Activation of glucocorticoid receptors and the effect of naloxone during hemorrhagic hypotension.

Evidence indicates that endogenous opioid peptides and glucocorticoids participate in the control of cardiovascular regulation during hemorrhagic shock. In the present study, we investigated a possible interaction between brain opioid peptides and adrenal corticosteroids regarding the control of arterial pressure during hemorrhage. The bleeding volumes required to lower arterial pressure to 80, 60 and 40 mmHg were studied in anesthetized sham-operated (SHAM) and adrenalectomized (ADX) rats. I.c.v. administration of 10 micrograms of naloxone resulted in a significant increase in the bleeding volume required to lower arterial pressure from 60 to 40 mmHg in SHAM animals, whereas no effect of naloxone was observed in ADX animals. Replacement therapy with a 100% corticosterone pellet (100 mg, s.c.), but not with a 12.5% corticosterone pellet (12.5 mg corticosterone and 87.5 mg cholesterol, s.c.), resulted in an effect of naloxone on the bleeding volume in ADX animals. The effect of replacement therapy could be inhibited by i.c.v. pretreatment with the synthetic glucocorticoid receptor antagonist, RU38486 (100 ng). These data suggest that (1) opioid mechanisms are involved in the regulation of blood pressure during hemorrhage, and (2) occupancy of glucocorticoid receptors is required for naloxone to exert its hemodynamic effect during hemorrhagic hypotension in ADX rats.     

Spatial Learning Deficits in Mice with a Targeted Glucocorticoid Receptor Gene Disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

Topography of the oxytocin receptor system in rat brain: an autoradiographical study with a selective radioiodinated oxytocin antagonist

A new, highly selective radio-iodinated oxytocin receptor antagonist [( 1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid, 2-O-methyltyrosine, 4-threonine, 8-ornithine, 9-tyrosylamide]-vasotocin) was used to identify and quantitate specific binding sites for the neurohypophyseal hormone oxytocin with in vitro incubation of rat brain sections and autoradiography. Exclusively oxytocin binding sites were detected in view of the high affinity of the [125I]-labelled oxytocin antagonist for oxytocin binding sites and the negligible affinity for the vasopressin liver (V1) and kidney (V2) receptor types. The putative oxytocin receptors were abundantly present in several brain regions, where previously discrimination between oxytocin and vasopressin binding was difficult, i.e. the olfactory nucleus, the islands of Calleja, the ventromedial nucleus of the hypothalamus, the central amygdaloid nucleus and the ventral subiculum of the hippocampus. In addition oxytocin receptors were demonstrated in other areas, such as the taenia tecta, dorsolateral caudate putamen, ventral pallidum, accumbens, lateral septum, bed nucleus of the stria terminalis, thalamic paraventricular nucleus, lateral, basolateral and medial amygdala, the dorsal subiculum, perirhinal cortex and the amygdaloid-hippocampal area. The high affinity and the low detection threshold of this [125I]-labelled oxytocin antagonist permitted identification of oxytocin receptors in new regions such as the ventral part of the lateral septum, medial septum, dorsal motor nucleus of the vagus nerve and the olive nuclei in the brain stem.     

Intracranial arteriovenous malformations in pregnant women]

Three women, aged 27, 32 and 30 years, respectively, suffered from headache, nausea and neurological abnormalities and were found to have an intracranial arteriovenous malformation (AVM). One of them after diagnosis had two pregnancies, both ended by caesarean section with good results. Another woman was 32 weeks pregnant when the AVM manifested itself with a haemorrhage; she recovered well and was delivered by caesarean section. After the AVM proved radiologically to have been obliterated, she delivered after her subsequent pregnancy by the vaginal route with vacuum extraction. The third woman was 15 weeks pregnant when major abnormalities developed. There was a large intracerebral haematoma with break-through to the ventricular system; this patient died. Intracranial haemorrhage during pregnancy is rate. It can result in maternal and foetal morbidity and mortality. It appears that pregnancy does not increase the rate of first cerebral haemorrhage from an AVM. The management of AVM rupture during pregnancy should be based primarily on neurosurgical rather than on obstetric considerations. Close collaboration with a team of neurologists, neurosurgeons, obstetricians and anaesthesiologists is mandatory.     

Composite (etched) bridge

An adhesive or resin-bonded bridge is a tooth saving construction for the replacement of a lost tooth, especially when the abutment teeth are relatively sound. In this article an overview is presented of the different types of resin-bonded bridges, their advantages and disadvantages and their indications. The direct methods are very suited for the immediate replacement of a lost anterior tooth. The all composite adhesive bridge has a survival rate that is surprisingly good.     

The active phase-related increase in corticosterone and aggression are linked

Recently we demonstrated that corticosterone exerts an acute facilitatory effect on aggression in male rats. Corticosterone production reaches a maximum at the onset of the dark period, while male rats are more aggressive in the dark. Here we present evidence demonstrating that the corticosterone increase at the beginning of the dark period is causally linked to the increase in aggressiveness. We measured plasma corticosterone and quantified aggressive behaviour of male territorial rats at various time points of the day-night transition. Low aggression levels were observed in the full light period when plasma concentrations of corticosterone were low. An increase in plasma corticosterone occurred just prior to the dark phase, when aggressive responding was the highest. Aggressive behaviour remained high in the early dark period when corticosterone was still high. We found that blocking the high affinity mineralocorticoid receptor (MR) with spironolactone (5 or 10 mg/kg) during the early dark period dramatically and specifically reduced territorial aggression.     

Effects of urinary and recombinant gonadotrophins on gene expression profiles during the murine peri-implantation period

BACKGROUND: Controlled ovarian stimulation (COS) with urinary gonadotrophins but not recombinant gonadotrophins, adversely affect the implantation process. In this study, we investigated the effects of urinary and recombinant gonadotrophins on gene expression profiles at implantation sites during the mouse peri-implantation period and the possible molecular mechanisms involved in the detrimental effects of urinary gonadotrophins using microarray technology. METHODS: Adult female CD1 mice were treated with (i) urinary human FSH (hFSH) and urinary HCG, (ii) recombinant hFSH and recombinant human LH or (iii) saline. Gene expression profiling with GeneChip mouse genome 430 2.0 arrays, containing 45 101 probe sets, was performed using implantation sites on embryonic day 5. Data were statistically analysed using Significance Analysis of Microarrays. Ten genes from the microarray analysis were selected for validation using quantitative RT-PCR (qRT-PCR). A parallel group of pregnant mice was allowed to give birth to study the effect of gonadotrophins on resorption. RESULTS: Urinary gonadotrophins differentially up-regulated the expression of 30 genes, increased resorption and reduced litter size, whereas recombinant gonadotrophins did not. Nine of the 10 genes were confirmed by qRT-PCR. CONCLUSIONS: Urinary gonadotrophins, but not recombinant gonadotrophins, exerted differential effects on gene expression during the murine peri-implantation period. These findings might contribute to improve protocols for COS, leading to higher successful pregnancy rates.     

Leu-Phe cleaving endopeptidase activity, gamma-endorphin, and beta-endorphin in the rat pituitary gland and brain. Effect of adrenalectomy and corticosterone substitution

The influence of adrenalectomy and corticosterone substitution was investigated on Leu-Phe cleaving endopeptidase activity and on the levels of gamma-endorphin and beta-endorphin in the pituitary gland and the brain. The enzyme activity was quantitated by a specific radiometric assay based on the cleavage of the Leu17-Phe18 bond in a NH2- and COOH-terminally protected synthetic substrate which was analogous to beta-endorphin-(15-19). This activity may mimick the formation of gamma-endorphin. beta-Endorphin and gamma-endorphin were measured by specific radioimmunoassays. After 14 days of adrenalectomy enzyme activity had increased in anterior (15%) and neurointermediate lobes of the pituitary gland (30%), hypothalamus (25%), and liver (15%). This increase was prevented when the adrenalectomized animals were subjected to chronic corticosterone substitution by subcutaneous implantation of a pellet of 100 mg. Extirpation of only the adrenal medulla did not affect the Leu-Phe cleaving activity. Enzyme activity in the septum, hippocampus, and cerebellum had not changed after adrenalectomy. Determination of immunoreactive levels of gamma- and beta-endorphins showed that in the anterior pituitary gland gamma- and beta-endorphins had increased by 275 and 300%, respectively, 14 days after adrenalectomy. No significant changes were observed in endorphin levels of the intermediate lobe of the pituitary gland, hypothalamus, hippocampus, and septum. The results indicate that Leu-Phe cleaving endopeptidase activity in sensitive to glucocorticoids in tissues containing proopiomelanocortin-producing cells, i.e., anterior and neurointermediate pituitary gland and the hypothalamus. In the anterior pituitary gland it is correlated with the levels of gamma- and beta-endorphins.