Acid Hydrolase Activities and Lysosomal Integrity in Liver Biopsies from Patients with Iron Overload

1976 ◽  
Vol 50 (1) ◽  
pp. 75-78 ◽  
Author(s):  
T. J. Peters ◽  
Carol A. Seymour
Keyword(s):  
Iron Overload ◽  
Liver Diseases ◽  
Cell Damage ◽  
Acid Hydrolase ◽  
Chronic Liver Diseases ◽  
Acid Hydrolases ◽  
Control Subjects ◽  
Essentially Normal ◽  
Patient Groups ◽  
Liver Biopsies

1. Iron, acid phosphatase and N-acetyl-β-glucosaminidase were assayed in liver biopsies from control subjects and patients with primary and secondary haemochromatosis. 2. The activities of the lysosomal enzymes were significantly higher in liver biopsies from patients with iron overload than in those from other patient groups. 3. Lysosomes from the livers of patients with iron overload were strikingly more fragile than those of control subjects as demonstrated by assays of latent and sedimentable N-acetyl-β-glucosaminidase. 4. Lysosomal integrity was essentially normal in biopsies from patients with a wide variety of chronic liver diseases. 5. It is suggested that iron accumulation damages the lysosomal membrane, releasing acid hydrolases into the cytoplasm and thus initiating cell damage.

scholarly journals Quantitative Analysis of Aldolase A mRNA in Liver Discriminates between Hepatocellular Carcinoma and Cirrhosis

2000 ◽  
Vol 46 (7) ◽  
pp. 901-906 ◽  
Author(s):  
Giuseppe Castaldo ◽  
Giuseppe Calcagno ◽  
Raffaella Sibillo ◽  
Rosario Cuomo ◽  
Gerardo Nardone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Quantitative Analysis ◽  
Hepatitis C ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Liver Biopsies ◽  
Aldolase A

Abstract Background: Chronic liver diseases can progress to cirrhosis and to hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic evolution of cirrhosis is critical. To this aim, we used a noncompetitive reverse transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from patients with chronic liver diseases at different stages. Methods: We studied 12 patients with hepatocellular carcinoma, 19 patients affected by chronic hepatitis C or cirrhosis, and 7 healthy controls. Aldolase A mRNA was reverse-transcribed to cDNA, which was then amplified by PCR. The amplified segments were “read” with a novel dot-blot procedure. A calibrator with the same sequence, synthesized in vitro using a T7 phage promoter, was processed at scalar dilutions in parallel to the target samples to generate a calibration curve and so quantify the target mRNA (detection limit, 0.03 amol; linearity spanning five orders of magnitude). Results: Aldolase A mRNA was ∼10-fold higher in liver biopsies from patients with hepatocellular carcinoma vs patients with chronic hepatitis C or cirrhosis, and healthy individuals. Furthermore, aldolase A mRNA concentrations were 1.2- to 21.3-fold higher in 12 liver biopsies compared with the paired surrounding cirrhotic tissue. Conclusions: The quantitative analysis of liver tissue aldolase A mRNA differentiates between nonneoplastic chronic liver diseases and hepatocellular carcinoma, which suggests that it has diagnostic potential.

scholarly journals Thrombin Generation in Chronic Liver Diseases—A Pilot Study

Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 550
Author(s):  
Liliana Vecerzan ◽  
Ariela Olteanu ◽  
Ionela Maniu ◽  
Adrian Boicean ◽  
Călin Remus Cipăian ◽  
...  
Keyword(s):  
Liver Disease ◽  
Pilot Study ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Thrombin Generation ◽  
Chronic Liver ◽  
Control Group ◽  
Coagulation Disorders ◽  
Chronic Liver Diseases ◽  
Control Subjects

The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.

scholarly journals Multispectral Imaging Differentiates Unique Macrophage Profiles in Patients with Distinct Chronic Liver Diseases

2019 ◽  
Author(s):  
Omar A. Saldarriaga ◽  
Adam L. Booth ◽  
Benjamin Freiberg ◽  
Jared Burks ◽  
Santhoshi Krishnan ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Multispectral Imaging ◽  
Treatment Strategies ◽  
Spectral Imaging ◽  
Spectral Unmixing ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Liver Biopsies ◽  
Anti Inflammatory

ABSTRACTIntrahepatic macrophages influence the composition of the microenvironment, host immune response to liver injury, and development of fibrosis. Compared to stellate cells, the role of intrahepatic macrophages in the development of fibrosis remains ill defined. Multispectral imaging allows detection of multiple markers in situ in human formalin-fixed, paraffin-embedded tissue. This cutting-edge technology is ideal for analyzing human liver tissues since it allows spectral unmixing of fluorophore signals, subtraction of auto-fluorescence, and preserves architecture and the in vivo hepatic milieu. We analyzed resident Kupffer cells (CD68+), monocyte-derived macrophages (Mac387+), pro-fibrogenic macrophages (CD163+), and co-expression of pro-inflammatory (CD14) and anti-inflammatory (CD16) markers in liver biopsies from patients with hepatitis C virus (HCV) and different stages of fibrosis. Liver biopsies with advanced fibrosis showed increased accumulation of CD163+, MAC387+ and CD68+ macrophages in the portal tracts when compared to those with minimal fibrosis. Imaging software generated t-distributed stochastic neighbor embedding (t-SNE) plots and phenotype matrices that facilitated comparison of macrophage profiles. These included monocyte-derived (CD68+/Mac387+) and pro-fibrotic/anti-inflammatory (CD163+/CD16+) phenotypes. We established that the utility of this platform could be extended to liver biopsies from patients with other chronic liver diseases including nonalcoholic steatohepatitis and autoimmune hepatitis. Each disease exhibited a unique profile after spectral imaging analysis and this platform holds the potential to identify patients predisposed to progressive liver disease based on the macrophage composition. In summary, spectral imaging is a powerful tool that enables analysis of macrophage profiles in different types of chronic liver diseases and has potential to change the manner in which we evaluate liver biopsies leading to more personalized treatment strategies.

PPARα Agonist Fenofibrate Attenuates Iron Induced Liver Injury in Mice by Modulating the Sirt3 and β-catenin Signaling

2021 ◽  
Author(s):  
Ashok Mandala ◽  
William J Chen ◽  
Austin Armstrong ◽  
Milan R Malhotra ◽  
Sanmathi Chavalmane ◽  
...  
Keyword(s):  
Liver Injury ◽  
Iron Overload ◽  
Liver Diseases ◽  
Critical Role ◽  
Chronic Liver ◽  
Iron Accumulation ◽  
Hepatic Iron ◽  
Chronic Liver Diseases ◽  
Pparα Agonist

Iron accumulation is frequently associated with chronic liver diseases. However, our knowledge on how iron contributes to the liver injury is limited. Aberrant Wnt/β-catenin signaling is a hallmark of several hepatic pathologies. We recently reported that peroxisome proliferator activated receptor alpha (PPARα) agonist, fenofibrate prevents iron induced oxidative stress and β-catenin signaling by chelating the iron. Sirtuin3 (Sirt3), a type of NAD+-dependent deacetylase that plays a critical role in metabolic regulation was found to prevent ischemia reperfusion injury by normalizing the Wnt/β-catenin pathway. In the present study, we explored if fenofibrate prevents iron induced liver injury by regulating the Sirt3 and β-catenin signaling. In-vitro and in-vivo iron treatment resulted in the downregulation of PPARα, Sirt3, active β-catenin and its downstream target gene c-Myc in the mouse liver. Pharmacological activation of Sirt3, both invitro and in vivo, by Honokiol (HK), a known activator of Sirt3, abrogated the inhibitory effect of iron overload on active β-catenin expression and prevented the iron induced upregulation of αSMA and TGFβ expression. Intrinsically, PPARα KO mice showed significant downregulation of hepatic Sirt3 levels. In addition, treatment of iron overload mice with PPARα agonist fenofibrate reduced hepatic iron accumulation and prevented iron induced downregulation of liver Sirt3 and active β-catenin, mitigating the progression of fibrosis. Thus, our results establish a novel link between hepatic iron and PPARα, Sirt3 and β-catenin signaling. Further exploration on the mechanisms by which fenofibrate ameliorates iron induced liver injury likely has significant therapeutic impact on iron associated chronic liver diseases.

scholarly journals Iron Overload andHFEGene Mutations in Czech Patients with Chronic Liver Diseases

2012 ◽  
Vol 32 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Marketa Dostalikova-Cimburova ◽  
Karolina Kratka ◽  
Jaroslav Stransky ◽  
Ivana Putova ◽  
Blanka Cieslarova ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis C ◽  
Hepatitis B ◽  
Iron Overload ◽  
Alcoholic Liver Disease ◽  
Liver Diseases ◽  
Gene Mutations ◽  
Chronic Liver ◽  
Chronic Liver Diseases

The aim of the study was to identify the prevalence ofHFEgene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence ofHFEgene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency ofHFEgene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence ofHFEgene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies ofHFEmutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases butHFEmutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

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