scholarly journals The Role of Rotational Thromboelastometry (ROTEM) in Understanding the Coagulation Problems in COVID-19 Associated Critical Illness

2021 ◽  
Author(s):  
Natalie Duric ◽  
Tamas Szakmany
Keyword(s):  
Disease Process ◽  
Rotational Thromboelastometry ◽  
Medical Interventions ◽  
Test Parameters ◽  
Bedside Test ◽  
Coagulation Tests ◽  
High Incidence ◽  
The Subject

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence. Standard coagulation tests are limited in their ability accurately to reflect the severity of the pro-thrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of rotational thromboelastometry (ROTEM) as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. Comprehensive literature search was conducted on PubMed, revealing 13 publications on the subject. The coagulopathy of this disease process appears to be insufficiently represented with often normal conventional coagulation test parameters. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hyper-coagulability) and reduced maximum lysis (consistent with “fibrinolytic shutdown”). ROTEM appears to be a possible tool for risk stratification and to monitor the potential modulation of fibrinogen-dependent coagulation processes with enhanced anti-coagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcome, however, remains unclear.

scholarly journals Antioxidant Properties of Ergosterol and Its Role in Yeast Resistance to Oxidation

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1024
Author(s):  
Sebastien Dupont ◽  
Paul Fleurat-Lessard ◽  
Richtier Gonçalves Cruz ◽  
Céline Lafarge ◽  
Cédric Grangeteau ◽  
...  
Keyword(s):  
Computational Study ◽  
Antioxidant Properties ◽  
Beneficial Effects ◽  
Tert Butyl Hydroperoxide ◽  
Resistance To Oxidation ◽  
Specific Accumulation ◽  
The Subject

Although the functions and structural roles of sterols have been the subject of numerous studies, the reasons for the diversity of sterols in the different eukaryotic kingdoms remain unclear. It is thought that the specificity of sterols is linked to unidentified supplementary functions that could enable organisms to be better adapted to their environment. Ergosterol is accumulated by late branching fungi that encounter oxidative perturbations in their interfacial habitats. Here, we investigated the antioxidant properties of ergosterol using in vivo, in vitro, and in silico approaches. The results showed that ergosterol is involved in yeast resistance to tert-butyl hydroperoxide and protects lipids against oxidation in liposomes. A computational study based on quantum chemistry revealed that this protection could be related to its antioxidant properties operating through an electron transfer followed by a proton transfer mechanism. This study demonstrates the antioxidant role of ergosterol and proposes knowledge elements to explain the specific accumulation of this sterol in late branching fungi. Ergosterol, as a natural antioxidant molecule, could also play a role in the incompletely understood beneficial effects of some mushrooms on health.

scholarly journals Regulation of Impaired Protein Kinase C Signaling by Chemokines in Murine Macrophages during Visceral Leishmaniasis

2005 ◽  
Vol 73 (12) ◽  
pp. 8334-8344 ◽  
Author(s):  
Ranadhir Dey ◽  
Arup Sarkar ◽  
Nivedita Majumder ◽  
Suchandra Bhattacharyya (Majumdar) ◽  
Kaushik Roychoudhury ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Leishmania Donovani ◽  
Disease Process ◽  
Kinase C ◽  
Parasitic Burden ◽  
Infected Cells

ABSTRACT The protein kinase C (PKC) family regulates macrophage function involved in host defense against infection. In the case of Leishmania donovani infection, the impairment of PKC-mediated signaling is one of the crucial events for the establishment of parasite into the macrophages. Earlier reports established that C-C chemokines mediated protection against leishmaniasis via the generation of nitric oxide after 48 h. In this study, we investigated the role of MIP-1α and MCP-1 in the regulation of impaired PKC activity in the early hours (6 h) of infection. These chemokines restored Ca2+-dependent PKC activity and inhibited Ca2+-independent atypical PKC activity in L. donovani-infected macrophages under both in vivo and in vitro conditions. Pretreatment of macrophages with chemokines induced superoxide anion generation by activating NADPH oxidase components in infected cells. Chemokine administration in vitro induced the migration of infected macrophages and triggered the production of reactive oxygen species. In vivo treatment with chemokines significantly restricted the parasitic burden in livers as well as in spleens. Collectively, these results indicate a novel regulatory role of C-C chemokines in controlling the intracellular growth and multiplication of L. donovani, thereby demonstrating the antileishmanial properties of C-C chemokines in the disease process.

Participatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studiesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Stewart C. Whitman ◽  
Tanya A. Ramsamy
Keyword(s):  
Natural Killer ◽  
Complex Disease ◽  
Immune Cell ◽  
Disease Process ◽  
Density Lipoprotein ◽  
Nkt Cells ◽  
Lessons Learned ◽  
Natural Killer T

Atherosclerosis is a multifactor, highly complex disease with numerous aetiologies that work synergistically to promote lesion development. One of the emerging components that drive the development of both early- and late-stage atherosclerotic lesions is the participation of both the innate and acquired immune systems. In both humans and animal models of atherosclerosis, the most prominent cells that infiltrate evolving lesions are macrophages and T lymphocytes. The functional loss of either of these cell types reduces the extent of atherosclerosis in mice that were rendered susceptible to the disease by deficiency of either apolipoprotein E or the LDL (low density lipoprotein) receptor. In addition to these major immune cell participants, a number of less prominent leukocyte populations that can modulate the atherogenic process are also involved. This review will focus on the participatory role of two “less prominent” immune components, namely natural killer (NK) cells and natural killer T (NKT) cells. Although this review will highlight the fact that both NK and NKT cells are not sufficient for causing the disease, the roles played by both these cells types are becoming increasingly important in understanding the complexity of this disease process.

scholarly journals Identification of Genes in Xanthomonas campestris pv. vesicatoria Induced during Its Interaction with Tomato

2007 ◽  
Vol 189 (17) ◽  
pp. 6359-6371 ◽  
Author(s):  
Dafna Tamir-Ariel ◽  
Naama Navon ◽  
Saul Burdman
Keyword(s):  
Xanthomonas Campestris ◽  
Disease Process ◽  
In Planta ◽  
Gene Encoding ◽  
Host Interaction ◽  
Citrate Transporter ◽  
Knockout Mutants ◽  
Bacterial Spot Disease

ABSTRACT Xanthomonas campestris pv. vesicatoria is the causal agent of bacterial spot disease of tomato and pepper. The disease process is interactive and very intricate and involves a plethora of genes in the pathogen and in the host. In the pathogen, different genes are activated in response to the changing environment to enable it to survive, adapt, evade host defenses, propagate, and damage the host. To understand the disease process, it is imperative to broaden our understanding of the gene machinery that participates in it, and the most reliable way is to identify these genes in vivo. Here, we have adapted a recombinase-based in vivo expression technology (RIVET) to study the genes activated in X. campestris pv. vesicatoria during its interaction with one of its hosts, tomato. This is the first study that demonstrates the feasibility of this approach for identifying in vivo induced genes in a plant pathogen. RIVET revealed 61 unique X. campestris pv. vesicatoria genes or operons that delineate a picture of the different processes involved in the pathogen-host interaction. To further explore the role of some of these genes, we generated knockout mutants for 13 genes and characterized their ability to grow in planta and to cause disease symptoms. This analysis revealed several genes that may be important for the interaction of the pathogen with its host, including a citH homologue gene, encoding a citrate transporter, which was shown to be required for wild-type levels of virulence.

scholarly journals Massive Hemorrhage: The Role of Whole Blood Viscoelastic Assays

2020 ◽  
Vol 40 (04) ◽  
pp. 515-523
Author(s):  
Emmanuelle Scala ◽  
Carlo Marcucci
Keyword(s):  
Whole Blood ◽  
Point Of Care ◽  
Turnaround Time ◽  
Massive Hemorrhage ◽  
Research Papers ◽  
Treatment Algorithms ◽  
Rotational Thromboelastometry ◽  
The Subject ◽  
Point Of Care Tests

AbstractViscoelastic whole blood tests are increasingly used to guide hemostatic therapy in bleeding patients in the perioperative, trauma, and obstetric settings. Compared with standard laboratory tests of hemostasis, they have a shorter turnaround time and provide simultaneous information on various aspects of clot formation and lysis. The two available brands TEG (thromboelastography) and ROTEM (rotational thromboelastometry) provide devices that are either manually operated or fully automated. The automation allows for the assays to be used as point-of-care tests increasing their usefulness in massively bleeding patients with rapidly changing hemostatic profiles. While the number of research papers on the subject and the number of published treatment algorithms increase rapidly, the influence of the use of these devices on patient outcome needs yet to be established. In this article, we first review the technology of these devices and the parameters provided by the assays. Next, we present the problems encountered when choosing cut-off values that trigger intervention. Furthermore, we discuss the studies examining their influence on clinical outcomes, and finally, we briefly highlight some of the most important limitations and pitfalls inherent to these assays.

Critical review of the publications on the genotoxicology of aluminium salts: 1990–2018

Mutagenesis ◽  
2021 ◽  
Author(s):  
Peter Jenkinson
Keyword(s):  
Oxidative Damage ◽  
Mode Of Action ◽  
Weight Of Evidence ◽  
Negative Results ◽  
Good Laboratory ◽  
The Subject ◽  
Toxicological Mechanism

Abstract Since the mid-1970s, there have been many reports that purport to implicate aluminium in the aetiology of neurodegenerative disease. After several decades of research, the role of aluminium in such disease remains controversial and is not the subject of this review. However, if aluminium is implicated in such disease then it follows that there must be a toxicological mechanism or mode of action, and many researchers have investigated various potential mechanisms including the involvement of oxidative damage, cytotoxicity and genotoxicity. This paper reviews many of the publications of studies using various salts of aluminium and various genotoxicity end points, both in vitro and in vivo, with a focus on oxidative damage. The conclusion of this review is that the majority, if not all, of the publications that report positive results have serious technical flaws and/or implausible findings and consequently should contribute little or no weight to a weight of evidence (WoE) argument. There are many high-quality, Good Laboratory Practice (GLP)-compliant genotoxicity studies, that follow relevant OECD test guidelines and the European Chemicals Agency (ECHA) integrated mutagenicity testing strategy, on several salts of aluminium; all demonstrate clear negative results for both in vitro and in vivo genotoxicity. In addition, the claim for an oxidative mode of action for aluminium can be shown to be spurious. This review concludes that there are no reliable studies that demonstrate a potential for genotoxicity, or oxidative mode of action, for aluminium.

scholarly journals Influence of condensation domains on activity and specificity of adenylation domains

2021 ◽  
Author(s):  
Janik Kranz ◽  
Sebastian L. Wenski ◽  
Alexnder A. Dichter ◽  
Helge B. Bode ◽  
Kenan A. J. Bozhueyuek
Keyword(s):  
Structural Features ◽  
Peptide Synthetases ◽  
In Situ Experiments ◽  
The Subject ◽  
New Perspective ◽  
Condensation Domain

Many clinically used natural products are produced by non-ribosomal peptide synthetases (NRPSs), which due to their modular nature should be accessible to modification and engineering approaches. While the adenylation domain (A) plays the key role in substrate recognition and activation, the condensation domain (C) which is responsible for substrate linkage and stereochemical filtering recently became the subject of debate - with its attributed role as a "gatekeeper" being called into question. Since we have thoroughly investigated different combinations of C-A didomains in a series of in vitro, in vivo, and in situ experiments suggesting an important role to the C-A interface for the activity and specificity of the downstream A domain and not the C domain as such, we would like to contribute to this discussion. The role of the C-A interface, termed 'extended gatekeeping', due to structural features of the C domains, can also be transferred to other NRPSs by engineering, was finally investigated and characterised in an in silico approach on 30 wild-type and recombinant C-A interfaces. With these data, we not only would like to offer a new perspective on the specificity of C domains, but also to revise our previously established NRPS engineering and construction rules.

scholarly journals COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 817 ◽  
Author(s):  
Argirios E. Tsantes ◽  
Andreas G. Tsantes ◽  
Styliani I. Kokoris ◽  
Stefanos Bonovas ◽  
Frantzeska Frantzeskaki ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Small Sample ◽  
Close Monitoring ◽  
Rotational Thromboelastometry ◽  
Coagulation Tests ◽  
Attractive Option ◽  
Small Sample Sizes ◽  
Fibrinolysis Shutdown ◽  
Insight Into

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy.

scholarly journals The Emerging Role of Micro RNA21 in Oral Cancer

2018 ◽  
Vol 11 (4) ◽  
pp. 1961-1966
Author(s):  
N. Sangeetha Narasimhan ◽  
N. Malathi Narasimhan
Keyword(s):  
Cancer Research ◽  
Protein Synthesis ◽  
Oral Cancer ◽  
Causes Of Death ◽  
Molecular Level ◽  
Disease Process ◽  
High Incidence ◽  
Non Coding Rnas ◽  
Very High

Oral cancer is one among the leading causes of death in developing countries of south Asia. A very high incidence of oral cancer in India has resulted due to the prevalence of tobacco use both in smokable and Chewable forms. Though molecular level changes that occur in the initiation and progression of oral cancer has been studied, the disease process is still poorly understood unlike other cancers. MicroRNAs are the trending name in cancer research. They are non-coding RNAs that control the genome by their complementarity and affect protein synthesis. Their role in various cancers have been well studied. This paper enlightens the role of MicroRNA21 in oral cancer.

Drugs and Platelet Activation in Migraine and Transient Ischemic Attacks

Cephalalgia ◽  
1985 ◽  
Vol 5 (2_suppl) ◽  
pp. 103-108 ◽  
Author(s):  
Giovanni D'Andrea ◽  
Antonio Cananzi ◽  
Moreno Toldo ◽  
Francesco Ferro-Milone
Keyword(s):  
Platelet Activation ◽  
Plasma Levels ◽  
Transient Ischemic Attacks ◽  
Platelet Factor ◽  
High Incidence ◽  
Complicated Migraine ◽  
One Year ◽  
Ischemic Attack

In order to study the role of platelets in migraine and cerebrovascular disease, beta-thromboglobulin (β-TG) and platelet factor 4 (PF4) plasma levels, indices of in vivo platelet activation, were assayed in two groups of patients suffering from migraine (common/classic and classic/complicated migraine, respectively) and in one group suffering from transitory ischemic attacks (TIAs). Plasma determinations were carried out in the absence of treatment and during the administration of aspirin (50 mg/daily) and flunarizine (10 mg/daily). Platelet activation was found in patients suffering from TIA; patients affected by classic and complicated migraine showed a high incidence of activation, in comparison with common migraine sufferers, also in headache-free periods. Administration of aspirin (ASA) was more effective than flunarizine in inducing a decrease in β-TG and PF4 plasma levels in migraineurs. Aspirin, however, did not affect platelet activation in subjects suffering from ischemic attack even though we did not observe any relapse after one year of treatment. The different effect of ASA in TIAs and migraine indicates that the platelet activation in TIA patients is due not only to cyclo-oxygenase pathway but also to other in vivo pathways.

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