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Fibrotic Area (fibrotic + area)

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Medical Sciences	100%

Selected Abstracts

Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats

HEPATOLOGY, Issue 5 2000
Yan Qing Wang
Proliferation and activation of hepatic stellate cells (HSCs) are critical steps for the development of postnecrotic fibrosis in the liver. The present study aimed to reveal the inhibitory effect of the semisynthetic analogue of fumagillin TNP-470 on these events for its possible use as an antifibrogenic agent. Rat models of carbon tetrachloride (CCl4)- and dimethylnitrosamine-induced hepatic fibrosis were used for an in vivo study. In both models, the fibrotic area was considerably decreased by concurrent repetitive subcutaneous injections of 30 mg/kg body weight of TNP-470. In CCl4 -induced fibrosis, factor VIII-related antigen-positive blood vessels, desmin-, or ,-smooth muscle actin (,SMA)-positive mesenchymal cells, bromodeoxyuridine (BrdU)-positive mesenchymal cells also decreased in number by treatment with TNP-470. In in vitro experiments, a supplement of 1,000 ng/mL TNP-470 suppressed BrdU incorporation and cyclins D1, D2, and E expression by cultured HSCs in the absence and/or presence of platelet-derived growth factor (PDGF). Expression of HSC activation markers, i.e., ,SMA and PDGF receptor ,, was also suppressed. The present results indicate that TNP-470 inhibits HSC proliferation by blocking the cell-cycle transition from G1 to S and HSC activation, and, as the consequence, prevents the progression of hepatic fibrosis, probably being coupled with its antiangiogenic effect. [source]

Apparent diffusion coefficient in pancreatic cancer: Characterization and histopathological correlations

JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2008
Noriaki Muraoka MD
Abstract Purpose To clarify the components primarily responsible for diffusion abnormalities in pancreatic cancerous tissue. Materials and Methods Subjects comprised 10 patients with surgically confirmed pancreatic cancer. Diffusion-weighted (DW) echo-planar imaging (b value = 0, 500 s/mm2) was employed to calculate the apparent diffusion coefficient (ADC). ADC values of cancer and noncancerous tissue were calculated. Furthermore, ADC values of the cancer were compared with histopathological results. Results The mean (±standard deviation) ADC value was significantly lower for tumor (1.27 ± 0.52 × 10,3 mm2/s) than for noncancerous tissue (1.90 ± 0.41 × 10,3 mm2/s, P < 0.05). Histopathological examination showed similar proportions of fibrotic area, cellular component, necrosis, and mucin in each case. Regarding the density of fibrosis in cancer, three cases were classified in the loose fibrosis group and the remaining seven cases were classified in the dense fibrosis group. The mean ADC value was significantly higher in the loose fibrosis group (1.88 ± 0.39 × 10,3 mm2/s) than in the dense fibrosis group (1.01 ± 0.29 × 10,3 mm2/s, P < 0.05). In quantitative analysis, ADC correlated well with the proportion of collagenous fibers (r = ,0.87, P < 0.05). Conclusion Collagenous fibers may be responsible for diffusion abnormalities in pancreatic cancer. J. Magn. Reson. Imaging 2008;27:1302,1308. © 2008 Wiley-Liss, Inc. [source]

Original Article: Left ventricular geometry and cardiovascular mortality based on haemodialysis patient autopsy analyses

NEPHROLOGY, Issue 5 2010
IMARI MIMURA
ABSTRACT Aim: In end-stage renal disease (ESRD) patients, left ventricular hypertrophy (LVH) is common and a risk for cardiovascular events. LVH is geometrically classified into two major groups, concentric and eccentric, and accumulating evidence suggests eccentric LVH has a more negative effect than concentric LVH on ESRD outcome. However, there have been very few studies on the cardiac findings from ESRD patient autopsy in which the relationship between LVH geometry and mortality was analyzed. Methods: An observational study was performed with the autopsy findings in 30 haemodialysis patient cases between 2001 and 2006 at Mitsui Memorial Hospital, Tokyo. Between those who died of a cardiovascular cause and those who died of non-cardiovascular causes, we compared the heart/bodyweight ratio, left ventricular dilatation, and the extent of fibrosis of the left ventricle. Results: Heart/bodyweight ratio was significantly higher (P < 0.0001) in the cardiovascular mortality group (n = 11, 11.7 ± 2.5 g/kg) compared to the non-cardiac cause of death group (n = 19, 8.05 ± 0.7 g/kg). The dilatation of the left ventricle was significantly more frequent in the cardiovascular than the non-cardiac cause of death group (P = 0.016). Additionally, the fibrotic area of left ventricular cross-section was larger in the cardiovascular (1.63 ± 1.6%) than the non-cardiac group (0.83 ± 1.7%, P = 0.04). Conclusion: This autopsy study indicates that eccentric LVH in haemodialysis patients is closely associated with cardiovascular mortality. LVH geometry, as well as LVH severity, is worthy of consideration as a clinical predictor for cardiovascular mortality. [source]

Effect of adamantylamide dipeptide as adjuvant therapy to praziquantel in mice infected with different S. mansoni isolates,

APMIS, Issue 7-8 2006
SANAA BOTROS
This work investigated the possible use of AdDP as adjuvant therapy to praziquantel (PZQ) in mice infected with PZQ-insusceptible Schistosoma mansoni isolate in a trial to increase the susceptibility of this isolate to the drug. Two batches of C57 BL/6 mice were infected with PZQ-susceptible and -insusceptible S. mansoni isolates, and each batch was divided into five groups. Seven weeks postinfection, the experimental group received AdDP (5 mg/kg) in addition to PZQ in reduced dose (3×100 mg/kg). Three of the remaining four groups were treated controls; they received AdDP, PZQ in reduced dose and in full dose (2×500 mg/kg), and the fourth group was infected untreated. In mice infected with PZQ-susceptible or -insusceptible S. mansoni isolate, praziquantel alone, and in addition to AdDP, reduced worm and egg loads and increased percentage dead eggs. Also, they improved the histopathological changes (reduction in granuloma diameter, percentage fibrotic area with increased percentage degenerated eggs). Inducible nitric oxide synthase (iNOS), nitric oxide (NO) in culture of peritoneal macrophages, and number of CD68-positive cells were decreased with improved alanine amino transaminase. In mice receiving combined therapy AdDP+PZQ, the antischistosomal efficacy and the reductions in the inflammatory granulomatous reactions, NO in cultured peritoneal macrophages, percentage fibrotic areas recorded, were comparable to that in mice receiving full dose of PZQ, with significantly higher reduction in CD68 cells denoting enhanced antischistosomal efficacy and healing of the inflammatory reactions in the liver. [source]

A morphometric analysis of bulbar urethral strictures

BJU INTERNATIONAL, Issue 2 2007
Andre G. Cavalcanti
In a beautifully descriptive paper, authors from Rio de Janeiro and San Francisco report a quantitative and qualitative histological analysis of spongiosal tissue in patients with bulbar urethral strictures. They found that stricture formation was characterised by major alterations in extracellular matrix features. OBJECTIVE To report a quantitative and qualitative histological analysis of spongiosum tissue in patients with bulbar urethral strictures. MATERIALS AND METHODS Urethral specimens from 15 patients who had end-to-end anastomotic urethroplasty were evaluated; the control group comprised five bulbar urethras from cadavers. The collagen content, elastic fibres, smooth muscle and vessels were analysed using stereological methods. RESULTS There was complete loss of the relationship between smooth muscle, extracellular matrix and sinusoids in the peri-luminal area (PLA), with collagen replacement. The extension of the fibrotic area was greater in those with a traumatic than in those with an atraumatic stricture. The content of smooth muscle and collagen in the peripheral spongiosum (PS) area was similar for the stricture and control groups, and results were comparable for traumatic and atraumatic groups and those with suprapubic cystostomy diversion or not before surgery. There was a remarkably lower vascular density in the traumatic than in the atraumatic group. There was an increase in type III collagen in the PLA and in type I collagen in the PS; collagen type III in the PLA was greater in the group with no suprapubic cystostomy diversion before surgery. There were fewer elastic fibres in both stricture areas (PLA and PS) than in the control group. CONCLUSIONS Urethral stricture formation is characterized by marked changes in extracellular matrix features, with consequent changes in organ function. [source]

Alternatively activated macrophages (M2 macrophages) in the skin of patient with localized scleroderma

EXPERIMENTAL DERMATOLOGY, Issue 8 2009
Nobuyo Higashi-Kuwata
Abstract:, Localized scleroderma is a connective tissue disorder that is limited to the skin and subcutaneous tissue. Macrophages have been reported to be particularly activated in patients with skin disease including systemic sclerosis and are potentially important sources for fibrosis-inducing cytokines, such as transforming growth factor ,. To clarify the features of immunohistochemical characterization of the immune cell infiltrates in localized scleroderma focusing on macrophages, skin biopsy specimens were analysed by immunohistochemistry. The number of cells stained with monoclonal antibodies, CD68, CD163 and CD204, was calculated. An evident macrophage infiltrate and increased number of alternatively activated macrophages (M2 macrophages) in their fibrotic areas were observed along with their severity of inflammation. This study revealed that alternatively activated macrophages (M2 macrophages) may be a potential source of fibrosis-inducing cytokines in localized scleroderma, and may play a crucial role in the pathogenesis of localized scleroderma. [source]

Expression of cystic fibrosis transmembrane conductance regulator in liver tissue from patients with cystic fibrosis

HEPATOLOGY, Issue 2 2000
Nils Kinnman M.D.
The authors examined the expression of cystic fibrosis transmembrane conductance regulator (CFTR) and its relationship to histopathological changes in cystic fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers in liver cryosections in 11 patients with CF-associated liver disease, and non-CF controls with (n = 17) and without (n = 3) liver disease. In CF patients prominent inflammatory infiltrates were not found, yet hepatic stellate cells were identified within fibrotic areas around bile ducts. Proliferating bile ducts displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise negative. In 2 patients homozygous for R764X and for 1112delT no CFTR immunoreactivity was detected. Bile-duct epithelial cells in patients carrying the ,F508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR, as determined with confocal laser scanning microscopy, in contrast to the distinct CFTR expression at the luminal surface seen in controls. No clear relationship between CFTR expression and fibrosis or inflammation was evidenced in CF patients. In conclusion, these findings are consistent with an impairment of ,F508 CFTR processing in intrahepatic biliary epithelium. ICAM-1 expression on bile-duct epithelial cells and inflammatory infiltrates were rare findings in CF liver tissue, indicating that immunological mechanisms are unlikely to be involved in initiation of CF-associated liver disease. [source]