22 research outputs found
The intestine under stress : effects of chemotherapy on the intestinal epithelium
In studying the effects of cytostatic drugs on
intestinal function, the use of experimental
animals is indispensable. Only they permit a
detailed analysis of the entire organ in time,
allowing each study of each phase of the
disease. This would be both unethical and
technically very difficult to perform in biopsies
of human patients, especially in cancer patients
who are already suffering from both disease
and treatment. In our studies, the rat was
chosen as a model, because of the similarities
to humans in intestinal physiology and the
availability of techniques and tools.
In this thesis, attention was focussed on the
absorptive and defensive functions of the
intestine during damage and regeneration
induced by the cytostatic drug methotrexate
(MTX). MTX was chosen among the various
cytostatic drugs available, because of the
considerable knowledge about its
pharmacology and its way of action in humans
and animal species. As folic acid analogue, MTX
directly seizes the proliferative machinery of
the intestine, thereby disturbing the normal
cell turnover of the epithelium
An evaluation of nutritional practice in a paediatric burns unit
Introduction. Burn injuries evoke a systemic metabolic response with profound effects on organ function, susceptibility to infection
Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats
Proliferation, differentiation, and cell death were studied in small
intestinal and colonic epithelia of rats after treatment with
methotrexate. Days 1-2 after treatment were characterized by decreased
proliferation, increased apoptosis, and decreased numbers and depths of
small intestinal crypts in a proximal-to-distal decreasing gradient along
the small intestine. The remaining crypt epithelium appeared flattened,
except for Paneth cells, in which lysozyme protein and mRNA expression was
increased. Regeneration through increased proliferation during days 3-4
coincided with villus atrophy, showing decreased numbers of villus
enterocytes and decreased expression of the enterocyte-specific genes
sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet
cells were spared at villus tips and remained functional, displaying Muc2
and trefoil factor 3 expression. On days 8-10, all parameters had returned
to normal in the whole small intestine. No methotrexate-induced changes
were seen in epithelial morphology, proliferation, apoptosis, Muc2, and
TFF3 immunostaining in the colon. The observed small intestinal sparing of
Paneth cells and goblet cells following exposure to methotrexate is likely
to contribute to epithelial defense during increased vulnerability of the
intestinal epithelium
Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration
The rapidly dividing small intestinal epithelium is very sensitive to the
cytostatic drug methotrexate. We investigated the regulation of epithelial
gene expression in rat jejunum during methotrexate-induced damage and
regeneration. Ten differentiation markers were localized on tissue
sections and quantified at mRNA and protein levels relative to control
levels. We analyzed correlations in temporal expression patterns between
markers. mRNA expression of enterocyte and goblet cell markers decreased
significantly during damage for a specific period. Of these,
sucrase-isomaltase (-62%) and CPS (-82%) were correlated. Correlations
were also found between lactase (-76%) and SGLT1 (-77%) and between I-FABP
(-52%) and L-FABP (-45%). Decreases in GLUT5 (-53%), MUC2 (-43%), and TFF3
(-54%) mRNAs occurred independently of any of the other markers. In
contrast, lysozyme mRNA present in Paneth cells increased (+76%). At the
protein level, qualitative and quantitative changes were in agreement with
mRNA expression, except for Muc2 (+115%) and TFF3 (+81%), which increased
significantly during damage, following independent patterns. During
regeneration, expression of each marker returned to control levels. The
enhanced expression of cytoprotective molecules (Muc2, TFF3, lysozyme)
during damage represents maintenance of goblet cell and Paneth cell
functions, most likely to protect the epithelium. Decreased expression of
enterocyte-specific markers represents decreased enterocyte function, of
which fatty acid transporters were least affected