scholarly journals Oxidative Stress in the Pathogenesis of Antiphospholipid Syndrome: Implications for the Atherothrombotic Process

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1790
Author(s):  
Cristina Nocella ◽  
Simona Bartimoccia ◽  
Vittoria Cammisotto ◽  
Alessandra D’Amico ◽  
Daniele Pastori ◽  
...  

Atherothrombosis is a frequent complication of the clinical history of patients with antiphospholipid syndrome (APS). Both atherothrombosis and APS are characterized by increased oxidative stress. Oxidative modifications are implicated in the formation of antiphospholipid antibodies, which in turn may favour the oxidative imbalance by increasing the production of reactive oxidant species (ROS) or by a direct interaction with pro-oxidant/antioxidant enzymes. As a result of these processes, APS patients suffer from an oxidative imbalance that may contribute to the progression of the atherosclerotic process and to the onset of ischemic thrombotic complications. The aim of this review is to describe mechanisms implicated in the formation of ROS in APS patients and their involvement in the atherothrombotic process. We also provide an overview of potential therapeutic approaches to blunt oxidative stress and to prevent atherothrombotic complications in these patients.

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1965-1971 ◽  
Author(s):  
R Landolfi ◽  
G Ciabattoni ◽  
P Patrignani ◽  
MA Castellana ◽  
E Pogliani ◽  
...  

Abstract Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.


Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1965-1971 ◽  
Author(s):  
R Landolfi ◽  
G Ciabattoni ◽  
P Patrignani ◽  
MA Castellana ◽  
E Pogliani ◽  
...  

Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.


2019 ◽  
Vol 2019 ◽  
pp. 1-32 ◽  
Author(s):  
Patricia Marchio ◽  
Sol Guerra-Ojeda ◽  
José M. Vila ◽  
Martín Aldasoro ◽  
Victor M. Victor ◽  
...  

Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. Oxidation of low-density lipoprotein (LDL) cholesterol is one of the key factors for the development of atherosclerosis. Nonoxidized LDL have a low affinity for macrophages, so they are not themselves a risk factor. However, lowering LDL levels is a common clinical practice to reduce oxidation and the risk of major events in patients with cardiovascular diseases (CVD). Atherosclerosis starts with dysfunctional changes in the endothelium induced by disturbed shear stress which can lead to endothelial and platelet activation, adhesion of monocytes on the activated endothelium, and differentiation into proinflammatory macrophages, which increase the uptake of oxidized LDL (oxLDL) and turn into foam cells, exacerbating the inflammatory signalling. The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment. In this review, we focus on early stages of the disease and we address both biomarkers and therapeutic approaches currently available and under research.


2004 ◽  
Vol 15 (3) ◽  
pp. 273-297 ◽  
Author(s):  
SOPHIA STONE ◽  
LUCILLA POSTON

Antiphospholipid antibodies (aPLs) are a diverse group of autoantibodies with specificity for phospholipid surfaces. Antiphospholipid antibodies may be found in individuals with a clinical history of thrombotic events or in women suffering severe pregnancy complications typically involving fetal compromise or demise. The association is known as the antiphospholipid syndrome (APS).


Author(s):  
Zohreh Hashemian ◽  
Parvaneh Afsharian

Introduction: Polycystic ovary syndrome is one of the most common causes of infertility. 6 to 8 percent of women of childbearing age have this endocrine disorder. Biochemical abnormalities in these patients lead to imbalance of female hormones and increased androgens, which can have consequences such as menstrual cycle disorder, hirsutism, acne vulgaris and androgenic alopecia. Despite the long history of studies on polycystic ovary syndrome, the cause is still unknown. Oxidative stress is an imbalance between the production of reactive oxygen species and the amount of antioxidant. When this balance is disturbed, the result is an increase in the level of oxidative stress. Oxidative stress is currently recognized as one of the major pathophysiologies of many disorders and diseases, including polycystic ovary syndrome. Understanding the mechanisms of oxidative stress is crucial for developing strategies for the prevention and treatment of this disease. In this article, we reviewed the data on the mechanism of oxidative stress in polycystic ovary syndrome.  


TH Open ◽  
2021 ◽  
Vol 05 (03) ◽  
pp. e239-e250
Author(s):  
Gualtiero Palareti ◽  
Cristina Legnani ◽  
Emilia Antonucci ◽  
Sophie Testa ◽  
Daniela Mastroiacovo ◽  
...  

Abstract Background Isolated distal deep vein thromboses (IDDVT) are frequently diagnosed; however, their natural history and real risk of complications are still uncertain. Though treatment is still not well standardized, international guidelines recommend no more than 3 months of anticoagulation therapy. We investigated how Italian clinicians treat IDDVT patients in their real life in our country. Methods Baseline characteristics and clinical history of the patients enrolled in the prospective, observational, multicenter START-Register for a first IDDVT or proximal DVT (PDVT) were analyzed. Results Overall, 412 IDDVT patients were significantly younger, with better renal function, and more frequent major transient risk factors, when compared with 1,173 PDVT patients. The anticoagulation duration was >180 days in 52.7% of IDDVT patients (70.7% in PDVT). During treatment, bleeding occurred in 5.6 and 2.8% patient-years in IDDVT and PDVT, respectively (p = 0082). Bleeding was more frequent in IDDVT than PDVT patients treated with warfarin (6.8 vs. 3.2 patient-years, p = 0.0228, respectively). Thrombotic complications occurred in 1.1 and 2.4% patient-years in IDDVT and PDVT patients, respectively. Analyzing together the two groups, 66.1% of bleeds and 86.1% thrombotic complications occurred after 90 days anticoagulation treatment. Conclusion The large majority of IDDVT patients received anticoagulation for more than 3 months. Most bleeding and thrombotic complications occurred after the first 90 days of anticoagulation therapy. These results indicate that an extended anticoagulation beyond 90 days in IDDVT patients is associated with increased risk of complications. Whether an extended treatment may lower recurrences after anticoagulation withdrawal should be assessed by specifically designed studies.


1999 ◽  
Vol 82 (S 01) ◽  
pp. 32-37 ◽  
Author(s):  
Karlheinz Peter ◽  
Wolfgang Kübler ◽  
Johannes Ruef ◽  
Thomas K. Nordt ◽  
Marschall S. Runge ◽  
...  

SummaryThe initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.


2020 ◽  
Vol 41 (5) ◽  
pp. 336-340
Author(s):  
Yasmin Hamzavi Abedi ◽  
Cristina P. Sison ◽  
Punita Ponda

Background: Serum Peanut-specific-IgE (PN-sIgE) and peanut-component-resolved-diagnostics (CRD) are often ordered simultaneously in the evaluation for peanut allergy. Results often guide the plans for peanut oral challenge. However, the clinical utility of CRD at different total PN-sIgE levels is unclear. A commonly used predefined CRD Ara h2 cutoff value in the literature predicting probability of peanut challenge outcomes is 0.35kUA/L. Objective: To examine the utility of CRD in patients with and without a history of clinical reactivity to peanut (PN). Methods: This was a retrospective chart review of 196 children with PN-sIgE and CRD testing, of which, 98 patients had a clinical history of an IgE-mediated reaction when exposed to PN and 98 did not. The Fisher's exact test was used to assess the relationship between CRD and PN-sIgE at different cutoff levels, McNemar test and Gwet’s approach (AC1 statistic) were used to examine agreement between CRD and PN-sIgE, and logistic regression was used to assess differences in the findings between patients with and without reaction history. Results: Ara h 1, 2, 3, or 9 (ARAH) levels ≤0.35 kUA/L were significantly associated with PN-sIgE levels <2 kUA/L rather than ≥2 kUA/L (p < 0.0001). When the ARAH threshold was increased to 1 kUA/L and 2 kUA/L, these thresholds were still significantly associated with PN-sIgE levels of <2, <5, and <14 kUA/L. These findings were not significantly different in patients with and without a history of clinical reactivity. Conclusion: ARAH values correlated with PN-sIgE. Regardless of clinical history, ARAH levels are unlikely to be below 0.35, 1, or 2 kUA/L if the PN-sIgE level is >2 kUA/L. Thus, if possible, practitioners should consider PN-sIgE rather than automatically ordering CRD with PN-sIgE every time. Laboratory procedures that allow automatically and reflexively adding CRD when the PN-sIgE level is ≤5 kUA/L can be helpful. However, further studies are needed in subjects with challenge-proven PN allergy.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1042-1047
Author(s):  
Khushbu Balsara ◽  
Deepankar Shukla

In a very short period of time, “COVID-19” has seized the consciousness globally by making remarkable changes in our day to day living and has superintended as a public health emergency globally. It has high radar of transmission, affecting an individual at work to frontline workers. The measures and planning for a response plays a key role from drawing up an emergency committee and this follows an equation which broadly deals with epidemiological to clinical history of the patient, management steps from isolation, screening, diagnostic assays for identification and treatment. The application of an organized plan with secure structure aids in better performance, increases efficacy of management and saves time. Also saves time for a health care worker to g through routine levels of channels of administration if already a familiar way of operation is known for such situations. Thus, planning and developing a ‘blueprint of approach’ towards management of patient while facing such situation is a must. This review provides an insight to the measures for detection, response and preparedness of the hospital and health care workers should largely be inclusive of; also highlights the measures to be taken at every step after coming in contact with a positive case of “COVID-19”.


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