| 11. |
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| 12. |
- Ericsson, Peter, et al.
(författare)
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ECL Cell Histamine Mobilization Studied byGastric Submucosal Microdialysis in Awake Rats:Methodological Considerations.
- 2003
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 1600-0773 .- 0901-9928. ; 93:2, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- The ECL cells are endocrine/paracrine cells in the acid-producing part of the stomach. They secrete histamine in response to circulating gastrin. Gastric submucosal microdialysis has been used to study ECL-cell histamine mobilization in awake rats. In the present study we assess the usefulness and limitations of the technique. Microdialysis probes were implanted in the gastric submucosa. Histological analysis of the stomach wall around the probe revealed a moderate, local inflammatory reaction 1-2 days after implantation; the inflammation persisted for at least 10 days. Experiments were conducted 3 days after the implantation. The "true" submucosal histamine concentration was determined by perfusing at different rates (the zero flow method) or with different concentrations of histamine at a constant rate (the no-net-flux method): in fasted rats it was calculated to be 87±5 (means±S.E.M.) nmol/l and 76±9 nmol/l, respectively. The corresponding histamine concentrations in fed rats were 93±5 and 102±8 nmol/l, respectively. With a perfusion rate of 74 mul/hr the recovery of submucosal histamine was 49%, at 34 mul/hr the recovery increased to 83%. At a perfusion rate below 20 mul/hr the microdialysate histamine concentration was close to the actual concentration in the submucosa. The ECL-cell histamine mobilization was independent of the concentrations of Ca2+ in the perfusion medium (0-3.4 mmol/l Ca2+). In one experiment, histamine mobilization in response to gastrin (10 nmol/kg/hr subcutaneously) was monitored in rats pretreated with prednisolone (60 mg/kg) or indomethacin (15 mg/kg). The two antiinflammatory agents failed to affect the concentration of histamine in the microdialysate either before or during the gastrin challenge, which was in accord with the observation that the inflammatory reaction was modest and that inflammatory cells were relatively few around the probe and in the wall of the probe. In another experiment, rats were given aminoguanidine (10 mg/kg) or metoprine (10 mg/kg) 4 hr before the start of gastrin infusion (5 nmol/kg/hr intravenously). Metoprine (inhibitor of histamine N-methyl transferase) did not affect the microdialysate histamine concentration, while aminoguanidine (inhibitor of diamine oxidase) raised both basal and gastrin-stimulated histamine concentrations. We conclude that microdialysis can be used to monitor changes in the concentration of histamine in the submucosa of the stomach, and that the inflammatory reaction to the probe is moderate and does not affect the submucosal histamine mobilization.
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| 13. |
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| 14. |
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| 15. |
- Johansson, Staffan, 1976, et al.
(författare)
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Mechanistic Proposal for the Formation of Specific Immunogenic Complexes via a Radical Pathway: A Key Step in Allergic Contact Dermatitis to Olefinic Hydroperoxides
- 2009
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Ingår i: Chem. Res. Toxicol.. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 22:11, s. 1774-1781
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Tidskriftsartikel (refereegranskat)abstract
- The widespread use of scented products causes an increase of allergic contact dermatitis to fragrance compounds in Western countries today. Many fragrance compounds are prone to autoxidation, forming hydroperoxides as their primary oxidation products. Hydroperoxides are known to be strong allergens and to form specific immunogenic complexes. However, the mechanisms for the formation of the immunogenic complexes are largely unknown. We have investigated this mechanism for (5R)-5-isopropenyl-2-methyl-2-cyclohexene-1-hydroperoxide (Lim-2-OOH) by studying the formation of adducts in the reaction between this hydroperoxide and 5,10,15,20-tetraphenyl-21H,23H-porphine iron(III) chloride (Fe(III)TPPCl) in the presence of protected cysteine (NAc-Cys-OMe) or glutathione (GSH). Isolated adducts originate from the addition of the thiol group of NAc-Cys-OMe over the carbon−carbon double bonds of carvone. Furthermore, adducts between NAc-Cys-OMe and carveol as well as between GSH and carvone have been identified. The formation of these adducts most likely proceeds via the radical thiol−ene mechanism. The addition of a terpene moiety to cysteine offers an explanation of the specificity of the immune response to structurally different hydroperoxides. These results also explain the lack of cross-reactivity between carvone and Lim-2-OOH. In conclusion, we propose that immunogenic complexes of olefinic hydroperoxides can be formed via the radical thiol−ene mechanism. These complexes will be specific for the individual olefinic hydroperoxides due to the inclusion of a terpene moiety derived from the hydroperoxide.
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| 16. |
- Karlsson, Isabella, 1980, et al.
(författare)
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Photodegradation of Dibenzoylmethanes: Potential Cause of Photocontact Allergy to Sunscreens
- 2009
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Ingår i: Chemical Research in Toxicology. - : American Chemical Society (ACS). - 0893-228X .- 1520-5010. ; 22:11, s. 1881-1892
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Tidskriftsartikel (refereegranskat)abstract
- One of the most frequently observed photoallergens today is the sunscreen agent 4-tert-butyl-4′-methoxy dibenzoylmethane (1a). The structurally similar compound, 4-isopropyldibenzoylmethane (1b), was a common cause of sunscreen allergy in the eighties and early nineties but was removed from the market in 1993 and replaced with dibenzoylmethane 1a. We have studied the photodegradation of the dibenzoylmethane 1a, to better understand how these substances cause an immune reaction. Several expected degradation products were formed and identified. Of these, arylglyoxals and benzils were of particular interest because they were unexplored as potential contact allergens. The allergenic potential of photodegraded 1a was evaluated by screening the formed arylglyoxals and benzils for their sensitizing capacity in the murine local lymph node assay. The arylglyoxals were found to be strong sensitizers. They were also found to be highly reactive toward the nucleophile arginine, which indicates that the immunogenic hapten-protein complex could be formed via an electrophilic-nucleophilic pathway. By varying the electron-withdrawing or -donating capacity of the substituent in the para position of the arylglyoxal, the electronic effects were shown to have no significant impact on either the sensitizing or the electrophilic power of arylglyoxals. Thus, a change in the substitution pattern of the parent dibenzoylmethane will not influence the sensitizing capacity of the products formed from them upon photodegradation. Furthermore, the combined studies of benzils, using the local lymph node assay and a cell proliferation assay, indicate that the benzils are cytotoxic rather than allergenic. Taken together, this study presents strong indication that photocontact allergy to dibenzoylmethanes is caused by the arylglyoxals that are formed upon photodegradation.
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| 17. |
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| 18. |
- Almquist, Martin, et al.
(författare)
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Reproductive history, lifestyle factors and season as determinants for serum calcium concentrations in women.
- 2008
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Serum calcium concentrations have been associated with the risk of malignant disease, especially breast cancer. Thus, determinants of serum calcium concentrations, with special regard to risk factors of breast cancer, are of great interest. Material and methods. Previous studies have either been small or they have not focused on reproductive factors. The present study examined serum calcium concentrations in relation to reproductive history, selected lifestyle factors and screening season in a large population-based cohort study comprising 8,114 women. ANOVA followed by the Bonferroni t-test were used for comparison of means, and logistic regression and multiple regression analysis were used to test associations. Results. Serum calcium concentrations were lower in hormone replacement therapy users versus non-users (2.321 mmol/L versus 2.364; p<0.001) and in users of oral contraceptives versus non-users (2.304 versus 2.348; p<0.001). They were higher in peri-/postmenopausal versus premenopausal women (2.357 versus 2.319; p<0.001). Overweight and obese women had higher mean calcium concentrations (2.350 and 2.355) than women with body mass index between 20 and 25 (2.342; p<0.001). Serum calcium concentrations were higher in spring and autumn than in winter (2.352 and 2.353 versus 2.343; p = 0.002). Both younger (40-45 years) (2.334; p = 0.001) and older age groups (>55 years) (2.363; p<0.001) had higher mean calcium concentrations compared to those of women aged 45-50 years (2.320), even when adjusting for menopausal status, suggesting that age has an independent influence on calcium concentrations. Conclusions. It is concluded that reproductive factors such as menopausal status, use of oral contraceptives or hormone-replacement therapy, and age, BMI and season are associated with serum calcium concentrations.
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| 19. |
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| 20. |
- Trouw, Leendert, et al.
(författare)
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C4b-binding protein is present in affected areas of myocardial infarction during the acute inflammatory phase and covers a larger area than C3.
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During myocardial infarction reduced blood flow in the heart muscle results in cell death. These dying/dead cells have been reported to bind several plasma proteins such as IgM and C-reactive protein (CRP). In the present study we investigated whether fluid-phase complement inhibitor C4b-binding protein (C4BP) would also bind to the infarcted heart tissue. METHODS AND FINDINGS: Initial studies using immunohistochemistry on tissue arrays for several cardiovascular disorders indicated that C4BP can be found in heart tissue in several cardiac diseases but that it is most abundantly found in acute myocardial infarction (AMI). This condition was studied in more detail by analyzing the time window and extent of C4BP positivity. The binding of C4BP correlates to the same locations as C3b, a marker known to correlate to the patterns of IgM and CRP staining. Based on criteria that describe the time after infarction we were able to pinpoint that C4BP binding is a relatively early marker of tissue damage in myocardial infarction with a peak of binding between 12 hours and 5 days subsequent to AMI, the phase in which infiltration of neutrophilic granulocytes in the heart is the most extensive. CONCLUSIONS: C4BP, an important fluid-phase inhibitor of the classical and lectin pathway of complement activation binds to jeopardized cardiomyocytes early after AMI and co-localizes to other well known markers such as C3b.
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