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Fibrosis
Kinds of Fibrosis Terms modified by Fibrosis Selected AbstractsRE: ANTIBIOTIC RENAL FAILURE AND CYSTIC FIBROSISJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2006Kingsley Coulthard Associate Professor No abstract is available for this article. [source] A NOVEL WAY TO DIAGNOSE CYSTIC FIBROSIS IN THE NEONATE WITH A BOWEL OBSTRUCTION AND POSSIBLE MECONIUM ILEUSJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9 2003V Sung No abstract is available for this article. [source] TRANSFORMING GROWTH FACTOR-,1 (TGF-,1) GENE EXPRESSION AND ACTIVATION IN THE PATHOGENESIS OF FIBROSIS IN PROTEINURIC RENAL DISEASE IN HUMANSNEPHROLOGY, Issue 1 2002Robyn Langham [source] RELATIONSHIP BETWEEN MYOFIBROBLAST APOPTOSIS AND GROWTH FACTORS IN THE PATHOGENESIS OF RENAL TUBULOINTERSTITIAL FIBROSISNEPHROLOGY, Issue 3 2000Lane Ac [source] PROTECTION BY AND ANTI-OXIDANT MECHANISM OF BERBERINE AGAINST RAT LIVER FIBROSIS INDUCED BY MULTIPLE HEPATOTOXIC FACTORSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2008Ben-Jian Zhang SUMMARY 1The aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors. 2Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl4, ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of a-smooth muscle actin (SMA) and transforming growth factor (TGF)-b1. 3The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine-treated groups in a dose-dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a-SMA and TGF-b1 was significantly downregulated in the berberine-treated groups (P < 0.01). 4These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti-oxidant system and lipid peroxidation. [source] Evaluation of Right Ventricular Fibrosis in Adult Congenital Heart Disease Using Gadolinium-enhanced Magnetic Resonance Imaging: Initial Experience in Patients with Right Ventricular Loading ConditionsCONGENITAL HEART DISEASE, Issue 5 2006Lopa P. Hartke MD ABSTRACT Objective., Gadolinium-enhanced cardiac magnetic resonance imaging has been used to show myocardial fibrosis, a finding that appears as late gadolinium enhancement. Its role in the evaluation of right ventricular fibrosis in congenital heart disease is unclear. The purpose of this study was to demonstrate late gadolinium enhancement of the right ventricle in adult and adolescent congenital heart disease and to investigate the relationship between this enhancement and clinical and pathophysiological data. Design., In total, 24 patients, 16 patients with congenital heart disease and right ventricular loading conditions and 8 controls, underwent gadolinium-enhanced viability imaging. Diagnoses varied and included repaired, palliated, and unrepaired lesions. The presence and extent of right ventricular late gadolinium enhancement was compared with patient clinical and hemodynamic data. Exact Wilcoxon tests, Fisher's exact tests, and Spearman's rank correlation were used to compare variables. Results., Nine of 16 patients (56%) were found to have right ventricular late gadolinium enhancement, ranging from 5% to 80% of right ventricular myocardium affected (mean 36.1%, SD 29.7). The combination of right ventricular systolic pressure ,98 mm Hg and systemic oxygen saturation ,93% strongly suggested the presence of right ventricular late gadolinium enhancement (positive predictive value 100%), but no single variable or combination of variables could reliably predict its absence (negative predictive values ,75%). Extent of right ventricular late gadolinium enhancement did not correlate with degree of either hypoxia or right ventricular hypertension. Conclusions., Gadolinium-enhanced cardiac magnetic resonance demonstrates right ventricular late gadolinium enhancement in some patients with congenital heart disease and right ventricular loading conditions. Clinical variables were associated with the presence of fibrosis but did not reliably predict severity. Myocardial preservation is likely a multifactorial process that may affect the right and left ventricles differently. [source] Patchy Myocardial Fibrosis 20 Years after Radiation TherapyECHOCARDIOGRAPHY, Issue 1 2007Rachael A. Wyman M.D. We describe a case of a young woman diagnosed with Ewings sarcoma at age 8 and treated with adriamycin and radiation therapy. Twenty years later the patient has a cardiomyopathy and a focal area of patchy infiltration of fibrotic tissue along the left ventricle and atrium. Although fibrosis due to radiation exposure has been demonstrated on biopsy and autopsy studies, we are not aware of previous reports of echocardiographic demonstration of this finding. The most likely explanation for the fibrosis location is the left posterolateral direction of the radiation beam. [source] Graft fibrosis after pediatric liver transplantation: Ten years of follow-up,HEPATOLOGY, Issue 3 2009Rene Scheenstra Previously we reported the presence of portal fibrosis in 31% (n = 84) of the grafts in protocol biopsies 1 year after pediatric liver transplantation (LTx). To assess the natural history of graft fibrosis after pediatric liver transplantation, we extended the analysis of graft histology in follow-up protocol biopsy specimens obtained 5 and 10 years after transplantation. We correlated histological results with clinical parameters at the time of LTx and during follow-up, to allow identification of risk factors for the development of fibrosis. From 1 year to 5 years after LTx, the prevalence of fibrosis increased from 31% to 65% (n = 66) but remained stable thereafter (at 10 years, 69%, n = 55). At 10 years after LTx, however, the percentage of patients with severe fibrosis had increased from 10% (at 5 years) to 29%. Of the 69% of children without fibrosis at 1 year post-transplantation, 64% (n = 39) had developed some degree of fibrosis at 10 years. Fibrosis was strongly related to transplant-related factors such as prolonged cold ischemia time, young age at the time of transplantation, high donor/recipient age ratio, and the use of partial grafts (P < 0.05). Fibrosis was not significantly related to rejection, chronic hepatitis, or the nature of the immunosuppressive therapy. Conclusion: Biopsies after pediatric LTx show that most grafts developed fibrosis within 5 years. At 10 years after LTx, the graft fibrosis had progressed to severe fibrosis in at least 25% of the patients. Development of fibrosis, starting either before or after the first year post-LTx, was strongly related to transplant-related factors, indicating the importance of these factors to long-term graft prognosis. (HEPATOLOGY 2008.) [source] Liver damage underlying unexplained transaminase elevation in human immunodeficiency virus-1 mono-infected patients on antiretroviral therapy,HEPATOLOGY, Issue 2 2009Patrick Ingiliz Liver damage associated with chronic unexplained high serum transaminases in human immunodeficiency virus (HIV)-infected patients under combined antiretroviral therapy is unknown. Liver histology was prospectively investigated in patients presenting serum transaminase elevation for more than 6 months, after exclusion of alcohol abuse, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection, autoimmune, and genetic liver diseases. In a subgroup of patients, liver mitochondrial activities were measured by spectrophotometry and mitochondrial DNA (mtDNA) by real-time polymerase chain reaction (PCR). Thirty patients were included with median values of alanine aminotransferase (ALT) levels: 80 U/L, age: 46 years, body mass index: 23 kg/m2, HIV RNA: 200 copies/mL, CD4 count: 365/mm3, duration of HIV infection: 13 years, and duration of treatment exposure: 118, 41, and 53 months for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. Histological anomalies were found in 22 of 30 patients. Steatosis was present in 18 patients, severe in nine patients, and associated with inflammation in 16 patients with a diagnosis of non-alcoholic steatohepatitis (NASH). Fibrosis was found in 18 patients, severe in six patients and associated with steatosis in 13 patients. Significant liver respiratory complex I defect, contrasting with high complex IV activity and normal mitochondrial DNA content, was observed in the group of patients compared with controls. The presence of NASH was correlated with high fasting glycemia and insulin levels, not with liver mitochondrial function or mitochondrial DNA content. Conclusions: HIV-infected patients on combined antiretroviral therapy with chronic transaminase elevation of unknown origin have a high rate of liver lesions, mostly consistent with NASH related to insulin resistance. (HEPATOLOGY 2008.) [source] A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),HEPATOLOGY, Issue 5 2005Markus Moser Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source] Sampling variability of liver fibrosis in chronic hepatitis CHEPATOLOGY, Issue 6 2003Pierre Bedossa M.D. Fibrosis is a common endpoint of clinical trials in chronic hepatitis C, and liver biopsy remains the gold standard for fibrosis evaluation. However, variability in the distribution of fibrosis within the liver is a potential limitation. Our aim was to assess the heterogeneity of liver fibrosis and its influence on the accuracy of assessment of fibrosis with liver biopsy. Surgical samples of livers from patients with chronic hepatitis C were studied. Measurement of fibrosis was performed on the whole section by using both image analysis and METAVIR score (reference value). From the digitized image of the whole section, virtual biopsy specimens of increasing length were produced. Fibrosis was assessed independently on each individual virtual biopsy specimen. Results were compared with the reference value according to the length of the biopsy specimen. By using image analysis, the coefficient of variation of fibrosis measurement with 15-mm long biopsy specimens was 55%; and for biopsy specimens of 25-mm length it was 45%. By using the METAVIR scoring system, 65% of biopsies 15 mm in length were categorized correctly according to the reference value. This increased to 75% for a 25-mm liver biopsy specimen without any substantial benefit for longer biopsy specimens. Sampling variability of fibrosis is a significant limitation in the assessment of fibrosis with liver biopsy. In conclusion, this study suggests that a length of at least 25 mm is necessary to evaluate fibrosis accurately with a semiquantitative score. Sampling variability becomes a major limitation when using more accurate methods such as automated image analysis. [source] Risk factors of fibrosis in alcohol-induced liver diseaseHEPATOLOGY, Issue 3 2002Bruno Raynard In patients with nonalcoholic steatohepatitis (NASH), age, obesity, and diabetes mellitus are independent predictors of the degree of fibrosis. The relative risk for fibrosis adjusted for sex was also associated with increasing grade of Perls stain. The aim of this study was to determine whether the risk factors for fibrosis described in NASH are also risk factors in alcohol-induced liver disease. A total of 268 alcoholic patients with negative hepatitis B virus and hepatitis C virus serology underwent liver biopsy. Fibrosis was assessed semiquantitatively by a score fluctuating between 0 to 8. Liver iron overload was assessed by Perls staining and graded in 4 classes. We have used multivariate regression with partial correlation analysis to assess the variability of fibrosis score according to the value of 7 variables: sex, age, body mass index (BMI) in the past year before the hospitalization when the patient was asymptomatic, daily alcohol intake over the past 5 years, total duration of alcohol abuse, Perls grade, and blood glucose level. In the multivariate regression, fibrosis score was positively correlated with age (P = .001), BMI (P = .002), female sex (P < .05), Perls grade (P < .05), and blood glucose level (P < .05). Twenty percent of the variability of fibrosis score was explained by the 7 variables. In conclusion, after adjustment for daily alcohol intake and total duration of alcohol abuse, BMI, Perls grade, and blood glucose are also independent risk factors for fibrosis in alcohol-induced liver disease, raising therapeutic implications for the management of these patients. [source] Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in ratsHEPATOLOGY RESEARCH, Issue 7 2008Kazunori Maeda Aim:, The aim of this study was to examine the preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation (BDL) in rats. Methods:, ME3738 (20 mg/day) was administered orally for 21 days immediately after BDL. Fibrosis was assessed by measuring hepatic hydroxyproline (Hyp) content. Activated hepatic stellate cells (HSCs) were assessed by ,-smooth muscle actin (,-SMA) immunostaining. Hepatic thiobarbituric acid-reactive substance (TBARS), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) immunostaining were used to analyze oxidative stress. The gene expressions of collagen-I, transforming growth factor-,1 (TGF-,1), tissue inhibitor of metalloproteinases-1 (TIMP-1), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the liver were examined by real-time reverse transcriptase polymerase chain reaction (RT,PCR). Results:, Hepatic Hyp content and the area of hepatic fibrosis in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non-treated BDL rats (hepatic Hyp, 9.40 ± 2.85 vs. 12.39 ± 3.91 mg/liver; P = 0.036; area of hepatic fibrosis, 13.1 ± 3.8 vs. 21.5 ± 10.9; P = 0.045). Furthermore, ,-SMA-positive cells were significantly reduced by 40% (22.3 ± 14.8 vs. 37.6 ± 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 ± 2.2 vs. 38.3 ± 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 ± 1.22 vs. 9.73 ± 1.80; P = 0.018) and hepatic HO-1 content by 26% (2.13 ± 0.80 vs. 2.87 ± 0.19; P = 0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG and mRNA levels of TGF-,1, TIMP-1 and IL-6 in the liver were unchanged by ME3738 treatment. Conclusion:, Oral ME3738 administration may prevent the progression of hepatic fibrosis in BDL rats through suppression of the activation and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has potential as a therapeutic drug for cholestatic liver fibrosis. [source] Immunopathogenesis of hepatitis C virus infection and hepatic fibrosis: New insights into antifibrotic therapy in chronic hepatitis CHEPATOLOGY RESEARCH, Issue 8 2007Rosângela Teixeira Fibrosis and cirrhosis represent the consequences of a sustained wound-healing response to chronic liver injury of any cause. Chronic hepatitis C virus (HCV) has emerged as a leading cause of cirrhosis in the USA and throughout the world. HCV may induce fibrogenesis directly by hepatic stellate cell activation or indirectly by promoting oxidative stress and apoptosis of infected cells. The ultimate result of chronic HCV injury is the accumulation of extracellular matrix with high density type I collagen within the subendothelial space of Disse, culminating in cirrhosis with hepatocellular dysfunction. The treatment of hepatitis C with the combination of pegylated interferon and ribavirin is still both problematic and costly, has suboptimal efficacy, serious side effects and a high level of intolerance, and is contraindicated in many patients. Hence, new approaches have assumed greater importance, for which there is an urgent need. The sustained progress in understanding the pathophysiology of hepatic fibrosis in the past two decades has increased the possibility of developing drugs specifically targeting the fibrogenic process. Future efforts should identify genetic markers associated with fibrosis risk in order to tailor the treatment of HCV infection based on genetically regulated pathways of injury and/or fibrosis. Such advances will expand the arsenal to overcome liver fibrosis, particularly in patients with hepatic diseases who have limited treatment options, such as those patients with chronic hepatitis C who have a high risk of fibrosis progression and recurrent HCV disease after liver transplantation. [source] Fibrosis in heart disease: understanding the role of transforming growth factor-,1 in cardiomyopathy, valvular disease and arrhythmiaIMMUNOLOGY, Issue 1 2006Razi Khan Summary The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-,1 (TGF-,1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-,1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-,1. In fact, the pathogenic effects of TGF-,1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-,1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-,1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-,1 is an appropriate target for therapy in a variety of cardiovascular diseases. [source] Low coronary driving pressure early in the course of myocardial infarction is associated with subendocardial remodelling and left ventricular dysfunctionINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2007Marcia Kiyomi Koike Summary Subendocardial remodelling of the left ventricular (LV) non-infarcted myocardium has been poorly investigated. Previously, we have demonstrated that low coronary driving pressure (CDP) early postinfarction was associated with the subsequent development of remote subendocardial fibrosis. The present study aimed at examining the role of CDP in LV remodelling and function following infarction. Haemodynamics were performed in Wistar rats immediately after myocardial infarction (MI group) or sham surgery (SH group) and at days 1, 3, 7 and 28. Heart tissue sections were stained with HE, Sirius red and immunostained for ,-actin. Two distinct LV regions remote to infarction were examined: subendocardium (SE) and interstitium (INT). Myocyte necrosis, leucocyte infiltration, myofibroblasts and collagen volume fraction were determined. Compared with SH, MI showed lower CDP and LV systolic and diastolic dysfunction. Necrosis was evident in SE at day 1. Inflammation and fibroplasia predominated in SE as far as day 7. Fibrosis was restricted to SE from day 3 on. Inflammation occurred in INT at days 1 and 3, but at a lower grade than in SE. CDP correlated inversely with SE necrosis (r = ,0.65, P = 0.003, at day 1), inflammation (r = ,0.76, P < 0.001, at day 1), fibroplasia (r = ,0.47, P = 0.04, at day 7) and fibrosis (r = ,0.83, P < 0.001, at day 28). Low CDP produced progressive LV expansion. Necrosis at day 1, inflammation at days 3 and 7, and fibroplasia at day 7 correlated inversely with LV function. CDP is a key factor to SE integrity and affects LV remodelling and function following infarction. [source] Inflammation-associated remodelling and fibrosis in the lung , a process and an end pointINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007William A.H. Wallace Summary Fibrosis by common usage in the pathological and clinical literature is the end result of a healing process and synonymous with scarring. We would argue that its use to describe a dynamic series of events which may be reversible is unhelpful and that the term ,lung remodelling' is a better description for this process as it reflects changes in tissue organization that may or may not progress to ,fibrosis' as a final fixed point. Resolution, through reversal of active lung remodelling, by therapeutic intervention is possible providing the alveolar architecture remains intact. If the lung architecture is lost then healing by permanent fibrosis with loss of organ function is inevitable. [source] Hypercalcemia and Overexpression of CYP27B1 in a Patient With Nephrogenic Systemic Fibrosis: Clinical Vignette and Literature Review,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Vivian Y Pao Abstract Nephrogenic systemic fibrosis (NSF) is a disease of thickened, hard, hyperpigmented skin lesions with or without systemic fibrosis occurring in patients with renal insufficiency and associated with the administration of gadolinium-containing contrast. The pathogenesis of this disease is unclear, and there is no definitive treatment. We describe a 71-yr-old patient with stable chronic lymphocytic leukemia (CLL), end-stage renal disease (ESRD), and NSF who presented with hypercalcemia in 2006. Before onset of renal insufficiency in 2002, serum calcium, phosphorus, and PTH levels were normal. In 2004, the patient began hemodialysis, and he was diagnosed with NSF in 2005, shortly after undergoing an MRI with gadolinium contrast administration. Over the next 6 mo, albumin-corrected serum total calcium levels rose from 9.9 to 13.1 mg/dl (normal range, 8.5,10.5 mg/dl) with normal serum phosphorus levels. On admission in September 2006, 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were elevated at 130.7 pg/ml (normal range, 25.1,66.1 pg/ml). Biopsy of an NSF lesion showed increased 25-hydroxyvitamin D3,1-, hydroxylase (CYP27B1) immunostaining compared with the biopsy from a normal control. This is the first reported association of NSF with hypercalcemia caused by elevated 1,25(OH)2D levels. This metabolic disturbance should be sought in future cases to determine a connection between NSF, 1,25(OH)2D metabolism, and CYP27B1 activation in the skin, which may shed light on the pathogenesis of this unusual local and systemic fibrosing disorder. [source] Aging-Related Increase to Inducible Atrial Fibrillation in the Rat ModelJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HIDEKI HAYASHI M.D. Aging and Atrial Fibrillation.Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. Methods and Results: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2,3 months) and 12 old (22,24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 ,M were studied in both groups. Heptanol 2 to 5 ,M promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 ,M, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 ,M. In the old rats, AF could still be induced during perfusion of 2 ,M heptanol. However, when its concentration was raised to 5 and 10 ,M, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. Conclusion: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model. [source] Topical superoxide dismutase reduces post-irradiation breast cancer fibrosisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004F. Campana Abstract Fibrosis following breast radiotherapy for mammary cancer is a frequent undesired effect with objective (esthetic) and subjective (pain) consequences. Forty-four patients with clinical radiofibrosis following conservative treatment of breast cancer were evaluated for the local antifibrosis effect of copper zinc superoxide dismutase [SOD(Cu/Zn)]. Extracted SOD(Cu/Zn) in a concentration of 3,600 units/mg was applied as ointment to the fibrotic affected area, b.i.d. for 90 days, in a total dose of 40 mg. The radiofibrosis intensity was scored on the basis of clinical criteria (pain and the fibrosis area) before and after SOD(Cu/Zn) treatment. SOD(Cu/Zn) was found to be effective in reducing radiation induced fibrosis by a lowering pain score in 36/39 patients and a decrease of the fibrotic area size in half cases, after 6 months. The intensity and changes of breast fibrosis were assessed also by mammography and, for the topographical distribution of subcutaneous temperature, by infrared thermography. Mammography density suggested decreased fibrosis in one third of patients. Thermography showed that fibrosis was accompanied by two zones clinically indistinctive: a central area with maximum thermal activity, called "Maximal Thermic zone" (MTZ) and a peripheral area with less thermal activity but higher than in the surrounding normal tissue, "Transitional Thermic Zone" (TTZ). Both MTZ and TTZ were significantly decreased in 36/44 patients after SOD(Cu/Zn) treatment. Clinical changes persisted all along the study. Treatment was well tolerated except for one case of local allergic reaction, and no important side effects. Molecular mechanisms involved are discussed. Further studies are running to confirm and explain these results. [source] Mechanisms of Cardiac Fibrosis in HypertensionJOURNAL OF CLINICAL HYPERTENSION, Issue 7 2007Javier Díez MD Changes in the composition of cardiac tissue develop in hypertensive patients with left ventricular hypertrophy (ie, hypertensive heart disease) and lead to structural remodeling of the myocardium. One of these changes is related to the disruption of the equilibrium between the synthesis and degradation of collagen types I and III molecules, which results in an excessive accumulation of collagen types I and III fibers within the myocardium. Myocardial fibrosis is the consequence of a number of pathologic processes mediated by mechanical, neurohormonal, and cytokine routes. The clinical relevance of fibrosis is that it may contribute to heart failure and other cardiac complications in patients with hypertensive heart disease. This brief review focuses on the mechanisms of hypertensive myocardial fibrosis. [source] Gadolinium-Induced Nephrogenic Systemic Fibrosis Is Associated with Insoluble Gd Deposits in Tissues: In Vivo Transmetallation Confirmed by MicroanalysisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 12 2009Charu Thakral Background: Nephrogenic systemic fibrosis (NSF) is an extremely debilitating systemic fibrosing disorder affecting renal failure patients. The association of NSF with gadolinium (Gd) containing magnetic resonance contrast agents was noted in 2006. Gd deposition in skin biopsies was demonstrated shortly thereafter. Methods: We used automated scanning electron microscopy (SEM)/energy dispersive x-ray spectroscopy for in situ quantitative analysis of insoluble Gd-containing deposits, recording multi-elemental composition and spatial distribution of detected features. Results: Gd was detected in all 29 patients (53 of 57 skin biopsies) with NSF, biopsied from 2 weeks to 3 years after Gd exposure. Gd concentration ranged from 1 to 2270 cps/mm2 and was detected predominantly in the deep dermis and subcutaneous fibrous septa. Gd was found associated with Ca, P and sometimes Fe or Zn. Patients with sequential biopsies showed persistence or increase of Gd in tissues (6 of 11). Transmission electron microscopy (TEM) identified the intracellular deposits in fibrocytes and macrophages. Conclusions: The demonstration of insoluble tissue deposits of Gd with co-associated elements clearly confirms in vivo transmetallation and dissociation of soluble Gd-chelates. Toxic Gd3+ may trigger fibrosis under permissive conditions, e.g., in renal insufficiency. Pathologists and clinicians need to be aware of this serious but preventable disease. [source] Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2007Yi-Chao Hsu Abstract Background:, Anti-inflammation strategies are one of the proposed therapeutic approaches to hepatic fibrosis. Tetrandrine (C38H42O8N2, molecular weight: 622; Tet), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to exert anti-inflammatory activity in pulmonary diseases. The purpose of the present study was to investigate the in vitro and in vivo effects of Tet on hepatic fibrosis. Methods:, A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-,1 (TGF-,1) or tumor necrosis factor-, (TNF-,). The inhibitory effects of Tet on the nuclear factor ,B (NF,B) signaling cascade and molecular markers including intercellular adhesion molecule-1 (ICAM-1) and ,-smooth muscle actin (,-SMA) secretion were assessed. Fibrosis was induced by dimethylnitrosamine (DMN) administration in rats for 4 weeks. Fibrotic rats were randomly assigned to one of the four groups: vehicle (0.7% carboxyl methyl cellulose, CMC), Tet (1 mg/kg), Tet (5 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. At the end of the study, liver tissues were scored for fibrosis and analyzed for molecular markers of fibrosis. Results:, Tetrandrine (0.5,5.0 µmol/L) concentration-dependently inhibited NF,B transcriptional activity induced by TNF-,, including I,B, phosphorylation and mRNA expressions of ICAM-1 in HSC-T6 cells. In addition, Tet also inhibited TGF-,1-induced ,-SMA secretion and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with high-dose Tet (1.3 ± 0.3) were significantly reduced in comparison with DMN-treated rats receiving saline (2.0 ± 0.2). Hepatic collagen content of DMN rats was significantly reduced by either Tet or silymarin treatment. Double-staining results showed that ,-SMA- and NF,B-positive cells were decreased in the fibrotic livers by Tet and silymarin treatment. In addition, mRNA expression of ICAM-1, ,-SMA, and TGF-,1 was attenuated by Tet treatment. Moreover, levels of plasma aspartate aminotransferase and alanine aminotransferase activities were reduced by Tet and silymarin treatment. Conclusion:, Tetrandrine exerts antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis. [source] Chronic hepatitis: Role of diffusion-weighted imaging and diffusion tensor imaging for the diagnosis of liver fibrosis and inflammationJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2008Bachir Taouli MD Abstract Purpose To determine the diagnostic performance of liver apparent diffusion coefficient (ADC) measured with conventional diffusion-weighted imaging (CDI) and diffusion tensor imaging (DTI) for the diagnosis of liver fibrosis and inflammation. Materials and Methods Breathhold single-shot echo-planar imaging CDI and DTI with b-values of 0 and 500 second/mm2 was performed in 31 patients with chronic liver disease and 13 normal volunteers. Liver biopsy was performed in all patients with liver disease with a median delay of two days from MRI. Fibrosis and inflammation were scored on a 5-point scale (0,4). Liver ADCs obtained with CDI and DTI were compared between patients stratified by fibrosis stage and inflammation grade. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the utility of the ADC measures for prediction of fibrosis and inflammation. Results Patients with liver fibrosis and inflammation had significantly lower liver ADC than subjects without fibrosis or inflammation with CDI and DTI. For prediction of fibrosis stage , 1 and stage , 2, area under the ROC curve (AUC) of 0.848 and 0.783, sensitivity of 88.5% to 73.7%, and specificity of 73.3% to 72.7% were obtained, for ADC ,1.40 × 10,3 mm2/second and ,1.30 × 10,3 mm2/second (using CDI), respectively. For prediction of inflammation grade , 1, AUC of 0.825, sensitivity of 75.0%, and specificity of 78.6% were obtained using ADC , 1.30 × 10,3 mm2/second (using CDI). CDI performed better than DTI for diagnosis of fibrosis and inflammation. Conclusion Liver ADC can be used to predict liver fibrosis and inflammation with acceptable sensitivity and specificity. J. Magn. Reson. Imaging 2008;28:89,95. © 2008 Wiley-Liss, Inc. [source] Stereology of the myocardium in Leontopithecus (Lesson, 1840) callitrichidae , primatesJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2003A. Pissinatti Abstract: Rare morphological features of the Leontopithecus cardiovascular system have been reported in the literature. The samples analyzed in this study came from 33 specimens of Leontopithecus from the collection of the Center of Primatology of Rio de Janeiro-FEEMA (CPRJ-FEEMA). Morphometry and stereological data were obtained from all animals. Adult body weights of L. rosalia were the lowest, the greatest being those of L. chrysopygus caissara; body weights of L. chrysomelas and L. c. chrysopygus were similar and in between those of the two former species. Cardiomyocytes (left ventricular myocardium) were bigger in adults than in infants. The myocardium of L. rosalia showed focal fibrosis, fatty vacuoles, and hyalinization. In L. chrysomelas the myocardium showed areas of fibrosis and presence of mononuclear cells. Fibrosis and areas of congestion were observed in L. c. chrysopygus; areas of disorganization and vascular congestion were found in L. c. caissara. In L. rosalia infants, a greater density of vessels per myocardial area and a greater length density of vessels were observed as compared with those of L. chrysomelas. In adults, L. chrysomelas showed greater density of connective tissue in the myocardium than L. c. chrysopygus and L. c. caissara did. In L. rosalia, cardiomyocyte nuclei had a greater area density than those of the other forms of Leontopithecus. These characteristics may explain the faster development of L. rosalia infants as compared with that of L. chrysomelas and L. c. chrysopygus kept under the same handling conditions at the CPRJ-FEEMA. [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] Development of Alcoholic Fatty Liver and Fibrosis in Rhesus Monkeys Fed a Low n-3 Fatty Acid DietALCOHOLISM, Issue 10 2004Robert J. Pawlosky Background: The amount and type of dietary fat seem to be important factors that modulate the development of alcohol-induced liver steatosis and fibrosis. Various alcohol-feeding studies in animals have been used to model some of the symptoms that occur in liver disease in humans. Methods: Rhesus monkeys (Macaca mulatta) were maintained on a diet that had a very low concentration of ,-linolenic acid and were given free access to an artificially sweetened 7% ethanol solution. Control and ethanol-consuming animals were maintained on a diet in which the linoleate content was adequate (1.4% of energy); however, ,-linoleate represented only 0.08% of energy. Liver specimens were obtained, and the fatty acid composition of the liver phospholipids, cholesterol esters, and triglycerides of the two groups were compared at 5 years and histopathology of tissue samples were compared at 3 and 5 years. Results: The mean consumption of ethanol for this group over a 5-year period was 2.4 g · kg,1· day,1. As a consequence of the ethanol-dietary treatment, there were significantly lower concentrations of several polyunsaturated fatty acids in the liver phospholipids of the alcohol-treated group, including arachidonic acid and most of the n-3 fatty acids and particularly docosahexaenoic acid, when compared with dietary controls. Liver specimens from animals in the ethanol group at 5 years showed a marked degree of steatosis, both focal and diffuse cellular necrosis, and an increase in the development of fibrosis compared with specimens obtained at 3 years and with those from dietary controls, in which there was no evidence of fibrotic lesions. Conclusion: These findings suggest that the advancement of ethanol-induced liver disease in rhesus monkeys may be modulated by the amount and type of dietary essential fatty acids and that a marginal intake of n-3 fatty acids may be a permissive factor in the development of liver disease in primates. [source] Applying incremental tree induction to retrieval from manuals and medical textsJOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY, Issue 5 2006Kieran J. White The Decision Tree Forest (DTF) is an architecture for information retrieval that uses a separate decision tree for each document in a collection. Experiments were conducted in which DTFs working with the incremental tree induction (ITI) algorithm of Utgoff, Berkman, and Clouse (1997) were trained and evaluated in the medical and word processing domains using the Cystic Fibrosis and SIFT collections. Performance was compared with that of a conventional inverted index system (IIS) using a BM25-derived probabilistic matching function. Initial results using DTF were poor compared to those obtained with IIS. We then simulated scenarios in which large quantities of training data were available, by using only those parts of the document collection that were well covered by the data sets. Consequently the retrieval effectiveness of DTF improved substantially. In one particular experiment precision and recall for DTF were 0.65 and 0.67 respectively, values that compared favorably with values of 0.49 and 0.56 for IIS. [source] Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis BALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010S. U. Kim Aliment Pharmacol Ther 2010; 32: 498,505 Summary Background, Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan. Aim, To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB). Methods, One hundred and ninety-nine patients were enrolled. Only procedures yielding ,10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens <15 mm were considered ineligible. Results, The mean age (142 men and 57 women) was 40.1 years. A significant discordance (discordance of at least two stages between LB and LSM) was identified in 38 (19.1%) and 47 (23.6%) patients respectively, according to Marcellin et al. and Chan et al.'s cutoff values. In multivariate analyses, BMI and fibrosis stage (F0,2 vs. F3,4) were identified as independent predictors for significant discordance (P = 0.040; hazard ratio [HR], 1.126; 95% confidence interval [CI], 1.005,1.261 and P = 0.036; HR, 0.450; 95% CI, 0.213,0.949 respectively) with Marcellin et al.'s cutoffs, whereas fibrosis stage was the only independent predictor (P = 0.004; HR, 0.300; 95% CI, 0.131,0.685) with Chan's cutoffs. Conclusions, Success rate and IQR/M were not predictive factors of the accuracy for diagnosing liver fibrosis by Fibroscan in CHB. Fibrosis stage (F0-2) was the only factor to predict significant discordance between LB and LSM. [source] Review article: anti-fibrotic agents for the treatment of Crohn's disease , lessons learnt from other diseasesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010H. SZABŇ Summary Background, The current therapies for Crohn's disease (CD) are mainly focused on blockade of inflammation. Fibrosis remains one of the major complications of CD often leading to surgery, affecting patients' quality-of-life. Aim, To summarize the published data regarding the potential anti-fibrotic role of drugs commonly used in CD and the most effective anti-fibrotic drugs used in other diseases evaluating their potential use to treat intestinal fibrosis in CD. Methods, A literature search was performed in the PubMed, Medline, Cochrane and EMBASE databases, considering in vitro, animal and human studies on fibrosis in inflammatory bowel disease and other similar chronic pathologies. Results, Treatment of fibrosis in CD is limited to surgery or endoscopic dilatation, although some of the drugs currently used may have anti-fibrotic activity. In other diseases, anti-fibrotic agents are already used or are in preclinical or clinical trials. ACE inhibitors, Angiotensin Receptor Blockers, and HMG-CoA inhibitors merit further investigation in CD because of their role in preventing fibrosis in cardiovascular and renal diseases. Conclusions, Anti-fibrotic drugs are under evaluation or already used in clinical practice in other chronic inflammatory diseases. In CD, there is a great need for investigation into agents that may prevent, reduce or reverse intestinal fibrosis. Aliment Pharmacol Ther,31, 189,201 [source] | |||||||||||||||||||||||||||||||||||||||||||