NOVEL ASSAY METHODS FOR METHANOL TOXICITY

甲醇毒性的新测定方法

• 批准号: 6211122
• 负责人: HANS G KLOEPFER
• 金额: $ 10万
• 依托单位: MICRONIX, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-25 至 2001-03-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6211122
• 关键词: alcohol oxidoreductases; aldehyde /ketone oxidoreductase; biomedical equipment development; enzyme activity; formates; methanol poisoning; method development; miniature biomedical equipment; multiple organ failure; toxicant screening

Poisoning from methanol is a potentially life threatening medical emergency that can cause multi-organ failure and permanent visual impairment. For the next century, methanol has been proposed as an alternative, environmentally cleaner automotive fuel. Since other industrial uses of methanol are also expected to expand, the incidence of poisonings is likely to increase. Methanol is metabolized in vivo to formic acid (formate), the major toxic metabolite. The only affirmative diagnostic tool is determination of blood levels of methanol or formate. Unfortunately, access to testing for methanol is restricted, and for formate essentially non-existent. This leaves practitioners with relatively unspecific physical signs and surrogate laboratory tests to make the diagnosis. As numerous other conditions can lead to anion/osmolol gap acidosis, diagnosis can be enshrouded in mystery. The applicant proposes to develop specific enzymic methods for blood methanol and formate for use on existing clinical analyzers and at the patient point-of-care (POC). The POC method is a dual-analyte test tab device for the simultaneous estimation of methanol and formate from approximately two microliters of whole blood without centrifugation or any other form of sample or reagent handling. PROPOSED COMMERCIAL APPLICATION: Poisoning from methanol can lead to permanent visual impairment and death. Acidosis from formic acid needs to be differentiated from other forms of metabolic acidosis. Assay of methanol is currently done by semi-quantitative gas chromatographic (GC) "volatile screens", following by confirmatory analysis by GC or GC/MS. These methods are not available in most labs. Testing for formate is esentially non-existent. No clinical analyzer currently offers either a methanol or formate method. The proposed products would solve these problems.

甲醇中毒是一种可能危及生命的医疗紧急情况， 可导致多器官衰竭和永久性视力障碍。为了下一个世纪， 甲醇已被提议作为一种替代的、更环保的汽车燃料。 由于甲醇的其他工业用途预计也会扩大，因此发生率 中毒事件可能会增加。甲醇在体内代谢为甲酸 酸（甲酸盐），主要有毒代谢物。唯一肯定的诊断 工具是测定血液中甲醇或甲酸盐的含量。很遗憾， 甲醇的检测受到限制，甲酸盐的检测基本上受到限制 不存在的。这使得练习者的身体状况相对不明确 体征和替代实验室检查来做出诊断。正如许多其他 条件可导致阴离子/渗透压间隙酸中毒，诊断可被掩盖 在神秘中。申请人建议开发特定的酶方法 血液甲醇和甲酸盐用于现有的临床分析仪和 患者护理点 (POC)。 POC 方法是一种双分析物测试片装​​置 用于同时估计大约两个中的甲醇和甲酸盐 未经离心的微升全血或任何其他形式的样品 或试剂处理。 拟议的商业应用： 甲醇中毒可导致永久性视力障碍和死亡。酸中毒来自 甲酸需要与其他形式的代谢性酸中毒区分开来。 化验 甲醇目前通过半定量气相色谱（GC）“挥发性筛选”进行， 随后通过 GC 或 GC/MS 进行验证分析。这些方法不适用于 大多数实验室。 甲酸盐测试基本上不存在。 目前没有临床分析仪提供 甲醇法或甲酸盐法。 所提出的产品将解决这些问题。