scholarly journals Anticoagulation in COVID-19: current concepts and controversies

2021 ◽  
pp. postgradmedj-2021-139923
Author(s):  
Atanu Chandra ◽  
Uddalak Chakraborty ◽  
Shrestha Ghosh ◽  
Sugata Dasgupta
Keyword(s):  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Mortality Rates ◽  
Comprehensive Strategy ◽  
Rising Incidence ◽  
Global Concern ◽  
Thrombogenic Potential ◽  
Guidelines And Recommendations ◽  
Primary Modality

Rising incidence of thromboembolism secondary to COVID-19 has become a global concern, with several surveys reporting increased mortality rates. Thrombogenic potential of the SARS-CoV-2 virus has been hypothesised to originate from its ability to produce an exaggerated inflammatory response leading to endothelial dysfunction. Anticoagulants have remained the primary modality of treatment of thromboembolism for decades. However, there is no universal consensus regarding the timing, dosage and duration of anticoagulation in COVID-19 as well as need for postdischarge prophylaxis. This article seeks to review the present guidelines and recommendations as well as the ongoing trials on use of anticoagulants in COVID-19, identify discrepancies between all these, and provide a comprehensive strategy regarding usage of these drugs in the current pandemic.

scholarly journals Refractory Toxic Shock-Like Syndrome fromStreptococcus dysgalactiaessp.equisimilisand Intravenous Immunoglobulin as Salvage Therapy: A Case Series

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Marjan Islam ◽  
Dennis Karter ◽  
Jerry Altshuler ◽  
Diana Altshuler ◽  
David Schwartz ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intravenous Immunoglobulin ◽  
Salvage Therapy ◽  
Adjunctive Therapy ◽  
Case Series ◽  
Ivig Therapy ◽  
Mortality Rates ◽  
Invasive Disease ◽  
Streptococcus Dysgalactiae ◽  
Toxic Shock

Infections fromStreptococcus dysgalactiaessp.equisimilis(SDSE) can cause a wide variety of infections, ranging from mild cellulitis to invasive disease, such as endocarditis and streptococcal toxic shock-like syndrome (TSLS). Despite prompt and appropriate antibiotics, mortality rates associated with shock have remained exceedingly high, prompting the need for adjunctive therapy. IVIG has been proposed as a possible adjunct, given its ability to neutralize a wide variety of superantigens and modulate a dysregulated inflammatory response. We present the first reported cases of successful IVIG therapy for reversing shock in the treatment of SDSE TSLS.

scholarly journals Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 994
Author(s):  
Natasha Ting Lee ◽  
Lin Kooi Ong ◽  
Prajwal Gyawali ◽  
Che Mohd Nasril Che Mohd Nassir ◽  
Muzaimi Mustapha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Small Vessel Disease ◽  
Ischemia Reperfusion ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Purinergic Signalling ◽  
Vessel Disease ◽  
The Brain

The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood–brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.

scholarly journals Effect of Anthocyanin-Rich Extract of Sour Cherry for Hyperglycemia-Induced Inflammatory Response and Impaired Endothelium-Dependent Vasodilation

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3373
Author(s):  
Arnold Markovics ◽  
Attila Biró ◽  
Andrea Kun-Nemes ◽  
Mónika Éva Fazekas ◽  
Anna Anita Rácz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Proinflammatory Cytokines ◽  
Sour Cherry ◽  
The Elderly ◽  
Human Umbilical Cord ◽  
Dependent Manner

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.

Oxidative stress, endothelial dysfunction and inflammatory response in rat heart to NO2 inhalation exposure

Chemosphere ◽  
2011 ◽  
Vol 82 (11) ◽  
pp. 1589-1596 ◽  
Author(s):  
Hongyan Li ◽  
Ming Han ◽  
Lin Guo ◽  
Guangke Li ◽  
Nan Sang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Rat Heart ◽  
Inhalation Exposure

scholarly journals Schistosomiasis in the People's Republic of China: the Era of the Three Gorges Dam

2010 ◽  
Vol 23 (2) ◽  
pp. 442-466 ◽  
Author(s):  
Donald P. McManus ◽  
Darren J. Gray ◽  
Yuesheng Li ◽  
Zheng Feng ◽  
Gail M. Williams ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Three Gorges Dam ◽  
Schistosomiasis Japonica ◽  
Three Gorges ◽  
Comprehensive Strategy ◽  
Transmission Season ◽  
Republic Of China ◽  
The Three Gorges ◽  
Global Concern ◽  
The Three Gorges Dam

SUMMARY The potential impact of the Three Gorges Dam (TGD) on schistosomiasis transmission in China has invoked considerable global concern. The TGD will result in changes in the water level and silt deposition downstream, favoring the reproduction of Oncomelania snails. Combined with blockages of the Yangtze River's tributaries, these changes will increase the schistosomiasis transmission season within the marshlands along the middle and lower reaches of the Yangtze River. The changing schistosome transmission dynamics necessitate a comprehensive strategy to control schistosomiasis. This review discusses aspects of the epidemiology and transmission of Schistosoma japonicum in China and considers the pathology, clinical outcomes, diagnosis, treatment, immunobiology, and genetics of schistosomiasis japonica together with an overview of current progress in vaccine development, all of which will have an impact on future control efforts. The use of synchronous praziquantel (PZQ) chemotherapy for humans and domestic animals is only temporarily effective, as schistosome reinfection occurs rapidly. Drug delivery requires a substantial infrastructure to regularly cover all parts of an area of endemicity. This makes chemotherapy expensive and, as compliance is often low, a less than satisfactory control option. There is increasing disquiet about the possibility that PZQ-resistant schistosomes will develop. Consequently, as mathematical modeling predicts, vaccine strategies represent an essential component in the future control of schistosomiasis in China. With the inclusion of focal mollusciciding, improvements in sanitation, and health education into the control scenario, China's target of reducing the level of schistosome infection to less than 1% by 2015 may be achievable.

scholarly journals Biomarkers of Hemostatic Activation and Inflammation Are Associated with Altered Coagulation Parameters in Sepsis Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2401-2401
Author(s):  
Emily Bontekoe ◽  
Matthew T. Rondina ◽  
Debra Hoppensteadt ◽  
Elizabeth Middleton ◽  
Antoinette Blair ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Inflammatory Response ◽  
Sepsis Group ◽  
P Value ◽  
Plasma Samples ◽  
Pronounced Increase ◽  
Coagulation Parameters ◽  
Simultaneous Activation ◽  
Pai 1 ◽  
D Dimer

Background : Sepsis is characterized by a simultaneous activation of inflammation and hemostasis in response to microbial infection. This systemic inflammatory response is due to the release of pro-inflammatory cytokines, pro-coagulants and adhesion molecules from immune cells and/or damaged endothelial tissue. Simultaneous activation of coagulation and fibrinolysis leads to consumption coagulopathy and severe vascular dysfunction. Profiling of biomarkers of hemostatic activation and inflammation along with the measurement of coagulation parameters has provided useful data in the understanding of the pathogenesis of sepsis. This study was designed to profile biomarkers of hemostatic activation, inflammation and endothelial dysfunction along with the measurement of coagulation parameters in a defined clinically confirmed sepsis population in conjunction with an IRB approved clinical trial. Materials & Methods: Citrated blood samples were collected from sepsis patients with suspected or confirmed infection, and organ dysfunction as defined by a SOFA ³ baseline. Plasma samples from septic shock patients were collected in citrated tubes within 72 hours of ICU admission under an IRB approved protocol in conjunction with an ongoing trial at the University of Utah and Veteran's Affair FFC Health Care System VAMC. Normal controls were comprised of commercially available 25 male and 25 female citrated plasma samples (George King Biomedical, Overland Park, Kansas City). Such biomarkers as CRP, PAI-1, D-Dimer, vWF and microparticle tissue factor complex (MP-TF) were measured using a commercially available sandwich ELISA methods. Nitric oxide (NO) levels were measured using a commercially available Griess reaction based colorimetric method. PT/INR, aPTT and fibrinogen measurements were based on clot based assays. All results were compiled as mean ± SD and SEM. Correlation analysis was carried out to determine relevance between different parameters. Results: Most of the biomarkers of hemostatic activation and inflammation were elevated in patients with sepsis as shown on table 1a, CRP (66 fold) and D-Dimer (23 fold) showed the most pronounced increase in comparison to the control. Other parameters also showed increase levels including MP-TF (5.3 fold), PAI-1 (3.5 fold), vWF (3.1 fold) and NO (3.0 fold). Clotting parameters such as PT/INR (2.0 fold), aPTT (2.5 fold) and fibrinogen (2.0 fold) were also significantly elevated in the sepsis patients. These differences were significant (p value ≤0.0009) for all of the parameters except for NO (p value 0.0937) and fibrinogen (p value 0.4694). As shown on table 1b, there was no correlation between various biomarkers and fibrinogen in the sepsis patients. Summary & Conclusion: In comparison to the control group, the sepsis patients showed wide variations in all of the parameters investigated in this study. The marked prolongation of PT and aPTT are suggestive of both the extrinsic and intrinsic pathway defects and consumption of clotting factors. The aPTT data showed wider scatter in comparison to PT data. The fibrinogen levels were also elevated and nearly 1/3 of the patients showed >1000 mg/dL levels. The markedly higher level of CRP in the sepsis group are indicative of severe inflammatory response. Marked elevation of D-Dimer is indicative of endogenous fibrin formation and its consumption consistent with activation of secondary fibrinolysis. MP-TF, vWF and PAI-1 were also increased in the sepsis patients suggesting marked endothelial dysfunction. This is consistent with increased NO levels which may be due to induction of iNOS in the endothelial lining of sepsis patients. These results further underscore the multifactorial pathophysiology of sepsis which results in the dysregulation of hemostasis, upregulation of inflammatory responses and generalized endothelialopathy. Profiling of the biomarkers included in this study and coagulation parameters may be helpful in the risk stratification and clinical management of patients with sepsis and related disorders. Disclosures No relevant conflicts of interest to declare.

scholarly journals Endothelial dysfunction and heart failure: A review of the existing bibliography with emphasis on flow mediated dilation

2019 ◽  
Vol 8 ◽  
pp. 204800401984304 ◽  
Author(s):  
Sofia Giannitsi ◽  
Bougiakli Maria ◽  
Aris Bechlioulis ◽  
Katerina Naka
Keyword(s):  
Heart Failure ◽  
Endothelial Dysfunction ◽  
Wide Spectrum ◽  
Mortality Rates ◽  
Targeted Treatment ◽  
Flow Mediated Dilation ◽  
Potential Target ◽  
Therapeutic Development ◽  
Underlying Pathophysiology

Heart failure affects 1–2% of the population worldwide, and it is characterized by episodes of decompensation often requiring hospitalization. Although targeted treatment has reduced the prevalence of rehospitalizations to 30–50%, mortality rates remain high. A complex blend of structural and functional alterations accounts for the genesis and progression of heart failure, but the exact underlying pathophysiology remains poorly understood. The aim of this review is to summarize endothelial dysfunction and its role in the pathogenesis and progression of heart failure. Moreover, it sums up all the appropriate methods of assessing endothelial dysfunction emphasizing on flow-mediated dilation and introduces endothelium as a potential target for new therapeutic development and research in the wide spectrum of the syndrome called heart failure.

Serum Amyloid A in Preeclampsia

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
K H Swidan ◽  
M S Sweed ◽  
A M Abbas ◽  
M K Jewi
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Level ◽  
Inflammatory Response ◽  
Pregnant Women ◽  
Serum Amyloid A ◽  
Normal Pregnancy ◽  
Maternal Plasma ◽  
Maternity Hospital ◽  
Serum Amyloid ◽  
Amyloid A

Abstract Background Preeclampsia is a common complication of pregnancy and remains a common cause of maternal and fetal mortality. The clinical symptoms of preeclampsia are caused by widespread endothelial dysfunction suggested to be a part of an exaggerated maternal inflammatory response to pregnancy. Since preeclampsia is associated with widespread endothelial dysfunction, proposed to be provoked by an increased maternal systemic inflammatory response, the maternal plasma level of SAA might be expected to be increased when compared to normal pregnancy levels. The maternal plasma level of SAA in normal pregnancy could differ from non-pregnant level due to increased hormone levels, increased adipose tissue and\or secondary to modifications of inflammatory response in normal pregnancy. Aims The aim of our study is to estimate the relation between serum amyloid A in pregnant women and preeclampsia. Methodology the study conducted this case control study in the emergency room of Ain Shams University Maternity Hospital starting from April 2018 on women with preeclampsia to estimate serum amyloid A in pregnant women with preeclampsia. Members of the control group are healthy, non-smoker pregnant women who had an uncomplicated antenatal course and all arterial blood pressure measurements were normal. Results The current study was conducted in Ain Shams University Maternity Hospital in the period between January 2017 and August 2018. A total of 75 women were included in the study. The process of recruitment and handling the study population during the course of the study is shown in the flow diagram (figure 1). In order to avoid any confounding effect for a possible subclinical ongoing pathophysiological process, four women with preeclampsia lacking severe features were excluded following the development of severe features shortly after measurement of serum amyloid A level. Conclusion Our data sustain the limited number of studies investigating the SAA levels in both preeclamptic and healthy pregnant women, in which it was hard to reach a consensus regarding the association between SAA levels and preeclampsia. Taken in consideration that an elevated plasma level of SAA in preeclamptic women should be considered pathologic, we believe that the response of relationship between the preeclampsia and SAA levels could be caused by an inflammatory condition associated with preeclampsia. Also, serum amyloid A can be used to discriminate between mild preeclampsia cases and controls and as discriminate between severe preeclampsia cases and controls. Recommendation We recommended further investigation on large sample size for the elucidation of the role of SAA in pre-eclampsia neonatal outcome and the possibility of these biochemical factors to be novel markers of such disorders in pregnant women.

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