In septic shock (SS), hydrogen peroxide (H2O2) and other reactive oxygen species (ROS) are released by inflammatory cells and have been implicated in tissue damage and inflammation. Recently, H2O2 has been established as an important signaling molecule and an important component of SS. The pathways involved in this process are not completely understood, but the formation of hydroperoxides (HPs), arachidonic acid (AA) metabolites and potassium (K+) channels have been implicated. In this study, we used a canine carotid ring preparation as a bioassay to determine the role of peroxyacetic acid (POX), a hydroperoxide (HP), in causing vasodilation and elucidate the subsequent pathways involved. We removed internal carotid artery segments from dogs and placed them in an organ bath. The segments were preconstricted after which we added POX to the preparation. We found that POX produced an endothelium and nitric oxide independent vasodilation in the carotid artery ring preparation. This decrease in tension could be prevented by high concentrations of K+ in the bath. This suggested that K+ channels were involved in POX’s action. Further investigation showed that the particular K+ channels implicated were the combination of small (SKCa) and intermediate conductance calcium activated K+ channels (IKCa). In addition we found that the prostaglandin H synthase (PGHS) inhibitor, indomethacin, could block POX’s mechanism of action. This finding indicates that PGHS takes part in the vasodilation caused by POX. Our results suggest that HPs that are released from inflammatory cells in sepsis could stimulate the PGHS pathway leading to prostaglandin synthesis and subsequently activating SKCa and IKCa to produce vasodilation. Inhibition of this pathway may be important component in the treatment of SS.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Ulm, Univ., Diss., 2008.

Ulm, Univ., Diss., 2008.

Regensburg, Univ., Diss., 2009.

Thesis (M.A.)--Boston University, 2012. / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Recent evidence has suggested that vitamin D may modulate innate immune function. We performed a prospective, observational investigation to assess the prevalence of vitamin D deficiency in adult critically ill patients with sepsis. Subjects were categorized by baseline 25-hydroxyvitamin D [25(0H)D]: Deficient: < 20 ng/ml, Insufficient: 21-29 ng/ml, or Normal: > 29 ng/ml. A total of 39 subjects were enrolled in the study. 25(0H)D deficiency is common with 23/39 (59%) of subjects either deficient or insufficient. In-hospital mortality was 15% (6/39) and 5/6 (83%) of the subjects who expired were 25(0H)D insufficient. There were modest differences in severity of illness across 25(0H)D categories (SAPS 3: p = 0.01) and statistically significant inverse associations between 25(0H)D and markers of inflammation (IL-6: p = 0.04; TN F-a: p = 0.03) and vascular endothelial dysfunction (E-selectin: p = 0.05). There is a high prevalence of vitamin D deficiency or insufficiency in critically ill patients with sepsis and an inverse association between vitamin D and inflammation and vascular endothelial dysfunction. Future studies should assess the causal relationship between vitamin D and inflammation and outcomes from sepsis. / 2031-01-02

Bakgrund: Sepsis är ett globalt hälsoproblem med oacceptabelt hög mortalitet. Som omvårdnadsansvarig har sjuksköterskan ett viktigt arbete i att identifiera patienten med sepsis för att behandling skall kunna ges i tid. Syfte: Syftet med litteraturstudien var att beskriva faktorer som påverkar sjuksköterskors identifiering av sepsis. Metod: Studien var en litteraturstudie och utformades enligt Polit och Becks (2017) flödesschema i nio steg. Databassökning genomfördes i CINAHL och PubMed. Litteraturstudiens resultat baserades på tio vetenskapliga artiklar som genomgick systematisk urvalsprocess innan kvalitetsgranskning. Resultat: Databearbetning och analys resulterade i tre huvudkategorier; klinisk kunskap, arbetsmiljö, utbildning och två underkategorier; erfarenhet, hjälpmedel i klinisk verksamhet.  Slutsats: Många faktorer påverkar sjuksköterskan i identifieringen av sepsis. Kunskapsbrist, hög arbetsbelastning, brist på utbildning och frånvaro av adekvata hjälpmedel var de vanligaste faktorerna som framkom i litteraturstudiens resultat. Kliniskt verksamma sjuksköterskor behöver fler hjälpmedel och mer utbildning för att öka kunskapen om sepsis.

Following the TLR-dependent initiation phase of acute systemic proinflammatory responses such as sepsis, an adaptive phase represses or activates a specific pattern of gene expression until the inflammation resolves. Here, we used the THP-1 sepsis cell model of bacterial LPS/endotoxin tolerance to show that TLR4- induced miR-146a supports the feed-forward adaptive processes that silence transcription and disrupt translation of acute proinflammatory genes. First, we found that miR-146a regulates a pathway that promotes the binding of transcription repressor RelB to the TNF-α promoter, a step known to precede histone and DNA modifications, which generate facultative heterochromatin to silence acute proinflammatory genes. However, once RelB binding occurred, miR-146a inhibition could not reverse compacted chromatin, and endotoxin tolerance persisted. Second, we observed that miR- 146a regulates a pathway that supports assembly of the translation repressor complex of TNF-α by preventing the interaction of the RNA-binding protein effector Ago2 and RBM4. We also determined that once endotoxin tolerance is established, and specific genes have been reprogrammed, transcription and translation disruption can be reversed only by simultaneously depleting RelB and inhibiting miR-146a. Thus, miR-146a induction supports the TLR4-dependent shift from initiation to gene-specific repression at two levels. Our results also imply that therapies designed to reverse endotoxin tolerance as potential therapies for sepsis should be directed at the transcription and translation pathways of reprogramming.

No description available.

Bakgrund: Sepsis är ett livshotande tillstånd med hög mortalitet. Upptäckten av tillståndet kompliceras av att kroppens reaktion mot den bakomliggande infektionen börjar innan kliniska symtom uppkommer vilket försvårar identifiering. Tidig upptäckt och omedelbara åtgärder är avgörande för framgångsrik handläggning av patienter med sepsis. Sjuksköterskan har en central roll i identifiering av sepsis vilket är en komplex och utmanande uppgift. Uppsatsens teoretiska referensram för att undersöka sjuksköterskans handläggning av patienter med sepsis var personcentrerad vård.  Syftet: Att kartlägga faktorer som var av betydelse för handläggningen av patienter med sepsis på akutmottagning.Metod: Litteraturöversikten som inkluderade 12 vetenskapliga artiklar med kvantitativ ansats, analyserades enligt Fribergs fyra steg.  Resultat: Tre kategorier identifierades: bedömning, diagnostisering och behandling. Resultatet visade att sjuksköterskans handläggande av sepsis är komplext och påverkades av identifieringstid, teamarbete, provtagning av laktat samt tid till administration av antibiotika. Förutom detta framkom det även att sepsisutbildning och bedömningsinstrument behövdes för att öka sjuksköterskornas kunskap om sepsis.  Slutsats: Litteraturöversikten lyfte fram faktorer av betydelse för handläggande av patienter med sepsis såsom vikten av tidiga insatser och att sjuksköterskor behöver mer kunskap om handläggandet vid sepsis och på det sättet stärka sitt kliniska handläggande. Därtill krävs bedömningsinstrument och tydliga protokoll. Förslag på vidare forskning är att studera hur en kombination av dessa faktorer kan påverka mortaliteten vid sepsis.  Nyckelord: Hantering, Kompetens, Sepsis, Sjuksköterska / Title: Important factors in the management of sepsis in the emergency department Background: Sepsis is a life-threatening condition with a high mortality rate. Discovery of the condition is complicated and is aggravated by the fact that the body ́s reaction to the infection begins before clinical symptoms appear which makes identification more difficult. Early identification and the initiation of rapid measurements are critical to successful management of patients with sepsis. The nurse’s role in identifying signs of sepsis is a complex and challenging task. In this thesis, the chosen theoretical frame of reference, to investigate nurses’ management of sepsis was person-centered care.  Aim: To chart factors that was of importance for management of patients with sepsis in the emergency department.Method: The literature review which included 12 scientific articles with quantitative approach, were were analysed according to Friberg’s method of four-step analysis. Results: Three categories were identified, assessment, diagnostics and treatment. The results show that the nurses’ management of sepsis is complex and influenced by time to identification, teamwork, measuring of lactate and time span before the initiation of antibiotics. Additionally, the study showed that education on sepsis and well- established assessment instruments are needed to increase nurses’ knowledge of sepsis.  Conclusion: The literature review highlights factors of importance for the management of patients with sepsis such as the need of further education and an in- depth knowledge for nurses about sepsis and how to properly handle patients at an early stage. Increased competence, improved assessment instruments as well as clear protocols are needed. Suggestions for further research are to study how the identified factors can affect mortality.  Key words: Competence, Management, Nurse, Sepsis