| 1. |
- Cervin, Anders, et al.
(författare)
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One-year low-dose erythromycin treatment of persistent chronic sinusitis after sinus surgery: clinical outcome and effects on mucociliary parameters and nasal nitric oxide.
- 2002
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Ingår i: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 126:5, s. 481-489
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In 17 patients with chronic sinusitis persistent after sinus surgery, long-term, low-dose erythromycin therapy was tested. The aim of the investigation was to study the clinical outcome and effects on nasal nitric oxide (NO), ciliary beat frequency (CBF), and mucociliary transport (saccharine transit time). STUDY DESIGN AND SETTING: We conducted a prospective open study at a tertiary teaching hospital. Symptoms were assessed using visual analog scales. NO was measured using a chemiluminescence analyzer, and mucociliary transport was measured with the saccharine crystal technique. CBF was measured in nasal brush samples using a phase contrast microscope. All patients were treated with erythromycin succinate 250 mg 2x daily or clarithromycin 250 mg 1x daily and were assessed after 3 months. In cases where there was no response, treatment was abandoned. The remaining patients (responders) were reassessed after 12 months of treatment. RESULTS: Of 17 patients, 12 responded to treatment. The 12-month follow-up showed an improvement in saccharine transit time (P < 0.05) but no significant change in CBF. There was a trend toward an increase in NO (P = 0.12). Endoscopic nasal examination scoring improved significantly (P < 0.01). In the visual analog scale scoring, the most pronounced improvements were seen in nasal congestion, sticky secretion, and runny nose at 3 and 12 months (P < 0.01). Improvements were also seen in headache (P < 0.05). CONCLUSION: The present study suggests that long-term, low-dose treatment with erythromycin is effective in persistent chronic sinusitis that does not respond to sinus surgery or systemic steroid/antibiotic treatment. SIGNIFICANCE: Long-term, low-dose erythromycin therapy seems to be a promising alternative when more conventional therapy fails. However, placebo-controlled studies are needed to validate the potential of this treatment.
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| 2. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate methods in the development of a new tablet formulation : optimization and validation
- 2004
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Ingår i: Drug Development and Industrial Pharmacy. - New York : M. Dekker. - 0363-9045 .- 1520-5762. ; 30:10, s. 1037-1049
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Tidskriftsartikel (refereegranskat)abstract
- In a previous study of the development of a tablet formulation approximately 100 excipients were characterized in screening experiments using multivariate design. Acceptable values for important responses were obtained with some of the formulations. The relationships between the properties of the excipients and the responses were evaluated using PLS. In this study additional experiments were performed in order to validate models obtained from the screening study and to find a formulation of suitable composition with desired tablet properties. A formulation with the desired disintegration time was found with the additional experiments and the agreement between observed and predicted values was fair for the tablets that did disintegrate. A limitation of this study was that tablets from four experiments did not disintegrate within the set time limit. The lack of agreement between observed and predicted values of these four experiments was probably due to the nature of one of the factors in the design. Considering the reduced experimental design the results are still encouraging.
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| 3. |
- Gabrielsson, Jon, et al.
(författare)
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Multivariate Methods in the Development of a New Tablet Formulation
- 2003
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Ingår i: Drug Development and Industrial Pharmacy. - New York : Marcel Dekker. - 0363-9045 .- 1520-5762. ; 29:10, s. 1053-1075
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Tidskriftsartikel (refereegranskat)abstract
- The overall objective of this article is to use an efficient approach to find a suitable tablet formulation for direct compression. By using traditional approaches to statistical experimental design in tablet formulation, the number of experiments quickly grows when many descriptive variables or many excipients are included. To facilitate the screening process, a multivariate design, which allows a systematical evaluation of a large number of excipients with a limited number of experiments, was implemented. Formulations with acceptable values for disintegration time and crushing strength were obtained with some of the formulations in the present study. The multivariate experimental design strategy yielded PLS models that will be used to identify a region of interest for the optimization. The strategy is general and can be applied in many different areas of pharmaceutical research and development.
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| 4. |
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| 5. |
- Lindberg, Nils-Olof, et al.
(författare)
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Use of software to facilitate pharmaceutical formulation : experiences from a tablet formulation
- 2004
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Ingår i: Journal of Chemometrics. - Chichester : John Wiley & Sons, Ltd. - 0886-9383 .- 1099-128X. ; 18:3-4, s. 133-138
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Tidskriftsartikel (refereegranskat)abstract
- This paper exemplifies the benefits of using experimental design together with software to facilitate the formulation of a tablet for specific purposes, from screening to robustness testing. By applying a multivariate design for the screening experiments, many excipients were evaluated in comparatively few experiments. The formulation work was generally based on designed experiments. Most of the experiments were fractional or full factorial designs, generated and evaluated in Modde with the centre point replicated. The robustness of the formulation was evaluated with experimental designs on two different occasions. Tested flavours were found to have limited influence on the important responses, which was key information in order to proceed with that particular composition. The formulation was also robust towards normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. A process step was investigated and, by applying experimental design and keeping in mind previous findings, important information could be gained from the study. The different studies yielded good and very useful models. Established relationships between design factors and responses provided information that was vital for the project. In cases of poor models, essential information regarding robustness was obtained.
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| 6. |
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| 7. |
- Lindén, Daniel, 1971, et al.
(författare)
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Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48.
- 2002
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 277:25, s. 23044-53
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Tidskriftsartikel (refereegranskat)abstract
- The peroxisome proliferator-activated receptor (PPAR) alpha agonist WY 14,643 increased the secretion of apolipoprotein (apo) B-100, but not that of apoB-48, and decreased triglyceride biosynthesis and secretion from primary rat hepatocytes. These effects resulted in decreased secretion of apoB-100-very low density lipoprotein (VLDL) and an increased secretion of apoB-100 on low density lipoproteins/intermediate density lipoproteins. ApoB-48-VLDL was also replaced by more dense particles. The proteasomal inhibitor lactacystin did not influence the recovery of apoB-100 or apoB-48 in primary rat hepatocytes, indicating that co-translational (proteasomal) degradation is of less importance in these cells. Treatment with WY 14,643 made the recovery of apoB-100 sensitive to lactacystin, most likely reflecting the decreased biosynthesis of triglycerides. The PPAR alpha agonist induced a significant increase in the accumulation of pulse-labeled apoB-100 even after a short pulse (2-5 min). There was also an increase in apoB-100 nascent polypeptides, indicating that the co-translational degradation of apoB-100 was inhibited. However, a minor influence on an early posttranslation degradation cannot be excluded. This decreased co-translational degradation of apoB-100 explained the increased secretion of the protein. The levels of apoB-48 remained unchanged during these pulse-chase experiments, and albumin production was not affected, indicating a specific effect of PPAR alpha agonists on the co-translational degradation of apoB-100. These findings explain the difference in the rate of secretion of the two apoB proteins seen after PPAR alpha activation. PPAR alpha agonists increased the expression and biosynthesis of liver fatty acid-binding protein (LFABP). Increased expression of LFABP by transfection of McA-RH7777 cells increased the secretion of apoB-100, decreased triglyceride biosynthesis and secretion, and increased PPAR alpha mRNA levels. These findings suggest that PPAR alpha and LFABP could interact to amplify the effect of endogenous PPAR alpha agonists on the assembly of VLDL.
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| 8. |
- Zhou, Ye, et al.
(författare)
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Protein Microarrays on Carboxymethylated Dextran Hydrogels : Immobilization, Characterization and Application
- 2004
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Ingår i: Microchimica Acta. - : Springer Science and Business Media LLC. - 0026-3672 .- 1436-5073. ; 147:1-2, s. 21-30
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Tidskriftsartikel (refereegranskat)abstract
- Tetraoctadecylammonium bromide (TOAB, (CH3(CH2)17)4N+Br–) has been used to print temporary hydrophobic barriers on carboxymethylated dextran (CMD) hydrogels to create a generic platform for protein microarray applications. The primary reason for printing temporary hydrophobic barriers is to prevent cross-contamination and overflow during microdrop dispensing. Equally important is to eliminate the risk for non-specific binding to the barriers during analyte exposure. This has been accomplished by introducing a regeneration step that removes the barriers after ligand immobilization. The overall fabrication process was characterized by microscopic wetting, atomic force microscopy, imaging ellipsometry, fluorescence microscopy, surface plasmon microscopy and biospecific interaction analysis. A series of model proteins including transferrin, Protein A, anti-myoglobin and bovine serum albumin was spotted into the TOAB-defined areas under different experimental conditions, e.g. at increased humidity and reduced substrate temperature or with glycerol as an additive in the protein solution. Much emphasis was devoted to studies aiming at exploring the homogeneity and activity of the immobilized proteins. The printed barriers were removed after protein immobilization using tert-n-butyl alcohol (TBA). TBA was found to be a very efficient agent as compared to previously used salt regeneration solutions, and the regeneration time could be reduced from 30 to 10 minutes. Finally, the potential of using the well established CMD hydrogel chemistry as a platform for protein microarrays was exploited using surface plasmon microscopy.
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| 9. |
- Zhou, Ye, et al.
(författare)
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Reversible hydrophobic barriers introduced by microcontact printing : Application to protein microarrays
- 2004
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Ingår i: Microchimica Acta. - : Springer Science and Business Media LLC. - 0026-3672 .- 1436-5073. ; 146:3-4, s. 193-205
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Tidskriftsartikel (refereegranskat)abstract
- Microcontact printing (µCP) has been used to introduce temporary hydrophobic barriers on carboxymethylated dextran (CMD) hydrogels on gold. Among the investigated types of inks, tetraoctadecylammonium bromide (TOAB), electrostatically bound to the CMD layer, provided the most well-defined features both with respect to pattern-definition and reversibility upon exposure to a regeneration solution. The printed patterns were characterized by atomic force microscopy (AFM), scanning electron microscopy (SEM), microscopic wetting and imaging null ellipsometry to explore the influence of concentration of ink solution and contact time on the appearance of the printed layer. AFM revealed that the printed TOAB molecules aggregated into clusters rather than into a homogeneous mono- or multilayer on the CMD hydrogel. It was also observed that printed areas of TOAB that are larger than 25?µm are inhomogeneous most likely because of an edge transfer lithography (ETL) mechanism. A protein model system based on Protein A-rabbit antimouse Fc ? was used to evaluate the potential of the patterned surface as a protein microarray chip by means of surface plasmon microscopy (SPM). Moreover, non-specific adsorption of several proteins onto TOAB barriers was also studied using surface plasmon resonance (SPR), and it is evident that undesired adsorption can be eliminated by removing barriers after ligand immobilization, but prior to analyte exposure, by treating the patterned surface with a simple salt regeneration solution. © Springer-Verlag/Wien 2004.
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