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- Fuks, Jonas M, et al.
(författare)
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GABAergic Signaling Is Linked to a Hypermigratory Phenotype in Dendritic Cells Infected by Toxoplasma gondii
- 2012
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:12, s. e1003051-
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Tidskriftsartikel (refereegranskat)abstract
- During acute infection in human and animal hosts, the obligate intracellular protozoan Toxoplasma gondii infects a variety of cell types, including leukocytes. Poised to respond to invading pathogens, dendritic cells (DC) may also be exploited by T. gondii for spread in the infected host. Here, we report that human and mouse myeloid DC possess functional γ-aminobutyric acid (GABA) receptors and the machinery for GABA biosynthesis and secretion. Shortly after T. gondii infection (genotypes I, II and III), DC responded with enhanced GABA secretion in vitro. We demonstrate that GABA activates GABA(A) receptor-mediated currents in T. gondii-infected DC, which exhibit a hypermigratory phenotype. Inhibition of GABA synthesis, transportation or GABA(A) receptor blockade in T. gondii-infected DC resulted in impaired transmigration capacity, motility and chemotactic response to CCL19 in vitro. Moreover, exogenous GABA or supernatant from infected DC restored the migration of infected DC in vitro. In a mouse model of toxoplasmosis, adoptive transfer of infected DC pre-treated with GABAergic inhibitors reduced parasite dissemination and parasite loads in target organs, e.g. the central nervous system. Altogether, we provide evidence that GABAergic signaling modulates the migratory properties of DC and that T. gondii likely makes use of this pathway for dissemination. The findings unveil that GABA, the principal inhibitory neurotransmitter in the brain, has activation functions in the immune system that may be hijacked by intracellular pathogens.
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| 8. |
- Li, Shunyi, et al.
(författare)
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Intrinsic energy band alignment of functional oxides
- 2014
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Ingår i: Physica Status Solidi - Rapid Research Letetrs. - : Wiley. - 1862-6254 .- 1862-6270. ; 8:6, s. 571-576
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Tidskriftsartikel (refereegranskat)abstract
- The energy band alignment at interfaces between different materials is a key factor, which determines the function of electronic devices. While the energy band alignment of conventional semiconductors is quite well understood, systematic experimental studies on oxides are still missing. This work presents an extensive study on the intrinsic energy band alignment of a wide range of functional oxides using photoelectron spectroscopy with in-situ sample preparation. The studied materials have particular technological importance in diverse fields as solar cells, piezotronics, multiferroics, photoelectrochemistry and oxide electronics. Particular efforts have been made to verify the validity of transitivity, in order to confirm the intrinsic nature of the obtained band alignment and to understand the underlying principles. Valence band offsets up to 1.6 eV are observed. The large variation of valence band maximum energy can be explained by the different orbital contributions to the density of states in the valence band. The framework provided by this work enables the general understanding and prediction of energy band alignment at oxide interfaces, and furthermore the tailoring of energy level matching for charge transfer in functional oxides. (C) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 9. |
- Magistro, Giuseppe, et al.
(författare)
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Contemporary Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.
- 2016
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 69:2, s. 286-297
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Tidskriftsartikel (refereegranskat)abstract
- Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that causes severe symptoms, bother, and quality-of-life impact in the 8.2% of men who are believed to be affected. Research suggests a complex pathophysiology underlying this syndrome that is mirrored by its heterogeneous clinical presentation. Management of patients diagnosed with CP/CPPS has always been a formidable task in clinical practice. Due to its enigmatic etiology, a plethora of clinical trials failed to identify an efficient monotherapy.
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- Stranne, Christian, et al.
(författare)
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Acoustic mapping of mixed layer depth
- 2018
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Ingår i: Ocean Science. - : Copernicus GmbH. - 1812-0784 .- 1812-0792. ; 14:3, s. 503-514
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Tidskriftsartikel (refereegranskat)abstract
- The ocean surface mixed layer is a nearly universal feature of the world oceans. Variations in the depth of the mixed layer (MLD) influences the exchange of heat, fresh water (through evaporation), and gases between the atmosphere and the ocean and constitutes one of the major factors controlling ocean primary production as it affects the vertical distribution of biological and chemical components in near-surface waters. Direct observations of the MLD are traditionally made by means of conductivity, temperature, and depth (CTD) casts. However, CTD instrument deployment limits the observation of temporal and spatial variability in the MLD. Here, we present an alternative method in which acoustic mapping of the MLD is done remotely by means of commercially available ship-mounted echo sounders. The method is shown to be highly accurate when the MLD is well defined and biological scattering does not dominate the acoustic returns. These prerequisites are often met in the open ocean and it is shown that the method is successful in 95% of data collected in the central Arctic Ocean. The primary advantages of acoustically mapping the MLD over CTD measurements are (1) considerably higher temporal and horizontal resolutions and (2) potentially larger spatial coverage.
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- Tuncel, J., et al.
(författare)
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Animal Models of Rheumatoid Arthritis (I) : Pristane-Induced Arthritis in the Rat
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. METHODS: We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. RESULTS: Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8+/-2.0 days, 20.3+/-5.1 days and 34.2+/-11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. CONCLUSIONS: PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics.
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- Vanfleteren, Lowie E G W, et al.
(författare)
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Biomarker-based clustering of patients with chronic obstructive pulmonary disease
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Rationale COPD has been associated repeatedly with single biomarkers of systemic inflammation, ignoring the complexity of inflammatory pathways. This study aimed to cluster patients with COPD based on systemic markers of inflammatory processes and to evaluate differences in their clinical characterisation and examine how these differences may relate to altered biological pathways. Methods 213 patients with moderate-to-severe COPD in a clinically stable state were recruited and clinically characterised, which included a venous blood sample for analysis of serum biomarkers. Patients were clustered based on the overall similarity in systemic levels of 57 different biomarkers. To determine interactions among the regulated biomarkers, protein networks and biological pathways were examined for each patient cluster. Results Four clusters were identified: two clusters with lower biomarker levels (I and II) and two clusters with higher biomarker levels (III and IV), with only a small number of biomarkers with similar trends in expression. Pathway analysis indicated that three of the four clusters were enriched in Rage (receptor for advanced glycation end-products) and Oncostatin M pathway components. Although the degree of airflow limitation was similar, the clinical characterisation of clusters ranged from 1) better functional capacity and health status and fewer comorbidities; 2) more underweight, osteoporosis and static hyperinflation; 3) more metabolically deranged; and 4) older subjects with worse functional capacity and higher comorbidity load. Conclusions These new insights may help to understand the functionally relevant inflammatory interactions in the pathophysiology of COPD as a heterogeneous disease.
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| 14. |
- Wagenlehner, F. M. E., et al.
(författare)
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Antibiotikaprophylaxe in der Urologie
- 2011
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Ingår i: Der Urologe. - : Springer Science and Business Media LLC. - 0340-2592 .- 1433-0563. ; 50:11, s. 1469-1478
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Tidskriftsartikel (refereegranskat)abstract
- The aim of perioperative antibiotic prophylaxis is the prevention of surgical site infections and urinary tract infections during urological procedures. The indication for antibiotic prophylaxis comprises several risk factors such as the degree of contamination of the operative site, duration of surgery, implantation of devices and comorbidities of the individual patient. In general this involves a single antibiotic administration before the operative procedure. The antibiotic prophylaxis is part of the total antibiotic consumption and thus a factor contributing to emergence of antibiotic resistance. It is not a substitute for hygiene measures or operative precision.
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- Wagenlehner, Florian M. E., et al.
(författare)
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Infective Complications After Prostate Biopsy: Outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, A Prospective Multinational Multicentre Prostate Biopsy Study
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:3, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infection is a serious adverse effect of prostate biopsy (P-Bx), and recent reports suggest an increasing incidence. Objective: The aim of this multinational multicentre study was to evaluate prospectively the incidence of infective complications after P-Bx and identify risk factors. Design, setting, and participants: The study was performed as an adjunct to the Global Prevalence Study of Infections in Urology (GPIU) during 2010 and 2011. Men undergoing P-Bx in participating centres during the 2-wk period commencing on the GPIU study census day were eligible. Outcome measurements and statistical analysis: Baseline data were collected and men were questioned regarding infective complications at 2 wk following their biopsy. The Fisher exact test, Student t test, Mann-Whitney U test, and multivariate regression analysis were used for data analysis. Results and limitations: A total of 702 men from 84 GPIU participating centres worldwide were included. Antibiotic prophylaxis was administered prior to biopsy in 98.2% of men predominantly using a fluoroquinolone (92.5%). Outcome data were available for 521 men (74%). Symptomatic urinary tract infection (UTI) was seen in 27 men (5.2%), which was febrile in 18 (3.5%) and required hospitalisation in 16 (3.1%). Multivariate analysis did not identify any patient subgroups at a significantly higher risk of infection after P-Bx. Causative organisms were isolated in 10 cases (37%) with 6 resistant to fluoroquinolones. The small sample size per participating site and in compared with other studies may have limited the conclusions from our study. Conclusions: Infective complications after transrectal P-Bx are important because of the associated patient morbidity. Despite antibiotic prophylaxis, 5% of men will experience an infective complication, but none of the possible factors we examined appeared to increase this risk. Our study confirms a high incidence of fluoroquinolone resistance in causative bacteria. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 17. |
- Weidner, G, et al.
(författare)
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Cardiovascular reactivity to mental stress in the Stockholm Female Coronary Risk Study
- 2001
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Ingår i: Psychosomatic Medicine. - SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. Univ Educ, Dept Hlth Psychol, Schwabisch Gmund, Germany. Karolinska Inst, Dept Prevent Med, Stockholm, Sweden. Karolinska Inst, Dept Cardiol, Stockholm, Sweden. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Stockholm, Student Hlth Ctr, Stockholm, Sweden. : LIPPINCOTT WILLIAMS & WILKINS. - 0033-3174 .- 1534-7796. ; 63:6, s. 917-924
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study evaluated the ability of mental stress testing to discriminate between women with and without CHD, and among women with different disease manifestations, taking into account history of hypertension and beta -blocker use. Methods: Analyses were based on data from a community-based case-control study of women aged 65 years or younger. The study group consisted of 292 women who were hospitalized for an acute event of CHD, either AMI or unstable AP in Stockholm between 1991 and 1994. Controls were matched to cases by age and catchment area. Cardiovascular reactivity and emotional response to an anagram task solved under time pressure were measured 3 to 6 months after hospitalization. Results: Patients reacted with smaller increases in heart rate (4 bpm) than their controls (7 bpm). Results for the rate-pressure product were similar. Cardiovascular reactions did not distinguish patients with AP from those with AML History of hypertension (present in 50% of patients and 11% of controls) was related to enhanced diastolic blood pressure reactivity. Patients on beta -blockers (66%) had lower heart-rate levels throughout testing, but did not differ in their cardiovascular stress reactions when compared with the remaining participants. Conclusions: Women with heart disease have somewhat lower heart-rate responses to stress than healthy age-matched controls. History of hypertension is related to enhanced diastolic blood pressure reactivity to mental stress in both patients and controls.
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