Inflammasomes in sepsis

Hurtado-Navarro, Laura; García-Palenciano, Carlos; Pelegrı́n, Pablo

doi:10.1016/b978-0-323-91802-2.00014-1

Cited by 2 publications

(2 citation statements)

References 66 publications

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“…26 Sepsis is a complicated clinical condition with high mortality and morbidity and is often accompanied by multiorgan dysfunction. 27 Acute inflammation bursts and subsequent immune constraint finally involve the brain, mediating diffuse brain disorders. 28,29 In this study, we utilized in vivo and in vitro models of LPS-induced endotoxemia to simulate the acute inflammatory response in sepsis and investigated whether propofol and dexmedetomidine, either alone or in combination, are involved in LPS-induced cognitive impairment and several neural pathological deficiencies.…”

Section: Discussionmentioning

confidence: 99%

Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis

Zhou,

Yang,

et al. 2024

DDDT

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Background: Sepsis is recognized as a multiorgan and systemic damage caused by dysregulated host response to infection. Its acute systemic inflammatory response highly resembles that of lipopolysaccharide (LPS)-induced endotoxemia. Propofol and dexmedetomidine are two commonly used sedatives for mechanical ventilation in critically ill patients and have been reported to alleviate cognitive impairment in many diseases. In this study, we aimed to explore and compare the effects of propofol and dexmedetomidine on the encephalopathy induced by endotoxemia and to investigate whether ferroptosis is involved, finally providing experimental evidence for multi-drug combination in septic sedation. Methods: A total of 218 C57BL/6J male mice (20-25 g, 6-8 weeks) were used. Morris water maze (MWM) tests were performed to evaluate whether propofol and dexmedetomidine attenuated LPS-induced cognitive deficits. Brain injury was evaluated using Nissl and Fluoro-Jade C (FJC) staining. Neuroinflammation was assessed by dihydroethidium (DHE) and DCFH-DA staining and by measuring the levels of three cytokines. The number of Iba1 + and GFAP + cells was used to detect the activation of microglia and astrocytes. To explore the involvement of ferroptosis, the levels of ptgs2 and chac1; the content of iron, malondialdehyde (MDA), and glutathione (GSH); and the expression of ferroptosis-related proteins were investigated. Conclusion:The single use of propofol and dexmedetomidine mitigated LPS-induced cognitive impairment, while the combination showed poor performance. In alleviating endotoxemic neural loss and degeneration, the united sedative group exhibited the most potent capability. Both propofol and dexmedetomidine inhibited neuroinflammation, while propofol's effect was slightly weaker. All sedative groups reduced the neural apoptosis, inhibited the activation of microglia and astrocytes, and relieved neurologic ferroptosis. The combined group was most prominent in combating genetic and biochemical alterations of ferroptosis. Fpn1 may be at the core of endotoxemia-related ferroptosis activation.

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Section: Discussionmentioning

confidence: 99%

Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis

Zhou,

Yang,

et al. 2024

DDDT

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“… 2 In many states with abortion bans, the list of exceptions is narrow and confusing, with few or no exceptions for maternal health or life endangerment. 3 , 4 In this context, clinicians may increasingly find themselves facing a difficult dilemma: either fail to provide appropriate, conscience-driven medical care or put themselves in legal and professional jeopardy. This conflicting experience may give rise to moral distress, or the emotional harm that occurs when a clinician’s conscience guides them to provide specific care that is in line with professional standards, but external constraints, such as state or institutional policies, block them from being able to do so.…”

Section: Introductionmentioning

confidence: 99%

State Abortion Policy and Moral Distress Among Clinicians Providing Abortion After the Dobbs Decision

Rivlin,

Bornstein,

Wascher

et al. 2024

JAMA Netw Open

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ImportanceMoral distress occurs when individuals feel powerless to do what they think is right, including when clinicians are prevented from providing health care they deem necessary. The loss of federal protections for abortion following the Dobbs v Jackson Women’s Health Organization Supreme Court decision may place clinicians providing abortion at risk of experiencing moral distress, as many could face new legal and civil penalties for providing care in line with professional standards and that they perceive as necessary.ObjectiveTo assess self-reported moral distress scores among abortion-providing clinicians following the Dobbs decision overall and by state-level abortion policy.Design, Setting, and ParticipantsThis survey study, conducted from May to December 2023, included US abortion-providing clinicians (physicians, advanced practice clinicians, and nurses). A purposive electronic survey was disseminated nationally through professional listservs and snowball sampling.ExposureAbortion policy in each respondent’s state of practice (restrictive vs protective using classifications from the Guttmacher Institute).Main Outcomes and MeasuresUsing descriptive statistics and unadjusted and adjusted negative binomial regression models, the association between self-reported moral distress on the Moral Distress Thermometer (MDT), a validated psychometric tool that scores moral distress from 0 (none) to 10 (worst possible), and state abortion policy was examined.ResultsOverall, 310 clinicians (271 [87.7%] women; mean [SD] age, 41.4 [9.7] years) completed 352 MDTs, with 206 responses (58.5%) from protective states and 146 (41.5%) from restrictive states. Reported moral distress scores ranged from 0 to 10 (median, 5) and were more than double for clinicians in restrictive compared with protective states (median, 8 [IQR, 6-9] vs 3 [IQR, 1-6]; P &lt; .001). Respondents with higher moral distress scores included physicians compared with advanced practice clinicians (median, 6 [IQR, 3-8] vs 4 [IQR, 2-7]; P = .005), those practicing in free-standing abortion clinics compared with those practicing in hospitals (median, 6 [IQR, 3-8] vs 4 [IQR, 2-7]; P &lt; .001), those no longer providing abortion care compared with those still providing abortion care (median, 8 [IQR, 4-9] vs 5 [IQR, 2-8]; P = .004), those practicing in loss states (states with the greatest decline in abortion volume since the Dobbs decision) compared with those in stable states (unadjusted incidence rate [IRR], 1.72 [95% CI, 1.55-1.92]; P &lt; .001; adjusted IRR, 1.59 [95% CI, 1.40-1.79]; P &lt; .001), and those practicing in surge states (states with the greatest increase in abortion volume since the Dobbs decision) compared with those in stable states (unadjusted IRR, 1.27 [95% CI, 1.11-1.46]; P &lt; .001; adjusted IRR, 1.24 [95% CI, 1.09-1.41]; P = .001).Conclusions and RelevanceIn this purposive national survey study of clinicians providing abortion, moral distress was elevated among all clinicians and more than twice as high among those practicing in states that restrict abortion compared with those in states that protect abortion. The findings suggest that structural changes addressing bans on necessary health care, such as federal protections for abortion, are needed at institutional, state, and federal policy levels to combat widespread moral distress.

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Inflammasomes in sepsis

Cited by 2 publications

References 66 publications

Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis

Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis

State Abortion Policy and Moral Distress Among Clinicians Providing Abortion After the Dobbs Decision

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