The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

NF-κB activation as a pathological mechanism of septic shock and inflammation

2006 ◽  
Vol 290 (4) ◽  
pp. L622-L645 ◽  
Author(s):  
Shu Fang Liu ◽  
Asrar B. Malik
Keyword(s):  
Septic Shock ◽  
Human Subjects ◽  
Myocardial Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pathological Mechanism ◽  
Proinflammatory Gene ◽  
Intensive Investigation ◽  
Sepsis And Septic Shock

The pathophysiology of sepsis and septic shock involves complex cytokine and inflammatory mediator networks. NF-κB activation is a central event leading to the activation of these networks. The role of NF-κB in septic pathophysiology and the signal transduction pathways leading to NF-κB activation during sepsis have been an area of intensive investigation. NF-κB is activated by a variety of pathogens known to cause septic shock syndrome. NF-κB activity is markedly increased in every organ studied, both in animal models of septic shock and in human subjects with sepsis. Greater levels of NF-κB activity are associated with a higher rate of mortality and worse clinical outcome. NF-κB mediates the transcription of exceptional large number of genes, the products of which are known to play important roles in septic pathophysiology. Mice deficient in those NF-κB-dependent genes are resistant to the development of septic shock and to septic lethality. More importantly, blockade of NF-κB pathway corrects septic abnormalities. Inhibition of NF-κB activation restores systemic hypotension, ameliorates septic myocardial dysfunction and vascular derangement, inhibits multiple proinflammatory gene expression, diminishes intravascular coagulation, reduces tissue neutrophil influx, and prevents microvascular endothelial leakage. Inhibition of NF-κB activation prevents multiple organ injury and improves survival in rodent models of septic shock. Thus NF-κB activation plays a central role in the pathophysiology of septic shock.

scholarly journals Pediatric Antiphospholipid Syndrome: from Pathogenesis to Clinical Management

2021 ◽  
Vol 23 (2) ◽  
Author(s):  
Silvia Rosina ◽  
Cecilia Beatrice Chighizola ◽  
Angelo Ravelli ◽  
Rolando Cimaz
Keyword(s):  
Antiphospholipid Syndrome ◽  
Fluid Phase ◽  
Multiple Organ ◽  
Clinical Settings ◽  
Glycoprotein I ◽  
Long Term Follow Up ◽  
Pediatric Populations ◽  
Cellular Components

Abstract Purpose of Review Elucidating the pathogenic mechanisms mediated by antiphospholipid antibodies (aPL) might exert important clinical implications in pediatric antiphospholipid syndrome (APS). Recent Findings aPL are traditionally regarded as the main pathogenic players in APS, inducing thrombosis via the interaction with fluid-phase and cellular components of coagulation. Recent APS research has focused on the role of β2 glycoprotein I, which bridges innate immunity and coagulation. In pediatric populations, aPL should be screened in appropriate clinical settings, such as thrombosis, multiple-organ dysfunction, or concomitant systemic autoimmune diseases. Children positive for aPL tests often present non-thrombotic non-criteria manifestations or asymptomatic aPL positivity. In utero aPL exposure has been suggested to result in developmental disabilities, warranting long-term follow-up. Summary The knowledge of the multifaceted nature of pediatric APS should be implemented to reduce the risk of underdiagnosing/undertreating this condition. Hopefully, recent pathogenic insights will open new windows of opportunity in the management of pediatric APS.

Septic Shock

1992 ◽  
Vol 7 (2) ◽  
pp. 90-100 ◽  
Author(s):  
Margaret M. Parker ◽  
Mitchell P. Fink
Keyword(s):  
Septic Shock ◽  
Supportive Care ◽  
Antimicrobial Therapy ◽  
Clinical Manifestations ◽  
Sepsis Syndrome ◽  
Adjunctive Treatment ◽  
Cardiovascular Changes ◽  
The Past ◽  
Sepsis And Septic Shock ◽  
Very High

The incidence of sepsis and septic shock has been increasing dramatically over the past 10 years. Despite advances in antimicrobial therapy, the mortality of septic shock remains very high. We review the clinical manifestations of sepsis and septic shock and describe the cardiovascular manifestations. Pathophysiology of the cardiovascular changes is discussed, and mediators believed to be involved in the pathogenesis are reviewed. Management of septic shock is also discussed, including antimicrobial therapy, supportive care, and adjunctive treatment aimed at affecting the mediators involved in producing the sepsis syndrome.

Ectomycorrhizae in the Agaricales and Gasteromycetes

1983 ◽  
Vol 61 (3) ◽  
pp. 909-916 ◽  
Author(s):  
Orson K. Miller Jr.
Keyword(s):  
Fruiting Body ◽  
Biological Role ◽  
Spore Morphology ◽  
Generic Level ◽  
Body Form ◽  
Ecological Conditions ◽  
Fungal Succession ◽  
The Past ◽  
Made In

Over the past decade much progress has been made in an effort to determine which fungi are mycorrhizal symbionts. It is now apparent that one ectomycorrhizal or ectendomycorrhizal host is often able to form mycorrhizae with a wide variety of higher fungi. Evidence is presented which supports the hypothesis that fungal succession occurs as the host matures. In addition, fungi which are normally ectomycorrhizal may sometimes form endomycorrhizae on different hosts or under altered ecological conditions. There has also been much evolution in fruiting-body form and mode of spore discharge especially under severe montane or desert conditions. As a result patterns are emerging in the Homobasidiomycetes at the order, family, and generic level in the evolution of the mycorrhizal habit. Spore morphology, habitat, and distribution are listed and discussed in relation to the biological role of the fungi.

Sepsis

2020 ◽  
Author(s):  
Steven P LaRosa ◽  
Steven M. Opal
Keyword(s):  
Intensive Care Unit ◽  
Septic Shock ◽  
Severe Sepsis ◽  
Intensive Care ◽  
Organ Dysfunction ◽  
Fluid Resuscitation ◽  
Multiorgan Failure ◽  
Sepsis Management ◽  
The Past ◽  
Sepsis And Septic Shock

Sepsis, along with the multiorgan failure that often accompanies this condition, is a leading cause of mortality in the intensive care unit. Although modest improvements in the prognosis have been made over the past two decades and promising new therapies continue to be investigated, innovations in the management of septic shock are still required. This chapter discusses the definitions, epidemiology, and pathogenesis (including microbial factors, host-derived mediators, and organ dysfunction) relating to sepsis. Management of severe sepsis and septic shock is also described.  This review contains 5 figures, 11 tables, and 99 references. Keywords:Organ dysfunction, sepsis, septic shock, infection, bacteremia, fluid resuscitation, vasopressor

The Role of Biography in Writing the History of Archaeology (1992)

2008 ◽  
Author(s):  
Douglas R. Givens
Keyword(s):  
No Value ◽  
History Of Archaeology ◽  
History Of Anthropology ◽  
Historical Evidence ◽  
Past Work ◽  
The Past ◽  
Institutional Influences ◽  
History Of ◽  
Made In

The history of any discipline involves the explanation of its past and how the past has influenced its development through time. Its ‘objects are events which have finished happening, and conditions no longer in existence. Only when they are no longer perceptible do they become objects of historical thought’ (Collingwood 1946: 233). Writing the history of archaeology involves the analysis of past events and of the contributions that individual archaeologists have made to its development through time. The roles of individuals in archaeology are best seen in biographical accounts of their labours and in the contributions to the discipline that they have made. In general, historians of archaeological science, who are interested in explaining the roles of the individuals in its development, must focus their attention on three important items. First, the most important item is evidence that something has occurred. If individuals’ contributions have no basis in truth and cannot be justified, then they are of no value to the historian of archaeology. Second, the historical picture of individuals’ lives and work must have defined boundaries in space and time. These provide the area of focus for study and description of individuals’ activities. Third, the efforts of individual practitioners must be couched within the intellectual climate in which they are made. Individuals’ contributions are not made in an intellectual vacuum, apart from collegial or institutional influences. Biography, as a tool for writing the history of archaeology, must embrace all of these requisites. For those engaged in explaining archaeology’s past, historical evidence of event and period provide the foundation upon which we can trace our science’s development. Studying and evaluating past work can be helpful in separating useful and outdated methodologies of the field and laboratory. Moreover, the study of the history of anthropology may give the anthropologist needed ‘distance from their own theoretical and methodological preoccupations’ (Darnell 1974: 2). What we see anthropology today as being is certainly not what the ultimate science of humankind will be in the future.

scholarly journals Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Giusy Tiseo ◽  
Elena Cavarretta ◽  
Arianna Forniti ◽  
Cristina Nocella ◽  
Sebastiano Sciarretta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Healthy Controls ◽  
Sample Collection ◽  
Oxidative Stress Status ◽  
Sepsis And Septic Shock ◽  
A Prospective Study

Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( n = 10 , age 67.8 ± 3.2 , male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, p < 0.001 ), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, p < 0.001 ), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, p < 0.001 ), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, p < 0.001 ). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed. Conclusions. Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.

scholarly journals Sciences and audiences along the last century: the impact of Astronomy Education

2018 ◽  
Vol 13 (S349) ◽  
pp. 474-478
Author(s):  
Rosa M. Ros ◽  
Beatriz Garca
Keyword(s):  
Secondary Teachers ◽  
Astronomy Education ◽  
Interest In Science ◽  
The Past ◽  
The World ◽  
History Of ◽  
The Impact ◽  
Made In ◽  
Science Activities

AbstractJust as in the past, the development of the natural sciences and in particular of astronomy has changed the history of humanity. If we think about the role of our discipline into the future, it shows its enormous power in the field of education, owing to the possibility of awakening interest in science in very varied audiences. Within the framework of the enormous progress made in the technologies related to astronomy, many of them of daily use, the role of the astronomer in the era of Communications acquires fundamental importance.In this presentation, we will try to make a journey through the different ways of presenting astronomical topics for different audiences over the last 100 years. In turn, we will show some specific achievements, associated with education programmes of the discipline. We discuss the impact produced by proposals that are both rigorous in terms of content, and also appeal to the development of the human being in an integral manner, within the framework of citizen science activities.For this research, we have taken into account the uninterrupted development of the NASE programme, which has performed 112 courses in 24 countries throughout the world and in different languages. NASE has involved 4966 secondary teachers in the last eight years.

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