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Biomedical subjects

G Fink

Publications and source records attributed to G Fink.

At least 19 recordsLinked to original sources
PubMed1992

Medial septal cholinergic lesions increase hippocampal mineralocorticoid and glucocorticoid receptor messenger RNA expression.

Loss of the cholinergic innervation of the hippocampus and failure of central (presumably hippocampal) suppressive control of hypothalamic-pituitary-adrenal axis activity are important features of Alzheimer's dementia. We have examined the effects of electrolytic lesions of the medial septal cholinergic innervation on mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA expression in rat hippocampus using in situ hybridization histochemistry. Expression of both MR and GR mRNA was significantly increased in a subregions of the hippocampus, but not neocortex, with the greatest increase in the CA1 area for MR mRNA and dentate gyrus for GR mRNA. Since glucocorticoids potentiate the effects of neurotoxins in the hippocampus, the increased expression of receptors following loss of cholinergic inputs in Alzheimer's disease may increase hippocampal neuronal vulnerability.

Acetylcholine↗
PubMed1992

[Cardiopulmonary exercise testing in asthmatic patients].

In order to obtain objective information on physical fitness of asthmatic patients, mainly those with severe chronic airway obstruction, an incremental exercise test was carried out in 50 asthmatics. A control group of 48 healthy subjects had similar anthropometric characteristics. The 2 groups achieved similar maximal heart rates: 96.1 +/- 8 of predicted rate in the asthmatics as compared to 98.4 +/- 4 in the controls. Maximum oxygen consumption (VO2max), anaerobic threshold and oxygen pulse (VO2/hr) were significantly lower in the asthmatics. While in mild and moderate cases performance was limited by the cardiovascular system, in severe asthmatics the limitation was respiratory. There was no correlation between severity of airway obstruction and cardiac parameters such as oxygen pulse, anaerobic threshold and VO2max. On the other hand, there was good correlation between FEV1% and the dyspnea index (Ve/MVV%). The latter was less than 60% in all asthmatics when measured during exercise testing at 75% of maximal predicted heart rate. It is thus possible for an asthmatic to engage in physical activity of the intensity that can potentially improve his physical fitness. We assume that reduction in cardiac parameters is a result of poor physical fitness related to prolonged inactivity, quite common in asthmatics as a result of inappropriate physical education.

Asthma↗
PubMed1992

The effects of cortisol infusion upon hormone secretion from the anterior pituitary and subjective mood in depressive illness and in controls.

The aims of this study were to determine whether the administration of cortisol has a significant effect on mood in patients with depression and whether the effects of cortisol on changes in plasma hormone concentrations are like those of synthetic corticosteroids. Twelve patients had major depression and one each had dysthymic disorder and a depressive adjustment disorder. Five were male and nine were female. All were in-patients. Eight normal subjects, two females and six males, were used as controls. Basal beta-endorphin concentrations were 2- to 3-fold higher in depressed patients than in control subjects, but there were no significant differences between the patient and control groups in the basal (pre-infusion) plasma concentrations of ACTH, cortisol, growth hormone or prolactin. Cortisol, but not saline infusion resulted in a significant improvement in self rated mood. Surprisingly, cortisol infusion at first increased plasma beta-endorphin concentrations. At later times after cortisol infusion, plasma beta-endorphin concentrations decreased as did the plasma concentrations of ACTH and growth hormone; prolactin levels were increased. These results show (i) that cortisol infusion raises mood significantly in major depression, (ii) that plasma beta-endorphin concentration is a potential marker of major depression (iii) that rather than blunting of corticosteroid effects, responses to cortisol may even be enhanced in depressive illness. The unexpected, initial increase in beta-endorphin stimulated by cortisol, suggests that the action of cortisol is not simply one of negative feedback inhibition, but may involve mineralocorticoid, as well as glucocorticoid receptors.

Adrenocorticotropic Hormone↗
PubMed1992

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.

Belize↗
PubMed1992

Antidepressants increase glucocorticoid and mineralocorticoid receptor mRNA expression in rat hippocampus in vivo.

Adrenal corticosteroids bind to hippocampal glucocorticoid (GR) and mineralocorticoid receptors (MR), thereby affecting neurochemical transmission leading to altered mood, behaviour and neuroendocrine control. Serotoninergic (5-HT) and noradrenergic projections innervate the hippocampus, interacting with corticosteroid-sensitive cells. We have previously demonstrated that lesions of 5-HT neurons reduce hippocampal GR and MR mRNA levels and now examine whether acute or chronic treatment with antidepressant drugs, which potentiate endogenous monoamines by inhibiting their reuptake, affect hippocampal GR and MR mRNA expression in vivo. Rats were treated with amitriptyline (20 mg/kg.day-1), desipramine (10 mg/kg.day-1) or citalopram (20 mg/kg.day-1). After 2 or 14 days animals were killed, RNA extracted and GR and MR mRNA expression quantified by slot blot hybridization. Amitriptyline for 2 days led to a significant increase in MR (by 23 +/- 6%, compared with saline-treated controls), but not GR, mRNA expression. After 14 days amitriptyline, expression of both MR (87 +/- 27% rise) and GR mRNA (56 +/- 18% rise) had increased significantly in hippocampus, but not in parietal cortex. Desipramine for 14 days also increased MR (60 +/- 9%) and GR (42 +/- 9%) mRNA expression, though 14 days of citalopram altered only MR mRNA expression (17 +/- 5%). Thus, antidepressant drug administration elevates MR and GR mRNA expression in hippocampus, but not parietal cortex, in a time-dependent manner.

Animals↗
PubMed1992

Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat.

The role of atrial natriuretic peptide (ANP) in the ACTH response to stress and the glucocorticoid negative feedback control of ACTH release was investigated in adult male homozygous Brattleboro and adrenalectomized Wistar rats respectively, using the technique of immunoneutralization. The relatively low ACTH response to stress and the lack of arginine vasopressin make the homozygous Brattleboro rat a more rigorous and simpler preparation in which to test the hypothesis that ANP is involved in the ACTH response to stress. In both sets of experiments, blood sampling and injection of sheep anti-ANP or control serum were carried out in conscious animals through intra-atrial cannulae implanted 2 days previously under halothane anaesthesia. A 30-s exposure to ether resulted in a brisk twofold increase in the plasma ACTH concentrations in homozygous Brattleboro rats infused with anti-ANP, but not control serum. The injection of either dexamethasone, a potent glucocorticoid receptor agonist, or corticosterone resulted in a rapid and marked reduction in the plasma concentrations of ACTH in Wistar rats which had been adrenalectomized, under halothane anaesthesia, at least 21 days before experimentation. The inhibitory action of dexamethasone, but not corticosterone, was significantly reduced in animals infused with anti-ANP serum. These results show that the inhibition of ANP release into hypophysial portal blood is probably important for triggering the ACTH response to stress and that ANP may play a role in corticosteroid negative feedback control of ACTH release mediated by type II (glucocorticoid) receptors.

Adrenalectomy↗
PubMed1991

Distribution of glucocorticoid and mineralocorticoid receptor messenger RNA expression in human postmortem hippocampus.

Corticosteroids bind to hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, thereby affecting behaviour and neurochemical transmission. Rat hippocampus has high levels of both receptors and their messenger RNAs (mRNA), but there is little information on receptors in human brain. We used in situ hybridization to determine the distribution of GR and MR mRNA expression in human hippocampus. Frozen sections of human postmortem hippocampus (5 patients, 58-88 years old, without cerebral pathology) were postfixed in paraformaldehyde and hybridized with 35S-UTP-labelled cRNA probes (transcribed in vitro from human cDNA subclones) under stringent conditions. Control included hybridization with sense probes and heterologous cRNA competition studies. GR mRNA was highly expressed in dentate gyrus, CA3 and CA4, but levels were significantly lower in CA1 and CA2. MR mRNA was also very highly expressed in hippocampus, with significantly higher levels in dentate gyrus and CA2, CA3 and CA4 than CA1. Controls confirmed the specificity of hybridization and there was little hybridization of sense probes. High GR and MR mRNA expression is found in both rat and human hippocampus but the subregional distributions clearly differ between the species.

Aged↗
PubMed1991

Positron emission tomography in the differential diagnosis of organic dementias.

At present, PET is the only technology affording the quantitative, three-dimensional imaging of various aspects of brain function. Since function and metabolism are coupled, and since glucose is the dominant substrate of the brain's energy metabolism, studies of glucose metabolism by PET of 2(18F)-fluoro-2-deoxy-D-glucose (FDG) are widely applied for investigating the participation of various brain systems in simple or complex stimulations and tasks. In focal or diffuse disorders of the brain, functional impairment of affected or inactivated brain regions is a reproducible finding. While glucose metabolism is decreased slightly with age in a regionally different degree, in most types of dementia severe changes of glucose metabolism are observed. Degenerative dementia of the Alzheimer type is characterized by a metabolic disturbance most prominent in the parieto-occipito-temporal association cortex and later in the frontal lobe, while primary cortical areas, basal ganglia, thalamus, and cerebellum are not affected. By this typical pattern Alzheimer disease can be differentiated from other dementia syndromes, as e.g., Pick's disease (with the metabolic depression most prominent in the frontal and temporal lobe), multi infarct dementia (with multiple focal metabolic defects), and Huntington's chorea (with metabolic disturbance in the neostriatum). In demented patients PET studies can also be applied to the quantification of treatment effects on disturbed metabolism.

Alzheimer Disease↗
PubMed1991

Steroid control of central neuronal interactions and function.

Steroids have potent actions on the brain which can be categorized as; (i) fast (approximately ms-s), (ii) intermediate (h-days), (iii) long-term reversible (days-weeks) and (iv) long-term irreversible. Here attention is focussed on the intermediate and long-term reversible effects of steroids with emphasis on glucocorticoids and oestrogen. Glucocorticoid negative feedback is generally classified as fast, delayed and long-term. Fast negative feedback would appear to depend mainly on a reduction in pituitary responsiveness to corticotrophin releasing factor-41 (CRF-41) and possibly arginine vasopressin (AVP). Delayed feedback is mediated by reduced AVP release into hypophysial portal blood and blockade of the ACTH response to CRF-41. Long-term negative feedback is a consequence of reduced CRF-41 and AVP release into portal blood. Lesion and electrical stimulation studies pinpoint the paraventricular nuclei as the main site at which glucocorticoids act to control ACTH release. Oestrogen at physiologically low plasma concentrations inhibits gonadotrophin secretion. At physiologically high plasma concentrations, such as those that occur during the preovulatory surge, oestradiol-17 beta stimulates the biosynthesis of LHRH mRNA and LHRH and the release of LHRH into hypophysial portal blood. Oestradiol also increases pituitary responsiveness to LHRH. The action of oestrogen on LHRH neurons is probably mediated by interneurons and may involve disinhibition; this view is supported by our in situ hybridization studies which show that oestrogen, in its positive feedback mode, significantly reduces the synthesis of proopiomelanocortin mRNA in arcuate neurons which when active are likely to inhibit LHRH neurons. The mechanism of action of oestrogen on the pituitary gland is not yet established, but clues from the action of the priming effect of LHRH suggests that oestrogen may potentiate phosphoinositide second messenger cascades. LHRH priming involves the synthesis of a 70 kDa protein the N-terminus of which is identical to an oestrogen-induced protein in the ventromedial hypothalamic nucleus involved in lordosis, and to that of phospholipase C alpha. Attention is drawn to the remarkable economy of the system by which a single steroid, oestrogen, has effects on the brain and pituitary gland which result in a co-ordinated sequence of amplifier cascades which lead first to the ovulatory surge of luteinizing hormone and then to mating behaviour, both of which are obviously essential for continuation of the species.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1991

Use of in situ hybridization to investigate the regulation of hippocampal corticosteroid receptors by monoamines.

The hippocampus receives major noradrenergic and serotoninergic (5-HT) innervations which interact with corticosteroid-sensitive cells. However, the subregional localization of these actions and the corticosteroid receptor types involved have not been defined and current ligand binding techniques for estimating corticosteroid receptors are hampered by several methodological limitations. We have developed in situ hybridization histochemical techniques to allow specific and sensitive estimation of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNA expression in rat hippocampus. Investigation of the effects of 5,7-dihydroxytryptamine lesions of 5-HT neurons showed significantly reduced GR and MR mRNA expression in some hippocampal subregions. Both abnormal 5-HT neurotransmission and excessive corticosteroid secretion are associated with major affective disorder, particularly depression. The crucial interaction between these two systems may occur, at least in part, at the level of regulation of hippocampal corticosteroid receptor expression.

5,7-Dihydroxytryptamine↗
PubMed1991

The pattern of cerebral activity underlying verbal fluency shown by split-dose single photon emission tomography (SPET or SPECT) in normal volunteers.

Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.

Aged↗
PubMed1991

Estimation of local cerebral glucose utilization by positron emission tomography: comparison of [18F]2-fluoro-2-deoxy-D-glucose and [18F]2-fluoro-2-deoxy-D-mannose in patients with focal brain lesions.

A comparative PET study of [18F]2-fluoro-2-deoxy-D-glucose (FDG) and [18F]2-fluoro-2-deoxy-D-mannose (FDM) uptake was performed in 13 patients with focal brain lesions. Differences between FDG and FDM with respect to model rate constants, lumped constant, and estimated metabolic rate for glucose were determined on a regional basis. Across whole brain, the transport rate constant K1* was almost unchanged, whereas k2*, describing the transport back from tissue to plasma, was 6% higher, and the phosphorylation rate constant k3* was 9% lower for FDM compared to FDG. This implies a 20% lower lumped constant for FDM. No significant regional variability of this differential tracer behavior was observed in normal or in lesioned brain tissue. Thus, results from previous FDG studies, where the radiotracer was not 100% pure FDG but contained varying amounts of FDM, can easily be corrected by adjustment of the lumped constant employed in metabolic quantitation.

Adult↗
PubMed1991

Effects of corticosterone on the secretion of corticotrophin-releasing factor, arginine vasopressin and oxytocin into hypophysial portal blood in long-term hypophysectomized rats.

To investigate the feedback effects of corticosterone on the secretion of corticotrophin-releasing factor-41 (CRF-41), oxytocin and arginine vasopressin (AVP), hypophysial portal vessel blood was collected from control (intact) and long-term (6-8 weeks) hypophysectomized rats. In preliminary experiments in rats anaesthetized with urethane, long-term hypophysectomy resulted in a significant increase in the secretion of oxytocin and AVP; the hypothalamic contents of oxytocin and AVP were also increased in comparison with pituitary-intact rats. In long-term hypophysectomized rats anaesthetized with sodium pentobarbitone, but not with urethane, the output of CRF-41 into portal blood was increased twofold in comparison with that in control rats. In long-term hypophysectomized rats anaesthetized with pentobarbitone, the i.v. infusion of corticosterone (7.2 nmol/min) for a 2 h period of portal blood collection did not alter the secretion of CRF-41, oxytocin or AVP into portal blood; however, the secretion of CRF-41 and, to a lesser extent, AVP was significantly reduced in hypophysectomized rats by continuous corticosterone replacement, by a pellet of corticosterone implanted s.c. for 5 days before portal blood collection. These results confirm that the secretion of CRF-41 is differently affected by the anaesthetics urethane and pentobarbitone, and in long-term hypophysectomized rats show (i) that there were no apparent feedback effects of corticosterone infusion over a 2 h period on the secretion of any of the peptides studied, (ii) that late delayed feedback effects of continuous administration of corticosterone are mediated by a reduction in CRF-41 and AVP output, and (iii) that corticosterone has no effects on oxytocin secretion into portal blood.

Anesthesia, General↗
PubMed1991

Corticotrophin-releasing factor-41, vasopressin and oxytocin release into hypophysial portal blood in the rat: effects of electrical stimulation of the hypothalamus, amygdala and hippocampus.

The role of the paraventricular nuclei (PVN), amygdala and hippocampus in the control of the hypothalamic-pituitary-adrenal axis has been studied by determining the effect of electrical stimulation of the PVN, amygdala and hippocampus on the release of corticotrophin-releasing hormone (CRF-41) and arginine vasopressin (AVP) into hypophysial portal blood and ACTH and corticosterone into peripheral blood. Adult female Wistar rats were anaesthetized with sodium pentobarbitone and stimulation was carried out through previously implanted bipolar, glass-insulated platinum electrodes. Hypophysial portal blood was collected 30 min before and 30 min during the application of the stimulus which consisted of trains (30 s on and 30 s off) of biphasic rectangular pulses with a frequency of 50 Hz, pulse width 1 ms and amplitude 1 mA. Bilateral stimulation of the PVN increased while unilateral stimulation of the amygdala decreased the release of CRF-41 into hypophysial portal blood. The threefold increase in release of CRF-41 induced by PVN stimulation correlated with a marked increase in peripheral plasma concentrations of ACTH and corticosterone. Stimulation of the hippocampus had no significant effect on CRF-41 release, and stimulation of each of the three brain regions had no effect on AVP release into portal blood. These findings were extended in a second study to compare the effects of unilateral bipolar electrical stimulation of the PVN and of the supraoptic nucleus (SON) on the release of CRF-41, AVP and oxytocin. This study was carried out on adult male rats, anaesthetized with sodium pentobarbitone, in which the stimulus was applied through previously implanted concentric stainless-steel electrodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1991

Hypothalamic release of atrial natriuretic factor and beta-endorphin into rat hypophysial portal plasma: relationship to oestrous cycle and effects of hypophysectomy.

The release of beta-endorphin and atrial natriuretic factor (ANF) into hypophysial portal plasma was investigated in male and female Wistar rats. The principal aim of the study was to investigate the possible role of beta-endorphin and ANF in the hypothalamic control of LH and prolactin secretion. In male rats, anaesthetized with urethane, the concentrations of beta-endorphin in portal blood collected immediately after hypophysectomy were within the same range as those in peripheral plasma. Furthermore, electrical stimulation of the median eminence did not increase the portal plasma concentrations of beta-endorphin. In female rats, anaesthetized with alphaxalone, the portal plasma concentrations in long-term (6-8 weeks) or acutely hypophysectomized rats were significantly greater than those in peripheral plasma. In acutely hypophysectomized female rats the concentrations and contents of beta-endorphin in portal plasma collected at 10.00-11.30 h of pro-oestrus were significantly (approximately sixfold) greater than at dioestrus or at 20.00-21.00 h of pro-oestrus, but these changes were not consistently seen in all experiments. In female rats in which the pituitary gland was not removed for portal blood collection, portal plasma contents of ANF remained unchanged throughout the day of pro-oestrus, suggesting that it is unlikely that ANF is involved in the spontaneous LH or prolactin surge. The effects of ovarian steroids on the secretion of hypothalamic ANF and beta-endorphin were determined by measuring the portal plasma concentration of ANF and beta-endorphin on the morning of presumptive pro-oestrus in rats ovariectomized 24 h previously and injected with either oil or oestradial benzoate (OB). Portal plasma contents of ANF were significantly lower in OB- compared with oil-treated rats, suggesting that oestradiol inhibits ANF release into rat hypophysial portal plasma. In contrast, there were no significant between-group differences in the content or concentration of beta-endorphin in portal plasma. Thus, the increased beta-endorphin in the portal plasma of some of the intact animals during the morning of pro-oestrus is not due to the preovulatory surge of oestradiol-17 beta. The output of beta-endorphin into portal blood in long-term hypophysectomized rats was lower than in dioestrous or pro-oestrous rats in which the pituitary gland was removed immediately before portal blood collection.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Atrial natriuretic peptide is a physiological inhibitor of ACTH release: evidence from immunoneutralization in vivo.

The brain is thought to exert a predominantly stimulatory action on ACTH secretion mediated mainly by corticotrophin-releasing factor-41 (CRF-41) and arginine vasopressin (AVP). Several data, however, also point to the existence of an ACTH-inhibiting factor. Atrial natriuretic peptide (ANP), at concentrations found in hypophysial portal blood, inhibits ACTH release in vitro. The aim of the present studies was to use ANP immunoneutralization to determine whether ANP does in fact inhibit ACTH release in vivo. Intracerebroventricular infusion (1 microliters/min for 30 min) of sheep anti-ANP serum into male rats anaesthetized with sodium pentobarbitone had no significant effect on jugular venous plasma concentrations of ACTH or LH but did decrease significantly the plasma concentrations of prolactin. Intravenous infusion of 0.8 ml sheep anti-ANP serum but not control (non-immune) sheep serum, through an indwelling intra-atrial cannula in conscious male rats resulted in a marked and significant increase in plasma ACTH and corticosterone concentrations. The ACTH and corticosterone response to a 30-s ether stress was not significantly potentiated in the same conscious rats infused with anti-ANP serum. Intra-atrial infusion of anti-ANP did not significantly affect plasma prolactin, LH, glucose or sodium concentrations or plasma osmolality. These results show for the first time that ANP is a potent inhibitor of ACTH secretion in the conscious male rat and that, therefore, ANP is a hypothalamic neurohormone which is likely to play an important inhibitory role in the neural control of ACTH release.

Adrenocorticotropic Hormone↗