Ascidian (chordate-tunicate) and mammalian heparin enemas attenuate experimental diversion colitis.

AIM: We sought to investigate whether mammalian or ascidian Styela plicata heparin enemas could diminish inflammation in experimental diversion colitis. METHODS: Wistar-specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing mammalian or Styela plicata heparin, or saline. Enemas were administered 3 times a week in the excluded colon segment from 4 to 8 weeks after operation. The effect of treatment was evaluated using video-endoscopic and histologic scores, measuring the cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and transforming growth factor-ß production in organ cultures by enzyme-linked immunosorbent assay, quantifying T cells and macrophages, and investigating nuclear factor-kappa B (NF-κB) and external mitogen-activated protein kinase (pERK) activation. RESULTS: Treatment with either mammalian or Styela plicata heparins decreased colonoscopic and histologic scores (P < .02) and restored the densities of collagen fibers and the number of goblet cells (P < .03) in the diverted colon. Both heparin treatments decreased the accumulation of T cells and macrophages (P < .03), and the activation of NF-κB and pERK (P < .04) in the diverted colon. The high levels of cytokines IL-1ß, TNF-α, and IL-6 from the diversion colitis explants decreased (P < .05) to near normal values with heparin treatments. CONCLUSION: The improvement of experimental diversion colitis with heparin treatments indicates the anti-inflammatory effect of these compounds, even after topical administration. Further studies with the nonhemorrhagic heparin obtained from the invertebrate Styela plicata will be necessary to confirm its efficacy for the treatment of human diversion colitis and possibly other forms of colitis.

Use of butyrate or glutamine in enema solution reduces inflammation and fibrosis in experimental diversion colitis.

AIM: To investigate whether butyrate or glutamine enemas could diminish inflammation in experimental diversion colitis. METHODS: Wistar specific pathogen-free rats were submitted to a Hartmann's end colostomy and treated with enemas containing glutamine, butyrate, or saline. Enemas were administered twice a week in the excluded segment of the colon from 4 to 12 wk after the surgical procedure. Follow-up colonoscopy was performed every 4 wk for 12 wk. The effect of treatment was evaluated using video-endoscopic and histologic scores and measuring interleukin-1ß, tumor necrosis factor-alpha, and transforming growth factor beta production in organ cultures by enzyme linked immunosorbent assay. RESULTS: Colonoscopies of the diverted segment showed mucosa with hyperemia, increased number of vessels, bleeding and mucus discharge. Treatment with either glutamine or butyrate induced significant reductions in both colonoscopic (P < 0.02) and histological scores (P < 0.01) and restored the densities of collagen fibers in tissue (P = 0.015; P = 0.001), the number of goblet cells (P = 0.021; P = 0.029), and the rate of apoptosis within the epithelium (P = 0.043; P = 0.011) to normal values. The high levels of cytokines in colon explants from rats with diversion colitis significantly decreased to normal values after treatment with butyrate or glutamine. CONCLUSION: The improvement of experimental diversion colitis following glutamine or butyrate enemas highlights the importance of specific luminal nutrients in the homeostasis of the colonic mucosa and supports their utilization for the treatment of human diversion colitis.

Heterologous mesenchymal stem cells successfully treat femoral pseudarthrosis in rats.

BACKGROUND: This study evaluated the effectiveness of treating pseudarthrosis in rats by using bone marrow cell suspensions or cultures of bone marrow mesenchymal stromal cells METHODS: Thirty-eight specific pathogen-free (SPF) animals were randomly assigned to four groups: Group 1, Control, without surgical intervention; Group 2 (Placebo), experimental model of femoral pseudarthrosis treated only with saline solution; Group 3, experimental model of femoral pseudarthrosis treated with heterologous bone marrow cells suspension; Group 4, experimental model of femoral pseudarthrosis treated with cultures of heterologous mesenchymal stromal cells from bone marrow. When pseudarthrosis was confirmed by simple radiological studies, digital radiography and histopathology after a 120-day postoperative period, Groups 2, 3 and 4 were treated as above. At 30, 60 and 90 days after the treatment, all animals were evaluated by simple radiological studies, and at the end of the experiment, the animals were assessed by computed axial tomography and anatomopathological and histomorphometric examinations. RESULTS: Injected cells were detected in the areas affected by pseudarthrosis using scintigraphy within the first 24 hours after their administration. After 60 days, the animals of Group 3 showed callus formation while the animals of Group 4 presented periosteal reaction and had some consolidated areas. In contrast, Group 2 showed a predominance of fibro-osteoid tissue. After 90 days, bone consolidation and remodeling was observed in all animals from Group 3 whereas animals from Group 4 exhibited partial consolidation and those ones from Group 2 persisted with pseudarthrosis. CONCLUSION: The treatment with heterologous bone marrow cells suspension proved to be effective in the treatment of pseudarthrosis whereas cultures of heterologous bone marrow mesenchymal stromal cells did not show the same potential to aid bone healing.

Glucose tolerance in the proximal versus the distal small bowel in Wistar rats.

BACKGROUND: Type 2 diabetes is an epidemic and insulin resistance is the central etiology of this disease. Obesity increases insulin resistance and glucose intolerance and also exacerbates metabolic abnormalities present in type 2 diabetes. Bariatric surgery is the most effective treatment for severe obesity. Most reported series show that return to euglycemia and normal insulin levels occur days after gastric bypass and biliopancreatic diversion, long before major weight loss has taken place. The mechanisms underlying this dramatic reversal of type 2 diabetes following these bariatric procedures are not well understood. METHODS: Twelve Wistar rats were fed with a palatable hyperlipidic diet for 12 weeks. Body weight, glucose, and intraperitoneal glucose tolerance test were measured regularly. On day 91, they were randomized in two groups (hindgut and controls) and operated. Twenty-one days later, the tests were done again and the hindgut group re-operated. A duodenal exclusion was done. The results of an intraperitoneal glucose tolerance test were compared after the procedures. RESULTS: Body weight increased regularly in all the rats. Some rats developed hyperglycemia 28 days after beginning hyperlipidic diet, but these levels returned to baseline on days 56 and 84. The glucose tolerance test showed an improvement in glycemic levels in the hindgut group 21 days after the first operation (151 +/- 21mg/dl). After the second operation, despite weight loss, the glucose tolerance test of the foregut group worsened again (267 +/- 53 mg/dl) (p < 0.01). CONCLUSION: Comparing the "hindgut hypothesis" and the "foregut hypothesis", our data show an improvement in the 30 min glucose tolerance test in the hindgut group.