DuPont H L, Ericsson C D, Mathewson J J, Marani S, Knellwolf-Cousin A L, Martinez-Sandoval F G
University of Texas Medical School/School of Public Health, Houston.
Gastroenterology. 1993 Mar;104(3):709-15. doi: 10.1016/0016-5085(93)91005-3.
The therapeutic value of zaldaride maleate (Zm), an intestinal calmodulin inhibitor, was examined in patients with travelers' diarrhea, known to be caused by enterotoxigenic Escherichia coli (ETEC) and other bacterial agents.
One hundred seventy-six American students acquiring diarrhea in Mexico during the summer of 1991 were given Zm in doses of 5 mg, 10 mg, or 20 mg, or a matching placebo, four times a day for 48 hours.
The duration of diarrhea was reduced by 53% in the group given the 20-mg Zm dose (overall P < 0.01). Curative antibiotics were required post-treatment only in the placebo and 5-mg Zm groups (P < 0.01). The number of unformed stools passed during 0-48 hours of therapy with the highest Zm dose was reduced compared with placebo by 36% for all subjects (P < 0.05), by 39% for ETEC diarrhea (NS), by 45% for those with any bacterial agents (NS), and by 38% for those without an identifiable bacterial agent (NS).
The fact that a calmodulin inhibitor decreases the severity and duration of travelers' diarrhea has therapeutic implications and suggests that calmodulin and intracellular calcium may serve as mediators of diarrhea in bacterial enteric infection.
马来酸扎尔达利德(Zm)是一种肠道钙调蛋白抑制剂,本研究检测了其对已知由产肠毒素大肠杆菌(ETEC)和其他细菌病原体引起的旅行者腹泻患者的治疗价值。
1991年夏天在墨西哥患腹泻的176名美国学生,分别给予5毫克、10毫克或20毫克剂量的Zm,或匹配的安慰剂,每日4次,共48小时。
给予20毫克Zm剂量组的腹泻持续时间缩短了53%(总体P<0.01)。仅安慰剂组和5毫克Zm组在治疗后需要使用治疗性抗生素(P<0.01)。与安慰剂相比,使用最高Zm剂量治疗的0至48小时内,所有受试者的不成形粪便数量减少了36%(P<0.05),ETEC腹泻患者减少了39%(无统计学意义),有任何细菌病原体感染的患者减少了45%(无统计学意义),无明确细菌病原体感染的患者减少了38%(无统计学意义)。
钙调蛋白抑制剂可减轻旅行者腹泻的严重程度并缩短其持续时间,这一事实具有治疗意义,并提示钙调蛋白和细胞内钙可能是细菌性肠道感染腹泻的介质。