Lymphokines in sensitized rats. III. Influence of prednisolone treatment of lymph node and spleen architecture in sensitized rats and upon MIF release in vitro.

The influence of prednisolone (corticosteroid, C.S.) treatment upon established cell-mediated immunity (CMI) induced by complete Freund's adjuvant (CFA) has been studied in rats by using in vitro migration inhibitory factor (MIF) assays, type IV skin reactions, and regional lymph node and spleen histology. Additionally, changes in the mononuclear-polymorphonuclear ratio of peripheral blood and T-cell accumulation in bone marrow in response to C.S. treatment have been determined. These results have been evaluated by comparison with equivalent experiments upon animals treated with anti-rat lymphocyte serum (ALS), oxisuran, or 2-[(methylsulfinyl)-acetyl]pyridine, which selectively suppresses CMI. The results suggest the existence of a population of “educated” T-cells in the thymic cortex of sensitized rats, and they suggest that prolonged C.S. administration does not suppress T-effector cells involved in established CMI but, rather, affects lymphocyte and monocyte migration patterns, including the migration of educated T-cells from the thymic cortex into other tissue compartments.     

Drug therapy: dose-response relationship of oral mesalazine in inflammatory bowel disease.

Mesalazine is widely used in the treatment of inflammatory bowel disease. Little is known about the dose-response relationship and about possible dose related side effects. In ulcerative colitis higher dosages of mesalazine (3 g) are more effective in maintaining a remission than lower dosages (1.5 g). In mild to moderately active ulcerative colitis, studies also indicate that higher dosages might be more effective in inducing remission. Dose-comparing studies in Crohn''s disease are even more sparse, but the available results indicate higher efficacy at higher dose levels. None of the known side effects of mesalazine are clearly dose-related. A pH-dependent release system, however, can cause a sudden release of high doses of mesalazine. Consequent peak levels in serum have been implicated in mesalazine induced nephrotoxicity. In conclusion, despite the current practice of using increasing dosages of mesalazine in inflammatory bowel disease, both efficacy and safety have been established tentatively.     

Gene expression patterns in anterior pituitary associated with quantitative measure of oestrous behaviour in dairy cows

Intensive selection for high milk yield in dairy cows has raised production levels substantially but at the cost of reduced fertility, which manifests in different ways including reduced expression of oestrous behaviour. The genomic regulation of oestrous behaviour in bovines remains largely unknown. Here, we aimed to identify and study those genes that were associated with oestrous behaviour among genes expressed in the bovine anterior pituitary either at the start of oestrous cycle or at the mid-cycle (around day 12 of cycle), or regardless of the phase of cycle. Oestrous behaviour was recorded in each of 28 primiparous cows from 30 days in milk onwards till the day of their sacrifice (between 77 and 139 days in milk) and quantified as heat scores. An average heat score value was calculated for each cow from heat scores observed during consecutive oestrous cycles excluding the cycle on the day of sacrifice. A microarray experiment was designed to measure gene expression in the anterior pituitary of these cows, 14 of which were sacrificed at the start of oestrous cycle (day 0) and 14 around day 12 of cycle (day 12). Gene expression was modelled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model on data from day 0 cows alone (analysis 1), day 12 cows alone (analysis 2) and the combined data from day 0 and day 12 cows (analysis 3). Genes whose expression patterns showed significant linear or non-linear relationships with average heat scores were identified in all three analyses (177, 142 and 118 genes, respectively). Gene ontology terms enriched among genes identified in analysis 1 revealed processes associated with expression of oestrous behaviour whereas the terms enriched among genes identified in analysis 2 and 3 were general processes which may facilitate proper expression of oestrous behaviour at the subsequent oestrus. Studying these genes will help to improve our understanding of the genomic regulation of oestrous behaviour, ultimately leading to better management strategies and tools to improve or monitor reproductive performance in bovines.     

Glucocorticoids increase osmotic water permeability (Pf) of neonatal rabbit renal brush border membrane vesicles

During postnatal maturation, there is an increase in renal brush border membrane vesicle (BBMV) osmotic water permeability and a parallel increase in aquaporin-1 (AQP1) protein abundance. The mechanisms responsible for these changes remain unknown. Because serum glucocorticoid levels rise postnatally and have previously been linked to other maturational changes in renal function, we examined the effects of glucocorticoids on osmotic (Pf) and diffusional (P(DW)) water permeability and AQP1 protein abundance of renal BBMV. Neonatal rabbits were treated with dexamethasone (10 microg/100 g) for three days and compared with control neonates and adults. Pf and P(DW) were measured at 20 degrees C with a stopped-flow apparatus using light-scattering and aminonaphthalene trisulfonic acid (ANTS) fluorescence, respectively. Pf was significantly higher in BBMV from dexamethasone-treated neonates compared with vehicle-treated neonates, but remained lower than in BBMV from adults (P<0.05). P(DW) in dexamethasone and vehicle-treated neonatal BBMV was lower than in adult BBMV. Pf/P(DW) ratio increased from neonate (5.1+/-0.3) to dexamethasone (7.0+/-0.1) and adult BBMV (6.3+/-0.1). AQP1 expression was increased by dexamethasone treatment to adult levels. Membrane fluidity, which is inversely related to generalized polarization (GP) of steady-state laurdan fluorescence, was significantly higher in neonatal BBMV than both dexamethasone and adult BBMV (GP: neonate 0.285+/-0.002, dexamethasone treatment 0.302+/-0.006, and adult 0.300+/-0.005; P<0.05). These combined results show that dexamethasone-treatment during days 4-7 of life increases BBMV water permeability despite a decrease in membrane fluidity. This occurs by increasing channel-mediated water transport, as reflected in an increase in AQP1 protein abundance and a higher Pf/P(DW) ratio. This mimics the maturational changes and suggests a physiological role for glucocorticoids in maturation of proximal tubule water transport.     

Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: Data from a cohort study

ABSTRACT: BACKGROUND: Since the introduction of medium-chain acyl coenzyme A dehydrogenase (MCAD) deficiency in population newborn bloodspot screening (NBS) programs, subjects have been identified with variant ACADM (gene encoding MCAD enzyme) genotypes that have never been identified in clinically ascertained patients. It could be hypothesised that residual MCAD enzyme activity can contribute in risk stratification of subjects with variant ACADM genotypes. METHODS: We performed a retrospective cohort study of all patients identified upon population NBS for MCAD deficiency in the Netherlands between 2007-2010. Clinical, molecular, and enzymatic data were integrated. RESULTS: Eighty-four patients from 76 families were identified. Twenty-two percent of the subjects had a variant ACADM genotype. In patients with classical ACADM genotypes, residual MCAD enzyme activity was significantly lower (median 0%, range 0-8%) when compared to subjects with variant ACADM genotypes (range 0-63%; 4 cases with 0%, remainder 20-63%). Patients with (fatal) neonatal presentations before diagnosis displayed residual MCAD enzyme activities <1%. After diagnosis and initiation of treatment, residual MCAD enzyme activities <10% were associated with an increased risk of hypoglycaemia and carnitine supplementation. The prevalence of MCAD deficiency upon screening was 1/8,750 (95% CI 1/7,210-1/11,130). CONCLUSIONS: Determination of residual MCAD enzyme activity improves our understanding of variant ACADM genotypes and may contribute to risk stratification. Subjects with variant ACADM genotypes and residual MCAD enzyme activities <10% should be considered to have the same risks as patients with classical ACADM genotypes. Parental instructions and an emergency regimen will remain principles of the treatment in any type of MCAD deficiency, as the effect of intercurrent illness on residual MCAD enzyme activity remains uncertain. There are, however, arguments in favour of abandoning the general advice to avoid prolonged fasting in subjects with variant ACADM genotypes and 10% residual MCAD enzyme activity.     

Migrating swans profit from favourable changes in wind conditions at low altitude

Because energy reserves limit flight range, wind assistance may be of crucial importance for migratory birds. We tracked eight Bewicks swans Cygnus columbianus bewickii, using 95-g satellite transmitters with altimeters and activity sensors, during their spring migration from Denmark to northern Russia in 1996. During the 82 occasions where a swans location was recorded in flight, average flight altitude was 165 m a.s.l. with a maximum of 759 m a.s.l., despite winds often being more favourable at higher altitudes. We also counted Bewicks swans departing from the Gulf of Finland and subsequently passing an observatory in the next major stop-over area 800 km further north in the White Sea, northern Russia, during the springs of 1994, 1995 and 1996. A comparison of these counts with wind data provided evidence for Bewicks swans using favourable changes in wind conditions to embark on migration. Changes in the numbers of birds arriving in the White Sea correlated best with favourable changes in winds in the Gulf of Finland 1 day earlier. Again, migratory volume showed a correlation with winds at low altitudes only, despite wind conditions for the swans being more favourable at high altitudes. We conclude that the relatively large Bewicks swan tends to gear its migration to wind conditions at low altitude only. We argue that Bewicks swans do not climb to high altitudes because of mechanical and physiological limitations with respect to the generation of power for flight and to avoid rapid dehydration.Communicated by F. Bairlein     

Non-electrolyte permeability as a tool for studying membrane fluidity

1. The reflection coefficient for the permeation of thiourea through bilayers of phosphatidylcholine is a function of the fatty-acid composition of the lipid molecules. By means of these reflection coefficients an index for membrane fluidity has been given to each of those lipids, relative to that of egg phosphatidylcholine. 2. The maximum number of water molecules that can copermeate with each molecule of solute by means of solute-solvent interaction is a function of the packing of the lipid molecules in the bilayer. This parameter has been used in this paper for characterizing the fluidity of cholesterol-containing membranes and for membranes with their lipids in the gel state.     

Influence of hydrodynamic conditions on naphthalene dissolution and subsequent biodegradation

The influence of hydrodynamic conditions on the dissolution rate of crystalline naphthalene as a model polycyclic aromatic hydrocarbon (PAH) was studied in stirred batch reactors with varying impeller speeds. Mass transfer from naphthalene melts of different surface areas to the aqueous phase was measured and results were modeled according to the film theory. Results were generalized using dimensionless numbers (Reynolds, Schmidt, and Sherwood). In combined mass transfer and biodegradation experiments, the effect of hydrodynamic conditions on the degradation rate of naphthalene by Pseudomonas 8909N was studied. Experimental results were mathematically described using mass-transfer and microbiological models. The experiments allowed determination of mass-transfer and microbiological parameters separately in a single run. The biomass formation rate under mass transfer limited conditions, which is related to the naphthalene biodegradation rate, was correlated to the dimensionless Reynolds number, indicating increased bioavailability at increased mixing in the reactor liquid. The methodology presented in which mass transfer processes are quantified under sterile conditions followed by a biodegradation experiment can also be adapted to more complex and realistic systems, such as particulate, suspended PAH solids or soils with intrapartically sorbed contaminants when the appropriate mass-transfer equations are incorporated.     

Effects of environmental enrichment for mice: variation in experimental results

This study focused on the effects of different enriched environments for mice in a number of behavioral and physiological parameters in 2 routine laboratory testing procedures: potency testing for tetanus vaccine and stress-induced hyperthermia. The variability in the results was studied by calculating and analyzing mean absolute deviations. Mice from enriched conditions weighed more and consumed more food than mice from standard housing conditions. However, mice from enriched conditions lost more body weight after being housed individually. Other physiological parameters showed no differences. Mice from standard conditions were more active in an open field, suggesting a tendency to overrespond to various stimuli in a testing environment. Mice from enriched environments were more tranquil and easier to handle. The enrichment did not influence the variability in any of the parameters measured, although earlier results and results of other studies suggest that the effects on the variability in results are parameter dependent. When enrichment does not influence variability, there is no reason for not introducing cage enrichment and by doing so contributing to the animals' welfare.