ABSTRACT
BACKGROUND: The trefoil peptides are major secretory products of mucus cells of the gastrointestinal tract and show increased expression after inflammatory or ulcerative damage. Recombinant human TFF2 (spasmolytic polypeptide) has been shown to be cytoprotective, and enhances repair in models of gastric injury. AIMS: To test the healing effects of recombinant human (h)TFF2 in a rat model of chronic colitis. METHODS: Colitis was induced by intracolonic administration of dinitrobenzene sulphonic acid in ethanol. Mucosal repair was quantified macroscopically, microscopically by image analysis of tissue histology, and by measuring myeloperoxidase activity. RESULTS: Initial validation studies showed that maximal injury and inflammation occurred at the end of the first week after colitis induction (active phase), and that spontaneous healing was complete by eight weeks. Once daily intrarectal application of hTFF2 (2.5 mg/kg; approximately 0.5 mg/rat) for five days after maximal damage had been sustained, reduced both microscopic and macroscopic injury by 80% and inflammatory index by 50% compared with vehicle controls. In addition, endogenous concentrations of rat TFF2 and TFF3 (intestinal trefoil factor) were increased in the active phase of colitis and were reduced to basal levels by hTFF2 treatment. CONCLUSIONS: This study has shown that hTFF2 enhances the rate of colonic epithelial repair, and reduces local inflammation in a rat model of colitis, and suggests that luminal application of trefoil peptides may have therapeutic potential in the treatment of inflammatory bowel disease.
Subject(s)
Colitis/drug therapy , Growth Substances/therapeutic use , Mucins , Muscle Proteins , Neuropeptides , Peptides/therapeutic use , Administration, Rectal , Animals , Benzenesulfonates , Chronic Disease , Colitis/chemically induced , Colitis/pathology , Disease Models, Animal , Ethanol , Humans , Male , Peroxidase/metabolism , Rats , Rats, Wistar , Recombinant Proteins/therapeutic use , Trefoil Factor-2 , Trefoil Factor-3ABSTRACT
Intestinal trefoil factor (ITF) gene expression was detected in five colon cancer cell lines. ITF was synthesized by mucous cells of LIM 1215 and LIM 1863 lines, from which it is secreted constitutively. The ITF mRNA transcript was estimated to be 0.6 kb. In LIM 1215 cells, the expression of ITF was potently and dose-dependently inhibited by short-chain fatty acids (butyrate > propionate > acetate) within 8 h of application. The inhibitory effect of butyrate was ablated by actinomycin D and preceded its effects on differentiation of LIM 1215 cells as indicated by induction of alkaline phosphatase activity and counting of periodic acid-Schiff-positive cells. The human ITF promoter contained an 11-residue consensus sequence with high homology to the butyrate response element of the cyclin D1 gene. Mobility shift assays show specific binding of this response element to nuclear protein extracts of LIM 1215 cells. We conclude that butyrate inhibits ITF expression in colon cancer cells and that this effect may be mediated transcriptionally and independently of its effects on differentiation.
Subject(s)
Colonic Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Growth Substances/metabolism , Intestinal Mucosa/metabolism , Mucins , Muscle Proteins , Neuropeptides , Peptides/metabolism , Transcription, Genetic/drug effects , Acetates/pharmacology , Alkaline Phosphatase/analysis , Animals , Base Sequence , Butyrates/pharmacology , Cell Differentiation/drug effects , Cell Line , Consensus Sequence , DNA Primers , DNA Probes , Dactinomycin/pharmacology , Growth Substances/genetics , Humans , Intestinal Mucosa/drug effects , Kinetics , Mice , Peptides/genetics , Polymerase Chain Reaction , Promoter Regions, Genetic , Propionates/pharmacology , RNA, Messenger/biosynthesis , Sequence Alignment , Sequence Homology, Nucleic Acid , Trefoil Factor-2 , Trefoil Factor-3 , Tumor Cells, CulturedABSTRACT
The radiocrystallographic study of 46 salivary calculi using the Debye and Scherrer powder methods showed that such stones, whether submaxillary, parotid or "accessory" consist essentially of hydroxyapatite with the frequent presence of tricalcium and octocalcium phosphates, Whitlockite and rarely Brushite and Calcite. In order for a stone to form, the following conditions would seem to be necessary; transient supersaturation of the saliva in Ca++ and PO4--, a pH greater than normal, intracellular precepitation of amorphous tricalcium phosphate which is transformed into crystalline hydroxyapatite and, then, the fixation of crystals on a "matrix" such as desquamated cells, fibrils and collagens.
Subject(s)
Crystallography , Salivary Duct Calculi , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Salivary Duct Calculi/diagnosis , Salivary Duct Calculi/etiology , X-Ray DiffractionSubject(s)
Salivary Duct Calculi/diagnostic imaging , Adult , Aged , Diagnosis, Differential , Female , Humans , SialographyABSTRACT
On the strength of three new cases, it is suggested that the term "calcifying parotiditis" must be replaced by "salivary calcinosis". This suggestion is based on clinical and pathological grounds. An analysis of 11 cases of salivary calcinosis encountered in the last eight years points to clinical analogies between this condition and Gougerot-Sjögren's disease as well as to the fairly frequent involvement of the immune system in the calcinoses.
