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Histological Scores (histological + score)
Selected AbstractsRegional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhageEQUINE VETERINARY JOURNAL, Issue 6 2009F. J. Derksen Summary Reasons for performing study: Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Hypothesis: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumulation of pulmonary collagen and haemosiderin, and to count pleural vascular profiles in the lungs of 5 EIPH-affected and 2 control horses. Results: Vein wall thickness was greatest in the dorsocaudal lung and significantly correlated with haemosiderin accumulation. Increased venous, interstitial, pleural and septal collagen; lung haemosiderin; and pleural vascular profiles occurred together and changes were most pronounced in the dorsocaudal lung. Further, haemosiderin accumulation colocalised with decreased pulmonary vein lumen size. Vein wall thickening, haemosiderin accumulation and histological score were highly correlated and these changes occurred only in the caudodorsal part of the lung. Conclusion: The colocalisation of these changes suggests that regional (caudodorsal) venous remodelling plays an important role in the pathogenesis of EIPH. Potential relevance: The results support the hypothesis that repeated bouts of venous hypertension during strenuous exercise cause regional vein wall remodelling and collagen accumulation, venous occlusion and pulmonary capillary hypertension. Subjected to these high pressures, there is capillary stress failure, bleeding, haemosiderin accumulation and, subsequently, lung fibrosis. [source] Bifidobacterium lactis inhibits NF-,B in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice,,INFLAMMATORY BOWEL DISEASES, Issue 9 2010Seung Won Kim MS Abstract Background: The aim of this study was to investigate the antiinflammatory effects of Bifidobacterium lactis on intestinal epithelial cells (IECs) and on experimental acute murine colitis and its tumor prevention effects on colitis-associated cancer (CAC) in mice. Methods: Human HT-29 cells were stimulated with IL-1,, lipopolysaccharides, or tumor necrosis factor-, with and without B. lactis, and the effects of B. lactis on nuclear factor kappa B (NF-,B) signaling in IEC were examined. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with and without B. lactis. Finally, we induced colonic tumors in mice by azoxymethane (AOM) and DSS and evaluated the effects of B. lactis on tumor growth. Results: B. lactis significantly suppressed NF-,B activation, including NF-,B-binding activity and NF-,B-dependent reporter gene expression in a dose-dependent manner, and suppressed I,B-, degradation, which correlated with the downregulation of NF-,B-dependent gene products. Moreover, B. lactis suppressed the development of acute colitis in mice. Compared with the DSS group, the severity of DSS-induced colitis as assessed by disease activity index, colon length, and histological score was reduced in the B. lactis -treated group. In the CAC model, the mean number and size of tumors in the B. lactis -treated group were significantly lower than those in the AOM group. Conclusions: Our data demonstrate that B. lactis inhibits NF-,B and NF-,B-regulated genes in IEC and prevents acute colitis and CAC in mice. These results suggest that B. lactis could be a potential preventive agent for CAC as well as a therapeutic agent for inflammatory bowel disease. (Inflamm Bowel Dis 2010) [source] Induced hypothyroidism accelerates the regression of liver fibrosis in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Rafael Bruck Abstract Background and Aim:, It has been shown in previous studies that hypothyroidism prevents the development of liver fibrosis in bile duct ligated rats and in rats chronically treated with thioacetamide (TAA). In recent years, regression of liver fibrosis (occurring spontaneously or during treatment) has been demonstrated in rodent models such as bile duct ligation and CCl4 administration. Therefore, in the present study, the potential therapeutic effect of hypothyroidism on liver fibrosis was investigated. Methods:, Liver fibrosis was induced in rats by administration of TAA (200 mg/kg, i.p., twice weekly) for 12 weeks. Hypothyroidism was then induced by either methimazole (0.04%) or propylthiouracil (0.05%) administered in drinking water for 8 weeks. Control euthyroid rats received normal drinking water. Hypothyroidism was confirmed by a significant elevation of serum thyroid-stimulating hormone levels. Results:, Eight weeks after the cessation of TAA administration, spleen weight, histological score of liver fibrosis, and hepatic hydroxyproline content were significantly lower in both groups of hypothyroid rats as compared to euthyroid controls (P < 0.001). In vitro studies using the rat hepatic stellate cell line HSC-T6 using northern blot analysis and zymography, respectively, showed that high concentrations of triiodotyronine (T3) enhanced transforming growth factor (TGF)-,-induced collagen I gene expression, and reduced metalloproteinase (MMP)-2 secretion, implying that reducing the levels of T3 may contribute to resolution of fibrosis. Additionally, low T3 concentration inhibited HSC-T6 proliferation. Conclusion:, Pharmacologically induced hypothyroidism accelerates the resolution of liver fibrosis in rats. This beneficial effect may in part be due to prevention of T3 -induced stimulation of collagen synthesis and reduction of MMP-2 secretion. [source] Glial-derived neurotrophic factor regulates intestinal epithelial barrier function and inflammation and is therapeutic for murine colitis,THE JOURNAL OF PATHOLOGY, Issue 2 2010Dei Kui Zhang Abstract Although enteric glial cells (EGCs) have been demonstrated to play a key role in maintaining intestinal epithelial barrier integrity, it is not known how EGCs regulate this integrity. We therefore hypothesized that glial-derived neurotrophic factor (GDNF) produced by EGCs might be involved in this regulation. Here we investigated the role of GDNF in regulating epithelial barrier function in vivo. Recombinant adenoviral vectors encoding GDNF (Ad-GDNF) were administered intracolonically in experimental colitis induced by dextran sulphate sodium (DSS). The disease activity index (DAI) and histological score were measured. Epithelial permeability was assayed using Evans blue dye. The anti-apoptotic potency of GDNF in vivo was evaluated. The expression of tumour necrosis factor- , (TNF- ,), interleukin-1, (IL-1,), and myeloperoxidase (MPO) activity were measured by ELISA assay and/or RT-PCR. The expression of ZO-1, Akt, caspase-3, and NF- ,B p65 was analysed by western blot assay. Our results showed that GDNF resulted in a significant reduction in enhanced permeability, inhibited MPO activity, IL-1, and TNF- , expression, and increased ZO-1 and Akt expression. Moreover, GDNF strongly prevented apoptosis in vivo and significantly ameliorated experimental colitis. Our findings indicate that GDNF participates directly in restoring epithelial barrier function in vivo via reduction of increased epithelial permeability and inhibition of mucosal inflammatory response, and is efficacious in DSS-induced colitis. These findings support the notion that EGCs are able to regulate intestinal epithelial barrier integrity indirectly via their release of GDNF in vivo. GDNF is namely an important mediator of the cross-talk between EGCs and mucosal epithelial cells. GDNF may be a useful therapeutic approach to the treatment of inflammatory bowel disease. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Effect of Different Doses of Thalidomide in Experimentally Induced Inflammatory Bowel Disease in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2008Om Prakash Adult Wistar rats of either sex were used (n = 36). Colitis was induced by a single intra-colonic application of 20 mg 2,4,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 35% ethanol into the descending colon. Rats were divided into six groups (n = 6). Animals were treated with vehicle (ethanol), TNBS dissolved in 35% ethanol, thalidomide (with different doses of 50, 100 and 150 mg/kg body weight), and sulfasalazine (360 mg/kg body weight) for 14 days. After completion of 14 days of treatment, animals were killed and the following parameters were assessed: morphological score, histological score and biochemical parameters (myeloperoxidase, malondialdehyde and tumour necrosis factor-,). Results showed thalidomide with different doses provided protection against TNBS-induced colonic damage. There was significant protection with thalidomide 150 mg/kg body weight compared to controls (P < 0.001). All the biochemical parameters were highly reduced in the entire thalidomide-treated group compared to controls particularly with thalidomide 150 mg/kg body weight (P < 0.001). Treatment with thalidomide restored malondialdehyde as well as reduction of myeloperoxidase and tumour necrosis factor-, towards normal levels. Morphological and histological score were significantly reduced in all the treated groups with significant effect found with 150 mg/kg (P < 0.001). Our results indicate efficacy of thalidomide in TNBS induce experimental colitis model in rats but present findings requires further investigation to establish the real safety and efficacy in human beings. [source] Use of lidocaine metabolism to test liver function during the long-term follow-up of liver transplant recipientsCLINICAL TRANSPLANTATION, Issue 3 2004Filoména Conti Abstract:, Background/Aims:, The aim of this study was to assess the usefulness of the monoethylglycinexylidide (MEGX) test to monitoring the long-term function of liver allografts. Methods:, MEGX production was measured prospectively in 60 consecutive liver transplant recipients undergoing their annual review. Results:, Median MEGX values in liver recipients (54 ng/mL; range 10,146) were lower than those found in healthy controls (78 ng/mL; range 44,118). MEGX values correlated negatively with alanine aminotransferase (ALT) activity (p = 0.004) and with the overall histological score (p = 0.01), and positively with sulfobromophthalein (BSP) and indocyanine green (ICG) clearances (p = 0.0002 and p = 0.002, respectively). A stepwise decline was observed with worsening liver fibrosis, from 71 ± 5 ,g/L in patients with no fibrosis to 27 ± 9 ,g/L in patients with bridging fibrosis (p = 0.002). BSP and ICG clearances correlated more closely than the MEGX test with the overall histological score (p = 0.001 and p = 0.001, respectively) and portal fibrosis (p = 0.002 and p = 0.001). Conclusions:, The measurement of MEGX formation is a simple and non-invasive method to monitor liver graft function. It may constitute a valuable tool for assessing the degree of fibrosis. [source] Nutriose, a prebiotic low-digestible carbohydrate, stimulates gut mucosal immunity and prevents TNBS-induced colitis in piglets,INFLAMMATORY BOWEL DISEASES, Issue 5 2010Philippe R. Pouillart PhD Abstract Background: We investigated a prebiotic low-digestible carbohydrate (LDC) as a possible food ingredient to stimulate bowel functions in the treatment of inflammatory bowel disease. The study aimed to assess a fermentable dextrin fiber (Nutriose) and its relationship to the immune management of the disease and the microbiota profile in colitis-bearing piglets. Methods: In a randomized placebo-controlled parallel blind preclinical study, 32 male piglets were fed LDC (4% Nutriose) or dextrose placebo for 44 days before being challenged with trinitrobenzene sulfonic acid (TNBS) to induce colitis. We followed the microbiota profile using real-time polymerase chain reaction (PCR) targeted to 9 bacterial genera. Secretory IgA was evaluated by enzyme-linked immunosorbent assay (ELISA). Inflammatory protein profiles were monitored in blood and colonic tissues. Both histological scoring of biopsy samples and live endoscopic scoring were used to measure colitis development. Results: Prior and continuing LDC supplementation alleviated the symptoms of colitis (body weight loss, bloody stools) induced by a TNBS challenge. This effect was associated with an improvement in endoscopic and histological scores. LDC was shown to selectively downregulate some of the proinflammatory factors and their concomitant pyretic events and to stimulate the Th2-related immune pathway (IL-10 and s-IgA). Conclusions: At the dose tested, LDC is a well-tolerated prebiotic agent able to not only stimulate butyrogenic bacteria strains and reduce intestinal transit disorders and energy intake, but also to prevent chronic inflammatory intestinal injuries. Inflamm Bowel Dis 2010 [source] Tetomilast suppressed production of proinflammatory cytokines from human monocytes and ameliorated chronic colitis in IL-10-deficient miceINFLAMMATORY BOWEL DISEASES, Issue 11 2008Hitoshi Ichikawa MD Abstract Background: Tetomilast (OPC-6535) was originally developed as a compound inhibiting superoxide production in neutrophils. Although its mechanism of action is not completely understood, phosphodiesterase type 4 inhibitory function has been postulated. The therapeutic effect of PDE4 inhibitors has been reported for chronic inflammatory disorders such as chronic obstructive pulmonary diseases. In this study we aimed to examine whether tetomilast could be a novel drug for inflammatory bowel diseases by further clarifying its antiinflammatory effects. Methods: Cytokines from human peripheral blood mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and Cytokine Beads Array. The transcripts were quantified by reverse-transcriptase polymerase chain reaction (RT-PCR). Phosphorylation of transcription factors was examined by phosflow. To examine its in vivo effect, a once-daily oral dose of tetomilast was tested in murine IL-10,/, chronic colitis. Results: Tetomilast suppressed TNF-, and IL-12 but not IL-10 production from lipopolysaccharide (LPS)-stimulated human monocytes. It suppressed TNF-,, IFN-,, and IL-10 from CD4 lymphocytes. Tetomilast suppressed cytokine production at the transcriptional level but did not alter phosphorylation of p65, ERK, p38, and STAT3. HT-89, a protein kinase A inhibitor, did not abolish the effect of tetomilast, suggesting that it was independent from the classical cAMP/PKA pathway. IL-10 was not essential to the inhibitory effect of tetomilast on TNF-, and IL-12. Tetomilast ameliorated IL-10,/, chronic colitis with reduced clinical symptoms, serum amyloid A, and histological scores with decreased TNF-, mRNA expression. Conclusions: Tetomilast exerts its antiinflammatory effects on human monocytes and CD4 cells. Combined with in vivo data these findings support the feasibility of tetomilast as a novel drug for inflammatory bowel diseases. (Inflamm Bowel Dis 2008) [source] Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic miceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2003TAKAHIRO ISHIKURA Abstract Background and Aim:, The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. Methods:, Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. Results:, The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. Conclusions:, These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice. [source] Repair of porcine articular cartilage defect with autologous chondrocyte transplantationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005Hongsen Chiang Abstract Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Adhesion molecule expression in experimental myositisMUSCLE AND NERVE, Issue 3 2002Tomoko Ito MD Abstract Experimental allergic myositis (EAM) in Lewis rats, induced with partially purified myosin, is regarded as a model of human polymyositis. To clarify the role of adhesion molecules in the pathogenesis of EAM in Lewis rats, we investigated intramysial expressions of the intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, and the serum level of soluble ICAM-1 in EAM rats. All the EAM rat muscles had scattered inflammatory foci, as well as cell infiltration and necrosis, by week 4 after the initial immunization (i.e., day 0 after the last immunization). As compared with the control muscles, ICAM-1 and VCAM-1 were strongly expressed immunohistochemically in the endothelium of vessels in the endomysium and perimysium, and to lesser extents in the inflammatory infiltrates and on the sarcolemma of nonnecrotic muscle fibers adjacent to the inflammatory infiltrates or invaded muscle fibers. ICAM-1 in the muscle extracts and sera from EAM rats increased on each test day, as compared with extracts from the normal controls. The values peaked on day 0 after the last immunization, then gradually decreased with time. ICAM-1 elevations in the muscle extracts were correlated with the percent of sections that had inflammatory lesions (P = 0.032) and the histological scores (P = 0.005) on day 0, whereas there was no significance on days 3 and 7. These findings suggest that the adhesion molecules ICAM-1 and VCAM-1 increase in the early stage of EAM, and function in the initiation of the inflammatory process of myositis. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] DOES MATRIX METALLOPROTEINASE ACTIVITY PREDICT SEVERITY OF ACUTE PANCREATITIS?ANZ JOURNAL OF SURGERY, Issue 9 2006Murat Aynaci Background: Matrix metalloproteinases (MMP) modulate end-organ complications of acute pancreatitis, but the correlation between increased MMP production and histological severity of disease remains unclear. We examined the role of MMP and pancreas histology on experimental acute pancreatitis. Methods: Forty male Wistar albino rats were subjected to cerulein-induced pancreatitis (8, 16, 24 and 32 h groups) or sham treatment. The animals were killed at different time points and pancreatic tissues were harvested to assess MMP (1, 2 and 9) activity and inflammatory changes. Results: Compared with other groups, 8 h group had decreased tissue MMP-1 concentrations. MMP-9 concentrations were lower in 24-h and 32-h groups, as were histological severity scores. MMP-2 activity did not differ among groups. Pancreatitis was prominent in 8-h, 16-h and 24-h groups by means of histology. Conclusion: Induction of pancreatitis by cerulein altered pancreatic MMP levels in the early phase of inflammation. Inhibition of MMP-2 and MMP-9 paralleled histological scores. Therefore, MMP may have a predictive value to assess histological severity. [source] 2262: Study of the role of P2Y receptors in the development of experimental autoimmune uveitisACTA OPHTHALMOLOGICA, Issue 20103Article first published online: 23 SEP 2010, L JUDICE DE MENEZES RELVAS Purpose During autoimmune uveitis (AU), retinal specific auto-reactive T lymphocytes (TL) are activated, alter blood retinal barrier(BRB) and penetrate the eye where they start an inflammatory reaction. Nucleotides, normally present at low concentration in extracellular media, can act as a danger signal, through P2 receptors activation and might be implicated in AU. In this work we would like to investigate if the expression of the nucleotide receptor P2Y2 has any role in experimental autoimmune uveitis (EAU). Methods EAU will be induced in WT and P2Y2 KO mice by IRBP peptide 1-20 injection. 12 days later, TL from spleen and lymph nodes will be purified and restimulated by IRBP. TL proliferation will be measured by thymidine incorporation and cytokines secretion by ELISA. TL from the 2 groups of mice will also be adoptively transfered in WT mice. Similarly, TL from WT mice will be adoptively transfered in WT and P2Y2 KO mice. EAU development will be graded by clinical and histological scores. Results TL generated in KO mice proliferate and produce less IFN, and IL-17, after IRBP restimulation than TL generated in WT mice. Accordingly, adoptive transfer of TL generated in KO mice induce significantly a lower grade of disease than those generated in WT mice. Finally, adoptive transfer of TL generated in WT mice induce disease of significantly lower grade in KO mice recipient than in WT mice recipient. Conclusion Our preliminary data shows that P2Y2 KO mice have a defective immune response after immunisation and develop lower intraocular inflammation following adoptive transfer with TL. Altogether this suggests that P2Y2, as danger receptor signals, play an important role in the development of uveitis. [source] | ||||||||||