| 1. |
|
|
| 2. |
- Axelsson, Susanna, et al.
(författare)
-
Effect of combined caries-preventive methods: a systematic review of controlled clinical trials.
- 2004
-
Ingår i: Acta odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 62:3, s. 163-9
-
Forskningsöversikt (refereegranskat)abstract
- The aim of this systematic review was to evaluate the caries-preventive effect of combined caries-preventive methods, defined as two or more different interventions in combination, each expected to prevent dental caries. The Medline database was searched for articles published in the period January 1966 to June 2003. Twenty-four controlled studies met the inclusion criteria, and their value as evidence was assessed according to predetermined criteria. The level of evidence for the overall conclusion regarding each method was graded according to the protocol of the Swedish Council on Technology Assessment in Health Care. The scientific evidence for the combination of treatments involving fluoride that had a preventive effect on caries in children and adolescents was graded as moderate. However, for elderly patients the scientific evidence for the caries-preventive effect of different combinations of treatments was found to be incomplete. No conclusion could be drawn regarding the evidence for combinations of treatments being effective for groups at high caries risk, as the results from the identified clinical studies were conflicting.
|
|
| 3. |
- Dahlgren, Anders, 1967-
(författare)
-
Design, Synthesis, and Structure-Activity Relationships Analysis of Potential Inhibitors of the Serine Protease Thrombin and the Malarial Aspartic Proteases Plasmepsin I and II
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The design, synthesis, and structure-activity relationships analysis of some potential protease inhibitors are outlined in this thesis. In particular, the serine protease thrombin and the malarial aspartic proteases plasmepsin I and II (Plm I and II) are described in regard to the roles they play in living organisms, and that is followed by discussions concerning the design, synthesis, and biological test results of inhibitors of these enzymes.A topic considered is why it is sometimes necessary to pharmacologically regulate the blood-coagulating capacity of thrombin. Moreover, various aspects of malaria arediscussed, including the geographical distribution of the disease, the biological features of the malaria parasites, and the consequences of malaria infection.The problems associated with designing enzyme inhibitors in general are briefly explained. Furthermore, the design of inhibitors of thrombin and Pim I and II is considered in greater detail, and the task of designing the novel potential inhibitors reported in the papers underlying this thesis is addressed.The synthesis of thrombin inhibitors based on tartaric acid and malic acid, and the synthesis of newly designed plasmepsin inhibitors based on a novel reversed-statine core are described in detail. The utilization of solid support chemistry in the work on plasmepsin inhibitors is explained thoroughly. Additionally, there are discussions extensively covering the challenges encountered regarding the syntesis of all types of inhibitors in this thesis, and alternative synthetic strategies are addressed. Biological test results of the synthesized target compounds are analyzed, and structure-activity relationships (SAR) discussions are conducted as thoroughly as possible.
|
|
| 4. |
- Dahlgren, Anders, et al.
(författare)
-
New inhibitors of the malaria aspartyl proteases plasmepsin I and II
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 11:16, s. 3423-3437
-
Tidskriftsartikel (refereegranskat)abstract
- New inhibitors of plasmepsin I and II, the aspartic proteases of the malaria parasite Plasmodium falciparum, are described. From paralell solution phase chemistry, several reversed-statine type isostere inhibitors, many of which are aza-peptides, have been prepared. The synthetic strategy delivers the target compounds in good to high overall yields and with excellent stereochemical control throughout the developed route. The final products were tested for their plasmepsin I and II inhibiting properties and were found to exhibit modest but promising activity. The best inhibitor exhibits Ki values of 250 nM and 1.4 µM for Plm I and II, respectively. © 2003 Elsevier Ltd. All rights reserved.
|
|
| 5. |
- Dahlgren, Anders, et al.
(författare)
-
Novel morpholinone-based D-Phe-Pro-Arg mimics as potential thrombin inhibitors : design, synthesis, and X-ray crystal structure of an enzyme inhibitor complex
- 2002
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 10:6, s. 1829-1839
-
Tidskriftsartikel (refereegranskat)abstract
- A morpholinone structural motif derived from d(+)- and l(−)-malic acid has been used as a mimic of d-Phe-Pro in the thrombin inhibiting tripeptide d-Phe-Pro-Arg. In place of Arg the more rigid P1 truncated p-amidinobenzylamine (Pab) or 2-amino-5-aminomethyl-3-methyl-pyridine have been utilized. The synthetic strategy developed readily delivers these novel thrombin inhibitors used to probe the α-thrombin inhibitor binding site. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 720 nM. The X-ray crystal structure of this candidate co-crystallized with α-thrombin is discussed.
|
|
| 6. |
- Dahlgren, Anders, 1948
(författare)
-
Optical Investigations of Chiral Liquid Crystals
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Optical investigations of course involve experimental work, but a theoretical basis is also needed. The first chapter can hopefully can give the non-expert an insight into the science of liquid crystals. Liquid crystals are optically birefringent, and a review of the phenomenon of birefringence follows in chapter 2. A wave equation is derived from Maxwell's equations and solved, thus relating birefringent properties to the dielectric tensor. This thesis mainly deals with spectrophotometer measurements, where the wavelength of the light is scanned, and the transmittance through the sample is registered. We have studied chiral smectic liquid crystals, with a helicoidal structure in some (the tilted) phases. The material washed between glass plates, or a free-standing film was prepared. The propagation of light coincides with the helix axis, and a reflex, "selective reflection", can be detected when the wavelength matches the helical pitch. To provide a firm theoretical basis for the interpretation of these experiments, a detailed theory of light propagation along helical axis is developed. The derivation is consistent with the previous work of Hl. de Vries, but the notation is somewhat different, and the theory is even slightly extended. An introduction to the 4X4 matrix method is also given. The use of this method is not pursued here, but since it is an important numerical method, something would be missing, if it were not included in a treatment of optical methods. Sample preparation and experimental methods are described. Spectrophotometer measurements, microscopy, including a special method with inclined incidence of light, and conoscopy are covered. Pitch measurements using light diffraction are also included. Results are presented in the included papers, and also discussed in the main text. These observations are related to the deformation andg of the helix, when an electric field is applied. When the helix of the ferroelectric phase is deformed, one can see additional reflexes corresponding to Fourier terms of the deformation. In the antiferroelectric phase, a widening of the reflection band has been observed, when a field is applied. Structure, optical properties and applications of antiferroelectric materials are also described and discussed.
|
|
| 7. |
- Dahlgren, Anders, et al.
(författare)
-
Solid-phase library synthesis of reversed-statine type inhibitors of the malarial aspartyl proteases plasmepsin I and II
- 2003
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 11:6, s. 827-841
-
Tidskriftsartikel (refereegranskat)abstract
- With the aim to develop inhibitors of the plasmepsin I and II aspartic proteases of the malaria parasite Plasmodium falciparum, we have synthesized sets of libraries from novel reversed-statine isosteres, using a combination of solution phase and solid phase chemistry. The synthetic strategy furnishes the library compounds in good to high overall yields and with excellent stereochemical control throughout the developed route. The products were evaluated for their plasmepsin I and II inhibiting properties and were found to exhibit modest but promising activity. The best inhibitor exhibits an in vitro activity of 28% inhibition of plasmepsin II at an inhibitor concentration of 0.5 µM (Ki for Plm II=5.4 µM). © 2003 Elsevier Science Ltd. All rights reserved.
|
|
| 8. |
- Dahlgren, Anders, et al.
(författare)
-
Synthesis of potential thrombin inhibitors. Incorporation of tartaric acid templates as P2 proline mimetics
- 2002
-
Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 10:5, s. 1567-1580
-
Tidskriftsartikel (refereegranskat)abstract
- With the objective to prepare novel non-peptidic thrombin inhibitors, bioisosteres of the inhibitory tripeptide D-Phe-Pro-Arg chain have been examined. Thus, the P1 Arg was replaced with p-amidinobenzylamine, an elongated homologue of the same and with 2,5-dichloro benzylamine. The P2-P3, D-Phe-Pro, was replaced with a novel tartaric acid template coupled to a series of readily available, mainly lipophilic, amines. Some of these compounds exhibit promising thrombin inhibition activity in vitro, IC50~5.9 µM. © 2002 Elsevier Science Ltd. All rights reserved.
|
|
| 9. |
|
|
| 10. |
|
|
