| 1. |
- van der Post, Sjoerd, 1981, et al.
(författare)
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Site-specific O-glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB).
- 2013
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 288:20, s. 14636-46
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Tidskriftsartikel (refereegranskat)abstract
- The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation.
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| 2. |
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| 3. |
- Dahlén, Johan, et al.
(författare)
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Spontaneous formation of gamma-hydroxybutyric acid from gamma-butyrolactone in tap water solutions
- 2011
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Ingår i: Forensic Science International. - : Elsevier Science B.V., Amsterdam.. - 0379-0738 .- 1872-6283. ; 210:1-3, s. 247-256
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Tidskriftsartikel (refereegranskat)abstract
- The spontaneous conversion of g-butyrolactone (GBL) to g-hydroxybutyric acid (GHB) in seven different Swedish tap waters was investigated. The waters used in the study were selected to represent the diversity among Swedish tap waters as well as possible, which was enabled by principal component analysis (PCA) of a number of water quality parameters. GBL solutions (5, 25 and 50% v/v) were prepared in each of the tap waters and in deionized water and the formation of GHB was followed over time. The GHB quantifications were made using a CZE method, employing a carrier electrolyte consisting of 25 mM benzoic acid, 54 mM tris(hydroxymethyl) aminomethane (Tris) and 1.7 mM tetradecyltrimethylammonium bromide (TTAB), which was developed as a part of the current study. Data evaluation showed that the formation of GHB was largely dependent on the type of tap water. For example, there was a negative correlation between the kinetics of the GHB formation and the alkalinity of the tap waters (r(2) = 0.990). This could be explained by a faster decrease in pH in the waters with low buffering capacity (i.e. low alkalinity), which catalysed the hydrolysis of GBL. Equilibrium was reached after 40-250 days depending on the initial GBL concentration and the type of tap water. The level of the equilibrium appeared to be dependent on the initial GBL concentration and ranged from 26 to 37%. Gained knowledge on the levels of the GHB/GBL equilibrium and the kinetics of the formation of GHB in tap water solutions of GBL, including the influence of the tap water quality, may be useful information for casework with the GHB/GBL problem in focus. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 4. |
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| 5. |
- Dyrager, Christine, 1975, et al.
(författare)
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Inhibitors and promoters of tubulin polymerization : Synthesis and biological evaluation of chalcones and related dienones as potential anticancer agents
- 2011
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 19:8, s. 2659-2665
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Tidskriftsartikel (refereegranskat)abstract
- A series of dihalogenated chalcones and structurally related dienones were synthesized and evaluated for their antiproliferative activity in 10 different cancer cell lines and for their effect on microtubule assembly. All compounds showed cytotoxic activity, with IC50 values in the 5-280 mu M range depending on the chalcone structure and the cell line. Five of the compounds were found to be tubulin polymerization inhibitors. In contrast, one of the compounds was found to stabilize tubulin to the same extent as the anticancer drug docetaxel. Molecular modeling suggested that the tubulin inhibitors bind to the colchicine binding site of beta-tubulin while the novel tubulin stabilization agent seems to interact with the paclitaxel binding site.
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| 6. |
- Edqvist, Malin, et al.
(författare)
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The effect of two midwives during the second stage of labour to reduce severe perineal trauma (Oneplus) : a multicentre, randomised controlled trial in Sweden
- 2022
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 399:10331, s. 1242-1253
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe perineal trauma (SPT) affecting the anal sphincter muscle complex is a serious complication following childbirth, associated with short-term and long-term maternal morbidity. Effective preventive strategies are still scarce. The aim of the Oneplus trial was to test the hypothesis that the presence of a second midwife during the second stage of labour, with the purpose of preventing SPT, would result in fewer injuries affecting the anal sphincter than if attended by one midwife.METHODS: In this multicentre, randomised, controlled parallel group, unmasked trial done at five obstetric units in Sweden, women were randomly assigned to be assisted by either one or two midwives in late second stage. Nulliparous women and women planning the first vaginal birth after caesarean section who were age 18-47 years were randomly assigned to an intervention when reaching the second stage of labour. Further inclusion criteria were gestational week 37+0, carrying a singleton live fetus in vertex presentation, and proficiency in either Swedish, English, Arabic, or Farsi. Exclusion criteria were a multiple pregnancy, intrauterine fetal demise, a planned caesarean section, or women who were less than 37 weeks pregnant. Randomisation to the intervention group of two midwives or standard care group of one midwife (1:1) was done using a computer-based program and treatment groups were allocated by use of sealed opaque envelopes. All women and midwives were aware of the group assignment, but the statistician from Clinical Studies Forum South, who did the analyses, was masked to group assignment. Midwives were instructed to implement existing prevention models and the second midwife was to assist on instruction of the primary midwife, when asked. Midwives were also instructed to complete case report forms detailing assistance techniques and perineal trauma prevention techniques. The primary outcome was the proportion of women who had SPT, for which odds ratios (ORs) and 95% CIs were calculated, and logistic regression was done to adjust for study site. All analyses were done according to intention to treat. The trial is registered with ClinicalTrials.gov, NCT0377096.FINDINGS: Between Dec 10, 2018, and March 21, 2020, 8866 women were assessed for eligibility, and 4264 met the inclusion criteria and agreed to participate. 3776 (88·5%) of 4264 women were randomly assigned to an intervention after reaching the second stage of labour. 1892 women were assigned to collegial assistance (two midwives) during the second stage of labour and 1884 women were assigned to standard care (one midwife). 13 women in each group did not meet the inclusion criteria and were excluded. After further exclusions, 1546 women spontaneously gave birth in the intervention group and 1513 in the standard care group. 1546 women in the intervention group and 1513 in the standard care group were included in the intention-to-treat analysis of the primary outcome. There was a significant reduction in SPT in the intervention group (3·9% [61 of 1546] vs 5·7% [86 of 1513]; adjusted OR 0·69 (0·49-0·97).INTERPRETATION: The presence of two midwives during the active second stage can reduce SPT in women giving birth for the first time.
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| 7. |
- Edqvist, Malin, et al.
(författare)
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The Effect of Two Midwives During the Second Stage of Labour to Reduce Severe Perineal Trauma (Oneplus) : A Multicentre, Randomized Controlled Trial in Sweden
- 2022
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Ingår i: Obstetrical and Gynecological Survey. - : Ovid Technologies (Wolters Kluwer Health). - 0029-7828 .- 1533-9866. ; 77:9, s. 513-515
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Tidskriftsartikel (refereegranskat)abstract
- In many high-income countries, severe perinatal trauma (SPT), affecting the anal sphincter muscle complex, has been on the rise over the last decade. However, effective strategies to prevent SPT are scarce. In randomized controlled trials, only perineal warm compresses and massage have shown benefit. Other cohort studies have shown that prevention models involving several components can decrease the occurrence of SPT, including a stepped-wedge design that reduced SPT from 3.3% to 3.0%. In Scandinavia, a preventive strategy called collegial assistance has been used to help prevent SPT. This strategy involves 2 mid-wives who assist the woman in the second stage of labor, with the second midwife primarily focused on preventing SPT. The aim of this study was to compare the rate of SPT in pregnancies managed by collegial assistance versus a single midwife. This Oneplus study was a randomized, controlled, unmasked trial, conducted at 5 obstetric units in Sweden between December 10, 2018, and March 21, 2020. Included were adult women with uncomplicated singleton pregnancies at >37 weeks of gestation, who were carrying their first child or having their first vaginal birth after cesarean delivery. Excluded were women who had multiple pregnancies, had intrauterine fetal demise, were undergoing a planned cesarean section, or were at <37 weeks' gestation. Women were randomly assigned to either the intervention group with 2 midwives in attendance during active second stage labor or standard care with 1 midwife. All midwives were asked to document the preventive methods used in case report forms. A total of 3750 women were included in the final analysis-with 1879 women receiving collegial assistance and 1871 women receiving standard care. Of the women who gave birth spontaneously, 1546 were in the intervention group and 1513 in the standard care group. Severe perinatal trauma occurred less frequently in the intervention group than the standard care group (3.9% vs 5.7%; odds ratio, 0.68; 95% confidence interval, 0.49-0.97; P = 0.025). In the intervention group, 0.2% had fourth-degree tears compared with 0.5% in the standard care group. The median time for collegial assistance was 15 minutes (interquartile range, 10-20 minutes). The use of perineal warm compresses was similar in the intervention group and standard care group (86.4% vs 85.7%, respectively). No differences were observed in birth positions, manual perineal protection, neonatal outcomes, or secondary maternal outcomes. In conclusion, the attendance of a second midwife dedicated to preventing SPT during the second stage of labor significantly reduced the risk of injury.
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| 8. |
- Edqvist, Malin, et al.
(författare)
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The effect of two midwives during the second stage of labour to reduce severe perineal trauma (Oneplus) : a multicentre, randomised controlled trial in Sweden
- 2022
-
Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 399:10331, s. 1242-1253
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSevere perineal trauma (SPT) affecting the anal sphincter muscle complex is a serious complication following childbirth, associated with short-term and long-term maternal morbidity. Effective preventive strategies are still scarce. The aim of the Oneplus trial was to test the hypothesis that the presence of a second midwife during the second stage of labour, with the purpose of preventing SPT, would result in fewer injuries affecting the anal sphincter than if attended by one midwife.MethodsIn this multicentre, randomised, controlled parallel group, unmasked trial done at five obstetric units in Sweden, women were randomly assigned to be assisted by either one or two midwives in late second stage. Nulliparous women and women planning the first vaginal birth after caesarean section who were age 18–47 years were randomly assigned to an intervention when reaching the second stage of labour. Further inclusion criteria were gestational week 37+0, carrying a singleton live fetus in vertex presentation, and proficiency in either Swedish, English, Arabic, or Farsi. Exclusion criteria were a multiple pregnancy, intrauterine fetal demise, a planned caesarean section, or women who were less than 37 weeks pregnant. Randomisation to the intervention group of two midwives or standard care group of one midwife (1:1) was done using a computer-based program and treatment groups were allocated by use of sealed opaque envelopes. All women and midwives were aware of the group assignment, but the statistician from Clinical Studies Forum South, who did the analyses, was masked to group assignment. Midwives were instructed to implement existing prevention models and the second midwife was to assist on instruction of the primary midwife, when asked. Midwives were also instructed to complete case report forms detailing assistance techniques and perineal trauma prevention techniques. The primary outcome was the proportion of women who had SPT, for which odds ratios (ORs) and 95% CIs were calculated, and logistic regression was done to adjust for study site. All analyses were done according to intention to treat. The trial is registered with ClinicalTrials.gov, NCT0377096.FindingsBetween Dec 10, 2018, and March 21, 2020, 8866 women were assessed for eligibility, and 4264 met the inclusion criteria and agreed to participate. 3776 (88·5%) of 4264 women were randomly assigned to an intervention after reaching the second stage of labour. 1892 women were assigned to collegial assistance (two midwives) during the second stage of labour and 1884 women were assigned to standard care (one midwife). 13 women in each group did not meet the inclusion criteria and were excluded. After further exclusions, 1546 women spontaneously gave birth in the intervention group and 1513 in the standard care group. 1546 women in the intervention group and 1513 in the standard care group were included in the intention-to-treat analysis of the primary outcome. There was a significant reduction in SPT in the intervention group (3·9% [61 of 1546] vs 5·7% [86 of 1513]; adjusted OR 0·69 (0·49–0·97).InterpretationThe presence of two midwives during the active second stage can reduce SPT in women giving birth for the first time.FundingThe Swedish Research Council for Health, Working Life and Welfare; Jan Hains Research Foundation; and Skane County Council's Research and Development Foundation.
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| 9. |
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| 10. |
- Gulliksson, Magdalena, et al.
(författare)
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Expression of 15-lipoxygenase type-1 in human mast cells
- 2007
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1771:9, s. 1156-65
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Tidskriftsartikel (refereegranskat)abstract
- Mast cells play a key role in the pathophysiology of asthma. These cells exert their effector functions by releasing a variety of proinflammatory and immunoregulatory compounds. Mast cells infiltrate the bronchial epithelium and smooth muscle to a higher degree in patients with asthma compared to control subjects. 15-Lipoxygenase type-1 (15-LO-1) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Here we report that interleukin-4 (IL-4) induced the expression of 15-LO-1 in human cord blood derived mast cells (CBMC) as demonstrated by RT-PCR, western blot and immunocytochemistry. The major metabolite of arachidonic acid formed via the 15-LO pathway in IL-4 treated CBMC was identified as 15-ketoeicosatetraenoic acid (15-KETE, also named 15-oxo-ETE) with smaller amounts of 15-hydroxyeicosatetraenoic acid (15-HETE) as identified by HPLC and mass spectrometry (MS/MS). Furthermore, immunohistochemical stainings demonstrated the expression of 15-LO-1 in mast cells in lung and skin in vivo. Osmotic activation of CBMC with mannitol resulted in activation of the 15-LO-1 pathway. In conclusion, the expression of 15-LO-1 and release of 15-LO-1 derived products by mast cells may contribute to the role of these cells in asthma and other inflammatory diseases.
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