Horse allergy: Curly Horses can mediate immune tolerance.

American Bashkir Curly Horses are claimed to be hypoallergenic, but this has not been clinically proven. In the present study, the effect of exposure to Curly Horses was investigated in 141 patients allergic to horses by measuring their lung function and nasal patency during Curly Horse contact. Continuous contact with Curly Horses, including riding and brushing, decreased the allergic riders' reactivity as measured by FEV1, PEF, and PNIF. Subsequent visits (up to 40 or more hours of riding) further reduced reactivity to the Curly Horses. Allergic events to horses occurred only in 72 out of 1312 riding hours, mainly in the first ten riding hours.In 41 out of the 141 patients, it was further investigated whether repeated exposure to Curly Horses could induce tolerance to other horses. Patients in the tolerance induction study were tested annually for horse allergy using a nasal provocation test. The tolerance induction study showed that exposure to Curly Horses induced immune tolerance to other horses in 88% of patients who completed the study.To understand the mechanism causing hypoallergenicity, we performed IgE immunoblots to determine whether Curly Horse hairs contain IgE binding proteins. However, no differences in IgE reactivity were found between Curly and non-Curly Horses. Moreover, the immune tolerance induction study patients did not show decreased IgE reactivity to hairs from Curly or non-Curly Horses even though patients had developed tolerance. However, we did find increasing levels of anti-horse IgG antibodies in the study patients.Overall, our data strongly suggests that continuous exposure to Curly Horses can induce immune tolerance, rendering these patients non-reactive to horses. The reason for the reduced clinical allergenicity of Curly Horses remains unclear, but the data suggest that blocking IgG antibodies may be of importance for immune tolerance development.

Demography of the giant monocarpic herb Rheum nobile in the Himalayas and the effect of disturbances by grazing.

BACKGROUND: Perennity of giant rosette species in combination with a single 'big bang' reproduction followed by death of the genetic individual is relatively rare among plants. Such long-lived monocarpic plants are usually slow growing and can be found in deserts, bogs or in alpine regions of the tropics or sub-tropics. Due to their longevity, monocarpic perennials risk losing everything before reproduction, which make them particularly susceptible to disturbances. Because of the inherent difficulties in assessing whether long-lived populations are growing or declining, usually neither their demography nor the consequences of increasing grazing pressure are known. METHODS: We used integral projection modelling (IPM) to measure the growth rate and passage time to flowering of Rheum nobile, a monocarpic perennial, and one of the most striking alpine plants from the high Himalayas. Rosettes which were no longer found due to disturbances or grazing by yaks were either treated as missing or as dead in two series of analysis, thereby simulating demography with and without the impact of grazing cattle. Data were collected from plants at 4500 m a.s.l. in Shangri-la County, Yunnan Province, south-west China. In four consecutive years (2011-2014) and in two populations, 372 and 369 individuals were measured, respectively, and size-dependent growth, survival and fecundity parameters were estimated. In addition, germination percentage, seedling survival and establishment probability were assessed. KEY RESULTS: The probability of survival, flowering and fecundity were strongly size dependent. Time to reach flowering size was 33.5 years [95 % confidence interval (CI) 21.9-43.3, stochastic estimate from pooled transitions and populations]. The stochastic population growth rate (λs) of Rheum nobile was 1.013 (95 % CI 1.010-1.017). When disturbance by grazing cattle (yaks) was accounted for in the model, λs dropped to values <1 (0.940, 95 % CI 0.938-0.943). CONCLUSION: We conclude that natural populations of this unique species are viable, but that conservation efforts should be made to minimize disturbances by grazing and to protect this slow-growing flagship plant from the high Himalayas.

Investigating the potential for genetic improvement of nitrogen and phosphorus efficiency in a Swiss large white pig population using chemical analysis.

Pig production contributes to environmental pollution through excretion of phosphorus and nitrogenous compounds. European pig production requires annual imports of currently 36 million tons of soya bean, because domestic plant protein sources often do not meet the required protein quality. Most of the mineral phosphate sources are also imported. It is therefore desirable to improve nutrient deposition efficiency through selective breeding, that is to realise similar growth rates and carcass compositions as currently achieved but with a lower intake of dietary crude protein or phosphate. For a preliminary evaluation of the potential of selecting for increased nutrient deposition efficiency, we estimated genetic parameters for nitrogen and phosphorus efficiencies in a Swiss Large White pig population including 294 individuals. Nutrient efficiency phenotypes were obtained from wet-chemistry analyses of pigs of various live weights. Heritability of nitrogen efficiency was estimated at 41%. Heritability of phosphorus efficiency was very low (0.3%), but positive genetic correlations with nitrogen efficiency suggest that breeding for nitrogen efficiency would positively affect phosphorus efficiency. Further studies are needed to improve the quality of estimates and to obtain accurate high-throughput measures of nutrient efficiency to be implemented on farms.

Relaxation of species-specific neighborhood effects in Bornean rain forest under climatic perturbation.

Evidence of negative conspecific density dependence (NDD) operating on seedling survival and sapling recruitment has accumulated recently. In contrast, evidence of NDD operating on growth of trees has been circumstantial at best. Whether or not local NDD at the level of individual trees leads to NDD at the level of the community is still an open question. Moreover, whether and how perturbations interfere with these processes have rarely been investigated. We applied neighborhood models to permanent plot data from a Bornean dipterocarp forest censused over two 10-11 year periods. Although the first period was only lightly perturbed, a moderately strong El Niño event causing severe drought occurred in the first half of the second period. Such events are an important component of the environmental stochasticity affecting the region. We show that local NDD on growth of small-to-medium-sized trees may indeed translate to NDD at the level of the community. This interpretation is based on increasingly negative effects of bigger conspecific neighbors on absolute growth rates of individual trees with increasing basal area across the 18 most abundant overstory species in the first period. However, this relationship was much weaker in the second period. We interpreted this relaxation of local and community-level NDD as a consequence of increased light levels at the forest floor due to temporary leaf and twig loss of large trees in response to the drought event. Mitigation of NDD under climatic perturbation acts to decrease species richness, especially in forest overstory and therefore has an important role in determining species relative abundances at the site.

Bos d 13, A Novel Heat-Stable Beef Allergen.

SCOPE: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown. METHODS AND RESULTS: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef. Two IgE-reactive proteins are identified by peptide mass fingerprinting as myosinlight chain 1 (MYL1) and myosin light chain 3 (MYL3) in cooked beef extract and are designated Bos d 13 isoallergens. MYL1 and MYL3 are produced recombinantly in Escherichia coli. ELISAs proved their IgE reactivity and circular dichroism analysis showed that they represent folded molecules with remarkable thermal stability. In vitro gastrointestinal digestion experiments showed the higher stability of rMYL1 as compared to rMYL3. Exposure of a monolayer of Caco-2 cells to rMYL1 indicated that the molecule is able to cross intestinal epithelial cells without disturbing the integrity of the tight junctions, suggesting the sensitizing capacity of MYL1. CONCLUSION: MYLs are identified as novel heat-stable bovine meat allergens.

Complex interactions between spatial pattern of resident species and invasiveness of newly arriving species affect invasibility.

Understanding the factors that affect establishment success of new species in established communities requires the study of both the ability of new species to establish and community resistance. Spatial pattern of species within a community can affect plant performance by changing the outcome of inter-specific competition, and consequently community invasibility. We studied the effects of spatial pattern of resident plant communities on fitness of genotypes from the native and introduced ranges of two worldwide invasive species, Centaurea stoebe and Senecio inaequidens, during their establishment stage. We experimentally established artificial plant mixtures with 4 or 8 resident species in intra-specifically aggregated or random spatial patterns, and added seedlings of genotypes from the native and introduced ranges of the two target species. Early growth of both S. inaequidens and C. stoebe was higher in aggregated than randomly assembled mixtures. However, a species-specific interaction between invasiveness and invasibility highlighted more complex patterns. Genotypes from native and introduced ranges of S. inaequidens showed the same responses to spatial pattern. By contrast, genotypes from the introduced range of C. stoebe did not respond to spatial pattern whereas native ones did. Based on phenotypic plasticity, we argue that the two target species adopted different strategies to deal with the spatial pattern of the resident plant community. We show that effects of spatial pattern of the resident community on the fitness of establishing species may depend on the diversity of the recipient community. Our results highlight the need to consider the interaction between invasiveness and invasibility in order to increase our understanding of invasion success.

Searching for gene flow from cultivated to wild strawberries in Central Europe.

BACKGROUND AND AIMS: Experimental crosses between the diploid woodland strawberry (Fragaria vesca L.) and the octoploid garden strawberry (F. × ananassa Duch.) can lead to the formation of viable hybrids. However, the extent of such hybrid formation under natural conditions is unknown, but is of fundamental interest and importance in the light of the potential future cultivation of transgenic strawberries. A hybrid survey was therefore conducted in the surroundings of ten farms in Switzerland and southern Germany, where strawberries have been cultivated for at least 10 years and where wild strawberries occur in the close vicinity. METHODS: In 2007 and 2008, 370 wild F. vesca plants were sampled at natural populations around farms and analysed with microsatellite markers. In 2010, natural populations were revisited and morphological traits of 3050 F. vesca plants were inspected. DNA contents of cell nuclei of morphologically deviating plants were estimated by flow cytometry to identify hybrids. As controls, 50 hybrid plants from interspecific hand-crosses were analysed using microsatellite analysis and DNA contents of cell nuclei were estimated by flow cytometry. KEY RESULTS: None of the wild samples collected in 2007 and 2008 contained F. × ananassa microsatellite markers, while all hybrids from hand-crosses clearly contained markers of both parent species. Morphological inspection of wild populations carried out in 2010 and subsequent flow cytometry of ten morphologically deviating plants revealed no hybrids. CONCLUSIONS: Hybrid formation or hybrid establishment in natural populations in the survey area is at best a rare event.

Including tree spatial extension in the evaluation of neighborhood competition effects in Bornean rain forest.

Classical tree neighborhood models use size variables acting at point distances. In a new approach here, trees were spatially extended as a function of their crown sizes, represented impressionistically as points within crown areas. Extension was accompanied by plasticity in the form of crown removal or relocation under the overlap of taller trees. Root systems were supposedly extended in a similar manner. For the 38 most abundant species in the focal size class (10-<100 cm stem girth) in two 4-ha plots at Danum (Sabah), for periods P1 (1986-1996) and P2 (1996-2007), stem growth rate and tree survival were individually regressed against stem size, and neighborhood conspecific (CON) and heterospecific (HET) basal areas within incremented steps in radius. Model parameters were critically assessed, and statistical robustness in the modeling was set by randomization testing. Classical and extended models differed importantly in their outcomes. Crown extension weakened the relationship of CON effect on growth versus plot species' abundance, showing that models without plasticity overestimated negative density dependence. A significant negative trend of difference in CON effects on growth (P2-P1) versus CON or HET effect on survival in P1 was strongest with crown extension. Model outcomes did not then support an explanation of CON and HET effects being due to (asymmetric) competition for light alone. An alternative hypothesis is that changes in CON effects on small trees, largely incurred by a drought phase (relaxing light limitation) in P2, and following the more shaded (suppressing) conditions in P1, were likely due to species-specific (symmetric) root competition and mycorrhizal processes. The very high variation in neighborhood composition and abundances led to a strong "neighborhood stochasticity" and hence to largely idiosyncratic species' responses. A need to much better understand the roles of rooting structure and processes at the individual tree level was highlighted.

Impact of renin-angiotensin system inhibitors and beta-blockers on dental implant stability.

BACKGROUND: Current experimental research suggests antihypertensive medication reduces the failure risk of dental implants due to enhanced bone remodeling. However, evidence from clinical studies evaluating the impact of antihypertensive medication on implant stability is lacking. METHODS: We retrospectively analyzed 377 implants in 196 patients (46 implants inserted in antihypertensive drug users (AH) and 331 implants in non-users (NAH)) for implant stability measured by radiofrequency analysis, and we determined the implant stability quotient (ISQ). AH subgroups were stratified by the use of beta-blockers, renin-angiotensin system (RAS) inhibitors, and both of the aforementioned. The impact of antihypertensive medication on ISQ values at implant insertion (primary stability) and implant exposure (secondary stability) was analyzed by a linear regression model with a regression coefficient and its 95% confidence interval (95% CI), adjusted for potential confounders. RESULTS: Time between implant insertion and implant exposure was 117.1 ± 56.6 days. ISQ values at insertion were 71.8 ± 8.7 for NAH and 74.1 ± 5.6 for AH, respectively. ISQ at exposure was 73.7 ± 8.1 for NAH and 75.7 ± 5.9 for AH. Regression analysis revealed that none of the AH subgroups were significantly related to ISQ at implant insertion. However, renin-angiotensin system inhibitors (RAS) were significantly associated with higher ISQ values at exposure (reg. coeff. 3.59, 95% CI 0.46-6.71 (p=0.025)). CONCLUSIONS: Outcome of the present study indicates enhanced bone remodeling and osseointegration following dental implant insertion in patients taking RAS inhibitors than in non-users. Future randomized prospective studies must confirm these indicative results.

Testing spatial theories of plant coexistence: no consistent differences in intra- and interspecific interaction distances.

Plants stand still and interact with their immediate neighbors. Theory has shown that the distances over which these interactions occur may have important consequences for population and community dynamics. In particular, if intraspecific competition occurs over longer distances than interspecific competition (heteromyopia), coexistence can be promoted. We examined how intraspecific and interspecific competition scales with neighbor distance in a target-neighbor greenhouse competition experiment. Individuals from co-occurring forbs from calcareous grasslands were grown in isolation and with single conspecific or heterospecific neighbors at distances of 5, 10, or 15 cm (Plantago lanceolata vs. Plantago media and Hieracium pilosella vs. Prunella grandiflora). Neighbor effects were strong and declined with distance. Interaction distances varied greatly within and between species, but we found no evidence for heteromyopia. Instead, neighbor identity effects were mostly explained by relative size differences between target and neighbor. We found a complex interaction between final neighbor size and identity such that neighbor identity may become important only as the neighbor becomes very large compared with the target individual. Our results suggest that species-specific size differences between neighboring individuals determine both the strength of competitive interactions and the distance over which these interactions occur.

Population dynamics of six land snail species in experimentally fragmented grassland.

1. The fragmentation of natural habitats is generally considered to be a major threat to biodiversity. Different species may respond differently to habitat fragmentation, depending on species-specific traits such as body size, dispersal ability, mating system, and habitat requirement. 2. The population sizes, extinction and recolonization frequencies of six naturally occurring land snail species (Cochlicopa lubrica, Vertigo pygmaea, Pupilla muscorum, Punctum pygmaeum, Helicella itala, and Trichia plebeia) were examined over 3 years in an experimentally fragmented nutrient-poor, calcareous grassland in the northern Swiss Jura mountains using a mark-recapture technique. Fragments of different size (0.25 m(2), 2.25 m(2), and 20.25 m(2)) were isolated by a 5-m wide strip of frequently mown vegetation. Control plots of corresponding size were situated in adjacent undisturbed grassland. 3. Experimental grassland fragmentation influenced the population size in all snail species except H. itala, which is the species with the biggest shell and it is also active under mild conditions in winter. However, fragmentation affected different species to a different extent. 4. Extinction (= disappearance from a plot) frequency increased with time, decreasing population size and decreasing plot size in all species. Large populations had a lower extinction probability than small populations. Fragmentation increased the probability of extinction, which also differed among snail species. The effect of plot size on extinction probability was still significant even after the effect of population size had been taken into account. 5. Fragments and control plots did not differ in recolonization frequencies when all six species were considered. However, fragmentation influenced recolonization frequency when the two species with large shells (H. itala and T. plebeia) were excluded from the analysis. 6. Our study shows that small-scale grassland fragmentation affects different land snail species to a different extent. This finding strengthens the claim for multi-species approaches to obtain general predictions of fragmentation impact.

Digestion of milk proteins: Comparing static and dynamic in vitro digestion systems with in vivo data.

In the frame of the COST action INFOGEST, a static in vitro digestion protocol has been elaborated aiming at the improvement of data comparability by harmonizing the experimental conditions. The success in harmonization was confirmed with inter-laboratory trials using skim milk powder as a standardized model food. Moreover, the physiological relevance of the gastric and intestinal endpoints of the static digestion protocol was demonstrated in a pig in vivo trial, with the same skim milk powder and samples collected from different sections of the digestive tract, as well as in a human study with from jejunal effluents. In vivo, digestion is a dynamic process influenced by peristalsis and by the gradual secretion of enzymes and juices and the dwell time of the food. To mimic these physiological mechanisms, dynamic in vitro digestion protocols are widely used. Until now, the differences of protein hydrolysis taking place during dynamic and static in vitro digestion have not been investigated. In this study, the gradual hydrolysis of the main milk proteins present in skim milk powder was digested with the dynamic DIDGI®-system using adult digestion protocol and the static harmonized INFOGEST method. Protein hydrolysis was analyzed by gel electrophoresis, peptide patterns were measured with mass spectrometry, and free amino acids with high pressure liquid chromatography. The peptide patterns at the gastric and intestinal endpoints of in vitro digestion showed a good approximation to the in vivo results from pigs. Moreover, gradual peptide generation was comparable in both in vitro digestion conditions. However, the dynamic protocol reflected the physiological situation better at the level of free amino acid release. Nonetheless, in both in vitro digestion protocols, absorption of free amino acids is not simulated, and they are therefore limited in reflecting the in vivo situation at this level.

Chronic intermittent stress exposure and access to grass silage interact differently in their effect on behaviour, gastric health and stress physiology of entire or castrated male growing-finishing pigs.

Entire male pigs display more aggressive and sexual behaviour. This might cause a condition of chronic stress and impair their welfare. In order to assess chronic stress in entire and castrated male pigs, as well as effects of providing grass silage as occupational and feed material on behaviour and health, we carried out a 2 × 2 × 2-factorial experiment with 147 growing-finishing pigs. Factors investigated were castration (entire/castrated), chronic intermittent social stress exposure (yes/no) and access to grass silage (yes/no), as well as their interactions. The stress exposure treatment consisted of repeated short-term confrontations and separations. We recorded different behavioural variables, circadian rhythm of salivary cortisol, response to an ACTH (adrenocorticotropic hormone) challenge test, pathological changes in the gastric mucosa and morphology of the intestinal epithelium. Stress exposure caused a decrease in posture changes and head knocks/bites in the home pen. Reference indicators affected by stress exposure did not differ between entire and castrated male pigs, indicating that there is no permanently increased baseline level of stress in entire male pigs. However, entire males responded more pronouncedly to the stress exposure compared to castrated males in terms of posture changes and play behaviour. Pigs provided with grass silage showed more play behaviour and less manipulative behaviours than pigs not receiving grass silage. Stress treated pigs had more hyperkeratosis in the gastric mucosa and gastric ulcers, while offering grass silage reduced such changes. In conclusion, our results indicate that the increased behavioural stress response of entire male pigs might require some adaptations in housing and management of entire male pigs. Gastric ulceration scoring turned out to be a potential post mortem indicator for chronic stress. Finally, providing roughages like grass silage could be a means to positively affect behaviour and gastric health in pigs.

Mass spectrometry data of in vitro and in vivo pig digestion of skim milk powder.

The data in this article are related to the research article entitled "Physiological comparability of the harmonized INFOGEST in vitro digestion method to in vivo pig digestion" (Egger et al., 2012). In this article, proteins identified in the different sections of pig skim milk powder (SMP) digestion are presented. In addition to the exemplary ß-casein profiles of the paper, the peptide patterns of the other most abundant milk proteins during in vivo digestion in individual pigs are shown as heatmaps and line graphs. These data clearly reveal the digestion resistant protein regions and illustrate the variability between the pigs in the different sampling sections. Moreover, peptide patterns of the same SMP proteins comparing the harmonized in vitro digestion (IVD) with pig in vivo digestion show the physiological relevance of the IVD protocol. Finally, correlation coefficients were calculated to indicate similarities between pig sampling sections and gastric and intestinal IVD endpoints.

Physiological comparability of the harmonized INFOGEST in vitro digestion method to in vivo pig digestion.

Recently, a static in vitro digestion (IVD) protocol was published by Minekus and coworkers (Minekus et al., 2014) within the COST INFOGEST network. The protocol, concentrating on physiological enzyme activities had the main goal to improve the comparability of experimental data between labs. The protocol was validated in several inter-laboratory studies using skim milk powder (SMP) and indeed demonstrated improved harmonization compared with previous experiments with individual IVD protocols (Egger et al., 2016). Although the enzyme activities and salt concentrations of the harmonized protocol are based on available human in vivo data, confirmation of the protocol's physiological relevance has been lacking until now. The main goal of the study was therefore to compare the harmonized IVD protocol with data from in vivo digestion. Towards this aim, an in vivo pig experiment with the same SMP as used for the validation of the IVD protocol was performed followed by a comparison of protein hydrolysis between in vivo and in vitro results. Protein hydrolysis at different levels was analyzed with gel electrophoresis, mass spectrometry, high performance liquid chromatography, and spectrophotometric o-phthaldialdehyde determination of free amino acids. Principle component analysis was used for graphical data comparison. Milk proteins detected after gastric IVD corresponded to gastric and duodenal in vivo samples and intestinal IVD samples corresponded to distal jejunal in vivo samples. Peptides identified after the gastric phase of IVD, correlated with in vivo gastric samples (r=0.8) and intestinal IVD peptides correlated best with in vivo samples collected from the median jejunum (r=0.57). Free amino acids were in both systems mainly released during the intestinal phase of digestion. Protein hydrolysis in the harmonized IVD was similar to in vivo protein hydrolysis in pigs at the gastric and intestinal endpoints. Therefore, the harmonized static in vitro protocol is suited to study protein hydrolysis at these endpoints.

A neighborhood analysis of the consequences of Quercus suber decline for regeneration dynamics in Mediterranean forests.

In forests, the vulnerable seedling stage is largely influenced by the canopy, which modifies the surrounding environment. Consequently, any alteration in the characteristics of the canopy, such as those promoted by forest dieback, might impact regeneration dynamics. Our work analyzes the interaction between canopy neighbors and seedlings in Mediterranean forests affected by the decline of their dominant species (Quercus suber). Our objective was to understand how the impacts of neighbor trees and shrubs on recruitment could affect future dynamics of these declining forests. Seeds of the three dominant tree species (Quercus suber, Olea europaea and Quercus canariensis) were sown in six sites during two consecutive years. Using a spatially-explicit, neighborhood approach we developed models that explained the observed spatial variation in seedling emergence, survival, growth and photochemical efficiency as a function of the size, identity, health, abundance and distribution of adult trees and shrubs in the neighborhood. We found strong neighborhood effects for all the performance estimators, particularly seedling emergence and survival. Tree neighbors positively affected emergence, independently of species identity or health. Alternatively, seedling survival was much lower in neighborhoods dominated by defoliated and dead Q. suber trees than in neighborhoods dominated by healthy trees. For the two oak species, these negative effects were consistent over the three years of the experimental seedlings. These results indicate that ongoing changes in species' relative abundance and canopy trees' health might alter the successional trajectories of Mediterranean oak-forests through neighbor-specific impacts on seedlings. The recruitment failure of dominant late-successional oaks in the gaps opened after Q. suber death would indirectly favor the establishment of other coexisting woody species, such as drought-tolerant shrubs. This could lead current forests to shift into open systems with lower tree cover. Adult canopy decline would therefore represent an additional factor threatening the recruitment of Quercus forests worldwide.

Size symmetry of competition alters biomass-density relationships.

As crowded populations of plants develop, the growth of some plants is accompanied by the death of others, a process called density-dependent mortality or 'self-thinning'. During the course of density-dependent mortality, the relationship between total population biomass (B) and surviving plant density (N) is allometric: B = aN(b). Essentially, increasing population biomass can be achieved only through decreasing population density. Variation in the allometric coefficient a among species has been recognized for many years and is important for management, assessment of productivity and carbon budgets, but the causes of this variation have not been elucidated. Individual-based models predict that size-dependent competition causes variation in the allometric coefficient. Using transgenic Arabidopsis with decreased plasticity, we provide experimental evidence that morphological plasticity of wild-type populations decreases the size asymmetry of competition for light and thereby decreases density-dependent mortality. This decrease in density-dependent mortality results in more biomass at a given density under size-symmetric compared with size-asymmetric competition.

HPA hyperactivity with increased plasma cortisol affects dexamethasone metabolism and DST outcome.

Data suggests that dexamethasone bioavailability or pharmacokinetic factors contribute importantly to the outcome of the dexamethasone suppression test, and a relationship between plasma cortisol and plasma dexamethasone levels has been shown. To evaluate these data further, we studied plasma dexamethasone pharmacokinetics in 24 patients with major depression (15 suppressors and nine nonsuppressors) who received a 1 mg IV dexamethasone bolus at 09:00 h with blood samples collected at intervals over the next 14 h. We found that nonsuppressors had significantly shorter plasma dexamethasone half-life (P = 0.003) as well as significantly lower dexamethasone levels 10 h (P = 0.02) following IV dexamethasone administration. Moreover, upon clinical improvement of patients, the shortened dexamethasone half-life and lower dexamethasone levels disappeared in the five patients who switched from nonsuppression to suppression and were restudied by IV bolus. These 10-h post IV plasma dexamethasone level findings paralleled the results of the 1 mg overnight oral DST performed in these depressed patients (N = 22) where we found significantly lower 10 h plasma dexamethasone levels in nonsuppressors on admission compared to suppressors (P = 0.002) and again at discharge (P = 0.007). Interestingly, in the few patients who switched from suppression to nonsuppression over the course of hospitalization, 10-h post dose plasma dexamethasone levels simultaneously dropped. No difference in dexamethasone half-life was observed in the patients studied by oral and IV dexamethasone administration. These findings support the concept that metabolism of dexamethasone is significantly related to the activity of the HPA axis (particularly by plasma cortisol levels), and that dexamethasone pharmacokinetics can be modified by state-dependent phenomena.

Charitable State-Controlled Foundation Human Tissue and Cell Research: Ethic and Legal Aspects in the Supply of Surgically Removed Human Tissue For Research in the Academic and Commercial Sector in Germany.

Tissue engineering using human cells and tissue has one of the greatest scientific and economical potential in the coming years. There are public concerns during the ongoing discussion about future trends in life sciences and if ethic boundaries might be respected sufficiently in the course of striving for industrial profit and scientific knowledge. Until now, the legal situation of using human tissue material for research is not clear. Accordingly, transparency of action and patients' information are a central component when handling patient material inside and outside of the patient-specific treatment. Whereas in the field of therapeutic use of tissue (e.g. transplantation) there is an emergency situation by the shortage of organs with the risk of the premature death of the potential recipient, this cannot be claimed for tissue donation for research. The basis of every surgical operation is the treatment contract, which places the doctor under obligation to the careful exercise of medical treatment containing the patient's informed consent. This contract only covers the treatment that is intended to cure the patient and the medical measures that are necessary therefor. The further scientific use of body-substances, which are discarded after an operation, are not included. Therefore a personal and independent written enlightenment of the patient and a declaration of informed consent is necessary. Examples of guidelines for tissue supply, Patients information and consent were worked out by theologists, lawyers, scientists and physicians reflecting their practical experience in transplant surgery and liver cell research. As a consequence to cover the ethical and legal aspect of tissue donation in Germany a charitable state-controlled foundation Human Tissue and Cell Research (HTCR) was introduced and established.