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Biomedical subjects

S Engström

Publications and source records attributed to S Engström.

18 recordsLinked to original sources
PubMed2004

Transdermal delivery from a lipid sponge phase--iontophoretic and passive transport in vitro of 5-aminolevulinic acid and its methyl ester.

The hydrochloride salts of 5-aminolevulinic acid (ALA) and its methyl ester (m-ALA), respectively, were dissolved in a lipid sponge phase comprising monoolein, propylene glycol and aqueous buffer at concentrations of approximately 0.25% and 16% w/w m-ALA. The iontophoretic and passive delivery of ALA and m-ALA from this formulation through porcine skin in vitro were measured and compared to formulations used in clinical practice, 20% w/w ALA in Unguentum M and Metvix (a cream containing 16% w/w m-ALA). A sponge phase with 16% w/w m-ALA showed a higher passive flux (approximately 140 nmol cm(-2) h(-1) at 5 h) but a lower iontophoretic flux (approximately 800 nmol cm(-2) h(-1) at 5 h) compared to the clinically used products but the differences are hardly significant due to large standard deviations. ALA and m-ALA in sponge phase formulation showed iontophoretic fluxes in the range 80-100 nmol cm(-2) h(-1) at 3 h, i.e. values comparable to the passive fluxes from the more concentrated vehicles. The results demonstrate that the lipid sponge phase, a thermodynamically stable liquid with amphiphilic character, may have potential as a transdermal drug delivery vehicle.

Administration, Cutaneous↗
PubMed2001

Inclusion of lignocaine base into a polar lipid formulation--in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat.

BACKGROUND: Slow-release formulations of local anaesthetics may produce nerve blocks of long duration. The present study aimed at investigating the in vitro and in vivo properties of a polar lipid formulation for slow release of lignocaine and the effects on nerve block duration by inclusion of dexamethasone into the system. METHODS: In vitro release of lignocaine from the lipid formulation was studied in a US Pharmacopoeia rotating apparatus. Sciatic nerve blocks were induced in rats by 0.1 ml of test formulations containing lignocaine HCl 20 mg. ml-1 in aqueous solution, lignocaine base 20, 100 or 200 mg. ml-1 in lipid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 mg. ml-1. The durations of sensory and motor block and the arterial blood concentrations of lignocaine were investigated. RESULTS: In vitro there was a sustained release of lignocaine from the lipid formulation, with 50% release at around 48 h. In vivo lignocaine base 20 mg. ml-1 in lipid formulation produced sciatic nerve blocks of significantly shorter duration than lignocaine HCl 20 mg. ml-1 in aqueous solution, while lignocaine base 100 and 200 mg. ml-1 in lipid formulation produced blocks lasting two and three times longer, respectively, than the lignocaine HCl solution. Addition of dexamethasone did not affect the duration of nerve block. Following administration of lignocaine base 200 mg. ml-1 in lipid formulation, as compared to lignocaine HCl 20 mg. ml-1 in aqueous solution, the maximal blood concentration of lignocaine was only three times higher in spite of the ten-fold difference in dose, and the mean terminal half-life was three times longer, reflecting the slow release from the formulation. CONCLUSIONS: Our findings indicate that lignocaine base in polar lipids acts as a slow-release preparation of local anaesthetic both in vitro and in vivo.

Algorithms↗
PubMed2001

Is general practice effective? A systematic literature review.

OBJECTIVE: To find evidence of the effectiveness of physicians working in primary care. DESIGN: Systematic literature search in the Medline and Cochrane databases. MATERIAL: Out of 7223 titles found in the search, 45 studies, comparing, from different aspects, primary care with specialist care, were extracted. MAIN OUTCOME MEASURES: Health indicators, health care costs, quality of health care. RESULTS: Primary care contributed to improved public health, as expressed through different health parameters, and a lower utilisation of medical care leading to lower costs. Physicians working in primary care, in comparison with other specialists, took care of many diseases without loss of quality and often at lower cost. The organisation of primary care was important in respect of reimbursement by capitation, more group practices, higher personal continuity, and having generalists as primary care physicians. CONCLUSIONS: To compare the effectiveness of primary care and specialist care is a complex task and there are limitations in all studies. However, we have found evidence that increased accessibility to physicians working in primary care contributes to better health and lower total costs in the health care system. It is also clear that studies with evaluation of how to most effectively organise primary care are far too few. There is an extensive need for future research in this area, a suitable task for collaborative research between the Nordic countries.

Cost-Benefit Analysis↗
PubMed2001

Green function method for calculating properties of static magnetic fields.

Given complete information about the normal component of a magnetic field in a plane, it is possible to directly calculate all aspects of the field at any point in a source-free, homogeneous volume above that plane. The magnetic scalar potential, the magnetic field, and its gradient have direct representations as integrals of the boundary data. This paper provides a Green function method for this problem, as well as examples of such calculations.

Magnetics↗
PubMed2000

The arithmetic mean of ratio-normalized experiments overestimates the true E/C ratio.

Biological assays often suffer from large systematic variation between sets of experiments. This variation is sometimes countered by normalizing the results of an "exposed" (E) experiment to that of a simultaneously performed "control" (C). We demonstrate that the arithmetic mean of such ratios overestimates the "true" E/C ratio. Fortunately, the overestimation may be calculated from experimentally accessible information, and it is generally possible to correct for this factor using formulas presented in this paper. We have studied the impact of this effect on a set of studies in the bioelectromagnetics literature and find that, although most results are weakened by the correction, few are significantly altered. Some of the papers used for our literature study are controversial; we believe that the present study may strengthen the quoted results by removing doubts about the statistical treatment of E/C ratios. Both false positives and negatives are possible if the proper correction is not made to the arithmetic mean of a set of E/C data. Realistic examples of erroneous statistical conclusions demonstrate that this is a real concern for E/C data which are marginal in both magnitude (mean < 2) and variance (standard deviation > 0.5).

Animals↗
PubMed2000

The skin barrier from a lipid perspective.

This contribution summarises the results from a number of investigations undertaken in the spirit of the Domain Mosaic Model proposed by Forslind in 1994. Atomic Force Microscopy (AFM) studies on the two-dimensional phase behaviour of some stratum corneum lipids revealed phase separation of the lipids in the typical case and the ability of cholesterol to reduce the line tension between phases. A theoretical model was developed describing the response of an oriented stack of polar lipid bilayers in the presence of a gradient in water chemical potential (water solution to humid air). The gradient gives rise to an inhomogeneous water swelling, and presumably to a liquid crystal-to-gel transition in the lamellar region closest to humid air. Skin penetration enhancers such as Azone and oleic acid cause phase transformations in lipid bilayer systems which may be relevant in the context of skin permeation.

Air↗
PubMed1999

Five hypotheses to examine the nature of magnetic field transduction in biological systems.

This paper postulates five experiments that may be used to characterize the nature of the transduction step in which a magnetic or electric field is converted into a biological signal. Each of the five experiments is formulated as a refutable hypothesis in such a manner that rejection of the hypothesis will provide information about the transduction process and an associated confidence level for evaluating each experiment. The proposed hypotheses are formulated to provide inferences about the mode of interaction (magnetic field or induced electric field transduction), spatial distribution of the detector elements in the biological system, and the timescale of the transductive step.

Algorithms↗
PubMed1999

Evidence for a slow time-scale of interaction for magnetic fields inhibiting tamoxifen's antiproliferative action in human breast cancer cells.

One critical biophysical feature of environmental-level magnetic field (MF) interactions with biological systems is the time-scale of interaction. A recently proposed fast/slow hypothesis states that a fast mechanism can only sense the instantaneous absolute value of the MF, and that a slow mechanism is potentially capable of sensing features such as frequency and relative orientation and magnitude of the field components. Here we applied the fast/slow hypothesis to a breast cancer model system: A 1.2 microT (rms), 60-Hz field inhibits tamoxifen's (TAM's) cytostatic action in MCF-7 cells via a MF interaction. We measured the growth of MCF-7 cells treated with TAM over 7 d, within different MFs: a sinusoidal, 60-Hz, 0.2-microT(rms) field; a sinusoidal, 60-Hz, 1.2-microT(rms) field; and a full-wave rectified version of the 1.2-microT(rms) sinusoidal field. A fast mechanism should not be able to distinguish between the latter two exposures. We observe that the rectified 1.2-microT field does not inhibit TAM's action, but that the 1.2-microT sinusoidal field does. Therefore, the 1.2-microT MF inhibition of TAM's cytostatic action operates via a relatively slow mechanism, and we predict that there exists a biologically dynamic complex capable of sensing a 1.2-microT, 60-Hz sinusoidal MF with an intrinsic time-scale of 17 ms or longer, the period of the 60-Hz applied field.

Breast Neoplasms↗
PubMed1999

Cubic phases for studies of drug partition into lipid bilayers.

Drug partition into lipid bilayers in a cubic liquid-crystalline phase was investigated. Glyceryl monooleate was used to form the lipid bilayer in a reversed bicontinuous cubic liquid-crystalline phase. The reason for using the cubic phase is that it may coexist with an external aqueous phase, and that the phase boundary (cubic phase/aqueous bulk) is well-defined due to the stiffness of the cubic phase. This makes the cubic phase a potential candidate for high throughput screening (HTS) of the lipophilicity and the dissociation constant (if any) of drug compounds. Clomethiazole (CMZ), lidocaine, prilocaine and 4-phenylbutylamine (4-PBA) were chosen as model drug compounds. It was shown that it is possible to determine a pH-dependent apparent partition coefficient, Kbl/w, of a drug compound using a lipid bilayer expressed as a cubic liquid-crystalline structure. Good agreement was found when the resulting Kbl/w vs. pH curves for CMZ, lidocaine and prilocaine were fitted to a mathematical expression. This included the bilayer/water partition coefficient for the unionised and ionised drug respectively and the pKa of the drug. The effect of different experimental conditions; such as amount of cubic phase, temperature, agitation, sample preparation and interfacial area between the cubic phase and the aqueous bulk on the partition kinetics were investigated as well. The studies reveal that the time needed to reach partition equilibrium was, as expected, substantially reduced (from days to hours) by decreasing the amount of cubic phase, increasing the interfacial area between the cubic phase and the aqueous phase, and increasing the temperature and the agitation of the sample. It was also shown that the bilayer affinity of 4-PBA was increased when a zwitterionic lipid (i.e. dioleoyl phosphatidylcholine, DOPC) was incorporated in the bilayer.

Anesthetics, Local↗
PubMed1998

Phase coexistence in cholesterol-fatty acid mixtures and the effect of the penetration enhancer Azone.

Small and wide-angle X-ray diffraction was used to study the phase behaviour of cholesterol-fatty acid mixtures in an attempt to understand lipid interaction occurring in the stratum corneum, the outermost layer of skin. The effect of the penetration enhancer Azone was investigated as well. It was found that equimolar mixtures of cholesterol, palmitic acid and oleic acid (with the acids neutralised to 41 mol%) in 25% (wt/wt) water typically showed three phases at room temperature, two crystalline and one gel phase. The crystalline phases consisted mainly of palmitic acid:soap and cholesterol, respectively. The water present was unevenly distributed and was associated with the gel phase. Both cholesterol and palmitic acid seemed to be depleted from their crystalline phases by Azone. The electrostatic effects on titration of fatty acids in lamellar aggregates were calculated in view of the present results, and the effects of phase separation were discussed.

Azepines↗
PubMed1998

Triglyceride-based microemulsion for intravenous administration of sparingly soluble substances.

A pharmaceutically acceptable microemulsion system composed of a medium-chain triglyceride (MCT), soybean phosphatidylcholine and poly(ethylene glycol)(660)-12-hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG 400) and ethanol as cosolvents is presented and characterized in terms of phase behavior, microstructure, solubilization capacity and in vivo effects after intravenous administration to conscious rats. At a total concentration of 11.9 wt % of soybean phosphatidylcholine and 12-HSA-EO15, a microemulsion region was formed over a wide range of alpha, where alpha is the weight fraction of MCT/(MCT + water + PEG 400 + ethanol). The microstructure of the microemulsion was of a bicontinuous nature even at high oil concentrations. The mean droplet diameter of the oil-in-water emulsion formed after dilution of microemulsions prepared at different alpha within the one-phase region was between 60 and 200 nm. It was concluded that it is possible to administer up to 0.5 mL/kg of the microemulsion (alpha = 0.5) without producing any significant effect on acid-base balance, blood gases, plasma electrolytes, mean arterial blood pressure (MAP), heart rate (HR), and PQ time (the time between depolarization of atrium and chamber). At a dose of 1.5 mL/kg, a temporary increase in MAP, a decrease in HR, and a prolongation of the PQ time were observed.

Animals↗
PubMed1997

What is the time scale of magnetic field interaction in biological systems?

An experimental test constraining the intrinsic time scale of a primary physical mechanism that detects extremely-low-frequency (ELF) magnetic fields in biological systems is proposed. The suggested test postulates that a transductive mechanism operating on time scales much shorter than the period of an applied magnetic field cannot obtain any information about the exposure conditions other than the absolute magnitude of the field. By generating field exposure that differ in their vector properties but are equivalent in their time-varying absolute amplitude, it is possible to differentiate between two broad classes of mechanisms: 1) those with intrinsic time scales comparable with or longer than those of the external influence, and 2) those that are much faster than the period of the applied field. The hypothesis assumes an experimental model proven to respond to magnetic fields and sensitive to a change of about a factor of two in one of the field parameters (AC, DC amplitude or frequency). The case of general linearly polarized fields is discussed, and an analytical solution for the case of perpendicular AC/DC fields is given.

Animals↗
PubMed1997

A novel approach to the understanding of human skin barrier function.

The basis for externally caused skin disorders is penetration of the skin barrier. A recent model for the skin barrier, the domain mosaic model, based on current knowledge of the physics of lipid bilayer organization gave tentative explanations for several aspects of function. It is demonstrated here that a development of the model explains how the requirements are met for a water-tight structure that will still allow a controlled, minute loss of water, the perspiratio insensibilis, necessary for maintaining plasticity of the keratin. A major advantage of the extended model is that it allows an interpretation of the changes imposed on the structure when in contact with detergents and/or penetration enhancers.

Administration, Cutaneous↗
PubMed1996

Dynamic properties of Lednev's parametric resonance mechanism.

This paper presents a further development of the mechanism for the detection of weak magnetic fields proposed by [Lednev (1991): Bioelectromagnetics 12:71-75]. The fraction of excited oscillator states of an unhydrated ion is studied in a dynamic model driven by the predicted (time-varying) transition probability in the presence of thermal noise and an unspecified excitation mechanism. The main results of Lednev are confirmed. In addition, I conclude that ultraharmonic and ultrasubharmonic resonances may also be observed, provided that the response time of the dynamic system is similar to the period of the oscillating magnetic field. I discuss the time scales involved in the mechanism and present theoretical constraints on these parameters. The crucial requirement for the theory's applicability is that the lifetime of the excited states of the affected ion oscillator exceeds the period of the applied magnetic field. Numerical solutions of the dynamic system are given and are shown to correspond well to theoretical expectations. The main discrepancy between the theories of Lednev and of Blanchard and Blackman [Blanchard and Blackman (1994): Bioelectromagnetics 15:217-238] appears to be due to an inconsistency in the latter paper. The general problem of robust analysis of experimental data is discussed, and I suggest a test of compliance with the Lednev model that is independent of all parameters except for the ratio of oscillating and static field strength (B1/B0) for many resonance conditions and experimental models.

Animals↗
PubMed1992

Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.

This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.

Biodegradation, Environmental↗
PubMed1991

Molecular dynamics simulation of the renin inhibitor H142 in water.

H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a -Leu-Val-peptide bond (i. e. C(= O)-NH----CH2-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding.

Amino Acid Sequence↗
PubMedDate not supplied

A static magnetic field modulates severity of audiogenic seizures and anticonvulsant effects of phenytoin in DBA/2 mice.

RATIONALE: In a search for potential supplements or alternatives to the pharmacological treatment of epilepsy, we examined the effects of static magnetic fields on audiogenic seizures of DBA/2 mice. METHODS: Two strains of DBA/2 mice were subjected to auditory stimulation that resulted sequentially in wild running, loss of righting, clonus, tonic hindlimb extension, and death in 80-95% of animals in different experiments. The incidence of seizure stages in groups of animals pretreated with a static magnetic field, phenytoin (PHT) or both was compared to the incidence in sham-exposed control mice. RESULTS: Depending on magnetic flux density and duration of exposure to the field, seizure severity decreased significantly, but not completely, in both strains. However, incidence of five seizure stages was reduced in one strain, with about half of the mice seizure free. Two seizure stages (tonic hindlimb extension and death) were reduced significantly in the other. Magnetic field pretreatment potentiated the effect of PHT. Clonic seizures refractory to PHT or magnetic field pretreatment in DBA/2J mice responded to pretreatment with a combination of PHT and the magnetic field. CONCLUSIONS: A static magnetic field had some anticonvulsant effects when employed alone. More robust effects were seen in combination with PHT. Further testing of magnetic fields for anticonvulsant effects and elucidation of mechanisms of action seem to be warranted.

Acoustic Stimulation↗