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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Cicardi, M., et al.
(författare)
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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema
- 2010
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 363:6, s. 532-541
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
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| 6. |
- Farahi, N, et al.
(författare)
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Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance.
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 41:5, s. 673-687
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophils are pro-inflammatory cells implicated in the pathogenesis of asthma and atopy. Apoptosis has been proposed as a potential mechanism underlying the resolution of eosinophilic inflammation and studies have indicated the ability of interventions that induce human eosinophil apoptosis to promote the resolution of eosinophilic inflammation. Recently, the cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to enhance neutrophil apoptosis and promote the resolution of neutrophilic inflammation. Objective The purpose of this study was to examine the expression of CDKs in human blood eosinophils, the effects of R-roscovitine on eosinophil survival in vitro and whether R-roscovitine could influence eosinophilic lung inflammation in vivo. Methods Eosinophils were isolated from human peripheral blood and the effects of R-roscovitine on apoptosis, degranulation and phagocytic uptake examined in vitro. The effects of R-roscovitine on eosinophilic lung inflammation in vivo were also assessed using an ovalbumin mouse model. Results Our data demonstrate that human eosinophils express five known targets for R-roscovitine: CDK1, -2, -5, -7 and -9. R-roscovitine induced eosinophil apoptosis in a time- and concentration-dependent manner but also accelerated transition to secondary necrosis as assessed by microscopy, flow cytometry and caspase activation. In addition, we show that R-roscovitine can override the anti-apoptotic signals of GM-CSF and IL-5. We report that the pro-apoptotic effect of R-roscovitine is associated with suppression of Mcl-1L expression and that this compound enhanced phagocytic clearance of eosinophils by macrophages. Finally, we show that R-roscovitine induces apoptosis in murine peripheral blood and spleen-derived eosinophils; despite this, R-roscovitine did not modulate the tissue and lumen eosinophilia characteristic of the ovalbumin mouse model of airway eosinophilia. Conclusion and Clinical Relevance These data demonstrate that R-roscovitine is capable of inducing rapid apoptosis and secondary necrosis in eosinophils but does not affect the onset or improve the resolution of eosinophilic airway inflammation in vivo.
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| 8. |
- Kilov, K, et al.
(författare)
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Integrated Management of Childhood Illnesses (IMCI): a mixed-methods study on implementation, knowledge and resource availability in Malawi
- 2021
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Ingår i: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 5:1, s. e001044-
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of the WHO’s Integrated Management of Childhood Illnesses (IMCI) guidelines in the mid-1990s contributed to global reductions in under-five mortality. However, issues in quality of care have been reported. We aimed to determine resource availability and healthcare worker knowledge of IMCI guidelines in two districts in Malawi.MethodsWe conducted a mixed-methods study, including health facility audits to record availability and functionality of essential IMCI equipment and availability of IMCI drugs, healthcare provider survey and focus group discussions (FGDs) with facility staff. The study was conducted between January and April 2019 in Mchinji (central region) and Zomba (southern region) districts. Quantitative data were described using proportions and χ2 tests; linear regression was conducted to explore factors associated with IMCI knowledge. Qualitative data were analysed using a pragmatic framework approach. Qualitative and quantitative data were analysed and presented separately.ResultsForty-seven health facilities and 531 healthcare workers were included. Lumefantrine-Artemether and cotrimoxazole were the most available drugs (98% and 96%); while amoxicillin tablets and salbutamol nebuliser solution were the least available (28% and 36%). Respiratory rate timers were the least available piece of equipment, with only 8 (17%) facilities having a functional device. The mean IMCI knowledge score was 3.96 out of 10, and there was a statistically significant association between knowledge and having received refresher training (coeff: 0.42; 95% CI 0.01 to 0.82). Four themes were identified in the FGDs: IMCI implementation and practice, barriers to IMCI, benefits of IMCI and sustainability.ConclusionWe found key gaps in IMCI implementation; however, these were not homogenous across facilities, suggesting opportunities to learn from locally adapted IMCI best practices. Improving on-going mentorship, training and supervision should be explored to improve quality of care, and programming which moves away from vertical financing with short-term support, to a more holistic approach with embedded sustainability may address the balance of resources for different conditions.
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| 9. |
- Kim, Joo-Hong, et al.
(författare)
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Salinity Control of Thermal Evolution of Late Summer Melt Ponds on Arctic Sea Ice
- 2018
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 45:16, s. 8304-8313
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Tidskriftsartikel (refereegranskat)abstract
- The thermal evolution of melt ponds on Arctic sea ice was investigated through a combination of autonomous observations and two-dimensional high-resolution fluid dynamics simulations. We observed one relatively fresh pond and one saline pond on the same ice floe, with similar depth. The comparison of observations and simulations indicates that thermal convection dominates in relatively fresh ponds, but conductive heat transfer dominates in salt-stratified ponds. Using a parameterized surface energy balance, we estimate that the heat flux to the ice is larger under the saline pond than the freshwater pond when averaged over the observational period. The deviation is sensitive to assumed wind, varying between 3 and 14 W/m(2) for winds from 0 to 5 m/s. If this effect persists as conditions evolve through the melt season, our results suggest that this imbalance potentially has a climatologically significant impact on sea-ice evolution. Plain Language Summary Sea ice provides key feedbacks on polar and global climate, with melt ponds being particularly significant. Melt ponds darken the ice surface, thereby increasing the absorption of sunlight and accelerating ice melt. This study provides a new perspective on melt-pond salinity, its previously unrecognized significance in controlling the thermal properties of ponds, and the potential impact on ice melting as we transition toward a younger sea ice cover. Many state-of-the-art sea ice models represent melt ponds as a freshwater layer with a surface temperature of 0 degrees C, consistent with a past Arctic ocean dominated by desalinated perennial ice and relatively fresh ponds. However, perennial ice has diminished in recent decades, with increasing prevalence of young saline ice. This leads to ponds with a wider range of salinities and temperatures. We show that salinity strongly impacts pond temperatures, using observations of adjacent freshwater and saline melt ponds on Arctic sea ice. Combining this data with model simulations, we find that melt-pond salinity impacts heat transfer to the ice below and the resulting melting rate. Our study reveals that melt-pond salinity and salt stratification are key variables influencing heat transfer in melt ponds, which need to be considered in future model development.
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