| 1. |
- Andersson, Charlotta Rydgard, et al.
(författare)
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Vaccine failures after active immunisation against tick-borne encephalitis
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:16, s. 2827-2831
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a major disease of the central nervous system in Europe and is endemic in Sweden with about 200 notified cases annually. The far most effective protective measure against TBE is active immunisation. The vaccines available today induce a high degree of protection in field studies. However, vaccine failures have occasionally been reported and may be overlooked due to different, and sometimes confusing, antibody kinetics in vaccinees with TBEV infection. In this study, 27 patients with clinical and serological evidences of TBE despite adequate immunisation are presented. Vaccination failure is characterized by a slow, and initially non-detectable, development of the specific TBEV-IgM response, seen together with a rapid rise of IgG and neutralising antibodies in serum. The majority (70%) of the patients were more than 50 years of age, which may implicate a need for a modified immunisation strategy in the elderly.
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| 2. |
- Ayesa, Susana, et al.
(författare)
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Solid-phase parallel synthesis and SAR of 4-amidofuran-3-one inhibitors of cathepsin S : Effect of sulfonamides P3 substituents on potency and selectivity.
- 2009
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 17:3, s. 1307-1324
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Tidskriftsartikel (refereegranskat)abstract
- Highly potent and selective 4-amidofuran-3-one inhibitors of cathepsin S are described. The synthesis and structure–activity relationship of a series of inhibitors with a sulfonamide moiety in the P3 position is presented. Several members of the series show sub-nanomolar inhibition of the target enzyme as well as an excellent selectivity profile and good cellular potency. Molecular modeling of the most interesting inhibitors describes interactions in the extended S3 pocket and explains the observed selectivity towards cathepsin K.
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| 3. |
- Hagström, Charlotta, et al.
(författare)
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The effect of prescribed burning on Pulsatilla vernalis at Marma military training area in Sweden
- 2023
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Ingår i: Conservation Evidence Journal. - : Department of Zoology, University of Cambridge. - 1758-2067. ; 20, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- Changes in habitat have led to a decline in many species which are now threatened. One of them is the spring pasque flower Pulsatilla vernalis, which grows on well-drained soils and is sensitive to competition. The species has in the past benefited from disturbances such as grazing, mowing and forest fires. Now that these do not occur as frequently, it has been suggested that prescribed burning could be used as a conservation intervention to benefit P. vernalis. In this study, we tested whether prescribed burning in 2018 benefited a population of P. vernalis at Marma military training area, outside Älvkarleby in eastern Sweden. Due to unexpected windy conditions on the day of the prescribed burning, not all the planned area was burned. This created a natural experiment that enabled us to compare burned areas with unburned areas (control) in both heathland and forested heathland habitats. The study includes data gathered before and after the experimental treatment. We found that compared to the control areas, the burned areas had a significantly higher number of P. vernalis tufts (clusters of leaf rosettes), as well as a greater number of flower stalks per tuft. Although limited due to lack of replication, this study supports the suggestion that prescribed burning benefits P. vernalis, both in open areas as well as in forests.
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| 4. |
- Lindquist, Charlotta, 1968-
(författare)
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Design & Synthesis of Protein Interacting Affinity Ligands and Protease Inhibitors
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is a growing need of both protein drugs and synthetic drugs in the fight against many life-threatening diseases. The first part of this thesis deals with the design and synthesis of high affinity binding ligands for the purification of protein drugs. The second part describes design and synthesis of protease inhibitors targeting the cysteine protease cathepsin S and the serine protease hepatitis C NS3/4A. In work with parallel synthesis of new affinity chromatography ligands, indole was used as the scaffold for both solid phase and solution phase syntheses. A library of 1,3-disubstituted indoles was prepared via an iterative Mannich reaction sequence. The first Mannich reaction provided 3-aminomethylindoles, while the second Mannich reaction introduced an additional aminomethyl group at the N1 position of the indole ring. A library of 25 substituted indoles was prepared in moderate to good yields and purity. Inhibition of the cysteine protease cathepsin S is an attractive target for drug development of inhibitors having potential for regulation of autoimmune diseases and allergic disorders. Syntheses targeting the cysteine protease cathepsin S were performed by a solid phase approach. The structure-activity-relationships (SAR) of variations in the P3 sulfonamide part of 4-amidofuran-3-one inhibitors are presented. Several highly potent inhibitors were found, in both enzyme and cellular assays. The hepatitis C virus (HCV), causes a chronic liver condition which can lead to cirrhosis and liver cancer. The serine protease hepatitis C NS3/4A is a promising target for development of HCV drugs. In the syntheses of novel HCV NS3/4A inhibitors, four new P2 substituents were first incorporated on a proline-based linear scaffold. The most potent P2 substituent, quinazoline, was evaluated in a larger study yielding more rigidified cyclopentane-based macrocyclic inhibitors. The SAR exercise resulted in several inhibitors with excellent potency in the low nanomolar range.
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| 5. |
- Lindquist, Charlotta
(författare)
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Development and evaluation of optical techniques for tumour detection
- 1997
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Different optical methods for tumour detection have been studied. Interference between photon density waves has been examined with the aim of investigating the potential of this technique for optical transillumination diagnostics. Simulations and experiments have been performed in the time domain on realistic tissue phantoms containing bodies with differing optical properties. The recorded data were Fourier transformed and interference reconstructed. The results suggest that this is a sensitive method for detecting inhomogeneities in turbid media such as tissue. In addition, time-resolved white-light measurements were performed in vivo and in vitro on female breast tissue to determine its optical properties. Fluorescence spectroscopy has been performed in vivo in the colon of 43 patients during a collaboration with Karolinska Hospital in Stockholm. Twenty-two of the patients were given ALA as a photosensitiser prior to the investigation. It was shown that adenomatous tissue can be distinguished from healthy tissue when using 337 nm excitation or when the patients had been given ALA and 405 or 436 nm excitation was used.
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| 6. |
- Lindquist, Charlotta, et al.
(författare)
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Microwave-Assisted Coupling of Carboxylic Acids to a Polymer Bound Hydrazine Linker
- 2003
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Ingår i: Synthetic Communications. - New York : Marcel Dekker, Inc.. - 0039-7911 .- 1532-2432. ; 33:13, s. 2257-2262
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Tidskriftsartikel (refereegranskat)abstract
- A set of carboxylic acids, all being potential scaffolds for combinatorial chemistry or peptide synthesis, were coupled to a polymer bound aryl hydrazine linker using microwave irradiation in good yields. Improved yields and reduced reaction times were achieved byusing microwave-assisted heating compared to conventional heating.
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| 7. |
- Lindquist, Charlotta, et al.
(författare)
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Parallel synthesis of an indole-based library via an iterativeMannich reaction sequence
- 2006
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Ingår i: Tetrahedron. - : Elsevier Ltd.. - 0040-4020 .- 1464-5416. ; 62:14, s. 3439-3445
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Tidskriftsartikel (refereegranskat)abstract
- A library of 1,3-disubstituted indoles has been prepared via an iterative Mannich reaction sequence. The first Mannich reaction with secondary amines and formaldehyde preferentially yields 3-aminomethyl indoles, while the second Mannich reaction introduces an additional aminomethyl group at the N1-position of the indole ring. A library of 25 substituted indoles has thus been prepared in moderate to good yields with purity.
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| 8. |
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| 9. |
- Nilsson, Magnus, et al.
(författare)
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Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease : exploration of P2 quinazoline substituents.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series of macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution for the P2 cyclopentane dicarboxylic acid series improved on the stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. properties were assessed in rat on selected compounds. Excellent exposure and liver–to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. In vivo pharmacokinetic properties were assessed in rat on selected compounds. Excellent exposure and liver–to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series.
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| 10. |
- Nilsson, Magnus, et al.
(författare)
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Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease : Exploration of P2 quinazoline substituents
- 2010
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 20:14, s. 4004-4011
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Tidskriftsartikel (refereegranskat)abstract
- Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. (C) 2010 Elsevier Ltd. All rights reserved.
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