| 1. |
- Hirsch, Jan-Mikael, et al.
(författare)
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A clinical evaluation of the Zygoma fixture: one year of follow-up at 16 clinics.
- 2004
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Ingår i: Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 62:9 Suppl 2, s. 22-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate treatment outcome with Zygoma fixtures (Nobel Biocare, Göteborg, Sweden) with regard to fixture survival, patient satisfaction, and function of prosthesis replacement. MATERIALS AND METHODS: The treatment outcome of 76 patients treated with 145 Zygoma fixtures at 16 centers was evaluated. Patient's and dentist's evaluations of the functional and aesthetic outcome of the treatment were assessed at delivery of prosthesis and at the 1-year follow-up visit. At the 1-year follow-up visit, the status of the peri-implant mucosa around the abutments and the amount of plaque were registered. RESULTS: Sixty-six of the 76 patients, with 124 Zygoma fixtures supporting the prosthetic restorations, were evaluated at the 1-year follow-up. The overall survival rate for the Zygoma fixtures was 97.9% after 1-year of follow-up. Eighty percent of the patients were fully satisfied with both aesthetic and functional outcome at the time of prosthetic insertion and at the 1-year follow-up. All reported data from the dentists, with the exception of one restoration with several abutment screw loosenings, scored from acceptable to excellent for the aesthetic and functional outcome of the treatment. The status of peri-implant mucosa was recorded as normal in approximately 60% of the sites. Plaque, when present, was more often detected on the palatal surfaces compared with the buccal surfaces. CONCLUSION: This 1-year follow-up of Zygoma fixtures has shown good results with an acceptable number of minor complications and a majority of satisfied patients.
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| 2. |
- Kahnberg, Karl-Erik, 1941, et al.
(författare)
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Clinical evaluation of the zygoma implant : 3-year follow-up at 16 clinics
- 2007
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Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 65:10, s. 2033-2038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this clinical investigation was to evaluate the treatment outcome with zygoma implants with regard to implant survival, patient satisfaction, and function of prosthesis replacement after 3 years. Patients and Methods: The treatment outcome of 76 patients treated with 145 zygoma fixtures at 16 centers was evaluated with regard to implant survival. Status of peri-implant mucosa and amount of plaque were registered annually. Patients' and dentists' evaluations of the functional and esthetic outcome of the treatment were assessed at delivery of prosthesis and thereafter at each follow-up visit. Results: Sixty of 76 patients were followed for 3 years after prosthetic delivery. Five of 145 placed zygoma implants failed during the course of the study resulting in an overall implant survival rate of 96.3%. At the 3-year follow-up, 75% of the implants sites were registered with normal peri-implant mucosa and 68% with no visible plaque. The patients were fully satisfied with the esthetic and functional outcome of the treatment in 86% and 71%, respectively, at the 3-year follow-up visit. All reported data from dentists scored from acceptable to excellent. Conclusion: The multicenter study showed a high predictability of the zygoma implant-supported rehabilitation.
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| 3. |
- Kahnberg, Pia, et al.
(författare)
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Alternative routes to pterulone
- 2002
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Ingår i: Tetrahedron. - 0040-4020. ; 58:26, s. 5203-5208
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Tidskriftsartikel (refereegranskat)abstract
- Two new synthetic routes to pterulone, a fungal metabolite possessing potent antifungal activity as an inhibitor of NADH/ubiquinone oxidoreductase, are reported. (C) 2002 Elsevier Science Ltd. All rights reserved.
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| 4. |
- Kahnberg, Pia
(författare)
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Natural Products as Leads for Pharmaceutically Active Compounds
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the search for new pharmaceutically active compounds, it is recognized that Nature produces structurally different compounds in a great variety. By having the compounds or extracts tested in defined systems, new drugs or more often leads (a compound that has an interesting but moderate activity) can be found. When a lead is found, structurally similar compounds with modified functional groups are synthesized to find the structure-activity relationships (SAR:s). The secondary metabolite pterulone, isolated from the basidomycete Pterula species 82168 shows an selective and interesting antifungal activity, inhibiting Complex I in the respiration chain. Methods to synthesize pterulone has been developed and a number of analogues have been synthesized and tested on four different fungi, Mucor meihei, Paecilomyces variotii, Penicillium notatum, and Nematospora coryli. The structure-activity relationships were studied but no more efficient compounds than the natural product pterulone was obtained. Flavones belong to a substance class flavonoids present in virtually all plants. 6-Methylflavone shows a quite high affinity for the benzodiazepine site of the GABAA receptor with a K1 value of 125 nM. A number of flavones have been synthesized and the final product, 5'-bromo-2'-hydoxy-6-methylflavone has 250 times higher affinity for the binding site compared to 6-methylflavone. An existing pharmacophore model has been refined and used in the design of new flavones. The flavones were tested in vitro on rat cortical membranes and the pharmacophore model was confirmed and further refined by the structure-activity relationships observed. The pharmacophore model was also built in the database search program Catalyst™, to find new structural classes of substances, i.e scaffold hopping, that fits the model and may bind to the receptor. Databases from Maybridge, NCI and ACD were used for this purpose and a number of hits were obtained.
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| 5. |
- Kahnberg, Pia, et al.
(författare)
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Refinement and evaluation of a pharmacophore model for flavone derivatives binding to the benzodiazepine site of the GABA(A) receptor
- 2002
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Ingår i: Journal of Medicinal Chemistry. - 1520-4804. ; 45:19, s. 4188-4201
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Tidskriftsartikel (refereegranskat)abstract
- To further develop and evaluate a pharmacophore model previously proposed by Cook and co-workers (Drug Des. Discovery 1995,12,193-248) for ligands binding to the benzodiazepine site of the GABA(A) receptor, 40 new flavone derivatives have been synthesized and their affinities for the benzodiazepine site have been determined. Two new regions of steric repulsive interactions between ligand and receptor have been characterized, and the receptor region in the vicinity of 6- and 8'-substituents has been mapped out. 2'-Hydroxy substitution is shown to give a significant increase in affinity, which is interpreted in terms of a novel hydrogen bond interaction with the previously proposed hydrogen bond-accepting site A2. On the basis of the results of these studies and the refined pharmacophore model, 5'-bromo-2'-hydroxy-6-methylflavone, the highest affinity flavone derivative reported so far (K-i = 0.9 nM), was successfully designed. A comparison of the pharmacophore model with a recently proposed alternative model (Marder; et al. Bioorg. Med. Chem., 2001, 9, 323-335) has been made.
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| 6. |
- Kahnberg, Pia, et al.
(författare)
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The use of a pharmacophore model for identification of novel ligands for the benzodiazepine binding site of the GABA(A) receptor
- 2004
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Ingår i: Journal of Molecular Graphics and Modelling. - : Elsevier BV. - 1093-3263. ; 23:3, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- A Catalyst pharmacophore model has been developed for the benzodiazepine site within the GABA(A) receptor complex. The model is based on a pharmacophore model originally proposed by Cook and co-workers (Drug Des. Discovery 1995, 12, 193-248) and further developed by Kahnberg et al. (J. Med. Chem. 2002,45, 4188-4201). The Catalyst pharmacophore model has been validated by using a series of flavonoids with varying affinities for the benzodiazepine receptor and has then been used as a search query in database searching with the aim of finding novel structures which have the possibility to be modified into novel lead compounds. Five of the hits from the database searching were purchased and their affinities for the benzodiazepine site of the GABA(A) receptor were determined. Two of the compounds displayed K-i values below 10 muM. The substance showing highest potency in-vitro displayed an affinity of 121 nM making it an interesting compound for optimization. The false positive compounds (K-i values > 10 muM affinities) have been analysed in terms of conformational energy penalties and possibilities for hydrogen bond interactions. The analysis clearly demonstrates the need for post processing of Catalyst hits. (C) 2004 Elsevier Inc. All rights reserved.
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| 7. |
- 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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| 8. |
- 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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