Robledo Mary Ann, Orduz Mariana
Calle 33# 42B-06 C.C Sandiego Torre sur 1122, Medellin, Colombia.
Universidad CES, Medellin, Colombia.
Med Hypotheses. 2015 Apr;84(4):408-12. doi: 10.1016/j.mehy.2015.01.036. Epub 2015 Jan 31.
Most of the patients with erythematotelangiectatic rosacea are characterized by flushing, oedema and telangiectasia. The etiopathogenesis of the flushing in rosacea patients is unknown. Clinically the flushing in rosacea is similar to the "Asian flushing syndrome". Most Asians have an overactive alcohol dehydrogenase (ADH) that tends to break down alcohol into acetaldehyde faster. People with "Asians flushing syndrome" have a genetic disorder with the Aldehyde Dehydrogenase 2(∗)2 (ALDH2(∗)2) allele. This is the reason why they do not metabolize very well the acetaldehyde that comes from the alcohol, which means that acetaldehyde takes much longer to clear from their blood. ALDH2 enzyme is primarily responsible for oxidation of acetaldehyde derived from ethanol metabolism, as well as oxidation of various other endogenous and exogenous aldehydes. Acetaldehyde produces the vasodilatation in the "Asian flushing syndrome". The antibodies against the GroEl chaperonin protein, a 62-kDa heat shock protein were found in the Bacillus oleronius isolated from Demodex mites, in rosacea patients. The GroEl chaperonin protein is a protein that plays a key role in normal folding of ALDH2. If the GroEl chaperonin antibodies found in patients with rosacea, cross react with the human GroEl chaperonin protein, they will not fold normally the ALDH2, and then the enzyme will not metabolize the acetaldehyde. Many of the patients with rosacea have a concomitant infection with Helicobacter pylori in their stomach. The H.pylori produces high amounts of acetaldehyde, which comes from their metabolism of ethanol or carbohydrates. As a result, high amounts of acetaldehyde will circulate for longer time in the blood, until the liver CYP2E1(p450) enzyme system finally metabilizes the acetaldehyde, during that period of time the patients will experience a flushing as well as the people with the "Asian flushing syndrome" suffer when they drink ethanol. To prove the hypothesis it is necessary to find the cross reaction between the GroEl chaperonin antibodies against the B.oleronius and human GroEl chaperonin. Four groups of patients will be studied with or without the GroEl chaperonin antibodies, and H.Pylori. The production of acetaldehyde will be tested by the ethanol-derived microbial production method. If the hypothesis proves to be true, the treatment of Demodex mites and the H. pylori could improve the flushing in the rosacea patients and it will prevent the angiogenesis (telangiectasia), and the association of the gastric injury and carcinogenesis in those patients.
大多数红斑毛细血管扩张型酒渣鼻患者的特征为面部潮红、水肿和毛细血管扩张。酒渣鼻患者面部潮红的发病机制尚不清楚。临床上,酒渣鼻的面部潮红与“亚洲潮红综合征”相似。大多数亚洲人的酒精脱氢酶(ADH)活性过高,倾向于将酒精更快地分解为乙醛。患有“亚洲潮红综合征”的人存在醛脱氢酶2()2(ALDH2()2)等位基因的遗传疾病。这就是他们不能很好地代谢来自酒精的乙醛的原因,这意味着乙醛从他们血液中清除的时间要长得多。ALDH2酶主要负责乙醇代谢产生的乙醛的氧化,以及各种其他内源性和外源性醛的氧化。乙醛在“亚洲潮红综合征”中会引起血管扩张。在从酒渣鼻患者的毛囊蠕形螨中分离出的奥勒龙芽孢杆菌中发现了针对GroEl伴侣蛋白(一种62 kDa的热休克蛋白)的抗体。GroEl伴侣蛋白是一种在ALDH2正常折叠中起关键作用的蛋白质。如果在酒渣鼻患者中发现的GroEl伴侣蛋白抗体与人类GroEl伴侣蛋白发生交叉反应,它们将无法使ALDH2正常折叠,进而该酶将无法代谢乙醛。许多酒渣鼻患者胃部同时感染幽门螺杆菌。幽门螺杆菌会产生大量乙醛,这些乙醛来自其对乙醇或碳水化合物的代谢。结果,大量乙醛将在血液中循环更长时间,直到肝脏细胞色素P450 2E1(CYP2E1)酶系统最终代谢乙醛,在此期间,患者会出现面部潮红,就像患有“亚洲潮红综合征”的人饮酒时一样。为了验证这一假设,有必要找到针对奥勒龙芽孢杆菌的GroEl伴侣蛋白抗体与人类GroEl伴侣蛋白之间的交叉反应。将对四组患者进行研究,分别有无GroEl伴侣蛋白抗体以及有无幽门螺杆菌。将通过乙醇衍生的微生物生产方法检测乙醛的产生。如果该假设被证明是正确的,那么治疗毛囊蠕形螨和幽门螺杆菌可能会改善酒渣鼻患者的面部潮红,并预防血管生成(毛细血管扩张),以及这些患者的胃损伤和癌变的关联。