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Sven Engström

Publications and source records attributed to Sven Engström.

13 recordsLinked to original sources
PubMed2006

Lipidic sponge phase crystallization of membrane proteins.

Bicontinuous lipidic cubic phases can be used as a host for growing crystals of membrane proteins. Since the cubic phase is stiff, handling is difficult and time-consuming. Moreover, the conventional cubic phase may interfere with the hydrophilic domains of membrane proteins due to the limited size of the aqueous pores. Here, we introduce a new crystallization method that makes use of a liquid analogue of the cubic phase, the sponge phase. This phase facilitates a considerable increase in the allowed size of aqueous domains of membrane proteins, and is easily generalised to a conventional vapour diffusion crystallisation experiment, including the use of nanoliter drop crystallization robots. The appearance of the sponge phase was confirmed by visual inspection, small-angle X-ray scattering and NMR spectroscopy. Crystals of the reaction centre from Rhodobacter sphaeroides were obtained by a conventional hanging-drop experiment, were harvested directly without the addition of lipase or cryoprotectant, and the structure was refined to 2.2 Angstroms resolution. In contrast to our earlier lipidic cubic phase reaction centre structure, the mobile ubiquinone could be built and refined. The practical advantages of the sponge phase make it a potent tool for crystallization of membrane proteins.

Binding Sites↗
PubMed2006

The influence of PVP incorporation on moisture-induced surface crystallization of amorphous spray-dried lactose particles.

We have recently shown that atomic force microscopy (AFM) may be an appropriate method for characterisation of the re-crystallization of amorphous particles. In this study, spray-dried composite particles consisting of lactose and polyvinyl pyrrolidon (PVP) were characterised by AFM and electron spectroscopy for chemical analysis (ESCA), and their response on increasing the relative humidity (RH) was investigated. The PVP content in the particles used was 0, 5 or 25 wt.% of either PVP K17 or PVP K90. All composite particles were found to be enriched with PVP at the surface. The incorporation of PVP in the particles influenced the way the particles responded to an increase in RH. The specific RH interval in which the surface of the particles smoothened and the RH where crystallization could be detected, increased with an increase in the amount and molecular weight of the PVP in the particles. The crystallization kinetics of single particles was analysed with AFM and by utilising the JMAK equation. The rate constant for this transformation increased in an exponential manner with increasing RH. Furthermore, above the RH needed for the crystallization to occur, the exponential increase in the crystallization rate was larger for particles with higher polymer content which indicates that the stabilising effect decreases as the water content in the particles becomes higher. In this study we report a method for determination of crystallization kinetics on single composite particles, which is valuable when evaluating the effect of stabilisers in amorphous powders.

Crystallization↗
PubMed2005

Diamond cubic phase of monoolein and water as an amphiphilic matrix for electrophoresis of oligonucleotides.

We used a cubic liquid crystal formed by the nonionic monoglyceride monoolein and water as a porous matrix for the electrophoresis of oligonucleotides. The diamond cubic phase is thermodynamically stable when in contact with a water-rich phase, which we exploit to run the electrophoresis in the useful submarine mode. Oligonucleotides are separated according to size and secondary structure by migration through the space-filling aqueous nanometer pores of the regular liquid crystal, but the comparatively slow migration means the cubic phase will not be a replacement for the conventional DNA gels. However, our demonstration that the cubic phase can be used in submarine electrophoresis opens up the possibility for a new matrix for electrophoresis of amphiphilic molecules. From this perspective, the results on the oligonucleotides show that water-soluble particles of nanometer size, typical for the hydrophilic parts of membrane-bound proteins, may be a useful separation motif. A charged contamination in the commercial sample of monoolein, most likely oleic acid that arises from its hydrolysis, restricts useful buffer conditions to a pH below 5.6.

Diamond↗
PubMed2005

Lipid cubic phases for improved topical drug delivery in photodynamic therapy.

We have evaluated the efficacy of lipid cubic phases, highly ordered self-assembly systems on the nanometer level, as drug delivery vehicles for in vivo topical administration of delta-aminolevulinic acid (ALA) and its methyl ester (m-ALA) on nude mice skin. ALA, a precursor of heme, induces the production of the photosensitizer protoporphyrin IX (PpIX) in living tissue. Measuring the PpIX fluorescence at the skin surface, after topical administration, makes indirect quantification of the penetration of ALA into the tissue possible. Cubic phases were formed of lipid (monoolein or phytantriol), water and drug. In some cases, propylene glycol was included in the cubic phase as well. The drug concentration was 3% (w/w, based on the total sample weight) in all investigated vehicles. When the formulations were applied for 1 h, the monoolein cubic systems and the three-component phytantriol sample showed higher fluorescence compared to the standard ointment during the 10 h of measurement. Both ALA and m-ALA yielded similar results, although the differences between the investigated vehicles were more pronounced when using m-ALA. For the 24-h applications, the monoolein cubic systems with m-ALA showed faster PpIX formation than the standard ointment, implying higher PpIX levels at short application times (less than 4 h). The systemic PpIX fluorescence of ALA was elevated by using the lipid cubic formulations. Notably, a small systemic effect was also observed for the monoolein cubic sample with m-ALA. These results imply improved PpIX formation when using the lipid cubic systems, most probably due to enhanced drug penetration.

Administration, Topical↗
PubMed2004

The effect of bacteriorhodopsin, detergent and hydration on the cubic-to-lamellar phase transition in the monoolein-distearoyl phosphatidyl glycerol-water system.

The cubic phase of monoolein (MO) has successfully been used for crystallization of membrane proteins. It is likely that the transition to a lamellar phase upon dehydration is important for the crystallization process, and that the internal dimensions of the lipid phases (i.e., water pore diameter) are crucial for the inclusion and the diffusion of membrane proteins. In the present study, we investigated the cubic-to-lamellar phase transitions in the MO-water and the MO-distearoyl phosphatidyl glycerol (DSPG) systems. The MO-water system was investigated by means of isothermal sorption and desorption microcalorimetry. We show that the transition from cubic to lamellar phase induced by desorption is driven by entropy. At 25 degrees C, this occurs at a water activity of 0.98 with a transition enthalpy of 860 J/mol (MO). The phase behavior was also investigated in the presence of a small amount of the transmembrane protein bacteriorhodopsin (bR), and a detergent, octyl glucoside (OG), and it was shown that both bR and OG stabilize the lamellar phase. Analogous results were obtained for the MO-DSPG-water system. The latter system resembles the MO-water system in that a cubic-to-lamellar phase transition is induced by dehydration, although the structural properties of these phases are slightly different. Finally, we demonstrate that bR can be crystallized from a cubic phase of MO-DSPG-buffer.

Bacteriorhodopsins↗
PubMed2004

Moisture-induced surface crystallization of spray-dried amorphous lactose particles studied by atomic force microscopy.

The aim of this study was to show that atomic force microscopy (AFM) can be used to obtain mechanistic and kinetic information about the process of moisture-induced surface crystallization of single particles of amorphous lactose. Completely amorphous lactose particles were prepared by spray-drying a solution of alpha-lactose monohydrate, and moisture-induced crystallization was monitored for a bed of particles by microcalorimetry and for single particles by AFM. From the AFM images it was found that crystallization of the surface of single particles can be described in terms of a sequence of three events: an initial smoothening of the surface, formation of crystalline nanostructures dispersed in amorphous material, and growth of these structures to a complete crystalline surface. The surface roughness parameter rugosity was used to estimate the fraction crystalline surface, and the growth kinetics were found to obey the JMAK equation. The fraction crystalline surface at different times could also be estimated by determining the growth rate of individual crystals. It was concluded that AFM offers a unique means of visualizing the process of moisture-induced surface crystallization of amorphous particles and enables mechanistic and kinetic information about the process to be extracted.

Calorimetry↗
PubMed2004

Excessive use of rapid tests in respiratory tract infections in Swedish primary health care.

A 1-y retrospective study of problem oriented electronic patient records, for encounters concerning respiratory tract infection, was performed. The aim was to analyse the management of respiratory tract infections in primary health care in terms of diagnostic coding, tests and antibiotic treatment using data from electronic patient records. 12 primary health care centres with a registered population of 102,050 residents in 3 counties in southeast Sweden participated. Data were retrieved electronically from records of patient encounters concerning respiratory tract infections. The data were: patient age and gender, date of contact, diagnostic code, CRP and GABHS tests and results, as well as antibiotic prescriptions. In a total of 19,965 encounters, the most frequent diagnoses were common cold (40%), acute tonsillitis (18%), and acute bronchitis (15%). A total of 4445 GABHS tests (in 22% of encounters) and 6141 CRP tests (31%) were performed, and both tests were done in 1910 encounters (10%). A total of 7934 antibiotic prescriptions were registered. The proportion of patients tested and prescribed an antibiotic varied greatly between centres. We found an excessive, and much varying, use of rapid tests in encounters for respiratory tract infections. Data retrieval from electronic patient record systems was a feasible method to study the use of laboratory tests in relation to pharmacological treatment.

Adolescent↗
PubMed2004

Data from electronic patient records are suitable for surveillance of antibiotic prescriptions for respiratory tract infections in primary health care.

Diagnoses and antibiotic treatments were analysed in relation to respiratory tract infections (RTI). A 1-y retrospective study was made of electronic patient records (EPR) for encounters concerning RTIs in primary health care in Sweden. The study covered a registered population of 102,050 individuals at 12 primary health care centres in 3 counties. Data were recorded on number of episodes, encounters, diagnostic codes and antibiotic prescriptions. The yearly number of episodes of RTIs was 16,964 or 166 per 1000 inhabitants per y. The total number of encounters was 19,965. The most frequent diagnoses were common cold (40%), acute tonsillitis (18%), and acute bronchitis (15%). The yearly number of antibiotic prescriptions was 7961, accounting for 47% of the episodes or 78 per 1000 inhabitants per y. The most frequently prescribed antibiotics were phenoxymethylpenicillin (61%), tetracyclines (18%) and macrolides 8%). Standard EPRs provide a feasible source of clinical information which, taking limitations into consideration, could be used for the follow-up of trends in antibiotic prescribing and of adherence to guidelines with regard to RTIs.

Adolescent↗
PubMed2003

Atomic force microscopy analysis and confocal Raman microimaging of coated pellets.

Polymer-coated pellets with different coating thicknesses have been studied regarding coating morphology and drug release properties with atomic force microscopy (AFM) and confocal Raman microscopy. The results were compared with those from scanning electron microscopy (SEM) and drug release profiles, which have been measured previously for these systems and found to vary depending on coating thickness. Results from AFM studies indicated that these pellets differ in the amount of crystalline material on the surface of the coating. The amount was found to be highest on the pellet with the thinnest coating. Confocal Raman microscopy studies confirmed that the active component (remoxipride hydrochloride monohydrate) is present at or close to the surface and that the amount is higher for the thinnest coating. AFM studies in aqueous media showed that the crystalline material on the surface was almost instantaneously dissolved and released into the liquid. AFM has proven to be a powerful tool in the study of the surface of dry formulations and in the study of the controlled release mechanism of a pharmaceutical in a liquid cell. The method can be combined with Raman, giving the added possibility to identify the chemical composition in selected small areas of the coating surface.

Crystallization↗
PubMed2003

Determinants of hospitalisation rates: does primary health care play a role?

OBJECTIVE: To analyse the influence of rates of general practitioner visits on rates of hospitalisations. DESIGN: Ecological cross-sectional study of factors influencing hospitalisation rates. Aggregated data on primary care centre area level. SETTING: The county of Ostergötland, Sweden, with 3 hospital districts and 41 primary health care centres, and the hospital district of Jönköping in the county of Jönköping, Sweden, with 11 primary health care centres. OUTCOME MEASURE: Hospitalisation rates. RESULTS: Age and rates of outpatient hospital visits were the most important factors explaining the variation in rates of hospitalisations between the primary health care centre areas. Hospital districts, socioeconomic factors and rates of GP visits also influenced the rates of hospitalisations. CONCLUSION: When evaluating the influence of primary health care on the rates of hospitalisations, both socioeconomic factors and health care structure must be taken into consideration. Doing this, the rates of GP visits correlated negatively with the rates of hospitalisations.

Aged↗