DUODENAL BIOPSIES OF HIV-INFECTED PATIENTS WITH DIARRHEA EXHIBIT EPITHELIAL BARRIER DEFECTS BUT NO ACTIVE SECRETION

Objectives: To characterize diarrhoeal mechanisms in HIV-infected pati ents, epithelial transport and barrier function of the duodenal mucosa was investigated in vitro. Patients: Twenty-one HIV-seropositive pati ents (13 asymptomatic and eight with diarrhoea) and 12 controls from a n urban referral-based tertiary care centre in Berlin who underwent du odenoscopy. Methods: A new miniaturized Ussing chamber allowed measure ments on duodenal forceps biopsies. Epithelial barrier function was ch aracterized by alternating current impedance analysis, which allows di fferentiation of epithelial and subepithelial resistance and by H-3-la ctulose and H-3-mannitol flux measurements. Na+-glucose cotransport wa s quantified as phlorizin-sensitive short circuit current (I-SC) and a ctive ion secretion by baseline and bumetanide-sensitive I-SC. Results : Duodenal biopsies from asymptomatic HIV-infected patients were no di fferent from controls, whereas biopsies from HIV-infected patients wit h diarrhoea showed a decrease in epithelial resistance from 21.2 +/- 1 .9 to 12.9 +/- 1.3 Omega cm(2) (P < 0.01). Concomitantly, mucosal-to-s erosal lactulose flux increased from 0.29 +/- 0.02 to 0.40 +/- 0.03 mu mol (hcm(2)) (P < 0.01). Phlorizin-sensitive I-SC indicating Na+-gluc ose cotransport, as well as baseline and bumetanide-sensitive I-SC ind icating active electrogenic chloride secretion were not different betw een the three groups. Conclusions: A miniaturized Ussing device was de veloped for electrophysiological investigations of duodenal forceps bi opsies, which allowed characterization of active ion transport mechani sms and epithelial barrier function. Duodenum of HIV-infected patients with diarrhoea showed no evidence for active ion secretion or Na+-glu cose malabsorption, but showed an impaired epithelial barrier function , which could contribute to diarrhoea by a leak flux mechanism.