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- Lowén, Mats, et al.
(författare)
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Effect of hypnotherapy and educational intervention on brain response to visceral stimulus in the irritable bowel syndrome
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 37:12, s. 1184-1197
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Tidskriftsartikel (refereegranskat)abstract
- Background Gut-directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown. Aim To determine the effect of hypnotherapy and educational intervention on brain responses to cued rectal distensions in IBS patients. Methods Forty-four women with moderate-to-severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high- (45mmHg) and low-intensity (15mmHg) rectal distensions. Twenty-five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty-one patients completed treatments and posttreatment fMRI. Results Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high-intensity distension in the dorsal and ventral anterior insula (cluster size 142, P=0.006, and cluster size 101, P=0.005 respectively). Moreover HYP responders demonstrated a prepost treatment BOLD attenuation in posterior insula (cluster sizes 59, P=0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P=0.05). Prepost differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS. Conclusions The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.
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- Tang, L., et al.
(författare)
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Estimation of the long-range transport contribution from secondary inorganic components to urban background PM10 concentrations in south-western Sweden during 1986-2010
- 2014
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310. ; 89, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of long-range transported (LRT) to urban background PM10 concentrations was investigated from a long-term view from 1986 to 2010. Regional air concentrations of sulphate (SO42-), nitrate (NO3-), and ammonium (NH4+) were used as a sum (C-ion) to investigate the contribution from these ions to the LRT PM10 concentrations at an urban background site in Gothenburg, Sweden. Utilizing backwards trajectory analysis, the LRT contribution from C-ion to the urban background PM10 concentrations (LRTCion) was estimated for six unique transport pathways and related source areas. Air masses transported over eastern Europe, UK/North Sea/Denmark and the vicinity of Scandinavia were associated with high C-ion concentrations observed in Gothenburg. For each pathway, multiple linear models based on the C-ion concentrations were used to estimate LRTCion and PM10 at the urban background site. The performances of the multiple linear models were satisfying with R-2 between estimated and observed annual mean PM10 concentrations of 0.81 during the monitoring years 1990-2010. The models were able to describe the main features of the day-to-day average PM10 concentrations, but underestimated high level values. The annual estimated LRTCion contribution decreased from 7 +/- 2 mu g/m(3) for 1986-2000 to 5 +/- 1 mu g/m(3) for 2001-2010. The higher LRTCion contribution was related to the transport cluster from eastern Europe, UK/North Sea/Denmark and the vicinity of South Scandinavia. (C) 2014 Elsevier Ltd. All rights reserved.
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- Vodnala, Suman K., et al.
(författare)
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In Vitro and In Vivo Activities of 2-Aminopyrazines and 2-Aminopyridines in Experimental Models of Human African Trypanosomiasis
- 2013
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 57:2, s. 1012-1018
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Tidskriftsartikel (refereegranskat)abstract
- New drugs for the treatment of human African trypanosomiasis are urgently needed. A number of 2-aminopyrazines/2-aminopyridines were identified as promising leads following a focused screen of 5,500 compounds for Trypanosoma brucei subsp. brucei viability. Described compounds are trypanotoxic in the submicromolar range and show comparably low cytotoxicity on representative mammalian cell lines. Specifically, 6-([6-fluoro-3,4-dihydro-2H-1-benzopyran-4-yl)]oxy)-N-(piperidin-4-yl)pyrazin-2-amine (CBK201352) is trypanotoxic for T. brucei subsp. brucei, T. brucei subsp. gambiense, and T. brucei subsp. rhodesiense and is nontoxic to mammalian cell lines, and in vitro preclinical assays predict promising pharmacokinetic parameters. Mice inoculated intraperitoneally (i.p.) with 25 mg/kg CBK201352 twice daily for 10 days, starting on the day of infection with T. brucei subsp. brucei, show complete clearance of parasites for more than 90 days. Thus, CBK201352 and related analogs are promising leads for the development of novel treatments for human African trypanosomiasis.
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- Vodnala, Suman K., et al.
(författare)
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Structure-Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African Trypanosomiasis
- 2013
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 56:24, s. 9861-9873
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Tidskriftsartikel (refereegranskat)abstract
- Novel methods for treatment of African trypanosomiasis, caused by infection with Trypanosoma brucei are needed. Cordycepin (3'-deoxyadenosine, la) is a powerful trypanocidal compound in vitro but is ineffective in vivo because of rapid metabolic,degradation by adenosine deaminase (ADA). We elucidated the structural moieties of cordycepin required for trypanocidal activity and designed analogues that retained trypanotoxicity while gaining resistance to ADA-mediated metabolism. 2-Fluorocordycepin (2-fluoro3'-deoxyadenosine, 1b) was identified as a selective, potent, and ADA-resistant trypanocidal compound that cured T. brucei infection in mice. Compound 1b is transported through the high affinity TbAT1/P2 adenosine transporter and is a substrate of T. b. brucei adenosine kinase. 1b has good preclinical properties suitable for an, oral drug, albeit a relatively short plasma half-life. We present a rapid and efficient synthesis of 2-halogenated cordycepins, also useful synthons. for the development of additional novel C2-substituted 3'-deoxyadenosine analogues to be evaluated in development of experimental therapeutics.
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- Wichmann, Janine, et al.
(författare)
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Association between ambient temperature and acute myocardial infarction hospitalisations in Gothenburg, Sweden: 1985-2010
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) is the number one cause of death globally and evidence is steadily increasing on the role of non-traditional risk factors such as meteorology and air pollution. Nevertheless, many research gaps remain, such as the association between these non-traditional risk factors and subtypes of CVD, such as acute myocardial infarction (AMI). The objective of this study was to investigate the association between daily ambient temperature and AMI hospitalisations using a case-crossover design in Gothenburg, Sweden (1985-2010). A secondary analysis was also performed for out-of-hospital ischemic heart disease (IHD) deaths. Susceptible groups by age and sex were explored. The entire year as well as the warm (April-September) and cold periods (October-March) were considered. In total 28,215 AMI hospitalisations (of 22,475 people) and 21,082 out-of-hospital IHD deaths occurred during the 26-year study period. A linear exposure-response corresponding to a 3% and 7% decrease in AMI hospitalisations was observed for an inter-quartile range (IQR) increase in the 2-day cumulative average of temperature during the entire year (11 degrees C) and the warm period (6 degrees C), respectively, with and without adjustment for PM(1)(0), NO(2), NOx or O(3). No heat waves occurred during the warm period. No evidence of an association in the cold period nor any association between temperature and IHD deaths in the entire year, warm or cold periods--with and without adjusting for PM(1)(0), NO(2), NOx or O(3) was found. No susceptible groups, based on age or sex, were identified either. The inverse association between temperature and AMI hospitalisations (entire year and warm period) in Gothenburg is in accordance with the majority of the few other studies that investigated this subtype of CVD.
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