Oxidative stress in fibroblasts from patients with pseudoxanthoma elasticum: possible role in the pathogenesis of clinical manifestations

2005 ◽  
Vol 208 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Ivonne Pasquali-Ronchetti ◽  
Maria Inmaculada Garcia-Fernandez ◽  
Federica Boraldi ◽  
Daniela Quaglino ◽  
Dealba Gheduzzi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum

scholarly journals Disruption of Abcc6 Transporter in Zebrafish Causes Ocular Calcification and Cardiac Fibrosis

2020 ◽  
Vol 22 (1) ◽  
pp. 278
Author(s):  
Jianjian Sun ◽  
Peilu She ◽  
Xu Liu ◽  
Bangjun Gao ◽  
Daqin Jin ◽  
...  
Keyword(s):  
Vitamin K ◽  
Cardiac Fibrosis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Matrix Gla Protein ◽  
Ectopic Calcification ◽  
Transcription Activator ◽  
Multisystem Disorder ◽  
Ectopic Mineralization ◽  
Extensive Calcification

Pseudoxanthoma elasticum (PXE), caused by ABCC6/MRP6 mutation, is a heritable multisystem disorder in humans. The progressive clinical manifestations of PXE are accompanied by ectopic mineralization in various connective tissues. However, the pathomechanisms underlying the PXE multisystem disorder remains obscure, and effective treatment is currently available. In this study, we generated zebrafish abcc6a mutants using the transcription activator-like effector nuclease (TALEN) technique. In young adult zebrafish, abcc6a is expressed in the eyes, heart, intestine, and other tissues. abcc6a mutants exhibit extensive calcification in the ocular sclera and Bruch’s membrane, recapitulating part of the PXE manifestations. Mutations in abcc6a upregulate extracellular matrix (ECM) genes, leading to fibrotic heart with reduced cardiomyocyte number. We found that abcc6a mutation reduced levels of both vitamin K and pyrophosphate (PPi) in the serum and diverse tissues. Vitamin K administration increased the gamma-glutamyl carboxylated form of matrix gla protein (cMGP), alleviating ectopic calcification and fibrosis in vertebrae, eyes, and hearts. Our findings contribute to a comprehensive understanding of PXE pathophysiology from zebrafish models.

Role of antioxidant therapy in patients with moderate and severe COVID-19

2021 ◽  
Vol 19 (1) ◽  
pp. 159-164
Author(s):  
E.K. Shavarova ◽  
◽  
E.R. Cazakhmedov ◽  
M.V. Alekseeva ◽  
L.G. Ezhova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervention Group ◽  
Clinical Manifestations ◽  
Organ Damage ◽  
Control Group ◽  
Reactive Protein ◽  
Virus Rna ◽  
Active Intervention Group ◽  
Group 2 ◽  
Novel Coronavirus

The coronavirus disease COVID-19 is characterized by high mortality and the lack of effective etiotropic therapy. Activation of oxidative stress may be one of the links in the pathogenesis of organ damage of this infection. Objective. To assess the ability of Mexidol® to influence the rate of clinical improvement in pneumonia caused by the SARSCoV-2 virus in hospitalized patients with the novel coronavirus disease COVID-19 and concomitant discirculatory encephalopathy. 62 patients over the age of 18 years with confirmed new coronavirus disease COVID-19 according to computed tomography (CT) of the lungs (stages CT1, CT2, CT3) and PCR of a swab from the nasopharynx and oropharynx for SARS-CoV-2 virus RNA were included. After randomization patients of group 1 received an infusion of Mexidol® at a dose of 1000 mg/day, patients of group 2 – an infusion of isotonic sodium chloride solution for 7 days. Compared with the control group, the patients receiving Mexidol® therapy showed a significantly more pronounced decrease in body temperature, a tendency towards a decrease in the severity of shortness of breath. In the Mexidol® group, the concentration of superoxidedismutase did not change, while in the control group there was a tendency to its decrease, C-reactive protein decreased 2.2 times more than in the control group (p = 0.09). There was a tendency for a more rapid decrease in ferritin in the active intervention group. Mexidol® therapy can have a positive effect on the clinical manifestations and severity of laboratory-inflammatory syndrome in patients with the new coronavirus disease COVID-19. Key words: coronavirus disease COVID-19, oxidative stress, Mexidol

scholarly journals Pseudoxanthoma elasticum and skin: Clinical manifestations, histopathology, pathomechanism, perspectives of treatment

2015 ◽  
Vol 4 (3) ◽  
pp. 113-122 ◽  
Author(s):  
Barbara Marconi ◽  
Ivan Bobyr ◽  
Anna Campanati ◽  
Elisa Molinelli ◽  
Veronica Consales ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum

scholarly journals Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1666
Author(s):  
Zijing Liu ◽  
Lihua Dong ◽  
Zhuangzhuang Zheng ◽  
Shiyu Liu ◽  
Shouliang Gong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Clinical Symptoms ◽  
Clinical Manifestations ◽  
Serious Adverse Event ◽  
Oral Infections ◽  
Normal Tissues ◽  
Radiation Induced ◽  
Swallowing Muscles

Radiation therapy is a common treatment for head and neck cancers. However, because of the presence of nerve structures (brain stem, spinal cord, and brachial plexus), salivary glands (SGs), mucous membranes, and swallowing muscles in the head and neck regions, radiotherapy inevitably causes damage to these normal tissues. Among them, SG injury is a serious adverse event, and its clinical manifestations include changes in taste, difficulty chewing and swallowing, oral infections, and dental caries. These clinical symptoms seriously reduce a patient’s quality of life. Therefore, it is important to clarify the mechanism of SG injury caused by radiotherapy. Although the mechanism of radiation-induced SG injury has not yet been determined, recent studies have shown that the mechanisms of calcium signaling, microvascular injury, cellular senescence, and apoptosis are closely related to oxidative stress. In this article, we review the mechanism by which radiotherapy causes oxidative stress and damages the SGs. In addition, we discuss effective methods to prevent and treat radiation-induced SG damage.

scholarly journals Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Speranza Rubattu ◽  
Maurizio Forte ◽  
Salvatore Raffa
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Stress Level ◽  
Mononuclear Cells ◽  
Pathological Condition ◽  
Clinical Manifestations ◽  
Therapeutic Interventions ◽  
Oxidative Stress Level ◽  
The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

scholarly journals ALOX5 , LPA , MMP9 and TPO gene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

2020 ◽  
Vol 7 (1) ◽  
pp. 190775
Author(s):  
Rafael Camacho-Mejorado ◽  
Rocío Gómez ◽  
Luisa E. Torres-Sánchez ◽  
Esther Alhelí Hernández-Tobías ◽  
Gino Noris ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Native Americans ◽  
Gene Polymorphisms ◽  
Clinical Manifestations ◽  
Cross Sectional Study ◽  
Middle Aged ◽  
Cross Sectional ◽  
Healthy Group ◽  
And Gender ◽  
And Oxidative Stress

Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group ( n = 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included. ALOX5 , LPA , MMP9 and TPO gene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution of ALOX5 , LPA , MMP9 and TPO polymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.

Effects of an oral superoxide dismutase enzyme supplementation on indices of oxidative stress, proviral load, and CD4:CD8 ratios in asymptomatic FIV-infected cats

2008 ◽  
Vol 10 (5) ◽  
pp. 423-430 ◽  
Author(s):  
Craig B. Webb ◽  
Tracy L. Lehman ◽  
Kelly W. McCord
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Proviral Load ◽  
Clinical Manifestations ◽  
Cell Types ◽  
Enzyme Concentration ◽  
Infected Group ◽  
Control Group ◽  
Post Inoculation ◽  
Antioxidant Supplementation

This study was designed to test the effect of antioxidant supplementation on feline immunodeficiency virus (FIV)-infected felines. Six acutely FIV-infected cats (≥16 weeks post-inoculation) were given a propriety oral superoxide dismutase (SOD) supplement (Oxstrin; Nutramax Laboratories) for 30 days. Following supplementation, the erythrocyte SOD enzyme concentration was significantly greater in the supplemented FIV-infected group than the uninfected control group or the unsupplemented FIV-infected group. The CD4+ to CD8+ ratio increased significantly (0.66–0.88) in the SOD supplemented FIV-infected cats but not in the unsupplemented FIV-infected cats. Proviral load and reduced glutathione (GSH) levels in leukocyte cell types did not change significantly following supplementation. Antioxidant supplementation resulted in an increase in SOD levels, confirming the oral bioavailability of the compound in FIV-infected cats. This result warrants further investigation with trials of antioxidant therapy in FIV-infected cats that are showing clinical manifestations of their disease, as well as in other feline patients where oxidative stress likely contributes to disease pathogenesis, such as diabetes mellitus and chronic renal failure.

scholarly journals Case Report: Pseudoxanthoma elasticum

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 9
Author(s):  
Catarina Lucas ◽  
João Aranha ◽  
Isabel da Rocha ◽  
Domingos Sousa
Keyword(s):  
Case Report ◽  
Genetic Analysis ◽  
Histological Analysis ◽  
Clinical Manifestations ◽  
Pseudoxanthoma Elasticum ◽  
Cervical Region ◽  
Elastic Fibres ◽  
Incurable Disease ◽  
Initial Stage ◽  
Retinal Complications

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and cardiovascular system. At an initial stage, the skin usually exhibits distinctive lesions and subsequently extra-dermal manifestations. The diagnosis is based on clinical manifestations, histological analysis of the lesions and genetic analysis. This is a case report of a 12-year-old child complaining of painless, mildly itchy yellow papules in the cervical region with 1 year of evolution. PXE is currently an incurable disease and has a favourable prognosis when cardiovascular and retinal complications are prevented and monitored.

scholarly journals Functional Analysis of the FOXO3 Gene on the Induction of Fetal Hemoglobin in K562 Cells

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2390-2390
Author(s):  
Flávia Peixoto Albuquerque ◽  
Pedro Luis Franca-Neto ◽  
Rafael de Oliveira Franca ◽  
Aderson da Silva Araujo ◽  
Fernando F. Costa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Expression System ◽  
Clinical Manifestations ◽  
Constitutive Expression ◽  
Fetal Hemoglobin ◽  
No Production ◽  
Clinical Prognosis ◽  
Expression Levels

Abstract The β-hemoglobinopathies are known as genetic disorders of high impact and wide distribution worldwide, with chronic and variable clinical prognosis. These pathologies have their symptoms and sequelae alleviated by increased levels of fetal hemoglobin (HbF; α2γ2). The Hydroxyurea, a drug used for the treatment of β-hemoglobinopathies, is effective for the maintenance and control of the development of the main clinical manifestations, however, it needs some prerequisites for its use, which indicates the need for new therapeutic approaches for this group of individuals. The family of Forkhead Box O transcription factors (FOXO), composed of FOXO1, FOXO3, FOXO4 and FOXO6, plays a key role in the regulation of several biological processes such as: regulation of the cell cycle, modulation oxidative stress, regulation mechanisms of response to DNA damage, controlling apoptosis and inflammatory response. Among members of the FOXO family, FOXO3 has been described as a physiological regulator of the erythroid maturation process and indicated as a positive regulator of HbF levels. In the present work, we evaluated the expression levels of the FOXO3 gene in patients with hemoglobinopathies and, in an attempt to better understand the pathophysiology of the disease, we performed a subcloning of the FOXO3 gene into a lentiviral expression system for its constitutive expression in vitro and subsequent evaluation of its activity as a possible transcription factor for γ globin genes (HBG1 and HBG2). In our clinical study, FOXO3 expression was significantly higher in patients with sickle cell anemia when compared to healthy donors (HbAA) (P <0.001) . In addition, a differential expression of FOXO3 was associated with the development of lower limb ulcer (P <0.005). Although we observed a tendency to increase FOXO3 expression in patients with 2 or more clinical manifestations, this association was not statistically significant (P = 0.06). The same was observed when we compared the number of clinical complications presented by patients last year with HbF levels: patients with 2 or more complications had lower levels of HbF, although this difference did not reach statistical significance (P = 0.182). There was no correlation between FOXO3 expression levels and HbF dosage (r = -0.12). Because of the activity of the FOXO3 gene in the control of oxidative stress, experiments were performed to evaluate the ROS and NO rates in the cell culture and a significant role was found, the FOXO3 increasing NO production (P = 0.0001) as well as in control of ROS produced in mitochondria. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document