Gomez H F, Miller M J, Trachy J W, Marks R M, Warren J S
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0305, USA.
Acad Emerg Med. 1999 Dec;6(12):1195-202. doi: 10.1111/j.1553-2712.1999.tb00133.x.
Bites from the brown recluse spider and other arachnids from the genus Loxosceles frequently induce necrotic skin lesions that can be recalcitrant to treatment and disfiguring. The authors used a rabbit model of dermonecrotic arachnidism to address the therapeutic efficacy of intradermal (id) polyclonal anti-Loxosceles Fab fragments (alphaLoxd Fab) raised against Loxosceles deserta spider venom.
Fab fragments were prepared by papain digestion and affinity chromatography from the IgG fraction of L. deserta antivenom raised in rabbits. Eighteen inbred New Zealand white rabbits were assigned to six groups of three. The rabbits received L. deserta venom (3 microg, id) injections into each flank. Cohorts of rabbits received single id injections (at one venom site/rabbit) of 30 microg alphaLoxd Fab at different times (T = 0, 1, 2, 4, 8, and 12 hours) after venom injection. In each rabbit the opposite flank was left untreated. As an additional control, one group of rabbits (T = 0) received nonspecific Fab (30 microg, id) in the opposite flank. Dermal lesions were quantified as a function of time through the use of a series of digital photographs and imaging software. In addition, myeloperoxidase (MPO) activity, a measure ofneutrophil accumulation, was determined in lesion biopsies. Lesion areas and MPO activities were analyzed by repeated-measures analysis of variance (ANOVA).
Lesion areas and MPO activity were markedly reduced when alphaLoxd Fab was administered very early after venom injections. As the interval between venom inoculation and antivenom treatment increased, the therapeutic benefit of alphaLoxd Fab decreased. The final time tested that demonstrated therapeutic efficacy of alphaLoxd Fab was T = 4 hours. Lesion attenuation was no longer apparent when alphaLoxd Fab was given 8 hours post inoculation.
Intradermal administration of alphaLoxd Fab attenuates Loxosceles-induced dermonecrotic lesion formation when given up to 4 hours after venom inoculation in this rabbit model.
棕色隐士蜘蛛及其他洛氏蛛属蜘蛛的叮咬常常会导致坏死性皮肤损伤,这种损伤治疗起来可能很棘手,还会造成毁容。作者利用皮肤坏死性蛛毒中毒的兔模型,来研究针对荒漠洛氏蛛蜘蛛毒液产生的皮内注射(id)多克隆抗洛氏蛛Fab片段(αLoxd Fab)的治疗效果。
通过木瓜蛋白酶消化和亲和层析从兔体内产生的荒漠洛氏蛛抗蛇毒血清的IgG组分中制备Fab片段。将18只近交系新西兰白兔分为6组,每组3只。给兔子的每一侧胁腹注射荒漠洛氏蛛毒液(3微克,皮内注射)。在毒液注射后的不同时间(T = 0、1、2、4、8和12小时),给每组兔子中的一只兔子在一个毒液注射部位皮内注射30微克αLoxd Fab。每只兔子的另一侧胁腹不做处理。作为额外对照,一组兔子(T = 0)在另一侧胁腹注射非特异性Fab(30微克,皮内注射)。通过一系列数码照片和成像软件,将皮肤损伤作为时间的函数进行量化。此外,在损伤活检中测定髓过氧化物酶(MPO)活性,作为中性粒细胞聚集的指标。通过重复测量方差分析(ANOVA)分析损伤面积和MPO活性。
在毒液注射后极早期给予αLoxd Fab时,损伤面积和MPO活性显著降低。随着毒液接种与抗蛇毒血清治疗之间的间隔时间增加,αLoxd Fab的治疗效果降低。证明αLoxd Fab具有治疗效果的最后测试时间是T = 4小时。在接种后8小时给予αLoxd Fab时,损伤减轻不再明显。
在该兔模型中,在毒液接种后4小时内给予αLoxd Fab皮内注射可减轻洛氏蛛引起的皮肤坏死性损伤形成。