The pathophysiology of sepsis and its accompanying systemic inflammatory response syndrome (SIRS) and the events that lead to multiorgan failure and death are poorly understood. It is known that, in ...septic humans and rodents, the development of SIRS is associated with a loss of the redox balance, but SIRS can also develop in noninfectious states. In addition, a hyperinflammatory state develops, together with impaired innate immune functions of phagocytes, immunosuppression, and complement activation, collectively leading to septic shock and lethality. Here, we discuss recent insights into the signaling pathways in immune and phagocytic cells that underlie sepsis and SIRS and consider how these might be targeted for therapeutic interventions to reverse or attenuate pathways that lead to lethality during sepsis.
Innate immune responses to trauma Huber-Lang, Markus; Lambris, John D; Ward, Peter A
Nature immunology,
04/2018, Letnik:
19, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent ...complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.
Summary
Sepsis occurs when an infection exceeds local tissue containment and induces a series of dysregulated physiologic responses that result in organ dysfunction. A subset of patients with sepsis ...progress to septic shock, defined by profound circulatory, cellular, and metabolic abnormalities, and associated with a greater mortality. Historically, sepsis‐induced organ dysfunction and lethality were attributed to the complex interplay between the initial inflammatory and later anti‐inflammatory responses. With advances in intensive care medicine and goal‐directed interventions, early 30‐day sepsis mortality has diminished, only to steadily escalate long after “recovery” from acute events. As so many sepsis survivors succumb later to persistent, recurrent, nosocomial, and secondary infections, many investigators have turned their attention to the long‐term sepsis‐induced alterations in cellular immune function. Sepsis clearly alters the innate and adaptive immune responses for sustained periods of time after clinical recovery, with immune suppression, chronic inflammation, and persistence of bacterial representing such alterations. Understanding that sepsis‐associated immune cell defects correlate with long‐term mortality, more investigations have centered on the potential for immune modulatory therapy to improve long‐term patient outcomes. These efforts are focused on more clearly defining and effectively reversing the persistent immune cell dysfunction associated with long‐term sepsis mortality.
Sepsis is a systemic inflammatory response induced by an infection, leading to organ dysfunction and mortality. Historically, sepsis-induced organ dysfunction and lethality were attributed to the ...interplay between inflammatory and antiinflammatory responses. With advances in intensive care management and goal-directed interventions, early sepsis mortality has diminished, only to surge later after "recovery" from acute events, prompting a search for sepsis-induced alterations in immune function. Sepsis is well known to alter innate and adaptive immune responses for sustained periods after clinical "recovery," with immunosuppression being a prominent example of such alterations. Recent studies have centered on immune-modulatory therapy. These efforts are focused on defining and reversing the persistent immune cell dysfunction that is associated with mortality long after the acute events of sepsis have resolved.
Our research addresses the confusion and inconsistency associated with “lean production.” We attempt to clarify the semantic confusion surrounding lean production by conducting an extensive ...literature review using a historical evolutionary perspective in tracing its main components. We identify a key set of measurement items by charting the linkages between measurement instruments that have been used to measure its various components from the past literature, and using a rigorous, two-stage empirical method and data from a large set of manufacturing firms, we narrow the list of items selected to represent lean production to 48 items, empirically identifying 10 underlying components. In doing so, we map the operational space corresponding to conceptual space surrounding lean production. Configuration theory provides the theoretical underpinnings and helps to explain the synergistic relationships among its underlying components.
It must be a fraught task, writing about long covid. The list of symptoms is huge and we don’t really know how it arises. I often feel inadequate faced with patients distressed by their long covid ...symptoms.
Oxidative stress in lung often occurs in humans during acute lung injury (ALI) and in the acute respiratory distress syndrome. The lung inflammatory response may proceed to the development of ...pulmonary fibrosis, a devastating complication that occurs in premature infants after prolonged exposure to high oxygen concentrations. Oxidant‐related ALI can be induced by airway deposition of lipopolysaccharide or IgG immune complexes, resulting in activation of recruited neutrophils and residential macrophages, whose oxidants and proteases produce reversible ALI. In the presence of a powerful trigger of leukocytes (phorbol myristate acetate), or following intrapulmonary deposition of enzymes that generate oxidants, extensive endothelial and epithelial damage and destruction occurs, overwhelming repair mechanisms of lung and resulting in pulmonary fibrosis. How residential or circulating stem cells participate in regeneration of damaged/destroyed cells may provide clues regarding therapy in humans who are experiencing lung inflammatory damage.
The medea hypothesis Ward, Peter Douglas
2009., 20090331, 2009, 2009-03-31, Letnik:
23
eBook
In The Medea Hypothesis, renowned paleontologist Peter Ward proposes a revolutionary and provocative vision of life’s relationship with the Earth’s biosphere--one that has frightening implications ...for our future, yet also offers hope. Using the latest discoveries from the geological record, he argues that life might be its own worst enemy. This stands in stark contrast to James Lovelock’s Gaia hypothesis--the idea that life sustains habitable conditions on Earth. In answer to Gaia, which draws on the idea of the "good mother" who nurtures life, Ward invokes Medea, the mythical mother who killed her own children. Could life by its very nature threaten its own existence? According to the Medea hypothesis, it does. Ward demonstrates that all but one of the mass extinctions that have struck Earth were caused by life itself. He looks at our planet’s history in a new way, revealing an Earth that is witnessing an alarming decline of diversity and biomass--a decline brought on by life’s own "biocidal" tendencies. And the Medea hypothesis applies not just to our planet--its dire prognosis extends to all potential life in the universe. Yet life on Earth doesn’t have to be lethal. Ward shows why, but warns that our time is running out.
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