[Risk factors for chronic perforating skin lesions in the area of the digits in cattle on Swiss alpine pastures]. / Risikofaktoren für chronisch perforierende Hautläsionen im Zehenbereich beim Rind auf Schweizer Alpen.

INTRODUCTION: Diseases of the digits often occur in cattle on larger cattle mountain pastures. In the late spring 2020, at the time of the ascent of 1554 cattle to 11 high altitude alpine pastures in the Lower Engadine region, lesions in the area of the digits were clinically assessed and documented. 254 cattle were of non-cantonal and 1300 of local origin (Lower Engadine; postal code CH-75XX). Skin lesions in the area of the digits, identified as digital dermatitis (DD; Mortellaro's disease), were further classified according to the DD scoring system. Nonspecific skin lesions with clinical evidence of granulation tissue formation were termed chronic penetrating skin lesions (CPSL). At the end of the alpine pasturing season, in the early fall (descent of cattle from the alpine pastures), the procedure was repeated, and biopsies were taken from randomly selected cattle with CPSL. Digital dermatitis lesions were found in 34 of 1551 cattle at ascent, but no case of CPSL was found at that time. At descent, 19 of 1529 cattle had DD lesions and 88 cattle had CPSL. The clinical appearance of the CPSL was consistent with chronic skin lesions caused by penetrating skin lacerations. Histologically, the majority of the CPSL were classified as chronic hyperplastic dermatitis with granulation tissue formation. In all CPSL biopsies examined by PCR, Fusobacterium necrophorum and Porphyromonas levii, but neither Dichelobacter nodosus nor the tested Treponema species were detected. Fluorescence in situ hybridization revealed a negative result for Treponema species in all biopsies. In the regression analysis, cattle in the age group of 365 to 730 days had an increased risk for the presence of CPSL compared to the age group of 160 to 365 days (odds ratio (OR) = 4,95; confidence interval (CI) = 1,97-12,43). Holstein cattle had an increased risk of developing CPSL compared to Brown cattle (OR = 2,92; CI = 1,46-5,86) and cattle of non-cantonal origin showed a massively higher risk compared to local cattle (OR = 10,59; CI = 5,79 - 19,37). The statistically significant associations found in the present study can be taken into account in the selection of animals for summer pasturing on high altitudes in the future in order to reduce the prevalence of CPSL and consequently reduce the antimicrobial use. Spread of DD during the alpine pasturing season within the cattle groups examined was not found.

INTRODUCTION: Des atteintes aux onglons sont souvent observées sur les grands alpages de bovins. Des altérations au niveau des onglons ont été examinées cliniquement et répertoriées chez 1554 bovins lors de leur arrivée sur 11 alpages en Basse-Engadine, en provenance d'un autre canton (n = 254) ou de la localité à laquelle l'alpage appartenait (n = 1300, numéro postal 75XX), au moment de la montée à l'alpage en 2020. Les altérations cutanées diagnostiquées comme dermatite digitale (DD; maladie de Mortellaro) ont de plus été classifiées selon les scores en usage pour la DD. Les lésions cutanées non-spécifiques présentant une formation de tissu de granulation ont été enregistrées comme lésions cutanées perforantes chroniques (LCPC). La procédure a été répétée lors de la désalpe et une biopsie a été prise de chez des animaux présentant des LCPC choisis au hasard. Les caractéristiques de la topographie de l'alpage et celles du sol, ainsi que la densité d'occupation ont été enregistrées pour chaque alpage. Des lésions de DD ont été constatées chez 34 des 1551 bovins lors de la montée à l'alpage, mais aucun cas de LCPC n'a été observé. Lors de la désalpe, 19 des 1551 bovins présentaient des lésions de DD et 88 une LCPC. L'apparence des LCPC correspondait à des lésions cutanées chroniques après une blessure perforante de la peau. À l'histologie, il s'agissait la plupart du temps d'une dermatite chronique hyperplastique avec formation de tissu de granulation. Fusobacterium necrophorum et Porphyromonas levii ont été mis en évidence dans toutes les biopsies de LCPC soumises à une analyse par PCR, mais ni Dichelobacter nodosus ni les Treponema spp. recherchées n'ont été mis en évidence. L'hybridation in-situ en fluorescence était négative pour les tréponèmes dans toutes les biopsies. Selon les résultats d'une analyse de régression, les génisses âgées de 366 à 730 jours avaient un risque augmenté (Odds Ratio (OR) = 4,95; intervalle de confiance (IC) = 1,97 ­ 12,43) de présenter une LCPC en comparaison avec le groupe d'âge de 161 à 365 jours. Les bovins de race Holstein avaient un risque augmenté de présenter une LCPC en comparaison avec ceux de race grise (OR = 2,92; IC = 1,46 ­ 5,86), et les animaux en provenance d'autres cantons présentaient un risque massivement plus élevé que le cheptel local (OR = 10,59; IC = 5,79 ­ 19,37). Aucune différence significative n'a été observée dans la topographie ou dans la densité d'occupation entre les alpages avec et sans cas de LCPC. Les associations statistiquement significatives constatées dans cette étude peuvent être prises en compte à l'avenir lors de la sélection d'animaux pour l'alpage, dans le but de réduire la prévalence de LCPC, de diminuer la quantité d'antibiotiques administrés et d'améliorer le bien-être animal. Une propagation de la DD pendant la saison d'alpage n'a pas été constatée dans les groupes de bovins inclus dans l'étude.

[Risk factors for infectious foot -disorders on two Swiss cattle -mountain pastures]. / Risikofaktoren für infektiöse Zehen­erkrankungen auf zwei Schweizer ­Rinderalpen.

INTRODUCTION: In the present study, risk groups for infectious foot disorders were identified on two large Swiss cattle mountain pastures by analyzing animal and treatment data of a total of 3256 animals of the bovine species. Both mountain pastures were part of the Federal Office for Agriculture (FOAG) consultancy project «Healthy animals, attractive herdsmen positions and less medication on large cattle mountain pastures¼. The project was launched in 2020 following the increased incidence of lameness on these mountain pastures. Bacteriological and histological analyses were to provide information as to whether the most common foot disorder was interdigital phlegmon (IP) or whether digital dermatitis also occurred. Further, the temporal distribution of cases over the mountain pasture season and the influence of mountain pasture and year were investigated and interpreted for the project years 2020 to 2022, and treatment incidences were compared between years. Multiple treatment cycles in the same individual were classified into persistent infections and new infections. Nineteen of 394 first-treated cattle were clinically examined, 12 of them were additionally sampled for bacteriological and histological analyses. All cases examined showed, both clinically and following laboratory analyses, typical characteristics for IP. In contrast, there was no specific evidence for the presence of digital dermatitis. No persistent infections occurred during treatment with benzylpenicillin. Multivariate logistic regression analyses identified > 365-730-day-old cattle (odds ratio OR 8,29), as well as inseminated (OR 5,30) and non-inseminated (OR 7,85) heifers as risk groups for the disease studied (p < 0,05). Association with the oestrus activity of non-inseminated heifers and a generally higher locomotor activity in heifers compared to cows - with a correspondingly increased risk of injury - is conceivable. Meat breeds had a reduced risk compared to dairy breeds (OR 0,29). Breed differences in behavior and/or the effectiveness of the local immune response might have an impact. Knowing about these risk groups can be put to use in the future when selecting animals to be taken to the mountain pastures and/or when planning pasture management in order to reduce the prevalence of infectious foot disorders and thereby the use of antibiotics.

INTRODUCTION: Dans la présente étude, nous avons identifié, grâce à l'analyse des données concernant les animaux et les traitements d'un total de 3256 animaux de l'espèce bovine, des groupes à risque pour les maladies infectieuses des onglons sur deux grands alpages bovins en Suisse. Les deux alpages faisaient partie du BLW-projet de conseil «Animaux sains, postes de bergers attractifs et moins de médicaments sur les grands alpages bovins¼. Le projet a débuté en 2020 suite à l'accumulation de problèmes de boiteries sur ces alpages. Des analyses bactériologiques et histologiques devaient fournir des indications afin de savoir si la maladie des onglons majoritaire était le phlegmon interdigité (PI) ou si la dermatite digitale était également présente. La répartition temporelle des cas de maladies durant la saison d'estivage et l'influence de l'alpage et de l'année pour les années de projet 2020 à 2022 ont été évaluées et interprétées, et les incidences des traitements comparées entre les années. Les cycles de traitement multiples chez le même individu ont été répartis en deux groupes: les infections persistantes et les nouvelles infections. Dix-neuf des 394 bovins primo-traités ont été évalués cliniquement. Douze de ces 19 animaux ont également été soumis à un échantillonnage bactériologique et histologique. Tous les cas étudiés présentaient, aussi bien cliniquement que suite à l'analyse technique en laboratoire, les caractéristiques typiques d'un PI. Par contre, il n'y a pas eu d'indication quant à la présence de dermatite digitale. Aucune infection persistante n'a été constatée après traitement avec de la Benzylpénicilline. Les bovins âgés > 365­730 jours (OR 8.29), ainsi que les génisses inséminées (odds ratio OR 5.30) et non inséminées (OR 7.85) ont été identifiés, suite à une analyse de régression logistique multivariée, comme faisant partie de groupes à risque pour la maladie étudiée (p < 0.05). Un lien avec l'activité en période de chaleurs des génisses non inséminées et une activité locomotrice généralement plus intensive des génisses par rapport aux vaches ­ avec par conséquent un risque accru de blessures ­ est concevable. Le risque était réduit pour les races à viande par rapport aux races laitières (OR 0.29). Des différences de comportement et/ou d'efficacité de l'immunité locale entre les races pourraient avoir une influence. Le fait de connaître ces groupes à risque pourrait être mis à profit à l'avenir lors de la sélection des animaux à monter à l'alpage et/ou lors de la planification de la gestion des prairies, afin de diminuer la prévalence des maladies infectieuses des onglons et ainsi l'utilisation d'antibiotiques.

CANreduce-SP-adding psychological support to web-based adherence-focused guided self-help for cannabis users: study protocol for a three-arm randomized control trial.

BACKGROUND: Cannabis is the most-frequently used illicit drug in Europe. Over the last few years in Spain, treatment demand has increased, yet most cannabis users do not seek treatment despite the related problems. A web-based self-help tool, like CANreduce 2.0, could help these users to control their consumption. METHODS: This study protocol describes a three-arm randomized controlled trial (RCT) comparing the effectiveness of three approaches, in terms of reducing cannabis use among problematic cannabis users, the first two treatment arms including the Spanish version of CANreduce 2.0 (an adherence-focused, guidance-enhanced, web-based self-help tool) (1) with and (2) without psychological support; and the third group (3) treatment as usual (TAU). Study hypotheses will be tested concerning the primary outcome: change in the number of days of cannabis use over the previous week, comparing assessments at 6 weeks and 3 and 6 months follow-up between groups and against baseline. Secondary outcomes related to cannabis use will be tested similarly. Mental disorders will be explored as predictors of adherence and outcomes. Analyses will be performed on an intention-to-treat basis, then verified by complete case analyses. DISCUSSION: This study will test how effective the Spanish version of CANreduce 2.0 (CANreduce-SP) is at reducing both the frequency and quantity of cannabis use in problematic users and whether adding psychological support increases its effectiveness. TRIAL REGISTRATION: This trial is registered with the Clinical Trials Protocol Registration and Results System (PRS) number: NCT04517474 . Registered 18 August 2020, (Archived by archive.is https://archive.is/N1Y64 ). The project commenced in November 2020 and recruitment is anticipated to end by November 2022.

Silver nanoparticles enter the tree stem faster through leaves than through roots.

A major environmental pollution problem is the release into the atmosphere of particulate matter, including nanoparticles (NPs), which causes serious hazards to human and ecosystem health, particularly in urban areas. However, knowledge about the uptake, translocation and accumulation of NPs in plant tissues is almost completely lacking. The uptake of silver nanoparticles (Ag-NPs) and their transport and accumulation in the leaves, stems and roots of three different tree species, downy oak (Quercus pubescens Willd.), Scots pine (Pinus sylvestris L.) and black poplar (Populus nigra L.), were assessed. In the experiment, Ag-NPs were supplied separately to the leaves (via spraying, the foliar treatment) and roots (via watering, the root treatment) of the three species. Uptake, transport and accumulation of Ag were investigated through spectroscopy. The concentration of Ag in the stem was higher in the foliar than in the root treatment, and in poplar more than in oak and pine. Foliar treatment with Ag-NPs reduced aboveground biomass and stem length in poplars, but not in oaks or pines. Species-specific signals of oxidative stress were observed; foliar treatment of oak caused the accumulation of H2O2 in leaves, and both foliar and root treatments of poplar led to increased O2- in leaves. Ag-NPs affected leaf and root bacteria and fungi; in the case of leaves, foliar treatment reduced bacterial populations in oak and poplar and fungi populations in pine, and in the case of roots, root treatment reduced bacteria and increased fungi in poplar. Species-specific mechanisms of interaction, transport, allocation and storage of NPs in trees were found. We demonstrated definitively that NPs enter into the tree stem through leaves faster than through roots in all of the investigated tree species.

Quality of life of parents of mentally-ill children: a systematic review and meta-analysis.

AIMS: To examine the quality of life (QOL) of parents of children with a specific mental disorder (any age). METHODS: Relevant articles were searched using different databases. Articles were included that compared the QOL of parents with mentally-ill children to parents of healthy controls or norm values or provided the required data for this comparison. A meta-analysis was conducted to obtain an overall mean effect size estimate. Additional analyses were performed to assess publication bias and moderation. RESULTS: Twenty-six out of 10 548 articles met the pre-defined inclusion criteria. Most of these studies focused on attention-deficit/hyperactivity disorder or autism spectrum disorder, used clinical samples that mainly included males and young children and studied the QOL of mothers. The meta-analysis revealed that parents of mentally-ill children are experiencing a clinically relevant reduction in their QOL relative to parents of healthy children and norm values (g = -0.66). CONCLUSIONS: The compromised QOL of parents of mentally-ill children needs to be considered and addressed by health professionals who are in contact with them. The paper provides insights into existing research gaps and suggests improvements for subsequent work.

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities.

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

Impact of interspecific competition and drought on the allocation of new assimilates in trees.

In trees, the interplay between reduced carbon assimilation and the inability to transport carbohydrates to the sites of demand under drought might be one of the mechanisms leading to carbon starvation. However, we largely lack knowledge on how drought effects on new assimilate allocation differ between species with different drought sensitivities and how these effects are modified by interspecific competition. We assessed the fate of (13) C labelled assimilates in above- and belowground plant organs and in root/rhizosphere respired CO2 in saplings of drought-tolerant Norway maple (Acer platanoides) and drought-sensitive European beech (Fagus sylvatica) exposed to moderate drought, either in mono- or mixed culture. While drought reduced stomatal conductance and photosynthesis rates in both species, both maintained assimilate transport belowground. Beech even allocated more new assimilate to the roots under moderate drought compared to non-limited water supply conditions, and this pattern was even more pronounced under interspecific competition. Even though maple was a superior competitor compared to beech under non-limited soil water conditions, as indicated by the changes in above- and belowground biomass of both species in the interspecific competition treatments, we can state that beech was still able to efficiently allocate new assimilate belowground under combined drought and interspecific competition. This might be seen as a strategy to maintain root osmotic potential and to prioritise root functioning. Our results thus show that beech tolerates moderate drought stress plus competition without losing its ability to supply belowground tissues. It remains to be explored in future work if this strategy is also valid during long-term drought exposure.

Application of in-situ measurement to determine 137Cs in the Swiss Alps.

Establishment of (137)Cs inventories is often used to gain information on soil stability. The latter is crucial in mountain systems, where ecosystem stability is tightly connected to soil stability. In-situ measurements of (137)Cs in steep alpine environments are scarce. Most studies have been carried out in arable lands and with Germanium (Ge) detectors. Sodium Iodide (NaI) detector system is an inexpensive and easy to handle field instrument, but its validity on steep alpine environments has not been tested yet. In this study, a comparison of laboratory measurements with GeLi detector and in-situ measurements with NaI detector of (137)Cs gamma soil radiation has been done in an alpine catchment with high (137)Cs concentration (Urseren Valley, Switzerland). The aim of this study was to calibrate the in-situ NaI detector system for application on steep alpine slopes. Replicate samples from an altitudinal transect through the Urseren Valley, measured in the laboratory with a GeLi detector, showed a large variability in (137)Cs activities at a meter scale. This small-scale heterogeneity determined with the GeLi detector is smoothed out by uncollimated in-situ measurements with the NaI detector, which provides integrated estimates of (137)Cs within the field of view (3.1 m(2)) of each measurement. There was no dependency of (137)Cs on pH, clay content and carbon content, but a close relationship was determined between measured (137)Cs activities and soil moisture. Thus, in-situ data must be corrected for soil moisture. Close correlation (R(2) = 0.86, p < 0.0001) was found for (137)Cs activities (in Bq kg(-1)) estimated with in-situ (NaI detector) and laboratory (GeLi detector) methods. We thus concluded that the NaI detector system is a suitable tool for in-situ measurements in alpine environments. This paper describes the calibration of the NaI detector system for field application under elevated (137)Cs activities originating from Chernobyl fallout.

Advances of air pollution science: from forest decline to multiple-stress effects on forest ecosystem services.

Over the past 20 years, the focus of forest science on air pollution has moved from forest decline to a holistic framework of forest health, and from the effects on forest production to the ecosystem services provided by forest ecosystems. Hence, future research should focus on the interacting factorial impacts and resulting antagonistic and synergistic responses of forest trees and ecosystems. The synergistic effects of air pollution and climatic changes, in particular elevated ozone, altered nitrogen, carbon and water availability, must be key issues for research. Present evidence suggests air pollution will become increasingly harmful to forests under climate change, which requires integration amongst various stressors (abiotic and biotic factors, including competition, parasites and fire), effects on forest services (production, biodiversity protection, soil protection, sustained water balance, socio-economical relevance) and assessment approaches (research, monitoring, modeling) to be fostered.

FR167653 Ameliorates expression of proinflammatory mediators in human umbilical venous endothelial cells and human monocytes.

p38MAP kinase plays a crucial role in intracellular signal transduction of inflammation. The inhibitor of p38 MAP kinase, FR167653, has been proven to be effective to suppress proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in various animal models. The aim of our study was to investigate p38MAP kinase inhibition by FR167653 on the inflammatory profile of cells involved in vascular injury. HUVEC incubated with FR167653 in concentrations of 0.1 to 20 mumol for 24 hours were stimulated with TNF-alpha (20 ng/mL). Human monocytes were incubated with equal concentrations of FR167653 and stimulated with lipopolysaccharides (LPS; 10 microg/mL). In monocytes, p38 MAP kinase could be inhibited by FR167653 (Western blot). The cytokines IL-6 and IL-8 were dose dependently downregulated by FR167653 (enzyme-linked immunosorbent assay) [ELISA]. These results were confirmed at a transcriptional level by real-time polymerase chain reaction (PCR). Gene expression of IL-6 and IL-8 was dose dependently downregulated. The expression pattern of ICAM-1 and VCAM-1 was not altered by FR167653 (ELISA). In HUVEC, the cytokines IL-6 and IL-8 were dose dependently downregulated by FR167653 (ELISA). These results were confirmed on a transcriptional level by real-time PCR. Gene expression of IL-6 and IL-8 were also dose dependently suppressed by FR167653. In addition FR167653 downregulated the expression of the adhesion molecules ICAM-1 and VCAM-1 (ELISA). FR167653 suppressed the development of a proinflamatory profile of HUVEC and human monocytes after stimulation with TNF-alpha or LPS, respectively. These results indicated anti-inflammatory properties of FR167653 on endothelial and inflammatory cells, which may be therapeutically useful to ameliorate vascular injury.

Apoptotic cell death during accelerated rejection in sensitized rat recipients of cardiac allografts.

Accelerated rejection due to host sensitization to major histocompatibility complex antigens is a critical problem in clinical organ transplantation in patients who have previously received an organ transplant, experienced acute rejection episodes, received blood transfusions, or been pregnant. The precise pathologic mechanisms underlying accelerated rejection have not been characterized. Herein, we describe apoptosis during T- and B-cell-driven accelerated rejection of cardiac allografts in presensitized recipients. In an established accelerated rejection model, Lewis rats were sensitized to skin grafts from Wistar-Furth rats; after 7 days, they received Wistar-Furth hearts. These grafts were rejected within 24 hours posttransplantation compared with 10 days in nonsensitized recipients (acute rejection, n = 5). Apoptosis was observed during accelerated rejection of cardiac allografts but not in naïve recipients of hearts, as demonstrated at DNA laddering and TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling) assay. Apoptosis was discovered as a thus far unknown effector mechanism in accelerated cardiac transplant rejection that accompanies combined cellular and humoral immune alloreactivity. Apoptotic cell death in accelerated rejection and the cascade of upstream and downstream events leading to or resulting from this process should be considered critical steps in the pathogenesis of accelerated rejection.

The influence of antigen-dependent and antigen-independent factors on the development of graft vasculopathy in a fully allogeneic cardiac allograft model in the rat.

Graft vasculopathy (GVP) is one of the major obstacles to long-term graft and patient survival after cardiac transplantation and a major reason for morbidity and mortality. Antigen-dependent and antigen-independent factors play causal roles in the development of GVP. The aim of this study was to evaluate antigen-dependent and -independent factors in the development of GVR in a clinically relevant fully allogeneic rat cardiac model under immunosuppression with cyclosporine (CyA). Lewis rats were challenged with Wistar-Furth cardiac allografts. Acute rejection occurred within 10 days after engraftment (n = 6). Daily SC administration of CyA (2.5 mg/kg body weight, n = 12) led to long-term graft survival (>100 days) but did not prevent GVP (Adams Score: 1.7 +/- 1.9, n = 4). Isografts did not develop GVP. In allografts, the dose modification of CyA to 5 mg or 1.25 mg/kg body weight as well as the prolongation of ischemia from 45 minutes to 4 hours did not increase the development of GVP. In isografts, the prolongation of ischemic time from 45 minutes to 4 hours significantly increased the development of GVP (Adams score, 0.3 +/- 0.8 [n = 7] vs 1.2 +/- 1.9 [n = 6]; P < .05). In this fully allogeneic cardiac allograft model with clinically relevant immunosuppressive therapy, GVP was induced independent of the applied CyA dose. In addition, the prolongation of ischemic time did not increase the development of GVP. Isografts only developed significant GVP with long ischemia times. Therefore, an initial injury, either prolonged ischemia time or an allogeneic immune response, predispressed to the development of GVP.

Deazaadenosine prevents leukozyte evasion during acute cardiac allograft rejection by suppression of adhesion molecule expression.

BACKGROUND: In the initial phase after cardiac transplantation, mononuclear cells infiltrate the graft initiating a relevant impulse for rejection. 3-Deazaadenosin (c3Ado), an analog of adenosine, has demonstrated in vitro anti-inflammatory properties. Furthermore, in vivo studies on arteriosclerosis development and septic myocardial dysfunction c3Ado revealed reduced cellular infiltration. In addition ischemia and reperfusion injury could be diminished in a pulmonary animal model. The aim of our study was to investigate the properties of c3Ado to reduce adhesion molecule expression and cellular infiltration in a fully allogeneic cardiac transplant model. METHODS AND RESULTS: Lewis rats were challenged with Wistar-Furth cardiac allografts. Untreated grafts were rejected within 7 days (group 1). In group 2, animals received 2 x 5 mg c3Ado SC per day. Grafts were harvested on days 1, 3, and 6 after transplantation for further examination (n = 4 per group and time point). Immunohistochemical examination revealed significant reduction of graft-infiltrating MHC II positive cells, T-cell receptor positive cells (R73), as well as ED1-positive monocytes and macrophages (P < .01) at days 3 and 6 after transplantation. Adhesion molecule (ICAM-1, VCAM-1) expression on days 1 and 3 after transplantation was almost completely diminished in c3Ado-treated grafts. CONCLUSION: Thus, c3Ado is able to reduce graft infiltration by preventing leukocyte evasion through the suppression of adhesion molecule expression. This may be a novel strategy to protect transplanted organs from early damage after transplantation and extend organ survival after transplantation.

Promoting the O3 flux concept for European forest trees.

Tropospheric ozone (O3) levels are predicted to stay high, being a factor within "global change" with potential effects on the carbon sink strength of forest trees. Hence, new approaches to O3 risk assessment and their validation are required, although appropriate databases for adult trees are scant. Approaches based on external O3 exposure are presently being evaluated against the ones on O3 flux into leaves, as the cumulative uptake has the capacity for deriving O3 risk from cause-effect relationships. The effective dose, however, needs to account for the trees' O3 defence and tolerance in addition to O3 uptake. The current status of promoting the preferable mechanistic O3 flux concept is highlighted for major regions of Europe, addressing refinements and simplifications needed for routine use. At the pan-European scale, however, the flux-based concept is ready for use in O3 risk assessment and has the potential of meso-scale application at the forest ecosystem level.

[Club drugs]. / Partydrogen.

The term club drugs refers to a variety of substances which are frequently used in the context of dance events or raves. MDMA - or more commonly ecstasy -, amphetamines, especially methamphetamine, ketamine and newly also GHB (and analoga) are frequently used club drugs. The spectrum of psychoactive effects of theses substances is broad and ranges from stimulant, entactogenig, halluzinogenic, to sedative aspects. Studies show that clubbers can be characterized by their high consumption of several substances; thus, can be considered a potential high risk group. Besides the classical club drug ecstasy more common substances such as alcohol, cannabis, and cocaine are also highly prevalent. The general practitioner has a key function in the early intervention and treatment of potentially problematic club drug users. It seems important that users are being informed in a balanced and evidenced based manner about possible risks associated with their drug use. In order to perform a psychosocial risk assessment an encompassing perspective should be adopted.

Risk assessments for forest trees: the performance of the ozone flux versus the AOT concepts.

Published ozone exposure-response relationships from experimental studies with young trees performed at different sites across Europe were re-analysed in order to test the performance of ozone exposure indices based on AOTX (Accumulated exposure Over a Threshold of X nmol mol(-1)) and AF(st)Y (Accumulated Stomatal Flux above a threshold of Y nmol m(-2) s(-1)). AF(st)1.6 was superior, as compared to AOT40, for explaining biomass reductions, when ozone sensitive species with differing leaf morphology were included in the analysis, while this was not the case for less sensitive species. A re-analysis of data with young black cherry trees, subject to different irrigation regimes, indicated that leaf visible injuries were more strongly related to the estimated stomatal ozone uptake, as compared to the ozone concentration in the air. Experimental data with different clones of silver birch indicated that leaf thickness was also an important factor influencing the development of ozone induced leaf visible injury.

Comparison of different stomatal conductance algorithms for ozone flux modelling.

A multiplicative and a semi-mechanistic, BWB-type [Ball, J.T., Woodrow, I.E., Berry, J.A., 1987. A model predicting stomatal conductance and its contribution to the control of photosynthesis under different environmental conditions. In: Biggens, J. (Ed.), Progress in Photosynthesis Research, vol. IV. Martinus Nijhoff, Dordrecht, pp. 221-224.] algorithm for calculating stomatal conductance (g(s)) at the leaf level have been parameterised for two crop and two tree species to test their use in regional scale ozone deposition modelling. The algorithms were tested against measured, site-specific data for durum wheat, grapevine, beech and birch of different European provenances. A direct comparison of both algorithms showed a similar performance in predicting hourly means and daily time-courses of g(s), whereas the multiplicative algorithm outperformed the BWB-type algorithm in modelling seasonal time-courses due to the inclusion of a phenology function. The re-parameterisation of the algorithms for local conditions in order to validate ozone deposition modelling on a European scale reveals the higher input requirements of the BWB-type algorithm as compared to the multiplicative algorithm because of the need of the former to model net photosynthesis (A(n)).

Effect of pre-treatment with catecholamines on cold preservation and ischemia/reperfusion-injury in rats.

Treatment of organ donors with catecholamines reduces acute rejection episodes and improves long-term graft survival after renal transplantation. The aim of this study was to investigate the effect of catecholamine pre-treatment on ischemia/reperfusion (I/R)- and cold preservation injury in rat kidneys. I/R-injury was induced by clamping the left kidney vessels for 60 min along with a contralateral nephrectomy. Cold preservation injury was induced by storage of the kidneys for 24 h at +4 degrees Celsius in University of Wisconsin solution, followed by syngeneic transplantation. Rats were pre-treated with either dopamine (DA), dobutamine (DB), or norepinephrine (2, 5, and 10 microg/kg/min, each group) intravenously via an osmotic minipump for 24 h before I/R- and cold preservation injury. Pre-treatment with DA (2 or 5 microg/kg/min) and DB (5 microg/kg/min) improved recovery of renal function after I/R-injury and dose dependently reduced mononuclear and major histocompatibility complex class II-positive cells infiltrating the kidney after I/R-injury. One day after I/R-injury, upregulation of transforming growth factor (TGF)-beta 1 and 2 and phosphorylation of p42/p44 mitogen-activated protein kinases was observed in kidneys of animals treated with DA or DB. DA (5 microg/kg/min) and DB (5 microg/kg/min) pre-treatment reduced endothelial cell damage after 24 h of cold preservation. Only DA pre-treatment improved renal function and reduced renal inflammation after 24 h of cold preservation and syngeneic transplantation. Our results demonstrate a protective effect of pre-treatment with catecholamines on renal inflammation and function after I/R- or cold preservation injury. This could help to explain the potent organoprotective effects of catecholamine pre-treatment observed in human kidney transplantation.

Anaesthetic preconditioning but not postconditioning prevents early activation of the deleterious cardiac remodelling programme: evidence of opposing genomic responses in cardioprotection by pre- and postconditioning.

BACKGROUND: Anaesthetic preconditioning (A_PreC) and postconditioning (A_PostC) both provide protection against ischaemia-reperfusion in the heart. However, post-ischaemic gene responses may differ between the two therapeutic strategies. METHODS: Isolated perfused rat hearts were exposed to 40 min test ischaemia followed by 3 h reperfusion and used to determine transcriptional changes in response to A_PreC and A_PostC. A_PreC was induced by 15 min of isoflurane 2.1 vol% followed by 10 min of washout, and A_PostC was induced by 15 min of isoflurane 2.1 vol% administered at the onset of reperfusion. Untreated hearts served as ischaemic control (ISCH). Coupled-two way clustering (CTWC) and principal component analysis (PCA) were used to identify gene expression patterns. RESULTS: A_PreC (7[sd 1]%) and A_PostC (6[2]%) produced a similar decrease in infarct size (ISCH 36[1]%, P<0.05). However, post-ischaemic genomic reprogramming was completely different. Few genes were jointly regulated (2.1 per thousand of upregulated genes and 1.3% of downregulated genes). Eight stable gene clusters including three subclusters emerged from CTWC and were related to inflammation, signalling, ion channels, transcription factors, long interspersed repetitive DNA, heat shock response and remodelling. Two stable sample clusters were identified for postconditioned hearts (first cluster) and for all other protocols (second cluster), emphasizing the unique cardiac phenotype elicited by A_PostC. PCA revealed a close genomic relationship between A_PreC and non-ischaemic healthy myocardium. CONCLUSIONS: A_PreC, but not A_PostC, induces a post-ischaemic gene expression profile similar to virgin myocardium and prevents activation of the deleterious cardiac remodelling programme. Hence A_PreC and A_PostC are not interchangeable with respect to their molecular outcome in the heart.