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Female Mice are Protected against High-Fat Diet Induced Metabolic Syndrome and Increase the Regulatory T Cell Population in Adipose Tissue
Ulrika S. Pettersson, Tomas B. Waldén, Per-Ola Carlsson, Leif Jansson, Mia Phillipson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046057
Abstract: Sex differences in obesity-induced complications such as type 2 diabetes have been reported. The aim of the study was to pinpoint the mechanisms resulting in different outcome of female and male mice on a high-fat diet (HFD). Mice fed control or HFD were monitored for weight, blood glucose, and insulin for 14 weeks. Circulating chemokines, islet endocrine function and blood flow, as well as adipose tissue populations of macrophages and regulatory T-lymphocytes (Treg) were thereafter assessed. Despite similar weight (43.8±1.0 and 40.2±1.5 g, respectively), male but not female mice developed hyperinsulinemia on HFD as previously described (2.5±0.7 and 0.5±0.1 pmol/l, respectively) consistent with glucose intolerance. Male mice also exhibited hypertrophic islets with intact function in terms of insulin release and blood perfusion. Low-grade, systemic inflammation was absent in obese female but present in obese male mice (IL-6 and mKC, males: 77.4±17 and 1795±563; females: 14.6±4.9 and 240±22 pg/ml), and the population of inflammatory macrophages was increased in intra-abdominal adipose tissues of high-fat-fed male but not female mice. In contrast, the anti-inflammatory Treg cell population increased in the adipose tissue of female mice in response to weight gain, while the number decreased in high-fat-fed male mice. In conclusion, female mice are protected against HFD-induced metabolic changes while maintaining an anti-inflammatory environment in the intra-abdominal adipose tissue with expanded Treg cell population, whereas HFD-fed male mice develop adipose tissue inflammation, glucose intolerance, hyperinsulinemia, and islet hypertrophy.
Increased Recruitment but Impaired Function of Leukocytes during Inflammation in Mouse Models of Type 1 and Type 2 Diabetes
Ulrika Sofia Pettersson,Gustaf Christoffersson,Sara Massena,David Ahl,Leif Jansson,Johanna Henriksn?s,Mia Phillipson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0022480
Abstract: Patients suffering from diabetes show defective bacterial clearance. This study investigates the effects of elevated plasma glucose levels during diabetes on leukocyte recruitment and function in established models of inflammation.
Lactobacillus reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction
Johan Dicksved, Olof Schreiber, Ben Willing, Joel Petersson, Sara Rang, Mia Phillipson, Lena Holm, Stefan Roos
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046399
Abstract: Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte- and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis.
Endothelial Domes Encapsulate Adherent Neutrophils and Minimize Increases in Vascular Permeability in Paracellular and Transcellular Emigration
Mia Phillipson, Jaswinder Kaur, Pina Colarusso, Christie M. Ballantyne, Paul Kubes
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0001649
Abstract: Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular) and more rarely directly through endothelial cells (transcellular). Recently, we reported that unlike in wild-type (wt) mice, Mac-1-/- (CD11b) neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20–30 min longer than the paracellular emigration (wt). In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/-) were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function.
Acute effects of Helicobacter pylori extracts on gastric mucosal blood flow in the mouse
Johanna Henriksn?s, Christer Atuma, Mia Phillipson, Stellan Sandler, Lars Engstrand, Lena Holm
World Journal of Gastroenterology , 2009,
Abstract: AIM: To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Helicobacter pylori (HPE).METHODS: The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laser-Doppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from H pylori strain 88-23. To investigate the role of a nerve- or iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/- mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) was also assessed.RESULTS: In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wild-type mice exposed to HPE.CONCLUSION: A H pylori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.
iNOS-Dependent Increase in Colonic Mucus Thickness in DSS-Colitic Rats
Olof Schreiber, Joel Petersson, Tomas Waldén, David Ahl, Stellan Sandler, Mia Phillipson, Lena Holm
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071843
Abstract: Aim To investigate colonic mucus thickness in vivo in health and during experimental inflammatory bowel disease. Methods Colitis was induced with 5% DSS in drinking water for 8 days prior to experiment, when the descending colonic mucosa of anesthetized rats was studied using intravital microscopy. Mucus thickness was measured with micropipettes attached to a micromanipulator. To assess the contributions of NOS and prostaglandins in the regulation of colonic mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed by 3 mg/kg/h), the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3 mg/kg/h) and the non-selective COX-inhibitor diclofenac (5 mg/kg) were administered intravenously prior to experiment. To further investigate the role of iNOS in the regulation of colonic mucus thickness, iNOS ?/? mice were used. Results Colitic rats had a thicker firmly adherent mucus layer following 8 days of DSS treatment than untreated rats (88±2 μm vs 76±1 μm). During induction of colitis, the thickness of the colonic mucus layer initially decreased but was from day 3 significantly thicker than in untreated rats. Diclofenac reduced the mucus thickness similarly in colitic and untreated rats (?16±5 μm vs ?14±2 μm). While L-NNA had no effect on colonic mucus thickness in DSS or untreated controls (+3±2 μm vs +3±1 μm), L-NIL reduced the mucus thickness significantly more in colitic rats than in controls (?33±4 μm vs ?10±3 μm). The importance of iNOS in regulating the colonic mucus thickness was confirmed in iNOS?/? mice, which had thinner colonic mucus than wild-type mice (35±3 μm vs 50±2 μm, respectively). Furthermore, immunohistochemistry revealed increased levels of iNOS in the colonic surface epithelium following DSS treatment. Conclusion Both prostaglandins and nitric oxide regulate basal colonic mucus thickness. During onset of colitis, the thickness of the mucus layer is initially reduced followed by an iNOS mediated increase.
Understanding the Baby Boom Generation: Comparative Perspectives
Chris Phillipson
International Journal of Ageing and Later Life , 2008,
Aksum and the Northern Horn of Africa
David Phillipson
Archaeology International , 2012, DOI: 10.5334/ai.1502
The optimal achievement model and underachievement in Hong Kong: an application of the Rasch model
Psychology Science Quarterly , 2008,
Abstract: Termed the optimal achievement model, a new method for the estimation of underachievement relies on measuring student potential (P) and achievement (A) using Rasch models and calculating an achievement index, IA, for each individual. This study extends a previous report (Phillipson & Tse, 2007) that estimated the proportion of Hong Kong students in Primary 5 to now include a sample of students from Primary 3 (n = 1406), Secondary 1 (n = 756) and Secondary 3 (n = 578), across six districts of Hong Kong. The students were administered a standardized test of mathematical achievement and the Ravens Progressive Matrices Test. Using the optimal achievement model, estimates of underachievement at six percentile bands showed that the proportion of students who were underachieving ranged from 10 % at the 50-59th percentile band up to 30 % at the >95th percentile band for Primary 3, Primary 5 and Secondary 1 students, and 50 % of Secondary 3 students. The estimation of IA at the level of the individual allows the researcher the possibility to directly study the interaction of the environment on student potential.
Observational Study of a Multi-Active Ingredient Over-the-Counter Cold Remedy Following Active Pharmacist Recommendation  [PDF]
Gillian Lisa Phillipson, John David Hull, Boles?aw Samoliński
Open Journal of Respiratory Diseases (OJRD) , 2017, DOI: 10.4236/ojrd.2017.71005
Abstract: Real-world user satisfaction with a fixed dose combination over-the-counter cold remedy (Vicks Symptomed Complete Cytrynowy hot drink; VSCC) was evaluated in a prospective, non-comparative, observational study involving 176 pharmacies in Poland from February to April 2015. 1391 participants completed a questionnaire in the pharmacy and several paper questionnaires at home following use of the product at their own discretion. Participants returned their completed questionnaires to the pharmacy. 1356 participants were included in the intent-to-treat analysis. Participants highly valued the advice from their pharmacist (97%, P < 0.0001, important vs. not important) and thought the quality of that advice was good (93%, P < 0.0001, good/very good vs. very bad-fair). 96% of participants found VSCC to be effective in some way against their cold symptoms (P < 0.0001, effective vs. not effective) and 68% of them stated that it was better than any other cold therapy they had used before (P < 0.0001, better/best vs. same/worse). Adverse event reporting was very low.
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