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Hydroxyproline Content (hydroxyproline + content)
Kinds of Hydroxyproline Content Selected AbstractsEffect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Patricio Ibañez Abstract Background and Aim:, Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH. Methods:, To induce NASH, a choline-deficient diet (CDD) was given to Sprague-Dawley rats for 12 weeks. These animals were then compared with a control group receiving choline-supplemented diet (CSD) and a group fed a CDD plus losartan (10 mg/kg/day). Biochemical (serum levels of alanine aminotransferase and aspartate aminotransferase) and histological evaluation of fatty liver was performed by conventional techniques. Hydroxyproline content in liver tissue was assayed by spectrophotometry. In addition, mRNA levels of procollagen I and transforming growth factor (TGF)-, were assessed by semiquantitative RT-PCR and stellate cell activation by ,-actin immunofluorescence stain. Results:, After 12 weeks CDD induced a marked elevation of serum aminotranferases, a severe fatty liver infiltration with mild histological inflammation and fibrosis. These findings correlated with a significant increase in mRNA levels of both procollagen I and TGF-, and significant increased liver hydroxyproline content. No differences were seen between rats receiving CDD alone and rats receiving CDD plus losartan with regard to the biochemical, morphological or molecular alterations induced by the CDD. Conclusion:, Losartan does not seem to influence liver injury and fibrogenic events in the CDD model of NASH. [source] Comparison of histologic, biochemical, and mechanical properties of murine skin treated with the 1064-nm and 1320-nm Nd:YAG lasersEXPERIMENTAL DERMATOLOGY, Issue 12 2005Yong-Yan Dang Abstract:, The goal of this study was to compare the effects of the Q-switched 1064-nm Nd:YAG laser and the 1320-nm Nd:YAG laser non-ablative treatments on mouse skin in vivo. Skin elasticity measurements were carried out with a Reviscometer, and skin samples were taken for histological study, hydroxyproline content assay and estimation of collagen type I and III. By the second month after non-ablative treatments, the 1064-nm laser treatment resulted in an average of 25% greater improvement of skin elasticity, 6% more increase of dermal thickness, and 11% higher synthesis of hydroxyproline than the 1320-nm laser. Collagen type III increased markedly after the 1064-nm laser treatment whereas more collagen type I was elicited by the 1320-nm laser. Our results demonstrated that the 1064-nm laser was more effective than the 1320-nm Nd:YAG laser in non-ablative treatments, but the results needed to be confirmed in humans. It appeared that photo-mechanic reaction could cause more collagen type III synthesis whereas the photo-thermal effect was in favor of the formation of collagen type I. [source] CCR2 promotes hepatic fibrosis in mice,HEPATOLOGY, Issue 1 2009Ekihiro Seki Chemokines and chemokine receptors contribute to the migration of hepatic stellate cells (HSCs) and Kupffer cells, two key cell types in fibrogenesis. Here, we investigate the role of CCR2, the receptor for monocyte chemoattractant protein (MCP)-1, MCP-2, and MCP-3, in hepatic fibrosis. Hepatic CCR2, MCP-1, MCP-2, and MCP-3 messenger RNA expression was increased after bile duct ligation (BDL). Both Kupffer cells and HSCs, but not hepatocytes, expressed CCR2. BDL- and CCl4 -induced fibrosis was markedly reduced in CCR2,/, mice as assessed through collagen deposition, ,-smooth muscle actin expression, and hepatic hydroxyproline content. We generated CCR2 chimeric mice by the combination of clodronate, irradiation, and bone marrow (BM) transplantation allowing full reconstitution of Kupffer cells, but not HSCs, with BM cells. Chimeric mice containing wild-type BM displayed increased macrophage recruitment, whereas chimeric mice containing CCR2,/, BM showed less macrophage recruitment at 5 days after BDL. Although CCR2 expressed in the BM enhanced macrophage recruitment in early phases of injury, CCR2 expression on resident liver cells including HSCs, but not on the BM, was required for fibrogenic responses in chronic fibrosis models. In vitro experiments demonstrated that HSCs deficient in CCR2,/, or its downstream mediator p47phox,/, did not display extracellular signal-regulated kinase and AKT phosphorylation, chemotaxis, or reactive oxygen species production in response to MCP-1, MCP-2, and MCP-3. Conclusion: Our results indicate that CCR2 promotes HSC chemotaxis and the development of hepatic fibrosis. (HEPATOLOGY 2009.) [source] Fractal dimension can distinguish models and pharmacologic changes in liver fibrosis in ratsHEPATOLOGY, Issue 4 2002Frédéric Moal Fractal analysis measures the complexity of geometric structures. The aim of this study was to evaluate the feasibility and accuracy of fractal analysis in liver fibrosis. A total of 77 rats were included: 10 sham, 46 with fibrosis secondary to bile duct ligation (BDL), and 21 with fibrosis due to CCl4 intoxication. Measurements included the fractal dimension of Kolmogorov (Dk), histologic lesions, the area of fibrosis by image analysis, liver hydroxyproline content, messenger RNA fibronectin, serum hyaluronate level, and portal pressure. Fibrotic rats were given placebo, octreotide, or O2 -vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO). Intraobserver agreement of Dk was excellent with the intraclass (ic) correlation coefficient ric = 0.91 (P < .0001) as well as the interobserver agreement with ric = 0.88 (P < .001). Dk was correlated with other measurements or markers of fibrosis: the area of fibrosis (r = 0.75; P < .0001), hydroxyproline content (r = 0.51; P < .001), serum hyaluronate level (r = 0.52; P < .001), and portal pressure (r = 0.52; P < .01). Dk was significantly different between the 2 models of fibrosis (P < .0001), unlike the area of fibrosis, and this relationship was independent of other histologic lesions. The significant decrease in fibrosis observed with octreotide or V-PYRRO/NO was similarly reflected by Dk or the area of fibrosis. The diagnostic accuracy for the fibrosis model was 97% with the 5 main measurements or markers of fibrosis studied, with Dk isolated at the first step by stepwise analysis. In conclusion, fractal analysis is suitable for analyzing liver fibrosis and has excellent reproducibility. This is the only quantitative morphometric method that can discriminate among the models of fibrosis and is sensitive enough to detect pharmacologically induced changes in liver fibrosis. [source] PROPERTIES OF DIFFERENT FISH PROCESSING BY-PRODUCTS FROM POLLOCK, COD AND SALMONJOURNAL OF FOOD PROCESSING AND PRESERVATION, Issue 2 2003PETER J. BECHTEL Individual fish processing waste stream components can be used to make feed ingredients or other products. Waste stream components obtained from commercial fish processing plants included heads, viscera, frames, and skins from Alaska pollock (Theragra chalcogramma) and Pacific cod (Gadus macrocephalus); and heads, and viscera from pink salmon (Oncorhynchus gorbuscha). The protein content of heads from all three species ranged from 13.9 to 16.4%; and the fat content ranged from 0.9 to 10.9%. Viscera protein content ranged from 13.0 to 15.3%, and the fat content from 2.0 to 19.1%. After heating to 85C the percent soluble protein in salmon heads was different (P < 0.05) from pollock or cod heads. Percent soluble protein of pollock and cod skin increased 8fold (P<0.05) after the 85C heat treatment. Connective tissue content was calculated from chemical determination of hydroxyproline content, and large differences in percent connective tissue content were found (1% for pollock viscera to 46% for skin). Estimated rat PER values ranged from a low of 2.1 for skin to a high of 3.1 for viscera and fillet samples (P<0.05). [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] Effect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2007Patricio Ibañez Abstract Background and Aim:, Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH. Methods:, To induce NASH, a choline-deficient diet (CDD) was given to Sprague-Dawley rats for 12 weeks. These animals were then compared with a control group receiving choline-supplemented diet (CSD) and a group fed a CDD plus losartan (10 mg/kg/day). Biochemical (serum levels of alanine aminotransferase and aspartate aminotransferase) and histological evaluation of fatty liver was performed by conventional techniques. Hydroxyproline content in liver tissue was assayed by spectrophotometry. In addition, mRNA levels of procollagen I and transforming growth factor (TGF)-, were assessed by semiquantitative RT-PCR and stellate cell activation by ,-actin immunofluorescence stain. Results:, After 12 weeks CDD induced a marked elevation of serum aminotranferases, a severe fatty liver infiltration with mild histological inflammation and fibrosis. These findings correlated with a significant increase in mRNA levels of both procollagen I and TGF-, and significant increased liver hydroxyproline content. No differences were seen between rats receiving CDD alone and rats receiving CDD plus losartan with regard to the biochemical, morphological or molecular alterations induced by the CDD. Conclusion:, Losartan does not seem to influence liver injury and fibrogenic events in the CDD model of NASH. [source] Effect of sodium houttuyfonate on myocardial hypertrophy in mice and ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Jian Ping Gao Abstract Objectives The aim of the study was to determine the effect of sodium houttuyfonate on myocardial hypertrophy and its mechanism of action in mice and rats. Methods A mouse model of myocardial hypertrophy was established by subcutaneous injection with isoproterenol. Mice were randomly divided into five groups: normal control; isoproterenol control; isoproterenol plus metoprolol; isoproterenol plus low- and high-dose sodium houttuyfonate. A rat model of myocardial hypertrophy was established by intraperitoneal injection with l -thyroxine. Rats were randomly divided into five groups: normal control; l -thyroxine control; l -thyroxine plus captopril; l -thyroxine plus low- and high-dose sodium houttuyfonate. At the end of the experiments, the left ventricular weight index and heart weight index were determined in mice and rats, the size of cardiomyocytes was measured in rats and the concentrations of cAMP in plasma and angiotensin II in ventricular tissue of mice were detected by radioimmunoassay. The endothelin-1 concentration was measured by radioimmunoassay and the hydroxyproline content was measured by a digestive method in ventricular tissue of rats. Key findings After 7,9 days of treatment, sodium houttuyfonate significantly reduced the left ventricular weight index and heart weight index in mice and rats with myocardial hypertrophy, decreased the size of cardiomyocytes in rats, and reduced the content of cAMP and angiotensin II in mice with myocardial hypertrophy. It also decreased the endothelin-1 concentration and the hydroxyproline content in ventricular tissue in rats. Conclusions Sodium houttuyfonate can inhibit myocardial hypertrophy in mouse and rat models by restricting the activity of the sympathetic nervous system and decreasing the levels of angiotensin II and endothelin-1 in ventricular tissue. [source] The Ethanol-soluble Part of a Hot-water Extract from Artemisia iwayomogi Inhibits Liver Fibrosis Induced by Carbon Tetrachloride in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000EUN-JEON PARK This study was carried out to investigate the protective effects of the hot-water extract from Artemisia iwayomogi (Compositae) on carbon tetrachloride-induced liver fibrosis in rats. Liver injury was induced by oral administration of carbon tetrachloride (1 mL kg,1) twice a week during 4 weeks of A. iwayomogi treatment. Extracts from A. iwayomogi were prepared and administered to rats orally (2 g kg,1 as A. iwayomogi for 4 weeks) as follows: group 1, hot-water extract; group 2, ethanol-soluble part of hot-water extract; group 3, ethanol-insoluble part of hot-water extract; and group 4, methanol extract. In rats treated with the ethanol-soluble part of the hot-water extract, liver hydroxyproline content was reduced to 74% that of carbon tetrachloride control rats (P < 0.05). Protein expression of alpha smooth muscle cell like actin was also decreased in rats treated with the ethanol-soluble part of the hot-water extract, which indicates inhibition of hepatic stellate cell activation. Liver malondialdehyde levels were significantly lowered in rats treated with the ethanol-soluble part of hot-water extract (P < 0.05). Serum cholesterol levels in rats treated with hot-water extract, ethanol-soluble or -insoluble parts of hot-water extract or methanol extract were significantly reduced when compared with those of carbon tetrachloride control rats (P < 0.05). The ethanol-soluble part of the hot-water extract from A. iwayomogi inhibited fibrosis and lipid peroxidation in rats with liver fibrosis induced by carbon tetrachloride. Both hot-water extract (either ethanol-soluble or -insoluble) and methanol extract of A. iwayomogi also lowered serum cholesterol levels in fibrotic rats. [source] Leptin deficiency reduces but does not eliminate the development of hepatic fibrosis in mice infected with Schistosoma mansoniLIVER INTERNATIONAL, Issue 2 2002James J. Potter Abstract: Aims/Background: Leptin, a product of the obese (ob) gene, was demonstrated previously in activated hepatic collagen-producing stellate cells, but not in quiescent retinol-storing stellate cells. The role of leptin in fibrogenesis is unknown. This study investigated the possible influence of leptin in the pathogenesis of fibrosis by determination of the amount of fibrosis produced by Schistosoma mansoni infection in leptin deficient male ob/ob mice as compared to control mice. Methods: The mice were infected percutaneously with cercaria of Schistosoma mansoni and the amount of liver fibrosis determined 12 weeks after infection. The amount of hepatic collagen deposited was quantified by morphometric analysis of liver sections stained with sirius red and by hydroxyproline content. Results: The amount of histologically detectable fibrosis was greater in the infected controls than in the infected ob/ob mice. In the infected control mice, but not in the ob/ob mice, the fibrosis surrounding the granuloma was broad and extended beyond the portal tracts into the lobule with the formation of fibrous septa. Conclusions: This study shows that leptin is a potentiating, but not an essential factor, for the development of hepatic fibrosis, because leptin deficiency reduces but does not prevent the development of hepatic fibrosis. [source] Pharmacological studies on Indian black tea (leaf variety) in acute and chronic inflammatory conditionsPHYTOTHERAPY RESEARCH, Issue 6 2008Dilip K. Roy Abstract Infusions of Indian black tea (BTI), when administered orally, produced significant inhibition of rat paw oedema, induced with carrageenin (pre and post treatment) and arachidonic acid. BTI was also found to inhibit peritoneal capillary permeability and caused a marked reduction of lipopolysaccharide induced PGE2 generation. In these models, the observed antioedema effect was similar to that of BW755C (a dual inhibitor of cyclooxygenase and 5-lipoxygenase enzymes). BTI was found to scavenge superoxide and hydroxyl radicals, and also protected rat erythrocytes from the damaging effects of hydrogen peroxide. In chronic studies, BTI inhibited granuloma formation along with the reduction of both lipid peroxidation and hydroxyproline content (in the granuloma tissue). Significant antiarthritic activity was observed with regular administration of BTI in the Freund's adjuvant induced model of arthritis. Chronic treatment with BTI (in arthritic rats) resulted in a decrease of paw diameter and tissue lipid peroxidation, along with a restoration of GSH, catalase and superoxide dismutase levels. Copyright © 2008 John Wiley & Sons, Ltd. [source] Changes of the hepatic proteome in murine models for toxically induced fibrogenesis and sclerosing cholangitisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 24 2006Corinna Henkel Abstract We investigated the changes in the hepatic proteome in murine models for toxic-induced fibrogenesis and sclerosing cholangitis. A comprehensive comparison of protein changes observed is made and the mechanistical basis of the expression changes is discussed. Hepatic fibrosis was induced by repetitive intraperitoneal CCl4 treatment of BALB/c mice or developed spontaneously in BALB/c-ATP-binding cassette, subfamily B, member 4 (Abcb4) knock out mice. Fibrosis was verified by a morphometric score and assessment of hydroxyproline content of liver tissue, respectively. The innovative difference in-gel electrophoresis (DIGE) technique was used to analyse protein expression levels of the mouse proteome. Results were confirmed by Western blotting and real-time RT-PCR. In CCl4 -induced fibrosis 20 out of 40 and in BALB/c- Abcb4,/, mice 8 out of 28 differentially expressed proteins were identified utilizing DIGE. Only two proteins, selenium-binding protein (Sbp2) and carbonic anhydrase 3, have been unidirectionally expressed (i.e. down-regulated) in both models. Relevant differences in the pathogenesis of toxically induced liver fibrosis and sclerosing cholangitis exist. The only novel protein with regard to liver fibrosis depicting a unidirectional expression pattern in both animal models was Sbp2. An explicit protein function could not be clarified yet. [source] Overexpression of nitric oxide synthase by the endothelium attenuates bleomycin-induced lung fibrosis and impairs MMP-9/TIMP-1 balanceRESPIROLOGY, Issue 5 2006Sho YOSHIMURA Background: Nitric oxide (NO) produced by endothelial NO synthase (eNOS) is thought to effect an anti-inflammatory response, but its mechanism is still unknown. Methods: eNOS transgenic (eNOS-TG) mice and their littermate controls (C57/BL6) were used to clarify the role of NO derived from eNOS. Bleomycin hydrochloride (1 U/body/day) or PBS was injected intraperitoneally. Results: Subpleural fibrotic changes and hydroxyproline content in the eNOS-TG mice were significantly reduced compared with those of the wild-type (WT) mice by day 56. Administration of N, -nitro- l -arginine methyl ester, a potent inhibitor of NO synthase, worsened the fibrotic response in bleomycin-treated eNOS-TG mice. Gelatinolytic activity in lung homogenates, corresponding to metalloproteinase-9 (MMP-9), was significantly increased in bleomycin-injured WT mice on day 14. In contrast, the level of tissue inhibitor of metalloproteinases-1 (TIMP-1), an endogenous MMP-9 inhibitor, was increased in the bleomycin-treated eNOS-TG mice compared with WT. Immunohistochemical analysis demonstrated that MMP-9 and TIMP-1 were strongly expressed in inflammatory cells, including subpleural fibrotic lesions. Conclusion: These data suggested that eNOS overexpression attenuates bleomycin-induced lung injury by ameliorating the MMP-9/TIMP-1 balance. [source] C-C chemokine receptor 2 (CCR2) deficiency improves bleomycin-induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage-derived matrix metalloproteinasesTHE JOURNAL OF PATHOLOGY, Issue 5 2004Toshiyuki Okuma Abstract Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2,/,) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 ,/, mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2,/, and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2,/, mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2,/, mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2,/, mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2,/, mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2,/, mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Role of Increased Penile Expression of Transforming Growth Factor-,1 and Activation of the Smad Signaling Pathway in Erectile Dysfunction in Streptozotocin-Induced Diabetic RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 10 2008Lu Wei Zhang MD ABSTRACT Introduction., It has been suggested that transforming growth factor-,1 (TGF-,1) plays an important role in the pathogenesis of diabetes-induced erectile dysfunction. Aim., To investigate the expression and activity of Smad transcriptional factors, the key molecules for the initiation of TGF-,-mediated fibrosis, in the penis of streptozotocin (STZ)-induced diabetic rats. Methods., Fifty-two 8-week-old Sprague,Dawley rats were used and divided into control and diabetic groups. Diabetes was induced by an intravenous injection of STZ. Main Outcome Measures., Eight weeks later, erectile function was measured by electrical stimulation of the cavernous nerve (N = 12 per group). The penis was harvested and stained with Masson trichrome or antibody to TGF-,1, phospho-Smad2 (P-Smad2), smooth muscle ,-actin, and factor VIII (N = 12 per group). Penis specimens from a separate group of animals were used for TGF-,1 enzyme-linked immunosorbent assay (ELISA), P-Smad2/Smad2, phospho-Smad3 (P-Smad3)/Smad3, fibronectin, collagen I, and collagen IV western blot, or hydroxyproline determination. Results., Erectile function was significantly reduced in diabetic rats compared with that in controls. The expression of TGF-,1, P-Smad2, and P-Smad3 protein evaluated by ELISA or western blot was higher in diabetic rats than in controls. Compared with that in control rats, P-Smad2 expression was higher mainly in smooth muscle cells and fibroblasts of diabetic rats, whereas no significant differences were noted in endothelial cells or in the dorsal nerve bundle. Cavernous smooth muscle and endothelial cell contents were lower in diabetic rats than in controls. Cavernous fibronectin, collagen IV, and hydroxyproline content was significantly higher in diabetic rats than in controls. Conclusion., Upregulation of TGF-,1 and activation of the Smad signaling pathway in the penis of diabetic rats might play important roles in diabetes-induced structural changes and deterioration of erectile function. Zhang LW, Piao S, Choi MJ, Shin H-Y, Jin H-R, Kim WJ, Song SU, Han J-Y, Park SH, Mamura M, Kim S-J, Ryu J-K, and Suh J-K. Role of increased penile expression of transforming growth factor-,1 and activation of the Smad signaling pathway in erectile dysfunction in streptozotocin-induced diabetic rats. J Sex Med 2008;5:2318,2329. [source] A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 11 2009Minoru Hasegawa Objective Tissue fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc), and an increasing number of promising molecular targets for antifibrotic therapies have been described recently. Transforming growth factor , (TGF,) is well known to be the principal factor that leads to tissue fibrosis. The present study was undertaken to investigate the ability of HSc025, a novel small compound that antagonizes TGF,/Smad signaling through the activation of nuclear translocation of Y-box binding protein 1, to prevent tissue fibrosis in vitro or in mouse models of SSc. Methods Human dermal fibroblasts were exposed to HSc025 at various concentrations in the presence of TGF,, and levels of collagen or fibronectin expression were determined. HSc025 (15 mg/kg/day for 14 days) was administered orally to tight skin mice and to mice with bleomycin-induced pulmonary fibrosis. Improvement of tissue fibrosis was evaluated by histologic or biochemical examination in each model. Results Pretreatment with HSc025 prevented Smad-dependent promoter activation, in a dose-dependent manner; however, HSc025 had no effect on TGF,-induced phosphorylation of Smad3. The inhibitory effects of HSc025 on TGF,-induced collagen or fibronectin expression were also confirmed in vitro. Orally administered HSc025 significantly reduced hypodermal thickness and hydroxyproline content in tight skin mice, and markedly decreased the histologic score and hydroxyproline content in the lungs of bleomycin-treated mice. Conclusion These results demonstrate that HSc025 is a novel inhibitor of TGF,/Smad signaling, resulting in the improvement of skin and pulmonary fibrosis. Orally available HSc025 might therefore be useful in the treatment of SSc. [source] Cartilage Tissue Engineering With Demineralized Bone Matrix Gelatin and Fibrin Glue Hybrid Scaffold: An In Vitro StudyARTIFICIAL ORGANS, Issue 2 2010Zheng-Hui Wang Abstract To develop a cartilage-like tissue with hybrid scaffolds of demineralized bone matrix gelatin (BMG) and fibrin, rabbit chondrocytes were cultured on hybrid fibrin/BMG scaffolds in vitro. BMG scaffolds were carefully soaked in a chondrocyte,fibrin suspension, which was polymerized by submerging the constructs into thrombin,calcium chloride solution. Engineered cartilage-like tissue grown on the scaffolds was characterized by histology, immunolocalization, scanning electron microscopy, biochemical assays, and analysis of gene expression at different time points of the in vitro culture. The presence of proteoglycan in the fibrin/BMG hybrid constructs was confirmed by positive toluidine blue and alcian blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene-encoded cartilage-specific markers, collagen type II, and aggrecan core protein. The glycosaminoglycan production and hydroxyproline content of tissue grown on the fibrin/BMG hybrid scaffolds were higher than that of the BMG group. In conclusion, the fibrin/BMG hybrid scaffolds may serve as a potential cell delivery vehicle and a structural basis for cartilage tissue engineering. [source] Attenuation of Bleomycin-Induced Lung Fibrosis by Oxymatrine Is Associated with Regulation of Fibroblast Proliferation and Collagen Production in Primary CultureBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2008Xiaohong Chen Oxymatrine is an alkaloid extracted from the Chinese herb Sophora japonica (Sophora flavescens Ait.) with capacities of anti-inflammation, inhibition of immune reaction, antivirus, protection against acute lung injury and antihepatic fibrosis. In this study, the effect of oxymatrine on pulmonary fibrosis was investigated using a bleomycin-induced pulmonary fibrosis mouse model. The results showed that bleomycin challenge provoked severe pulmonary fibrosis with marked increase in hydroxyproline content of lung tissue and lung fibrosis fraction, which was prevented by oxymatrine in a dose-dependent manner. In addition, bleomycin injection resulted in a marked increase of myeloperoxidase activity and malondialdehyde level that was attenuated by oxymatrine. Administration of oxymatrine inhibited the proliferation of murine lung fibroblasts, arrested the cells at G0/G1 phase and reduced the expression of cell cycle regulatory protein, cyclin D1 in vitro. Furthermore, the steady-state production of collagen and the expression of ,1(I) pro-collagen and ,2(I) pro-collagen mRNA in fibroblasts were inhibited by oxymatrine in a dose-dependent manner. These results suggested that oxymatrine may attenuate pulmonary fibrosis induced by bleomycin in mice, partly through inhibition of inflammatory response and lipid peroxidation in lung induced by bleomycin and reduction of fibroblast proliferation and collagen synthesis. [source] Insulin-like growth factor 1-coated sutures improve anastomotic healing in an experimental model of colitis,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2010E. Rijcken Background: Exogenously applied insulin-like growth factor (rhIGF-1) may improve normal intestinal healing. This study examined the effect of rhIGF-1-coated sutures on anastomotic healing in experimental colitis. Methods: Acute colitis was induced in rats by dextran sodium sulphate (DSS). Inflammation was assessed by clinical Disease Activity Index (DAI), myeloperoxidase (MPO) measurement and histological examination. A distal colonic anastomosis was performed using sutures coated with rhIGF-1 dissolved in poly(D,L -lactide) (PDLLA) under general anaesthetic. Anastomotic healing was evaluated histologically, and by hydroxyproline measurement and bursting parameters after 1, 3 and 7 days, and compared with healthy, DSS and DSS + PDLLA controls. Results: DAI, MPO and histological inflammation scores were significantly increased in all animals treated with DSS. Bursting occurred less often within the anastomotic line on day 3 in the IGF group than in DSS controls (three versus eight of ten). On day 7, the IGF group had significantly increased histological healing scores (mean(s.e.m.) 12·5(0·7) versus 9·2(0·8) (P < 0·050)) and hydroxyproline content (4·6(0·3) versus 3·6(0·1) mg/g tissue; P < 0·050) compared with DSS controls. Conclusion: IGF-1-coated sutures improve important aspects of anastomotic healing in rats with experimental colitis. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] IMPROVING THE CADMIUM-INDUCED CENTRIACINAR EMPHYSEMA MODEL IN RATS BY CONCOMITANT ANTI-OXIDANT TREATMENTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2008S Heili Frades SUMMARY 1The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N -acetylcysteine (NAC) administration. 2Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2 - and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2 -treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 ± 2 vs 127 ± 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2 -treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2 -treated rats. 5In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2 -induced fibrotic component of centriacinar emphysema. [source] REGULATION OF FIBROGENESIS DURING THE EARLY PHASE OF COMMON BILE DUCT OBSTRUCTIONANZ JOURNAL OF SURGERY, Issue 7 2006Atilla Engin Background: Both nitric oxide (NO) and prostaglandins have been proposed as inhibitor substances involved in collagen deposition in the hepatic parenchyma. The possible reciprocal connections between NO and eicosanoids in the development of liver fibrosis were investigated during the initial phase of common bile duct obstructions. Methods: A total of 30 male albino guinea pigs were randomly and equally assigned to three groups. Group 1 underwent sham laparotomy. Group 2 and group 3 were subjected to permanent common bile duct ligature for 24 and 72 h , respectively. Changes in the liver prostaglandin E2 (PGE2), leukotriene C4, malondialdehyde contents and plasma nitrite plus nitrate concentrations were measured. To evaluate the extent of hepatic fibrosis, histological assessment of liver was confirmed with the equivalent hydroxyproline contents of liver. Results: Twenty-four hours after ligature, the amount of malondialdehyde and PGE2 and plasma nitrite plus nitrate concentrations increased significantly, whereas liver hydroxyproline contents did not change. However, 72 h after ligature (Group 3), lipid peroxidation and collagen deposition were significantly higher than that of the group 2 animals. The PGE2 : leukotriene C4 ratio peaked at 24 h and later decreased, whereas PGE2 : NO ratio remained unchanged in both group 2 and group 3 animals. Conclusions: The initiation of collagen synthesis occurred in portal tract as early as within the first 72 h of bile duct obstruction. The optimum function of reactive oxygen species on the stellate cell activation might be determined by the interaction between NO and PGE2. [source] | ||||||||||||||||||||||||||||