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Introduction Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce Osteopontin (OPN), a profibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Methods Cultured cholangiocytes, kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by qRTPCR and ELISA; cell proliferation assessed by BrdU. Mice were infected with S. mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry, and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n= 72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. Results SEA induced cholangiocyte proliferation and OPN secretion (p<0.001 vs. controls). Cholangiocytes were OPN (+) in schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, p=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, p=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; p=0.001). Conclusions S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity.

Little is known about the action of laser rays on normal adipose cells. The present study attempts to observe the behavior of fatty cells submitted to laser therapy. Dorsal fat pads of normal adult rats were submitted to low-level laser irradiation applied locally through intact skin, with four different dose schedules (4, 8, 12, and 16 J/cm(2)), with a further group being sham-irradiated. Histology, morphometry, immunofluorescence, and electron microscopy were all used to analyze irradiated tissues. Changes were restricted to the brown fatty tissue, in which a tendency was shown for multivacuolar cells to be transformed into the unilocular type. The number of cells which exhibited enlargement and fusion of small vacuoles was greater in the 4- and 16-J/cm(2) groups (p<0.05). Increased vascular proliferation and congestion was another more evident finding in laser-treated animals compared to nontreated animals. Low-level laser rays cause brown adipose fat droplets to coalesce and fuse. Additionally, they stimulated proliferation and congestion of capillaries in the extracellular matrix.

BackgroundSymptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.Methodology/Principal FindingsSerum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7–11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.Conclusions/SignificanceS. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.