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Excerpt
Mucosal cell-mediated inflammation promotes mitosis in small bowel enteropathy. We have shown tropical enteropathy to be associated with significant mucosal inflammation (TNF-α+ cell numbers in the range of inflammatory bowel disease, high numbers of CD25+ lymphocytes and macrophages). However previous studies in The Gambia have shown that mitotic activity is low in these children compared to UK controls 1, although there is no data to show how severe malnutrition interferes with the cell division cycle in these children. We have used Ki67, a nuclear antigen expressed in the early phases of cell division and thus a marker of early mitotic events.
38 children with malnutrition from The Gambia, with or without diarrhoea (mean weight z score -4.3 SD 1.1), mean age of 1.5 years (SD 0.5) underwent endoscopic small bowel biopsy. Samples were snap frozen and stored in liquid nitrogen for later immunohistochemical analysis. Analysis was observer blinded and the percentage of Ki67-immunoreactive enterocytes (Ki67+ cells) were counted in cross-cut crypts compared to UK controls.
All children had evidence of tropical enteropathy. The mean percentage of Ki67+ cells was actually higher in Gambian children than in UK controls (mean 32 [SD 14.7]% vs 6-15% in UK children), and there was a negative relationship between height (or weight z score) and % Ki67 positive cells (r = 0.59, P = 0.006) by regression analysis. Thus early mitotic events increased with worsening malnutrition.
The low rate of final enterocyte proliferation replication in tropical enteropathy and malnutrition is due either to factors acting later on in the cell mitotic cycle or to early shedding before mitosis can proceed. It is not due to a lack of stimulus to enter the replication cycle.
