What can we learn about the lipid vesicle structure from the small-angle neutron scattering experiment?

Small-angle neutron scattering (SANS) on the unilamellar vesicle (ULV) populations (diameter 500 and 1,000 Å) in D₂O was used to characterize lipid vesicles from dimyristoylphosphatidylcholine (DMPC) at three phases: gel L_β′, ripple P_β′ and liquid L_α. Parameters of vesicle populations and internal structure of the DMPC bilayer were characterized on the basis of the separated form factor (SFF) model. Vesicle shape changes from nearly spherical in the L_α phase to elliptical in the P_β′ and L_β′ phases. This is true for vesicles prepared via extrusion through pores with the diameter 500 Å. Parameters of the internal bilayer structure (thickness of the membrane and the hydrophobic core, hydration and the surface area of the lipid molecule) were determined on the basis of the hydrophobic–hydrophilic (HH) approximation of neutron scattering length density across the bilayer ρ(x) and of the step function (SF) approximation of ρ(x). DMPC membrane thickness in the L_α phase (T=30°C) demonstrates a dependence on the membrane curvature for extruded vesicles. Prepared via extrusion through 500 Å diameter pores, vesicle population in the L_α phase has the following characteristics: average value of minor semi-axis 266±2 Å, ellipse eccentricity 1.11±0.02, polydispersity 26%, thickness of the membrane 48.9±0.2 Å and of the hydrophobic core 19.9±0.4 Å, surface area 60.7±0.5 Ų and number of water molecules 12.8±0.3 per DMPC molecule. Vesicles prepared via extrusion through pores with the diameter 1,000 Å have polydispersity of 48% and membrane thickness of 45.5±0.6 Å in the L_α phase. SF approximation was used to describe the DMPC membrane structure in L_β′ (T=10°C) and P_β′ (T=20°C) phases. Extruded DMPC vesicles in D₂O have membrane thickness of 49.6±0.5 Å in the L_β′ phase and 48.3±0.6 Å in the P_β′ phase. The dependence of the DMPC membrane thickness on temperature was restored from the SANS experiment.     

Sex differences in the rate of fatigue development and recovery

Background

Many musculoskeltal injuries in the workplace have been attributed to the repetitive loading of muscle and soft tissues. It is not disputed that muscular fatigue is a risk factor for musculoskeltal injury, however the disparity between gender with respect to muscular fatigability and rate of recovery is not well understood. Current health and safety guidelines do not account for sex differences in fatiguability and may be predisposing one gender to greater risk. The purpose of this study was to quantify the sex differences in fatigue development and recovery rate of lower and upper body musculature after repeated bouts of sustained isometric contractions.

Methods

Twenty-seven healthy males (n = 12) and females (n = 15) underwent bilateral localized fatigue of either the knee extensors (male: n = 8; female: n = 8), elbow flexors (male: n = 8; female: n = 10), or both muscle groups. The fatigue protocol consisted of ten 30-second sub-maximal isometric contractions. The changes in maximum voluntary contraction (MVC), electrically evoked twitches, and motor unit activation (MUA) were assessed along with the ability to control the sustained contractions (SLP) during the fatigue protocol using a mixed four-factor repeated measures ANOVA (gender × side × muscle × time) design with significance set at p < 0.05.

Results

There was a significant loss of MVC, MUA, and evoked twitch amplitude from pre- to post-fatigue in both the arms and legs. Males had greater relative loss of isometric force, a higher rate of fatigue development, and were less capable of maintaining the fatiguing contractions in the legs when compared to the females.

Conclusion

The nature of the induced fatigue was a combination of central and peripheral fatigue that did not fully recover over a 45-minute period. The results appear to reflect sex differences that are peripheral, and partially support the muscle mass hypothesis for explaining differences in muscular fatigue.

     

A Novel Approach for In Vitro Studies Applying Electrical Fields to Cell Cultures by Transformer-Like Coupling

The purpose of this study was to develop a new apparatus for in vitro studies applying low frequency electrical fields to cells without interfering side effects like biochemical reactions or magnetic fields which occur in currently available systems. We developed a non-invasive method by means of the principle of transformer-like coupling where the magnetic field is concentrated in a toroid and, therefore, does not affect the cell culture. Next to an extensive characterization of the electrical field parameters, initial cell culture studies have focused on examining the response of bone marrow-derived human mesenchymal stem cells (MSCs) to pulsed electrical fields. While no significant differences in the proliferation of human MSCs could be detected, significant increases in ALP activity as well as in gene expression of other osteogenic markers were observed. The results indicate that transformer-like coupled electrical fields can be used to influence osteogenic differentiation of human MSCs in vitro and can pose a useful tool in understanding the influence of electrical fields on the cellular and molecular level.     

Adverse Drug Reactions in Hospitalised Children in Germany Are Decreasing: Results of a Nine Year Cohort-Based Comparison

Background

In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period.

Methodology

Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis.

Results

A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001).

Conclusions

Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still needed.     

Saddle-Point Approximations,Integrodifference Equations,and Invasions

Invasion, the growth in numbers and spatial spread of a population over time, is a fundamental process in ecology. Governments and businesses expend vast sums to prevent and control invasions of pests and pestilences and to promote invasions of endangered species and biological control agents. Many mathematical models of biological invasions use nonlinear integrodifference equations to describe the growth and dispersal processes and to predict the speed of invasion fronts. Linear models have received less attention, perhaps because they are difficult to simulate for large times. In this paper, we use the saddle-point method, alias the method of steepest descent, to derive asymptotic approximations for the solutions of linear integrodifference equations. We work through five examples, for Gaussian, Laplace, and uniform dispersal kernels in one dimension and for asymmetric Gaussian and radially symmetric Laplace kernels in two dimensions. Our approximations are extremely close to the exact solutions, even for intermediate times. We also employ an empirical saddle-point approximation to predict densities using dispersal data. We use our approximations to examine the effects of censored dispersal data on estimates of invasion speed and population density.     

Potent bradykinin antagonists containing N-benzylglycine or N-benzyl-l-alanine in position 8.

Two new analogues of a previously designed bradykinin (BK) antagonist, d-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-d-Phe-Thi-Arg, substituted in position 8 by N-benzylglycine and N-benzyl-l-alanine were designed, synthesized and bioassayed. The results show an impressive enhancement of B2 antagonistic potencies of both peptides in comparison with the model. In two further analogues these modifications were combined with acylation of the N-terminus with 1-adamantanacarboxylic acid. Acylated analogues exhibited higher antagonistic potency in comparison with the parent compounds, however, the range of effect was not as high as in previously described cases. The activity of analogues was assessed by their ability to inhibit vasodepressor response to exogenous BK (rat blood pressure test). Our results may be of value in the design of more potent BK antagonists.     

Is it possible to orally vaccinate juvenile red foxes against rabies in spring campaigns?

The rabies antibody status of juvenile foxes (Vulpes vulpes) was evaluated in large-scale, long-term oral vaccination campaigns. Between 9% (n = 659) and 21% (n = 42) of the juvenile foxes examined in 1993-94 and 1997, respectively, showed rabies virus neutralizing antibody (nAb)-titers > or = 0.5 IU/ml following bait distribution in spring. The presence of nAb may be due to either the passive transfer of maternal antibodies, or active immunization derived from spring vaccination campaigns. The latter alternative is supported by the finding of nAb throughout late spring and the summer months, and the finding of the tetracycline (TC) biomarker, used in the vaccine-baits, in 27% (n = 43) and 37% (n = 155) of juveniles in 1993-94 and 1997, respectively. It was not possible to distinguish nAb originating from passive immunity from that arising from active immunization. However, biological data on the whelping period of red foxes, on dynamics of maternal antibodies and the timing of oral vaccination, gave evidence that a superposition of these processes is likely. Evidence from these studies suggests that oral vaccination coinciding with the spring perinatal period may produce immunity in both parents and only in a certain percentage of the offspring simultaneously. This phenomenon should be useful in further enhancing the efficacy of oral vaccination in red foxes.     

Bau und Entwicklung des menschlichen Pankreas

Ohne Zusammenfassung     

Impact of the long chain ω-acylceramides on the stratum corneum lipid nanostructure. Part 1: Thermotropic phase behaviour of CER[EOS] and CER[EOP] studied using X-ray powder diffraction and FT-Raman spectroscopy

The stratum corneum (SC), the outermost layer of the mammalian skin, is the main skin barrier. Ceramides (CERs) as the major constituent of the SC lipid matrix are of particular interest. At the moment, 11 classes of CERs are identified, but the effect of each single ceramide species is still not known.Therefore in this article, the thermotropic behaviour of the long chain ω-acylceramides CER[EOS] and CER[EOP] was studied using X-ray powder diffraction and FT-Raman spectroscopy.It was found that the ω-acylceramides CER[EOS] and CER[EOP] do not show a pronounced polymorphism which is observed for shorter chain ceramides as a significant feature. The phase behaviour of both ceramides is strongly influenced by the extremely long acyl-chain residue. The latter has a much stronger influence compared with the structure of the polar head group, which is discussed as extremely important for the appearance of a rich polymorphism. Despite the strong influence of the long chain, the additional OH-group of the phyto-sphingosine type CER[EOP] influences the lamellar repeat distance and the chain packing. The less polar sphingosine type CER[EOS] is stronger influenced by the long acyl-chain residue. Hydration is necessary for the formation of an extended hydrogen-bonding network between the polar head groups leading to the appearance of a long-periodicity phase (LPP). In contrast, the more polar CER[EOP] forms the LPP with densely packed alkyl chains already in the dry state.