Search results for "alpha 1-Antitrypsin"
showing 10 items of 41 documents
Dual proteotoxic stress accelerates liver injury via activation of p62‐Nrf2
2021
Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and H…
Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.
2018
ObjectiveHomozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants (‘Pi*Z’ and ‘Pi*S’), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse.DesignWe analysed multicentric case–control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed.ResultsThe Pi*Z variant presented in 13.8% of p…
Oxidative Stress and Endoplasmic Reticulum Stress in Rare Respiratory Diseases
2021
Several studies have shown that some rare respiratory diseases, such as alpha-1 antitrypsin deficiency (AATD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD) present oxidative stress (OS) and endoplasmic reticulum (ER) stress. Their involvement in these pathologies and the use of antioxidants as therapeutic agents to minimize the effects of OS are discussed in this review.
Accelerated telomere attrition in children and teenagers with α1-antitrypsin deficiency.
2016
Numerous studies have shown that oxidative stress accelerates telomere shortening in several lung pathologies. Since oxidative stress is involved in the pathophysiology of α1-antitrypsin deficiency (AATD), we hypothesised that telomere shortening would be accelerated in AATD patients. This study aimed to assess telomere length in AATD patients and to study its association with α1-antitrypsin phenotypes.Telomere length, telomerase activity, telomerase reverse transcriptase (hTERT) expression and biomarkers of oxidative stress were measured in 62 children and teenagers (aged 2–18 years) diagnosed with AATD and 18 controls (aged 3–16 years).Our results show that intermediate-risk (MZ; SZ) and …
Liver cirrhosis associated with heterozygous alpha-1-antitrypsin deficiency type Pi MS and autoimmune features.
1995
Patients with homozygous protease inhibitor (Pi) type ZZ or a few rare M-like types may develop liver cirrhosis due to intracellular storage of alpha-antitrypsin (AAT), whereas some patients with heterozygous Pi MZ or SZ normally present with transient abnormal liver function tests in childhood. We report a 42-year-old obese patient who developed liver cirrhosis in association with heterozygous Pi MS (AAT) deficiency. Immunohistological and electron microscope examination showed storage of AAT in the hepatocytes. Interestingly, autoimmune features in this patient suggest that abnormal immune responses may contribute to the pathology of chronic liver disease.
Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease
1988
In a six-month multicenter feasibility and safety study, 20 patients, who all had a congenital deficiency of alpha-1-protease inhibitor (A1PI) of the PiZ phenotype accompanied by a chronic obstructive lung disease, were treated with human-plasma-derived A1PI. A weekly dose of 60 mg/kg, administered intravenously, was shown to be sufficient to maintain patient serum levels above the threshold limit of 35 percent, the serum level of healthy persons of the MZ phenotype. This is supposed to be the minimal effective level for protection against the elastolytic attack of the lung and, therefore, satisfies one of the most important criteria of feasibility of long-term replacement therapy. The glob…
Antiinflammatory treatment and intestinal alpha 1-antitrypsin clearance in active Crohn's disease.
1985
Intestinal alpha 1-antitrypsin clearance was quantified in 17 patients with clinically active Crohn's disease before and after a six-week period of treatment with sulfasalazine and methylprednisolone. Before the study, alpha 1-antitrypsin clearance and, hence, enteric protein loss was elevated as being above control values in 16 patients. After therapy, clearance values decreased in 11 and were normalized in five patients. Serum albumin level was normalized in 11 of 12 patients who had hypoalbuminemia before the study. Clinical condition was improved in all but 1 patient after treatment. There was no close correlation between alpha 1-antitrypsin clearance and disease activity index. These r…
Impact of Different Texture of Polypropylene Mesh on the Inflammatory Response
2008
Over the past decade, hernia surgery has undergone a considerable transformation with the use of prosthetic materials. The most used polypropylene meshes induce a rapid acute inflammatory response followed by chronic foreign body reaction. Many factors influence this response such as density, size, physical characteristics, different texture and porosity of each biomaterial. The aim of this study is to assess whether the implant of monofilament or multifilament meshes, in the inguinal hernioplasty, determine a different inflammatory response. Thirty-two male patients were included in the study and were randomly divided into two groups. In the first group (MO) inguinal hernioplasty was perf…
Tension-free hernia repair is associated with an increase in inflammatory response markers against the mesh.
2000
Abstract Background: The purpose of this study was to evaluate the involvement of inflammatory mediators in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia repair (BH). Methods: Thirty patients male with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent LH or BH. Peripheral venous bloods samples were collected 24 hours prior to surgery and then 6, 24, 48 and 168 hours postoperatively. Results: We present evidences that LH patients showed a higher increased serum level of fibrinogen, C-reactive protein, alpha-1-antitrypsin, and interle…
Increased Levels of Elastase and α1-Antitrypsin in Sputum of Asthmatic Patients
1998
Asthma and chronic bronchitis are inflammatory diseases associated with remodeling of the extracellular matrix (ECM). Elastin, a major component of the ECM in the airways, has been previously found to be disrupted in asthma and chronic bronchitis. This study was aimed at evaluating whether elastin disruption might be associated with an imbalance between elastase (active and total) and alpha1-proteinase inhibitor (alpha1-PI), the main inhibitor of elastase. We measured elastase and alpha1-PI in induced sputum obtained from 16 control subjects, 10 healthy smokers, 19 asthmatic patients, and 10 chronic bronchitis patients. We also assessed the possible origin of elastase, evaluating its levels…