| 1. |
- Hannan, T. J., et al.
(författare)
-
Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
-
Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
-
Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
|
|
| 2. |
- Kirsebom, O. S., et al.
(författare)
-
Precise and accurate determination of the B-8 decay spectrum
- 2011
-
Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 83:6
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate measurements of the B-8 neutrino spectrum are important for the interpretation of solar neutrino data. Experimentally, the B-8 neutrino spectrum can be obtained from the measurement of the beta-delayed alpha spectrum. We report on an alpha-alpha coincidence measurement performed at the IGISOL facility in Jyvaskyla, Finland. Our measurement allows extensive cross-checks to be performed and gives a more intense neutrino spectrum at high energies compared to the present standard. The deviation reaches 4% at the end point of the spectrum. Below 11 MeV, the deviation is less than 1%.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Kirsebom, O. S., et al.
(författare)
-
The 8B neutrino spectrum
- 2010
-
Ingår i: 11th Symposium on Nuclei in the Cosmos, NIC 2010; Heidelberg; Germany; 19 July 2010 through 23 July 2010. - 1824-8039.
-
Konferensbidrag (refereegranskat)abstract
- Knowledge of the energy spectrum of the neutrinos emitted in the β decay of8B in the Sun is needed to interpret the neutrino spectrum measured on Earth. Experimentally, the 8B neutrino spectrum may be αextracted from the measurement of the β -delayed a spectrum. In this contribution, the results of a recent α-α coincidence measurement are presented and compared to previous measurements. The implications for the neutrino spectrum are clarified.
|
|
| 6. |
- Ohlsson, Jörgen, et al.
(författare)
-
Structure–activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins
- 2005
-
Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 3:5, s. 886-900
-
Tidskriftsartikel (refereegranskat)abstract
- Four collections of Gal1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the PN and PO adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3 and methoxymethylation at O2 of galabiose provided inhibitors of the S. suis strains type PN adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure–activity relationship models for E. coli PapG adhesin and S. suis adhesin type PO were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Berglund, Martin, 1979, et al.
(författare)
-
Toll-like receptor cross-hyporesponsiveness is functional in interleukin-1-receptor-associated kinase-1 (IRAK-1)-deficient macrophages : differential role played by IRAK-1 in regulation of tumour necrosis factor and interleukin-10 production
- 2008
-
Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 67:5, s. 473-479
-
Tidskriftsartikel (refereegranskat)abstract
- Signalling downstream Toll-like receptors (TLR) is regulated at several levels in order to activate the immune response and prevent excessive inflammation. Altered intracellular signalling may be one reason that repeated stimulation of various TLRs results in hyporesponsiveness and cross-tolerance. We report that TLR cross-tolerance is inducible in the absence of interleukin-1 receptor-associated kinase-1 (IRAK-1) in peritoneal macrophages. Similar to wild-type macrophages, IRAK-1-deficient macrophages respond with decreased tumour necrosis factor (TNF) production to a secondary TLR stimulation, but in opposite to IRAK-1(+/+), IRAK-1(-/-) macrophages display increased interleukin (IL)-10 production at TLR restimulation. IRAK-1-deficient peritoneal macrophages have a defective TNF and IL-10 production in response to lipoteichoic acid stimulation as well as a defective IL-10-but a normal TNF production in response to high concentration of lipopolysaccharide. Our results demonstrate that IRAK-1 is not necessary for induction of TLR cross-tolerance as judged by TNF production.
|
|
| 10. |
- Engström, Patrik, et al.
(författare)
-
A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
- 2015
-
Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen Chlamydia trachomatis, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect Escherichia coli or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections.
|
|
