-PI (S-NO-αィイD21ィエD2PI). S-NO-αィイD21ィエD2PI thus obtained has multiple pharmacological functions, including potent antimicrobial activity and inhibition of cell apoptosis, and sustaining blood flow and organ functions. Also, it is of considerable importance that S-NO-αィイD21ィエD2PI shows a potent anti-neutrophil and anti-oxidant activities during ischemia-reperfusion injuries in rat livers. The present evidence, concerning the unique biological activities of S-NO-αィイD21ィエD2PI, may lead to further clinical application of S-NO-αィイD21ィエD2PI for treatment of various inflammatory and infectious diseases including endotoxin shock. Less