| 1. |
- Bergstrom, Anna, et al.
(författare)
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Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia
- 2023
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Ingår i: Shock. - : Shock Society. - 1073-2322 .- 1540-0514. ; 59:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.
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| 2. |
- Chew, Michelle S., et al.
(författare)
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Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
- 2022
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Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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| 3. |
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| 4. |
- Elander, Louise, 1980-, et al.
(författare)
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Cyclooxygenase-1 mediates the immediate corticosterone response to peripheral immune challenge induced by lipopolysaccharide
- 2010
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Ingår i: Neuroscience letters. - : Elsevier BV. - 1872-7972 .- 0304-3940. ; 470:1, s. 10-2
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Tidskriftsartikel (refereegranskat)abstract
- Immune-induced activation of the hypothalamus-pituitary-adrenal axis is mediated by cyclooxygenase derived prostaglandins. Here we examined the role of cyclooxygenase-1 in this response, by using genetically modified mice as well as pharmacological inhibition. We found that mice with a deletion of the gene encoding cyclooxygenase-1, in contrast to wild type mice, did not show increased plasma corticosterone at 1h after immune challenge by peripheral injection of bacterial wall lipopolysaccharide, whereas the corticosterone levels were similarly elevated in both genotypes at 6h post-injection. Pretreatment of mice with the selective cyclooxygenase-1 inhibitor SC-560, given orally, likewise inhibited the rapid corticosterone response. These findings, taken together with our recent demonstration that the delayed stress hormone response to immune challenge is dependent on cyclooxygenase-2, show that the two cyclooxygenase isoforms play distinct, but temporally supplementary roles for the stress hormone response to inflammation.
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| 5. |
- Elander, Louise, 1980-, et al.
(författare)
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IL-1β and LPS induce anorexia by distinct mechanisms differentially dependent on microsomal prostaglandin E synthase-1
- 2007
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 292:1, s. R258-R267
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Tidskriftsartikel (refereegranskat)abstract
- Recent work demonstrated that the febrile response to peripheral immune stimulation with proinflammatory cytokine IL-1β or bacterial wall lipopolysaccharide (LPS) is mediated by induced synthesis of prostaglandin E2 by the terminal enzyme microsomal prostaglandin E synthase-1 (mPGES-1). The present study examined whether a similar mechanism might also mediate the anorexia induced by these inflammatory agents. Transgenic mice with a deletion of the Ptges gene, which encodes mPGES-1, and wild-type controls were injected intraperitoneally with IL-1β, LPS, or saline. Mice were free fed, and food intake was continuously monitored with an automated system for 12 h. Body weight was recorded every 24 h for 4 days. The IL-1β induced anorexia in wild-type but not knock-out mice, and so it was almost completely dependent on mPGES-1. In contrast, LPS induced anorexia of the same magnitude in both phenotypes, and hence it was independent of mPGES-1. However, when the mice were prestarved for 22 h, LPS induced anorexia and concomitant body weight loss in the knock-out animals that was attenuated compared with the wildtype controls. These data suggest that IL-1β and LPS induce anorexia by distinct immune-to-brain signaling pathways and that the anorexia induced by LPS is mediated by a mechanism different from the fever induced by LPS. However, nutritional state and/or motivational factors also seem to influence the pathways for immune signaling to the brain. Furthermore, both IL-1β and LPS caused reduced meal size but not meal frequency, suggesting that both agents exerted an anhedonic effect during these experimental conditions. Copyright © 2007 the American Physiological Society.
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| 6. |
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| 7. |
- Elander, Louise, et al.
(författare)
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Inducible Prostaglandin E-2 Synthesis Interacts in a Temporally Supplementary Sequence with Constitutive Prostaglandin-Synthesizing Enzymes in Creating the Hypothalamic-Pituitary-Adrenal Axis Response to Immune Challenge
- 2009
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 29:5, s. 1404-1413
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis has been suggested to depend on prostaglandins, but the prostaglandin species and the prostaglandin-synthesizing enzymes that are responsible have not been fully identified. Here, we examined HPA axis activation in mice after genetic deletion or pharmacological inhibition of prostaglandin E-2-synthesizing enzymes, including cyclooxygenase-1 (Cox-1), Cox-2, and microsomal prostaglandin E synthase-1 (mPGES-1). After immune challenge by intraperitoneal injection of lipopolysaccharide, the rapid stress hormone responses were intact after Cox-2 inhibition and unaffected by mPGES-1 deletion, whereas unselective Cox inhibition blunted these responses, implying the involvement of Cox-1. However, mPGES-1-deficient mice showed attenuated transcriptional activation of corticotropin-releasing hormone (CRH) that was followed by attenuated plasma concentrations of adrenocorticotropic hormone and corticosterone. Cox-2 inhibition similarly blunted the delayed corticosterone response and further attenuated corticosterone release in mPGES-1 knock-out mice. The expression of the c-fos gene, an index of synaptic activation, was maintained in the paraventricular hypothalamic nucleus and its brainstem afferents both after unselective and Cox-2 selective inhibition as well as in Cox-1, Cox-2, and mPGES-1 knock-out mice. These findings point to a mechanism by which ( 1) neuronal afferent signaling via brainstem autonomic relay nuclei and downstream Cox-1-dependent prostaglandin release and ( 2) humoral, CRH transcription-dependent signaling through induced Cox-2 and mPGES-1 elicited PGE(2) synthesis, shown to occur in brain vascular cells, play distinct, but temporally supplementary roles for the stress hormone response to inflammation.
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| 8. |
- Elander, Louise, 1980-
(författare)
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Prostaglandin E2 in Brain-mediated Illness Responses
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- We are unceasingly exposed to potentially harmful microorganisms. The battle against threatening infectious agents includes activation of both the innate and of the adaptive immune systems. Illness responses are elicited and include inflammation, fever, decreased appetite, lethargy and increased sensitivity to painful stimuli in order to defeat invaders. While many of these signs of disease are controlled by the central nervous system, it has remained an enigma how signals from the peripheral immune system reach the brain through its blood-brain barrier, which precludes macromolecules, including cytokines, from diffusing into the brain parenchyma.Previous findings indicate the existence of a pathway across the blood-brain barrier, which includes binding of the cytokine interleukin-1 (IL-1) to its receptor in the brain vessels, thereby inducing the production of the prostaglandin E2 (PGE2) synthesizing enzymes cyclooxygenase-2 (Cox-2) and microsomal prostaglandin E synthase-1 (mPGES-1), which ultimately synthesize PGE2. PGE2 subsequently binds to any of the four prostaglandin E2 (EP) -receptors. Previous results from our laboratory have suggested that this pathway plays a critical role in the febrile response to infectious stimuli. The present thesis aims at further investigating the molecular events underlying immune-to-brain signalling, with special emphasis on fever, hypothalamic-pituitary-adrenal (HPA) -axis activation and anorexia and their connection to signalling molecules of the cytokine and prostaglandin families, respectively.In paper I, the molecular processes linking the proinflammatory cytokine interleukin-6 (IL-6) and PGE2 in the febrile response were investigated. Both IL-6 and PGE2 have been shown to be critical players in the febrile response, although the molecular connections are not known, i.e. if IL-6 exerts its effects up- or downstream of PGE2. Mice deficient in IL-6 were unable to respond to bacterial lipopolysaccharide (LPS) with a febrile response, but displayed similar induction of Cox-2 and mPGES-1, and similar concentrations of PGE2 in the cerebrospinal fluid as wild-type mice. Paradoxically, the IL-6 deficient mice responded with a dose-dependent elevation of body temperature in response to intracerebroventricularly injected PGE2. Furthermore, IL-6 per se was not pyrogenic when injected peripherally in mice, and did not cause increased levels of PGE2 in cerebrospinal fluid. IL-6 deficient mice were not refractory to the action of PGE2 because of excess production of some hypothermia-producing factor, since administration of a Cox-2 inhibitor in LPS-challenged IL-6 deficient mice did not unmask any hypothermic response, and neutralization of tumor necrosis factor α (TNFα), associated with hypothermia, did not produce fever in LPS-challenged IL-6 deficient mice. These data indicate that IL-6 rather than exerting its effects up- or down-stream of PGE2 affects some process in parallel to PGE2, perhaps by influencing the diffusion and binding of PGE2 onto its target neurons.In papers II and III, we injected the proinflammatory cytokine IL-1β in free-fed wild-type mice, in mice with a deletion of the gene encoding mPGES-1, or in mice deficient in the EP1, EP2 and EP3. Food intake was continuously measured during their active period, revealing that mPGES-1 deficient mice were almost completely resistant to anorexia induced by IL-1β. However, all of the investigated EP receptor deficient mice exhibited a normal profound anorexic response to IL-1β challenge, suggesting that the EP4 is the critical receptor that mediates IL-1β-induced anorexia. We also investigated the role of mPGES-1 in anorexia induced by lipopolysaccharide (LPS) in mPGES-1 deficient mice. The profound anorexic response after LPS-challenge was similar in mPGES-1 deficient and wild-type mice. To further investigate the anorectic behaviour after LPS injection, we pre-starved the animals for 22 hours before injecting them with LPS. In this paradigm, the anorexia was less profound in mPGES-1 knock-out mice. Our results suggest that while the inflammatory anorexia elicited by peripheral IL-1β seems largely to be dependent on mPGES-1-mediated PGE2 synthesis, similar to the febrile response, the LPS-induced anorexia is independent of this mechanism in free-fed mice but not in pre-starved animals.In papers IV and V, the role of prostanoids for the immune-induced HPA-axis response was investigated in mice after genetic deletion or pharmacological inhibition of prostanoid-synthesizing enzymes, including Cox-1, Cox-2, and mPGES-1. The immediate LPS-induced release of ACTH (adrenocorticotropic hormone and corticosteroids was critically dependent on Cox-1 derived prostanoids and occurred independently of Cox-2 and mPGES-1 derived PGE2. In contrast, the delayed HPA-axis response was critically dependent on immune-induced PGE2, synthesized by Cox-2 and mPGES-1, and occurred independently of Cox-1 derived enzymes. In addition, in the mPGES-1 deficient mice, the synthesis of CRH hnRNA and mRNA was decreased in the paraventricular nucleus of the hypothalamus after LPS-challenge, indicating that the delayed hormone secretion was mediated by PGE2-induced gene-transcription of CRH in the hypothalamus. The expression of the c-fos gene and Fos protein, an index of synaptic activation, was maintained in the paraventricular nucleus and its brainstem afferents both after unselective and Cox-2 selective inhibition as well as in Cox-1, Cox-2, and mPGES-1 knock-out mice. This suggests that the immune-induced neuronal activation of autonomic relay nuclei occurs independently of prostanoid synthesis and that it is insufficient for eliciting stress hormone release.
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| 9. |
- Elander, Louise, 1980-, et al.
(författare)
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Prostaglandin E2 receptors in IL-1β induced anorexia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Anorexia in response to immune challenge by Interleukin-1β (IL-1β) has been shown to be dependent on Prostaglandin E2 (PGE2) produced by the inducible enzyme microsomal prostaglandin E synthase-1 (mPGES-1). However, it is not known which of the four known PGE2 receptors EP1-4, encoded by the genes Ptger 1-4, that mediates the PGE2-induced anorexia. Here we examined food intake in mice deficient in EP1, EP2 and EP3, respectively, during normal conditions and following treatment with IL-1β. Neither of the gene deletions affected baseline food intake, and all the three genotypes displayed anorexia following IL-1β injection, similar to wild type mice. Previous work has demonstrated that the EP3 receptor is critical for the generation of fever, and that EP1 and EP3 receptors mediate inflammationinduced activation of the hypothalamic-pituitary-adrenal (HPA) axis. The present data, showing intact anorexigenic responses in EP1 and EP3 deficient mice, as well as in mice with deletion of the EP2 receptor, hence suggest that PGE2-elicited acute phase responses are mediated by distinct set or sets of PGE2-receptors.
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| 10. |
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| 11. |
- Engström, Linda, et al.
(författare)
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Acetaminophen reduces lipopolysaccharide-induced fever by inhibiting cyclooxygenase-2
- 2013
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Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 71, s. 124-129
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen is one of the world's most commonly used drugs to treat fever and pain, yet its mechanism of action has remained unclear. Here we tested the hypothesis that acetaminophen blocks fever through inhibition of cyclooxygenase-2 (Cox-2), by monitoring lipopolysaccharide induced fever in mice with genetic manipulations of enzymes in the prostaglandin cascade. We exploited the fact that lowered levels of a specific enzyme make the system more sensitive to any further inhibition of the same enzyme. Mice were immune challenged by an intraperitoneal injection of bacterial wall lipopolysaccharide and their body temperature recorded by telemetry. We found that mice heterozygous for Cox-2, but not for microsomal prostaglandin E synthase-1 (mPGES-1), displayed attenuated fever, indicating a rate limiting role of Cox-2. We then titrated a dose of acetaminophen that did not inhibit the lipopolysaccharide-induced fever in wild-type mice. However, when the same dose of acetaminophen was given to Cox-2 heterozygous mice, the febrile response to lipopolysaccharide was strongly attenuated, resulting in an almost normalized temperature curve, whereas no difference was seen between wild-type and heterozygous mPGES-1 mice. Furthermore, the fever to intracerebrally injected prostaglandin E2 was unaffected by acetaminophen treatment. These findings reveal that acetaminophen, similar to aspirin and other non-steroidal anti-inflammatory drugs, is antipyretic by inhibiting cyclooxygenase-2, and not by inhibiting mPGES-1 or signaling cascades downstream of prostaglandin E2.
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| 12. |
- Forsberg, Gustaf, et al.
(författare)
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Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden
- 2024
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Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 68:2, s. 226-235
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.Conclusion: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.
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| 13. |
- Gabrielsson, Britt, 1957, et al.
(författare)
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Evaluation of reference genes for studies of gene expression in human adipose tissue.
- 2005
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Ingår i: Obesity research. - 1071-7323 .- 1550-8528. ; 13:4, s. 649-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to evaluate reference genes for expression studies of human adipose tissue. RESEARCH METHODS AND PROCEDURES: Using 52 human adipose tissue expression profiles (HU95), 10 putative reference genes with the lowest variation in expression levels were selected for further studies. Expression stability of these 10 novel and 5 previously established reference genes was evaluated by real-time reverse transcriptase-polymerase chain reaction analysis. For this purpose, 44 adipose tissue biopsies from 27 subjects were chosen to include a wide range of parameters such as sex, age, BMI, depot origin, biopsy procedure, and effects of nutrition. RESULTS: LRP10 was identified as the gene with the least variation in expression levels. The frequently used reference genes RPLP0, 18S rRNA, PPIA, ACTB, and GAPD were ranked as 4, 6, 7, 8, and 10, respectively. DISCUSSION: Our results suggest that LRP10 is a better choice as reference for expression studies of human adipose tissue compared with the most frequently used reference genes.
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| 14. |
- Lidell, Martin, 1970, et al.
(författare)
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Evidence for two types of brown adipose tissue in humans
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:5, s. 631-634
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Tidskriftsartikel (refereegranskat)abstract
- The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was
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| 15. |
- Nilsberth, Camilla, et al.
(författare)
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The Role of Interleukin-6 in Lipopolysaccharide-Induced Fever by Mechanisms Independent of Prostaglandin E-2
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 150:4, s. 1850-1860
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Tidskriftsartikel (refereegranskat)abstract
- Fever has been shown to be elicited by prostaglandin E-2 (PGE(2)) binding to its receptors on thermoregulatory neurons in the anterior hypothalamus. The signals that trigger PGE(2) production are thought to include proinflammatory cytokines, such as IL-6. However, although the presence of IL-6 is critical for fever, IL- 6 by itself is not or only weakly pyrogenic. Here we examined the relationship between IL-6 and PGE(2) in lipopolysaccharide (LPS)-induced fever. Immune-challenged IL- 6 knockout mice did not produce fever, in contrast to wild-type mice, but the expression of the inducible PGE(2)-synthesizing enzymes, cyclooxygenase-2 and microsomal prostaglandin E synthase-1, was similarly up-regulated in the hypothalamus of both genotypes, which also displayed similarly elevated PGE(2) levels in the cerebrospinal fluid. Nevertheless, both wild-type and knockout mice displayed a febrile response to graded concentrations of PGE(2) injected into the lateral ventricle. There was no major genotype difference in the expression of IL-1 beta and TNF alpha or their receptors, and pretreatment of IL- 6 knockout mice with soluble TNF alpha receptor ip or intracerebroventricularly or a cyclooxygenase-2 inhibitor ip did not abolish the LPS unresponsiveness. Hence, although IL- 6 knockout mice have both an intact PGE(2) synthesis and an intact fever-generating pathway downstream of PGE(2), endogenously produced PGE(2) is not sufficient to produce fever in the absence of IL-6. The findings suggest that IL- 6 controls some factor(s) in the inflammatory cascade, which render(s) IL- 6 knockout mice refractory to the pyrogenic action of PGE(2), or that it is involved in the mechanisms that govern release of synthesized PGE(2) onto its target neurons.
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| 16. |
- Nilsson, Anna, et al.
(författare)
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The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent
- 2017
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Ingår i: Brain, behavior, and immunity. - : Academic Press. - 0889-1591 .- 1090-2139. ; 60, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- From experiments in mice in which the prostaglandin E2 (PGE2) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE2 was injected directly into the brain, PGE2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE2 receptor (EP1–4) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP1, EP2, and EP3) or selectively in the nervous system (EP4), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE2 in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE2 in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice.
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| 17. |
- Romu, Thobias, et al.
(författare)
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Characterization of Brown Adipose Tissue by Water-Fat Separated Magnetic Resonance Imaging
- 2015
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 42:6, s. 1639-1645
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Tidskriftsartikel (refereegranskat)abstract
- Background: To evaluate the possibility of quantifying brown adipose tissue (BAT) volume and fat concentration with a high resolution, long echo time, dual-echo Dixon imaging protocol. Methods: A 0.42 mm isotropic resolution water-fat separated MRI protocol was implemented by using the second opposite-phase echo and third in-phase echo. Fat images were calibrated with regard to the intensity of nearby white adipose tissue (WAT) to form relative fat content (RFC) images. To evaluate the ability to measure BAT volume and RFC contrast dynamics, rats were divided into two groups that were kept at 48 or 22 degrees C for 5 days. The rats were then scanned in a 70 cm bore 3.0 Tesla MRI scanner and a human dual energy CT. Interscapular, paraaortal, and perirenal BAT (i/pa/pr-BAT) depots as well as WAT and muscle were segmented in the MRI and CT images. Biopsies were collected from the identified BAT depots. Results: The biopsies confirmed that the three depots identified with the RFC images consisted of BAT. There was a significant linear correlation (P< 0.001) between the measured RFC and the Hounsfield units from DECT. Significantly lower iBAT RFC (P=0.0064) and significantly larger iBAT and prBAT volumes (P=0.0017) were observed in the cold stimulated rats. Conclusion: The calibrated Dixon images with RFC scaling can depict BAT and be used to measure differences in volume, and fat concentration, induced by cold stimulation. The high correlation between RFC and HU suggests that the fat concentration is the main RFC image contrast mechanism.
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| 18. |
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| 19. |
- Sörme, Louise, et al.
(författare)
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Indikatorer för att följa konsumenters omställning till en hållbar konsumtion
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Generationsmålet är det övergripande målet för miljöpolitiken i Sverige och innebär att vi till nästa generation ska kunna lämna över ett samhälle där de stora miljöproblemen är lösta, utan att orsaka ökade miljö- och hälsoproblem utanför Sveriges gränser. Som del av detta mål ska miljöpolitiken bland annat fokusera på att konsumtionsmönstren av varor och tjänster orsakar så små miljö- och hälsoproblem som möjligt. Naturvårdsverket ska på uppdrag av Regeringen redovisa en fördjupad utvärdering av generationsmålet och miljökvalitetsmålen 2015. Uppdraget ska redovisas senast den 1 september 2015. Redovisningen ska bland annat innehålla en målövergripande analys av utvecklingen mot generationsmålet och miljökvalitetsmålen. En del av denna analys genomförs inom ramen för tre utvalda fokusområden, däribland hållbar konsumtion. Projektet syftade till att ta fram ett av flera faktaunderlag till Regeringens ovanstående uppdrag om fördjupad utvärdering av miljökvalitetsmålen. Det konkreta målet var att ta fram förslag på möjliga indikatorer samt att beskriva för- och nackdelar med olika förslag samt att dataförsörja fyra indikatorer som följer konsumenters/individers omställning till en mer hållbar konsumtion. De fyra indikatorerna valdes ut av Naturvårdsverket. För att få fram det preliminära indikatorurvalet hämtades bland annat inspiration från andra projekt och sammanställningar av indikatorer i Sverige och utomlands, samt från aktuell diskussion i media och liknande. Därefter gjordes en genomgång ifall det fanns data tillgängliga eller inte. Fanns det data tillgängligt och indikatorn i övrigt uppfyllde kriterier som Naturvårdsverket satt upp ingick den i det urval av 27 indikatorer som beskrevs mer utförligt. I beskrivningen ingick enhet, för- och nackdelar, tidsserie och datakälla. Indikatorerna delades upp i olika områden; mat, textil, elektronik, boende samt transporter. Rapporten nämner också indikatorer som skulle vara önskvärda men där det saknas data, totalt 42 stycken. Naturvårdsverket valde ut följande indikatorer som också har dataförsörjts inom projektet: M1 - Konsumtion av nötkött, kg/person och år M8 - Energiöverskott i matkonsumtionen, procent Tr1 - Persontransporter (totalt och uppdelat på gång/cykel, kollektivtrafik, bil, och övrigt), km/person och år B3 - Uppvärmd boendeyta i hushåll, m2/person
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| 20. |
- Zeuchner, Jakob, et al.
(författare)
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Introduction of a rapid sequence induction checklist and its effect on compliance to guidelines and complications
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:9, s. 1205-1212
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Tidskriftsartikel (refereegranskat)abstract
- Background Current evidence for the conduct of rapid sequence induction (RSI) is weak. This increases the risk of clinicians modifying the RSI procedure according to personal preferences. Checklists may help increase compliance to best practice guidelines and reduce complication rates. Their value during RSI, a critical procedure in anaesthesia, is unknown. The aim of this study was to investigate compliance to local guidelines and frequency of RSI-related complications before and after introduction of an RSI checklist. Methods This was a prospective, observational, pre- and post-intervention study conducted at two hospitals. There were two interventions: the first was a standardized educational lecture to all staff at both hospitals, consisting of an educational instruction of the checklist and general information about RSI, and the second intervention was the introduction of a RSI checklist. The checklist consisted of 16 items. Compliance to guidelines was categorized as high, moderate and low, and was assessed pre- and post-intervention. The frequency of RSI-related complications was also measured. Results We registered 811 RSI procedures of which 412 were pre-intervention. After intervention, the proportion of procedures with high compliance to RSI guidelines increased from 49% to 70% (P < .001). The proportion with partial and low compliance decreased from 37% to 26% (P < .001) and 13% to 3.3% (P < .001) respectively. No change in RSI-related complication rates was detectable post-intervention (16.6%-16.7% P = .56). Conclusion The introduction of a structured RSI checklist significantly increased compliance to RSI guidelines. A change in RSI-related complications could not be detected due to the size of the study. A checklist may be a useful tool to reduce variance during the RSI procedure.
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