Diazepam-binding inhibitor/acyl-CoA-binding protein mRNA and peripheral benzodiazepine receptor mRNA in endocrine and immune tissues after prenatal diazepam exposure of male and female rats.

Peripheral benzodiazepine (BDZ) receptor (PBR) and diazepam-binding inhibitor/acyl-CoA-binding protein (DBI/ACBP) characterized as a ligand at central BDZ receptors, at PBR with involvement in the regulation of steroidogenesis, and as an intracellular acyl-CoA transporter, are both known to interact with BDZ in adult systems. We investigated their expression after prenatal exposure to BDZ. Diazepam (1.25 mg/kg per day s.c.) was administered to time-pregnant Long Evans rats from gestational day (GD) 14 to 20. Expression of mRNAs encoding for PBR and for DBI/ACBP was studied in the same animals with (33)P-labeled 60 mer oligonucleotides (oligos) by in situ hybridization at GD20, and with (32)P-labeled oligos by Northern blot in steroidogenic and immune organs at postnatal day (PN) 14 and in adult offspring. Prenatal diazepam increased DBI/ACBP mRNA expression in male fetal adrenal and in fetal and PN14 testis. Thymus exhibited increased DBI/ACBP mRNA in male fetuses and in adult female offspring, and reduced organ weight at PN14 in both sexes. In female spleen, an increase in DBI/ACBP mRNA and a decrease in PBR mRNA was seen at PN14. Apart from the finding in spleen, no drug-induced changes in PBR mRNA were observed. The effects of prenatal diazepam were superimposed on treatment-independent sex differences in DBI/ACBP mRNA and PBR mRNA expression. Our data indicate that expression of DBI/ACBP mRNA in steroidogenic and immune organs can be affected by exposure to BDZ during ontogeny, while PBR mRNA expression appears to be less sensitive. They further reveal marked sex differences in the developmental patterns of the two proteins during pre- and postpubertal ontogeny.

Ontogeny of diazepam binding inhibitor/acyl-CoA binding protein mRNA and peripheral benzodiazepine receptor mRNA expression in the rat.

The Diazepam Binding Inhibitor/Acyl-CoA Binding Protein (DBI/ACBP) has been implicated in different functions, as acyl-CoA transporter and as an endogenous ligand at the GABA(A) receptor and the peripheral benzodiazepine receptor (PBR). The latter is thought to be involved in control of steroidogenesis. We studied the ontogeny of DBI/ACBP and PBR mRNA expression in embryos and offspring of time-pregnant Long Evans rats by in-situ hybridization with 33P-endlabelled oligonucleotides. Both mRNAs were present in embryo and placenta at gestational day (G)11, the earliest stage studied. DBI/ACBP mRNA was strongly expressed from embryonic through mid-foetal stages in central nervous system (maximum in neuroepithelium), cranial and sympathetic ganglia, anterior pituitary, adrenal cortex, thyroid, thymus, liver and (late foetal) brown adipose tissue, moderately in testis, heart, lung and kidney. In brain, a late foetal decrease of DBI/ACBP mRNA was followed by an increase at postnatal day 6. Peripheral benzodiazepine receptor mRNA expression started very low and increased to moderate levels in adrenal cortex and medulla, testis, thyroid, brown adipose tissue, liver, heart, lung, salivary gland at mid- to late-foetal stages. Data suggest a significant role of DBI/ACBP at early developmental stages. Both proteins may be involved in the control of foetal steroidogenesis. However, differences in developmental patterns indicate that additional functions may be equally important during ontogeny, such as the involvement in lipid metabolism in the case of DBI/ACBP.

Basophil priming by neurotrophic factors. Activation through the trk receptor.

There is increasing evidence that nerve growth factor (NGF) acts on cells of the immune system, apart from its neurotrophic effects. In human basophils, NGF potentiates mediator release and primes the cells to produce leukotriene C4 in response to C5a. It is, however, unknown whether other homologous neurotrophins also act outside the nervous system, and whether activation of basophils by NGF requires interaction with trk tyrosine kinase receptors, the low affinity NGF receptor (LNGFR), or both. A triple mutant NGF designed to interrupt binding to the LNGFR was found to activate basophils with equal efficacy as wild-type NGF, demonstrating that the LNGFR is not necessary. Despite a 10 times lower potency of mutant NGF, no LNGFR expression was detected by FACS analysis. Brain-derived neurotrophic factor, which interacts with trkB, was inactive at concentrations up to 1000 ng/ml (> 30,000-fold lower potency than NGF), while neurotrophin-3, which is thought to interact with trkC, trkB, and more weakly with trk, induced a threshold effect at 300 ng/ml (approximately 10,000-fold lower potency), demonstrating that 1) the LNGFR cannot deliver a direct signal; and 2) basophils do not express functional trkB and trkC receptors. In agreement with the functional data, basophils (in contrast to other granulocyte types) expressed mRNA for trk, but not trkB or trkC, and no or minimal mRNA for LNGFR. These data demonstrate that human blood basophils express functional trk receptors that do not require the participation of LNGFR, and that, among the neurotrophin family, NGF is unique in priming basophils.

[Emergency nurses investigate their patients' needs]. / Pflegende einer traumatologischen Klinik erforschen die Bedürfnisse ihrer Patienten.

This article reports on a study in which clinical nurses contributed actively to the scientific investigation of the nursing needs of their patients. The study revealed valuable information relating to both the psycho-social needs caused by the accident and the integration of nurses in clinical nursing research.

The degradation product of the C5a anaphylatoxin C5adesarg retains basophil-activating properties.

The complement cleavage product C5a is a potent agonist of different leukocyte types and also has anaphylatoxic properties through the release of mediators by basophils and tissue mast cells. C5a is very rapidly degraded by serum carboxypeptidase N which cleaves the functionally important carboxy-terminal arginine, generating C5desarg, a chemotactic agonist with little mast cell-activating ability. Here we show that natural human C5adesarg is still a trigger for basophil mediator release superior to other endogenous IgE-independent agonists such as monocyte chemotactic protein (MCP)-1, interleukin (IL)-8, C3a and platelet-activating factor. On a molar basis C5adesarg is only one order of magnitude less potent and about half as efficacious as C5a at inducing basophil degranulation. Priming of basophils with either IL-3, IL-5, granulocyte-macrophage-colony-stimulating factor (GM-CSF) or nerve growth factor (NGF) (with comparable efficacies, but different potencies: IL-3 > NGF > IL-5 > GM-CSF) enhanced histamine release and conditioned the cells to produce large amounts of leukotriene C4 (LTC4), which is not generated by basophils exposed to C5adesarg alone. The efficacy of C5a and C5adesarg at inducing histamine and LTC4 release by primed basophils was similar. Thus, C5adesarg is a stable inducer of release of inflammatory mediators by human basophils, particularly in primed cells, and complement may, therefore, play a role in immediate-type hypersensitivity diseases in allergic late-phase reactions.