31.
Blomkvist, Josefin, et al.
(författare)
Perspective on Roseroot (Rhodiola rosea) Studies
2009
Ingår i: Planta Medica. - : Verlag KG Stuttgart -New York. - 0032-0943 .- 1439-0221. ; 75:11, s. 1187-1190
Tidskriftsartikel (refereegranskat) abstract
Rhodiola rosea (roseroot) extract is a commercially successful product, primarily used to reduce the effect of fatigue on physical and mental performance. In this perspective we present our investigation of the most recent studies performed on human subjects. With a focus on the statistical methods we found considerable shortcomings in all but one of the studies that claim significant improvement from roseroot extract. Overall, the study designs have not been well explained. Experimental results have been confused and appear to be in some cases incorrect. Some of the conclusions are based on selected results and contradicting data have not been adequately taken into account. We point to other studies of higher quality performed on roseroot, several that found no significant effect and one that did. We conclude that the currently available evidence for the claimed effects is insufficient and that the effect of Rhodiola rosea is in need of further investigation before therapeutic claims can be made.
32.
Borde, Annika, 1979, et al.
(författare)
Osmotic-driven mass transport of water: Impact on the adhesiveness of hydrophilic polymers
2009
Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 341:2, s. 255-260
Tidskriftsartikel (refereegranskat) abstract
Adhesion is an important property for the functionality of many medical devices. One reason for the development of adhesive forces is dehydration caused by mass transport of water. Osmotic pressure is one main driving force for mass transport and the correlation between osmotic pressure and adhesive force has not been studied yet, which was the aim of the present study. A model system was used where a Carbopol tablet was lowered onto a 1% (w/w) agarose gel. The force required to detach the tablet (adhesive force) and the weight gain of the tablet (as a measure of transported water) were determined. Sodium chloride and mannitol were added to the agarose gel to decrease the osmotic pressure difference between the agarose gel and the partially hydrated Carbopol tablet. This resulted in a decrease of both mass transport and adhesive force. In addition, experiments with restricted water transport within the agarose gel were performed by preparing gels with different agarose concentrations. An increase of the agarose concentration resulted in decreased water transport and higher adhesive forces. Hence, the results confirmed our hypothesis that osmotic-driven mass transport and restricted mass transport of water correlate very well with the adhesive force.
33.
Bramer, Tobias, et al.
(författare)
Implications of regular solution theory on the release mechanism of catanionic mixtures from gels
2009
Ingår i: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 71:2, s. 214-225
Tidskriftsartikel (refereegranskat) abstract
The aim of this study was to apply the regular solution theory of mixed micelles to gain new insights on the drug release mechanism, when using catanionic mixtures as a method of obtaining prolonged release from gels. Synergistic effects were investigated at equilibrium and quantified in terms of regular solution theory interaction parameters. The drug release from catanionic aggregates was studied both in a polymer free environment, using dialysis membranes, and in gels, using a modified LISP paddle method. The drug release kinetics was modelled theoretically by combining the regular solution theory with Fick's diffusion laws assuming a contribution to the transport only from monomeric species (stationary aggregates). The theoretical predictions were found to be in reasonably good agreement with experiments. An analysis of the calculated distribution of species between aggregated and monomeric states was shown to provide further insights into the release mechanism.
34.
Bysell, Helena, et al.
(författare)
Binding and release of consensus peptides by poly(acrylic acid) microgels
2009
Ingår i: Biomacromolecules. - : American Chemical Society. - 1525-7797 .- 1526-4602. ; 10:8, s. 2162-2168
Tidskriftsartikel (refereegranskat) abstract
The interaction between positively charged consensus peptides and poly(acrylic acid) microgels was investigated with micromanipulator-assisted light microscopy and confocal laser scanning microscopy. Peptide binding and release was monitored by microgel deswelling and swelling for monodisperse multiples of heparin-binding Cardin and Weintraub motifs, (AKKARA)(n) (1 <= n <= 4) and (ARKKAAKA)(n) (1 <= n <= 3), as well as the corresponding titratable (AHHAHA)(4) and (AHHHAAHA)(3) peptides (A, K. R and H, refering to alanine, lysine, arginine, and histidine, respectively). When fully charged, these peptides distribute homogenously throughout the microgels and display concentration-dependent deswelling, which increases with increasing peptide length. Both (AKKARA)(4) and (ARKKAAKA)(3) display potent and fast microgel deswelling but only marginal subsequent electrolyte-induced desorption. In contrast, reducing the peptide charge for (AHHAHA)(4) and (AHHHAAHA)(3) at neutral and high pH, or the peptide length, substantially reduces the peptide affinity for the microgels and facilitates rapid peptide release. Taken together, the results also show that quite short peptides of moderate charge density interact strongly and cause extensive gel deswelling of oppositely charged microgels, precluding peptide release. They also show, however, that desirable triggered release can be achieved with peptides of lower charge density.
35.
Bysell, Helena, 1978-
(författare)
Interaction Between Microgels and Oppositely Charged Peptides
2009
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
Lightly cross-linked polyelectrolyte microgels are materials with interesting properties for a range of applications. For instance, the volume of these particles can be drastically changed in response to pH, ionic strength, temperature, or the concentration of specific ions and metabolites. In addition, microgel particles can bind substantial amounts of oppositely charged substances, such as proteins and peptides, and release them upon changes in the external environment. Consequently, microgels have potential in catalysis, photonics, biomaterials, and not at least, as protective and stimuli-sensitive carriers for protein and peptide drugs. In this thesis, the interaction between anionic microgels and cationic peptides was investigated by monitoring microgel deswelling and reswelling in response to peptide binding and release using micromanipulator-assisted light microscopy. In addition, peptide distribution in microgels was analyzed with confocal laser scanning microscopy and peptide uptake determined with solution depletion measurements. The aim of the thesis was to clarify how parameters such as peptide size, charge density, pH, ionic strength and hydrophobicity influences the peptide binding to, distribution in and release from, polyelectrolyte microgels. Results obtained in this thesis show that electrostatic attraction is a prerequisite for interaction to occur although non-electrostatic contributions are responsible the finer details of the interactions. The size and charge density of the interacting peptides play a major role, as large and highly charged peptides are restricted to enter and interact with the microgel core, thus displaying a surface-confined distribution. The peptide-microgel interaction strength is highly reflected in the probability of peptides to be detached from the gel network. For instance, reducing the electrostatic interactions by adding salt induces significant peptide release of sufficiently small and moderately charged peptides, whereas longer and more highly charged peptides is retained in the microgel network due to the strong interaction, insufficient salt screening, and gel network pore size restriction. Decreasing the charge density of microgel network and/or peptides increases the probability for peptide detachment tremendously. To summarize, interactions occurring in oppositely charged microgel-peptide systems can be tuned by varying parameters such as charge density and peptide size and through this, the peptide uptake, distribution and release can be controlled to alter the performance of microgels in peptide drug delivery.
36.
Bysell, Helena, et al.
(författare)
Interactions between Homopolypeptides and Lightly Cross-Linked Microgels
2009
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 25:1, s. 522-528
Tidskriftsartikel (refereegranskat) abstract
The relative importance of electrostatic and nonelectrostatic interactions in peptide-microgel systems was evaluated by micromanipulator-assisted light microscopy, confocal microscopy, and circular dichroism. For this purpose, the interaction of various homopolypeptides with lightly cross-linked polyelectrolyte gel particles ( approximately 70 mum in diameter) was studied with focus on peptide-induced microgel deswelling and its relation to peptide distribution within the microgel particles. Negatively charged poly-l-glutamic acid (pGlu) and poly-l-aspartic acid (pAsp), as well as uncharged poly-l-proline (pPro) and poly-l-threonine (pThr), were found to not bind to negatively charged poly(acrylic acid) microgels under the conditions investigated, but were instead depleted from the microgel particles. Positively charged poly-l-arginine (pArg), poly-l-histidine (pHis), and poly-l-lysine (pLys), on the other hand, interacted strongly with the oppositely charged microgel particles and caused significant deswelling of these. In parallel, cationic acrylamidopropyltriethylammoniumchloride (APTAC) microgels bound negatively charged polypeptides to a much higher extent than positively charged and uncharged ones. These findings suggest that electrostatic interactions dominate peptide binding and resulting microgel deswelling in these systems. Nevertheless, although the amount of cationic peptide bound to the anionic microgel particles was similar for cationic pLys, pArg, and pHis, peptide-induced gel deswelling differed significantly, as did the change in peptide conformation after microgel binding and the peptide distribution within the microgels. These effects, as well as pH dependent binding and release of titrable pHis, are discussed in terms of the effects of the charge density of, and structural differences between, the cationic homopolypeptides on the interaction with the oppositely charged microgel particles.
37.
Chieng, Norman, et al.
(författare)
Formation Kinetics and Stability of Carbamazepine−Nicotinamide Cocrystals Prepared by Mechanical Activation
2009
Ingår i: Crystal Growth & Design. - : American Chemical Society. - 1528-7483 .- 1528-7505. ; 9:5, s. 2377-2386
Tidskriftsartikel (refereegranskat) abstract
Co-milling of various carbamazepine (CBZ) polymorphic forms (form I, III and dihydate) with nicotinamide (NIC) was performed in this study to investigate the formation kinetics of carbamazepine−nicotinamide cocrystals (CBZ−NIC) and to evaluate their physical stability. Milling was carried out at room temperature using an oscillatory ball mill at a 1:1 molar ratio of CBZ and NIC for various times up to 60 min. A freshly prepared sample was used for each milling. In the stability study, the milled samples (4, 10, 15, and 30 min) were stored under four conditions (20 and 40 °C; 33 and 75%RH) for up to four weeks. Samples were analyzed by X-ray powder diffraction (XRPD) and differential scanning calorimetry. XRPD showed that all CBZ forms used in this study formed cocrystals when co-milled with NIC (characteristic XRPD peaks at 6.6, 8.9, 10.1, 20.4, and 26.5 °2θ). Cocrystal formation was qualitatively found to be fastest for CBZ dihydrate (CBZ DH, ∼1 min), followed by CBZ form I (∼6 min), and CBZ form III (∼15 min). Upon storage, cocrystals formed from CBZ DH were found to be physically stable under all conditions studied, regardless of a small amount of impurity. For the two anhydrous forms (CBZ I and III), the physical stability of the co-milled CBZ−NIC samples was dependent on the duration of milling, the relative humidity, and temperature of the storage conditions. Under “mild” storage conditions (i.e., 20 °C/33%RH), either partially or fully formed CBZ−NIC cocrystals were found to revert back to pure CBZ and NIC. Under “moderate” storage conditions (i.e., 20 °C/75%RH and 40 °C/33%RH), CBZ−NIC cocrystals reverting to pure CBZ and NIC would occur initially, followed by cocrystal formation with increasing storage time. On the other hand, “stress” storage conditions (i.e., 40 °C/75%RH) were found to be ideal for cocrystal formation and stability. Moisture has been found to favor cocrystallization. Water molecules appear to have a significant effect on the formation (water molecules from CBZ DH) and the stability (high humidity) of the CBZ−NIC cocrystal. The “purity” of the cocrystal samples (i.e., presence of CBZ and/or NIC seeds) can affect the physical stability of CBZ−NIC cocrystals prepared by mechanical activation.
38.
Chong, Julianne J., et al.
(författare)
What Affects Asthma Medicine Use in Children? : Australian Asthma Educator Perspectives
2009
Ingår i: Journal of Asthma. - : Informa UK Limited. - 0277-0903 .- 1532-4303. ; 46:5, s. 437-444
Forskningsöversikt (refereegranskat) abstract
The global burden of childhood asthma is significant. Health care systems are faced with increasing financial costs, while children with asthma and their caretakers are faced with poorer physical health, emotional health, and quality of life. Despite the availability of effective treatment, the quality use of asthma medicines in children remains suboptimal. An investigation was conducted to explore issues related to children's asthma medicine usage from the perspective of the health care professional. Although current literature has elicited the views of caretakers and children, the health care professional viewpoint has been relatively unexplored. Semi-structured qualitative interviews were conducted with a convenience sample of 21 Australian asthma educators. Interviews were audiotaped and transcribed, and transcripts were thematically analyzed with the assistance of NVivo 7. Emergent themes associated with health care professionals, parents, medicines, children, and educational resources were found. Major issues included a lack of information provided to parents, poor parental understanding of medicines, the high cost of medicines and devices, child self-image, the need for more child responsibility over asthma management, and the lack of standardization, access to, and funding for educational resources on childhood asthma. There are multitudes of key issues that may affect asthma medicines usage in children. This research will help inform the development of educational tools on the use of medicines in childhood asthma that can be evaluated for their effectiveness in getting key messages to target audiences such as children, caretakers, and teachers.
39.
Collins, P. W., et al.
(författare)
Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A
2009
Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:3, s. 413-420
Tidskriftsartikel (refereegranskat) abstract
BACKGROUND: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level <1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. OBJECTIVES: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. PATIENTS/METHODS: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII <1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). RESULTS: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.
40.
