Smetana Z, Malik Z, Orenstein A, Mendelson E, Ben-Hur E
Central Virology Laboratory, Sheba Medical Center, Tel Hashomer, Israel.
Lasers Surg Med. 1997;21(4):351-8. doi: 10.1002/(sici)1096-9101(1997)21:4<351::aid-lsm6>3.0.co;2-p.
When 5-aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work.
STUDY DESIGN/MATERIALS AND METHODS: ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT.
Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced approximately two-fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (> 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by > or = 5 log10. ALA-PDT treated AIDS patient suffering from Molluscum contagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment.
It is concluded that ALA-PDT could be effective in treating certain viral infections, particularly those resulting in warts.
当外源性供给5-氨基乙酰丙酸(ALA)时,原卟啉IX(PpIX)会在各种细胞中蓄积并使其对光敏感。本研究探讨了利用这种方法治疗病毒感染的可能性。
研究设计/材料与方法:将ALA添加到感染人类免疫缺陷病毒(HIV)的培养细胞中。评估光动力治疗(PDT)后细胞中PpIX的蓄积情况以及病毒感染性。在体内研究中,豚鼠感染单纯疱疹病毒(HSV),然后在感染后每隔一段时间给予ALA。在给予ALA 3小时后,对动物感染部位进行PDT照射。每天进行临床观察和病毒滴定。在临床研究中,两名传染性软疣和寻常疣患者接受了用铁螯合剂和二甲基亚砜强化的ALA治疗,4小时后进行PDT。
在体外添加ALA后,感染HIV的细胞会蓄积PpIX。在铁螯合剂存在的情况下,这种蓄积增加了约两倍。随后暴露于红光PDT可显著降低病毒滴度(对于潜伏感染HIV的U1细胞,降低>99%)。在感染HSV的豚鼠中,随后给予ALA并对病变部位进行红光照射,使水疱出现的持续时间从超过一周缩短至几天,并使病变部位的HSV滴度降低>或=5 log10。接受ALA-PDT治疗的患有传染性软疣的艾滋病患者或患有寻常疣的肾移植患者在治疗一个月后临床症状有显著改善。
得出结论,ALA-PDT可能对治疗某些病毒感染有效,特别是那些导致疣的感染。