scholarly journals Clotting Dysfunction in Sepsis: A Role for ROS and Potential for Therapeutic Intervention

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 88
Author(s):  
Maria Elisa Lopes-Pires ◽  
Jéssica Oliveira Frade-Guanaes ◽  
Gregory J. Quinlan
Keyword(s):  
Vascular Endothelium ◽  
Causes Of Death ◽  
Nitrosative Stress ◽  
Therapeutic Option ◽  
Healthcare Providers ◽  
Inflammatory Cells ◽  
Nitrogen Species ◽  
Homeostatic Control ◽  
Significant Challenge ◽  
Expansive Process

Sepsis is regarded as one of the main causes of death among the critically ill. Pathogen infection results in a host-mediated pro-inflammatory response to fight infection; as part of this response, significant endogenous reactive oxygen (ROS) and nitrogen species (RNS) production occurs, instigated by a variety of sources, including activated inflammatory cells, such as neutrophils, platelets, and cells from the vascular endothelium. Inflammation can become an inappropriate self-sustaining and expansive process, resulting in sepsis. Patients with sepsis often exhibit loss of aspects of normal vascular homeostatic control, resulting in abnormal coagulation events and the development of disseminated intravascular coagulation. Diagnosis and treatment of sepsis remain a significant challenge for healthcare providers globally. Targeting the drivers of excessive oxidative/nitrosative stress using antioxidant treatments might be a therapeutic option. This review focuses on the association between excessive oxidative/nitrosative stress, a common feature in sepsis, and loss of homeostatic control at the level of the vasculature. The literature relating to potential antioxidants is also described.

scholarly journals Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber’s Hereditary Optic Neuropathy Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Micol Falabella ◽  
Elena Forte ◽  
Maria Chiara Magnifico ◽  
Paolo Santini ◽  
Marzia Arese ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Optic Neuropathy ◽  
Nitrosative Stress ◽  
Mononuclear Cells ◽  
Reactive Oxygen ◽  
Leber’S Hereditary Optic Neuropathy ◽  
Oxygen Species ◽  
Nitrogen Species ◽  
Leber's Hereditary Optic Neuropathy ◽  
Hereditary Optic Neuropathy

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber’s hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

scholarly journals Angiographic patency of streptokinase in STEMI patients: smokers vs. non-smokers

2018 ◽  
Vol 6 (12) ◽  
pp. 3813
Author(s):  
Iranna Hirapur ◽  
Srinivas Setty ◽  
Ravindran Rajendran ◽  
Manjunath Nanjappa
Keyword(s):  
Myocardial Infarction ◽  
Causes Of Death ◽  
Therapeutic Option ◽  
Coronary Syndrome ◽  
Quit Smoking ◽  
Timi Flow ◽  
Younger Age ◽  
Single Centre Study ◽  
Streptokinase Therapy ◽  
St Elevation

Background: Acute coronary syndrome is one of the leading causes of death. Smoking is known to be associated  with many influencing factors for accelerating Myocardial Infarction (MI). In a country like India, Streptokinase (SK) is used as a leading therapeutic option for the treatment of ST elevation myocardial Infarction (STEMI). SK combines with plasminogen; this SK-plasminogen complex is responsible for fibrinolysis. The aim of this study was to determine angiographic patency after SK infusion in STEMI patients and comparison between smokers and non-smokers.Methods: In this observational, prospective and single-centre study conducted between September 2011 and April 2012, a total of 398 patients who were diagnosed with STEMI were included. Patients were divided in two groups i.e. smokers and non-smokers. The patients were treated with thrombolytic (streptokinase) therapy and evaluated for TIMI 3 flow by performing angiography within 72hours of thrombolysis with SK.Results: Of total 398 patients, 348 (87.4%) were male. The ratio of non-smokers and smokers was 1:2. Smokers were younger than the non-smokers (48.8±10.2 vs. 54.57±9.51). Post thrombolytic therapy, patients were evaluated for TIMI flow grades. Total of 202 patients achieved TIMI 3 flow, of which 157 were smokers and 45 were non-smokers.Conclusions: Smokers have relatively hypercoagulable state than non-smokers. Better outcome in smokers group may be because of younger age and lesser comorbidities. Smokers should be motivated and guided properly to quit smoking.

scholarly journals Understanding vernal keratoconjunctivitis in children

2020 ◽  
Vol 79 (1) ◽  
Author(s):  
Hlupheka L. Sithole
Keyword(s):  
Healthcare Providers ◽  
Public Health Problem ◽  
Inflammatory Cells ◽  
Relevant Information ◽  
Vernal Keratoconjunctivitis ◽  
Management Approach ◽  
Comprehensive Management ◽  
Causative Factors ◽  
History Of ◽  
Management Challenge

Background: Vernal keratoconjunctivitis (VKC) is a public health problem that mostly affects children in warm subtropical climates. Unfortunately, the causative factors of the disease are not clearly defined, thus posing a serious management challenge to healthcare providers. It is therefore argued that understanding the pathogenesis of the disease and how various inflammatory cells affect the conjunctiva and the cornea may assist in the management of the disease.Aim: As visual impairment and avoidable blindness are indicated, it is advisable for optometrists to understand the clinical presentation of this chronic condition in order to initiate appropriate interventions and/or immediate referrals where necessary.Methods: A thorough literature search was conducted on peer-reviewed publications on VKC and children. All material obtained were then studied and the information extracted was used to document relevant information required for understanding VKC amongst children.Results: The results in the studied material revealed that VKC was prevalent amongst children aged 2 to 18 years, affecting mostly male children of African and Indian origins. Different strategies of management of the disease have been proposed, including but not limited to explaining to parents the nature of the disease, environmental strategies and preventive measures as well as possible surgical intervention.Conclusion: In view of the nature of this disease, healthcare providers should therefore seek to understand the history of the patient better when such patients present for their first consultation in order to develop a comprehensive management approach.

Overexpression of the Superoxide Anion and NADPH Oxidase Isoforms 1 and 4 (NOX1 and NOX4) in Allergic Nasal Mucosa

2009 ◽  
Vol 23 (4) ◽  
pp. 370-376 ◽  
Author(s):  
Joon Hwan Moon ◽  
Tae Hoon Kim ◽  
Heung Man Lee ◽  
Seung Hoon Lee ◽  
Whan Choe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Allergic Rhinitis ◽  
Nadph Oxidase ◽  
Nasal Mucosa ◽  
Vascular Endothelium ◽  
Superoxide Anion ◽  
Nasal Polyps ◽  
Inflammatory Cells ◽  
Submucosal Glands ◽  
Cellular Source

Background The purpose of this study was to investigate the expression and distribution of superoxide anion, NADPH oxidase (NOX)1, and NOX4 in healthy, allergic nasal mucosa and nasal polyps to evaluate the possible influence of oxidative stress on the development of allergic rhinitis and nasal polyps. Methods The expression and distribution of superoxide anion, NOX1 and NOX4 were evaluated in healthy and allergic nasal mucosa and nasal polyps, using dihydroethidium fluorescence, semiquantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blot. Results NOX1 and NOX4 were localized mainly in the epithelial layer, submucosal glands, vascular endothelium, and inflammatory cells in healthy and allergic nasal mucosa and nasal polyps. The cellular source that generated superoxide anion is also localized in the epithelial cells, submucosal glands, vascular endothelium, and inflammatory cells, demonstrating the similar sites of expression of NOX1 and NOX4 in healthy and allergic nasal mucosa and nasal polyps. NOX1 and NOX4 mRNA and proteins and superoxide anions had increased levels of expression in allergic nasal mucosa and nasal polyps compared with healthy nasal mucosa. Conclusions These results indicate that NOX1 and NOX4 may play an important role in reactive oxygen species production, contributing to the oxidative stress in allergic rhinitis and nasal polyp tissues.

Abstract 5455: A Novel Haplotype on GCH1 Gene, Encoding GTP Cyclohydrolase 1, Regulates Vascular Biopterin Synthesis, eNOS Coupling and Vascular Redox in Human Vessels

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Charalambos Antoniades ◽  
Cheerag Shirodaria ◽  
Thomasz Guzik ◽  
Tim Van-Assche ◽  
Ravi Pillai ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Inflammatory Cells ◽  
Gtp Cyclohydrolase ◽  
Gene Encoding ◽  
Enos Uncoupling ◽  
Key Enzyme ◽  
Biopterin Synthesis ◽  
No Bioavailability ◽  
Gch1 Gene ◽  
O2 Production

Background: GTP cyclohydrolase (GTPCH) is a key enzyme in biopterins synthesis, while tetrahydrobiopterin (BH4) is a regulator of eNOS coupling in vascular endothelium. A novel haplotype in GCH1 gene, combining dbSNPs: rs8007267G/A, rs3783641A/T and rs10483639C/G, affects GTPCH activity and biopterins levels in inflammatory cells. We examined the effect of this haplotype on vascular biopterins, eNOS coupling and redox state in human vessels from patients with coronary atherosclerosis. Methods: Samples of saphenous veins (SV) were obtained from 347 patients undergoing CABG. Vasorelaxations of SV to acetylcholine (ACh) and vascular O2- (± eNOS inhibitor LNAME) were determined. Biopterins were measured by HPLC. The haplotypes were defined as X (rs8007267A+ rs3783641T+ rs10483639G) or O (all other haplotypes). Results: The haplotype distribution was OO:245(71%), OX:95(27%) and XX:7(2%). Carriers of the X haplotype had lower plasma (Fig. a ) and vascular (Fig. b ) BH4. The X haplotype was associated with higher vascular O2- (XX+XO: 2.97±0.44 vs OO:1.90±0.10 RLU/Sec/mg, p<0.01), greater LNAME-inhibitable O2- (Fig. c ) suggesting eNOS uncoupling) and lower NO bioavailability (Fig. d ) in human vessels. The X haplotype was also associated with higher plasma ox-LDL (51.0±2.2 in XX+XO vs 44.2±1.4 U/L in OO p<0.05) and lower BH4:total biopterins ratio (43.1±3.2 in XX+XO vs 51.7±2.1% in OO, p<0.05). Conclusions: This novel haplotype on GCH1 gene regulates biopterins biosynthesis in both plasma and vascular endothelium. This haplotype also regulates eNOS coupling, O2- production and NO bioavailability in human vessels, and may play a role in atherogenesis.

Implementation of a pet visitation program in critical care

1999 ◽  
Vol 19 (3) ◽  
pp. 43-50 ◽  
Author(s):  
KK Giuliano ◽  
E Bloniasz ◽  
J Bell
Keyword(s):  
Critically Ill ◽  
Emotional Support ◽  
Critically Ill Patients ◽  
Quantitative Research ◽  
Therapeutic Option ◽  
Healthcare Providers ◽  
Research Data ◽  
Staff Members ◽  
Common Problems ◽  
Patients Experience

We have no quantitative research data to document that these visits are actually helpful to patients in any measurable way, although we certainly hope to have some soon. However, observations of staff members and evaluations from participants in the program have been quite positive thus far. The program has been in place for more than 2 years, and about 30 pets have visited so far, including 28 dogs and 2 cats. Implementing a pet visitation program for critically ill patients affords healthcare providers the opportunity to offer a unique and humanistic therapeutic intervention to appropriate patients. Although it is a time-consuming endeavor, it has been well received by those patients and families that have participated in pet visits. Critically ill patients are often denied many simple pleasures because they are in physiological crisis. Such patients experience loneliness, isolation, depression, and lack of emotional support. Pet visitation is one way to address these common problems of ICU patients. For this reason, pet visitation will remain a therapeutic option for the support of our critically ill patients.

New evidence for vascular interactions between aldosterone, angiotensin II and antioxidants in isolated smooth muscle cells of rats

Open Medicine ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. 704-712
Author(s):  
Raducu Popescu ◽  
Walther Bild ◽  
Alin Ciobica ◽  
Veronica Bild
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cells ◽  
Nitrosative Stress ◽  
Reactive Oxygen ◽  
Muscle Cells ◽  
No Production ◽  
Nitrogen Species ◽  
First Case

AbstractAccumulating evidence suggests that the nongenomic cardiovascular actions of aldosterone are produced by varied cellular pathways and mediated by a multitude of messenger systems including the reactive oxygen and nitrogen species. Considering the involvement of the oxidative and nitrosative stress in the pathways leading to the activation of the angiotensin — aldosterone system, in the current study we tried to evaluate the functional interactions between aldosterone, angiotensin II and antioxidants in isolated vascular smooth muscle of aortic rings from rats. Our data provide additional arguments that the nongenomic actions of aldosterone on aortic smooth muscle cells of rats are a question of cross-talk and balance between its rapid vasoconstrictor and vasodilator effects, as result of the activation of reactive oxygen species in the first case and of nitrogen species in the second. In this way, it seems that at low ambient oxidative stress, aldosterone promotes nitric oxide (NO) production and vasodilatation, while in situations with increased oxidative stress the endothelial dysfunction and detrimental effects induced by vasoconstriction will prevail. Thus, aldosterone could be considered both “friend and foe”. This could be relevant for the ways in which aldosterone damages cardiovascular functions and could lead to significant therapeutic improvements.

scholarly journals Free radicals and the pancreatic acinar cells: role in physiology and pathology

2005 ◽  
Vol 360 (1464) ◽  
pp. 2273-2284 ◽  
Author(s):  
M Chvanov ◽  
O.H Petersen ◽  
A Tepikin
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Acute Pancreatitis ◽  
Vascular Endothelium ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Nitrogen Species ◽  
Key Enzyme ◽  
Oxide Synthase

Reactive oxygen and nitrogen species (ROS and RNS) play an important role in signal transduction and cell injury processes. Nitric oxide synthase (NOS)—the key enzyme producing nitric oxide (NO)—is found in neuronal structures, vascular endothelium and, possibly, in acinar and ductal epithelial cells in the pancreas. NO is known to regulate cell homeostasis, and its effects on the acinar cells are reviewed here. ROS are implicated in the early events within the acinar cells, leading to the development of acute pancreatitis. The available data on ROS/RNS involvement in the apoptotic and necrotic death of pancreatic acinar cells will be discussed.

Alopecia areata: pathogenesis and potential for therapy

2006 ◽  
Vol 8 (14) ◽  
pp. 1-19 ◽  
Author(s):  
Wei Lu ◽  
Jerry Shapiro ◽  
Mei Yu ◽  
Armin Barekatain ◽  
Blanche Lo ◽  
...  
Keyword(s):  
Hair Loss ◽  
Alopecia Areata ◽  
Disease Onset ◽  
Inflammatory Cells ◽  
Disease Development ◽  
Therapeutic Approaches ◽  
Disease Mechanism ◽  
Disease Pathogenesis ◽  
Significant Challenge ◽  
Cd4 Lymphocytes

Although the complete picture for alopecia areata (AA) pathogenesis has yet to be determined, recent research has made much progress in our understanding of the disease mechanism. Numerous circumstantial evidence supports the notion that AA is fundamentally a disease mediated by inflammatory cells and may be autoimmune in nature. Recent research has shown the hair-loss phenotype is precipitated predominantly by CD8+ lymphocytes, but the disease mechanism is driven by CD4+ lymphocytes. Although genetic susceptibility is a key contributor to disease development, disease onset and phenotypic presentation are probably modified by complex environmental interplay. On the basis of our current understanding of AA disease pathogenesis, several experimental and theoretical therapeutic approaches might be possible. However, the pathogenetic disease mechanism is particularly robust and the development of a cure for AA will be a significant challenge.

scholarly journals From Experimental Procedure to Clinical Practice: How Much Evidence Do We Need in Uterine Transplantation?

2018 ◽  
Author(s):  
Sabina Gainotti ◽  
Carlo Petrini
Keyword(s):  
Clinical Practice ◽  
Therapeutic Option ◽  
Clinical Care ◽  
Embryo Implantation ◽  
Healthcare Providers ◽  
The United States ◽  
Public Healthcare ◽  
Routine Practice ◽  
Functional Abnormality ◽  
Experimental Procedure

Background: Absolute uterine factor infertility (AUFI) is a kind of infertility that is completely attributable to uterine absence (surgical or congenital for women with Mayer-Rokitansky-K&uuml;ster-Hauser syndrome: MRKH) or anatomic or functional abnormality that prevents embryo implantation or completion of pregnancy to term. Until recently, the only viable option to parenthood for couples with AUFI were adoption or surrogacy. Since a first attempt of uterus transplant (UTx) in 2000, nine babies were born from women with a transplanted uterus from 2014, eight of which in Sweden, and one in the United States. These promising results are raising immense hopes for the women with AUFI and there is optimism about the possibility for UTx to become part of clinical care even though, besides encouraging results, the procedure has also resulted in increased risks and harms for both the donors and recipients and increased risks of premature birth for the fetus. At present UTx is still considered as experimental and requiring more research and safety assessment before becoming a therapeutic option for AUFI. The transition from experimental procedure to therapeutic care would result in less strict ethical scrutiny for UTx and in the possibility for patients to get reimbursement for the procedure by the relevant healthcare insurance or public healthcare providers. In turn, an increase in the number of UTx performed yearly by specialized surgical teams would result in a general improvement of the &ldquo;field strength&rdquo;. However, at present it is difficult to establish the amount of evidence that we need in order to consider UTx as no longer experimental but routine clinical practice. The literature on UTx provides recommendations on the different outcomes that should be monitored in this experimental phase but no study is anticipating the number of subjects that should be followed and for how long. Conclusion: As for other transplants that have become routine practice, like renal transplant and heart transplant, it is likely that the decision on &ldquo;routine practice readiness&rdquo; will result from available cumulated evidences, from expert capacity to find a consensus on best practices and on political considerations as well, including pressures form patients and patient groups.

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