Long-term sequelae of congenital gambiense human African trypanosomiasis.

BACKGROUND: The clinical presentation of gambiense human African trypanosomias (gHAT) is generally considered to be the same among children and adults. In general, when describing the clinical presentation of children with gHAT, no differentiation is made between congenital gHAT and gHAT acquired later. There is a lack of knowledge regarding the signs and symptoms attributable to congenital gHAT and its long-term sequelae. METHODS: Following an evaluation of the hospital register for gHAT, the authors observed that six children born to mothers with gHAT during their pregnancies still had sequelae of the infection. The six mothers were interviewed about their respective pregnancies and the developmental history of the children borne to the infected mothers. Furthermore, the children then underwent a complete physical examination with a focus on neuropsychiatric signs and symptoms. RESULTS: Five of the six patients are still seriously disabled. Behavioral changes are present in four patients, tremor, speech impairment, involuntary movements and pathologic the Barrés test and Mingazzini test in three patients and convulsions, pyramidal signs and decreased muscle tonus in two patients. Two patients cannot work and one has a sphincter disorder. CONCLUSIONS: Our study suggests that congenital gHAT may lead to long-lasting sequelae in babies born to mothers treated after delivery. The risk of embryo toxicity of treatment of mothers with gHAT must be balanced against the risk of congenital gHAT with long-term sequelae.

A bipartite butyrate-responsive element in the human calretinin (CALB2) promoter acts as a repressor in colon carcinoma cells but not in mesothelioma cells.

The short-chain fatty acid butyrate plays an essential role in colonic mucosa homeostasis through the capacity to block the cell cycle, regulate differentiation and to induce apoptosis. The beneficial effect of dietary fibers on preventing colon cancer is essentially mediated through butyrate, derived from luminal fermentation of fibers by intestinal bacteria. In epithelial cells of the colon, both in normal and colon cancer cells, the expression of several genes is positively or negatively regulated by butyrate likely through modulation of histone acetylation and thereby affecting the transcriptional activity of genes. Calretinin (CALB2) is a member of the EF-hand family of Ca(2+)-binding proteins and is expressed in a majority of poorly differentiated colon carcinoma and additionally in mesothelioma of the epithelioid and mixed type. Since CALB2 is one of the genes negatively regulated by butyrate in colon cancer cells and butyrate decreases calretinin protein expression levels in those cells, we investigated whether expression is regulated via putative butyrate-responsive elements (BRE) in the human CALB2 promoter. We identified two elements that act as butyrate-sensitive repressors in all colon cancer cell lines tested (CaCo-2, HT-29, Co-115/3). In contrast, in cells of mesothelial origin, MeT-5A and ZL34, the same two elements do not operate as butyrate-sensitive repressors and calretinin expression levels are insensitive to butyrate indicative of cell type-specific regulation of the CALB2 promoter. Calretinin expression in colon cancer cells is negatively regulated by butyrate via a bipartite BRE flanking the TATA box and this may be linked to butyrate's chemopreventive activity.