Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative determination of Schistosoma mansoni infection was carried out on 1995 cane cutters of the Hippo Valley and Triangle Sugar Estates. A total of 315 cutters were chosen for the study on the basis of S. mansoni infection and lack of anti-schistosomal chemotherapy during the previous three years. Stool consistency and blood and mucus in stool were determined for all the infected cutters. Overt and occult blood in stool was detected in a significantly high number of infected people compared to the control subjects (chi 2 p less than 0.001). However, the blood loss was found to have no anaemia-producing effect as determined by haemoglobin and red blood cell counts. Watery stool was prevalent among people with egg output exceeding 500 eggs per gram of stool. Mucus in stool was found to be more prevalent among infected people compared to the control subjects but the difference was not significant (p greater than 0.05). Symmer's periportal fibrosis (PPF) of various degrees of severity was detected in 47% of the infected people and grade one liver fibrosis was found in 7.5% of the control subjects (p less than 0.0001). Some 54.5% of those infected complained of abdominal pains compared to 35% of uninfected controls (p less than 0.01). There was a significant difference in the rate of absenteeism from work due to abdominal pains and diarrhoea among the infected and uninfected cane cutters (p less than 0.02).
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PMID:Morbidity due to Schistosoma mansoni among sugar-cane cutters in Zimbabwe. 195 65

Twenty-eight Zairean patients with Schistosoma mansoni infection were investigated and treated with praziquantel. Of these, 22 were re-examined 18 months later and 13 were found to be re-infected. Eighteen uninfected Zaireans were monitored concurrently to control for variations unrelated to schistosomiasis. Pathophysiological changes related to liver fibrosis were assessed by the determination of serum cholylglycine and procollagen-III-peptide. Circulating T-cell subsets were quantitated, and shedded T-cell antigens were measured in sera. In patients initially presenting with hepatomegaly, the biochemical indicators for egg-induced immunopathology became normal after therapy and remained normal even after re-infection, when the parasite load attained about 50% of the pretreatment level. Among T-cell phenotypes, CD4+ cells transiently increased by three months after treatment, but after 18 months the CD4/CD8 ratios both in patients then re-infected and in those not re-infected had reverted to the respective balances which had been observed at the start of the investigation. Both soluble CD8 antigen and interleukin 2 receptor in patients' sera were significantly elevated throughout the study period. The results indicate a dissociation of factors regulating fibrogenesis and immunomodulation after treatment and re-infected.
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PMID:Re-infection in human schistosomiasis mansoni: a prospective field study 18 months after praziquantel therapy. 212 97

Schistosomiasis mansoni is characterized by granulomatous inflammations, deposition of collagen, and irreversible liver fibrosis. In chronic infections fibrosis is cumulative, while collagen synthesis and degradation are diminished. In the present study, we compared collagenase, elastase, and nonspecific neutral protease (NP) activities in isolated vigorous (8-week infection) and immunomodulated (18-20-week infection) liver granulomas. Enzyme activity was localized in the adherent macrophage (greater than 90% purity) and nonadherent eosinophil-rich (greater than 70% purity) cell fractions of the disaggregated granulomas. Collagenase levels were approximately two times higher in granuloma extracts and explant culture supernates of the vigorous as compared with the immunoregulated lesions. However, macrophages and eosinophil-rich cells derived from either type of granuloma secreted similar enzyme levels. Elastase and NP levels in granuloma extracts and secretions of adherent macrophage and eosinophil-rich cell populations were the same in vigorous or immunomodulated lesions but were significantly greater in vigorous granuloma culture supernates. In addition to active collagenase, trypsin activatable latent collagenase was also present in both types of granuloma extracts, explants and eosinophil-rich cell culture supernates. Latent elastase was also detected in granuloma extracts or explant supernates but was absent from secretions of granuloma cells. These results suggest that the presence of active neutral proteases within granulomas may play an important role in the regulation of tissue repair and remodeling during the fibrotic process.
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PMID:Collagenase, elastase, and nonspecific protease production by vigorous or immunomodulated liver granulomas and granuloma macrophages/eosinophils of S mansoni-infected mice. 299 60

The collagen content of the liver, measured as hepatic hydroxyproline, was examined for a period of up to 52 weeks following Schistosoma mansoni infection. Hepatic fibrosis was much more marked in S. mansoni-infected mice of an outbred ICR strain than in C57BL/6J mice, while C3H/HeN mice occupied an intermediate position. The marked difference in hepatic fibrosis in ICR and C57BL/6J mice correlated with more rapid in vitro synthesis of collagen by the livers of infected ICR mice. Strains of mice exhibiting high and low levels of fibrosis provide an excellent tool for examining mechanisms of murine schistosomal hepatic fibrosis and its genetic regulation.
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PMID:Differences in hepatic fibrosis in ICR, C3H, and C57BL/6 mice infected with Schistosoma mansoni. 665 Jul 37

Between August 1988 and July 1990, 176 patients with Schistosoma mansoni infection attending the University Hospital, Recife, Brazil received a complete clinical examination including stool examination for intestinal parasites, liver function tests, and ultrasonography. The majority were also examined by upper digestive tract endoscopy. The clinical distribution of their disease was as follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high, with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation between the degree of hepatic periportal fibrosis and the clinical stage of disease (P < 0.0001). Of the patients with the intestinal form of schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3% of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic disease had grade II or grade III fibrosis. The degree of liver fibrosis detected by ultrasonography correlated with the degree of oesophageal varices detected by endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior to liver biopsy, permitting a dynamic approach to the study of schistosomiasis morbidity with precise diagnosis and simple sequential follow-up of post-treatment results.
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PMID:An ultrasonographic study of liver fibrosis in patients infected with Schistosoma mansoni in north-east Brazil. 826 9

In clinical practice, Octreotide has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of Octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A&B) subdivided each, into normal control, infected control, Octreotide treated, Praziquantel treated and Octreotide with Praziquantel treated subgroups. Groups A & B were sacrificed at the 8th week and the 18th week post infection respectively. By analysis of the obtained results, Octreotide has induced reduction of the portal pressure, the weight of the spleen and the liver, the number of liver egg load, granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum PIIINP, serum laminin and tissue collagen using sirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with Octreotide in association with Praziquantel revealed better results than the subgroups treated with Praziquantel alone. Data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastuctural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.
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PMID:Octreotide decreases connective tissue formation and improves vascular changes associated with hepatic schistosomiasis. 961 40

In clinical practice, octreotide (CAS 83150-76-9) has its greatest impact in the management of bleeding varices. The present work is the first one which was undertaken to investigate the possible use of octreotide as an antifibrotic agent and to study its effect on hepatic vasculature in Schistosoma mansoni infection. The material of this investigation consisted of two groups of albino mice (A, B), subdivided each into normal control, infected control, subgroups treated with octreotide, praziquantel (CAS 55268-74-1), and a combination of octreotide and praziquantel. Groups A and B were sacrificed at the 8th week and the 18th week post infection, respectively. By analysis of the obtained results, octreotide induced a reduction of the portal pressure, the weight of the spleen and the liver, the liver egg load (number of eggs) granuloma size and cellularity, and of the degree of hepatic fibrosis quantified by serum N-terminal peptide of type III procollagen in serum, serum laminin and tissue collagen using a Picrosirius red dye assay. Moreover, the biochemical state of hepatocytes has been improved. The subgroups treated with octreotide in association with praziquantel revealed better results than the subgroups treated with praziquantel alone. These obtained data were analysed in terms of histological extent of liver fibrosis in sections stained with Masson trichrome and sirius red, hepatocytic and sinusoidal changes at an ultrastructural level and by immunohistochemical demarcation of endothelial cells of blood vessels through the determination of factor VIII-related antigen. The promising results detected in this study may encourage to further investigate the positive findings of this drug with the intention of its possible application on a clinical level.
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PMID:Effect of octreotide on the pathology of hepatic schistosomiasis. 974 16

Liver fibrosis is a serious complication of schistosomiasis infection, is associated with increased amounts of collagen and the collagen cross-link, pyridinoline. Non-invasive markers of liver fibrosis have been developed. Serum and urinary markers of collagen synthesis and degradation have been studied to assess the balance between collagen synthesis, measured with markers of collagen synthesis such as amino-terminal propeptide of type III procollagen (PIIINP), and markers of degradation such as pyridinoline or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP). It has been shown that mice infected with Schistosomiasis mansoni excrete excess pyridinoline cross links in urine and this was correlated with the collagen content of granulomas from the liver. Treatment of infected mice with an anti-parasitic drug, praziquantel, decreased the collagen content of parenchyma and excretion of pyridinoline in the urine. Although the connective tissue protein, elastin, is present in the liver, the role of elastin in liver fibrosis has not been investigated. However, it has been shown that the urinary concentration of elastin specific crosslinks, desmosine and isodesmosine, as well as the urinary concentration of the collagen crosslink, pyridinoline, correlated well with liver fibrosis score in biopsy specimens from patients with liver disease secondary to hepatitis C virus and alcohol. Each biopsy specimen was reviewed by two pathologists who were blinded as to the clinical data. The pathological evaluation generated scores for both inflammation and fibrosis. No correlation was seen between the urinary markers and inflammation scores. The measurement of non-invasive markers of collagen synthesis and degradation may be useful in monitoring the reversal of fibrosis following therapeutic intervention in schistosome infections.
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PMID:Potential use of collagen and elastin degradation markers for monitoring liver fibrosis in schistosomiasis. 1099 25

In several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection-induced liver fibrosis, we show that interleukin (IL)-13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL-4 production was preserved in IL-13-deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection. Significant fibrosis develops in all infected mice, although the magnitude of the response varies widely in inbred mice. C3H/HeN, BALB/c, and C57BL/6 mice develop high, intermediate, and low levels of fibrosis, respectively. Despite these differences, IL-13 antagonism resulted in a marked amelioration of fibrosis in all strains. The fibrotic mechanism in the high- and low-responder strains was unrelated to their tissue eosinophil or mast cell responses, but did correlate with their patterns of IL-13, IL-10, and interferon gamma (IFN-gamma) mRNA expression. Indeed, severe fibrosis correlated with a high IL-13 and low IFN-gamma/IL-10 mRNA response. Because fibrotic diseases are typically progressive disorders, an important issue was to determine whether IL-13 inactivation might be used to treat an established and ongoing fibrotic disease. Here, IL-13 antagonism was highly efficacious, even after fibrosis and the Th2 cytokine response were firmly established. These studies demonstrate the central role played by IL-13 in fibrogenesis and suggest that therapeutic approaches aimed at disrupting the IL-13 pathway will be highly effective at preventing fibrotic disease caused by chronic Th2-mediated inflammatory reactions.
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PMID:Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. 1148 12

Hepatic fibrosis is the hallmark of Schistosoma mansoni infection and often results in portal hypertension and bleeding from esophageal varices. The fibrotic process is highly dependent on type 2 cytokines, yet their role in the regulation of extracellular matrix remodeling genes remains largely unknown. Here, we examined the expression of matrix metalloproteases (MMP) -2, -3, -9, -12, and -13 and their inhibitors, tissue inhibitor of metalloproteases (TIMP) -1, -2, and -3, in the livers of infected mice and correlated their expression profiles with fibrosis and type 2 cytokine production. Expression of MMP-2, -3, -9, -12, and -13 and of TIMP-1 and -2 mRNA rapidly increased at the onset of egg laying in infected mice, while TIMP-3 was unchanged. Because TIMP are presumed to be important regulators of the extracellular matrix, and their expression correlated with the development of fibrosis, we studied their role in fibrogenesis by infecting TIMP-1- and TIMP-2-deficient mice. Strikingly, our data revealed no role for TIMP-1 or -2 in the fibrotic pathology induced by S. mansoni eggs. Because of these findings, we infected IL-10/IFN-gamma-deficient mice that develop an exaggerated fibrotic response to determine whether changes in type 2 cytokine dominance influence the pattern of MMP and TIMP expression. Fibrosis and type 2 cytokine production correlated with increased MMP-2/MMP-9 vs TIMP-1/TIMP-2 expression. These data, in addition to our knockout studies, demonstrate that TIMP-1/TIMP-2 play no essential role in fibrogenesis in schistosomiasis. Indeed, our findings suggest that inhibiting profibrotic cytokines or specific MMP may be a more effective strategy to ameliorate fibrotic pathology.
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PMID:Regulation of hepatic fibrosis and extracellular matrix genes by the th response: new insight into the role of tissue inhibitors of matrix metalloproteinases. 1173 22


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