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Biomedical subjects

D Jordan

Publications and source records attributed to D Jordan.

At least 127 records · Page 7Linked to original sources

In vitro effects of endogenous opiate peptides on thyrotropin function: inhibition of thyrotropin-releasing hormone release and absence of effect on thyrotropin release.

Thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH) was measured by radioimmunoassay in the incubation medium of rat hypothalami or anterior pituitary halves, respectively. We studied the effect of opioid peptide addition (10(-8) to 10(-6) M) on TRH or TSH release. alpha- or beta-Endorphin decreased TRH release in a dose-dependent manner while only 10(-6) M Leu- or Met-enkephalin decreased TRH release. These inhibitory effects were prevented by addition of naloxone (10(-5) M). In the dose range used none of the opioid peptides modified TSH release. These results indicate that opioid peptides may play a role in the regulation of thyrotropin secretion via a hypothalamic action on TRH release.

Animals↗

Presynaptic depolarization in myelinated vagal afferent fibres terminating in the nucleus of the tractus solitarius in the cat.

The presynaptic influences that act on terminals of slowly adapting lung stretch receptor afferents and aortic baroreceptor afferents within the nucleus of the solitary tract were assessed using intracellular recording and antidromic stimulation techniques. Central respiratory influences on the excitability of lung stretch receptor terminals were observed in 29% (4 of 14) of measurements. These were confirmed in intracellular recordings where membrane depolarizations in synchrony with phrenic nerve discharge were seen in 17% (4 of 24) of fibres. In three cases membrane depolarization also occurred synchronously with artificial lung inflation. Neither tests of excitability nor intracellular recording revealed any evidence for equivalent presynaptic influences on 16 myelinated aortic baroreceptor terminals. Stimulation of the superior laryngeal nerve evoked depolarizations in 50% (7 of 14) of lung stretch receptor terminals. These took the form of complex waves of depolarization with both short (3-8 ms) and long latency (27-35 ms) components. The amplitude of the long latency response increased during the period of phrenic nerve discharge, i.e. during "central inspiration". These effects are discussed in relation to the central respiratory influences on both respiratory and cardiovascular reflexes.

Animals↗

Amygdaloid influences on brain-stem neurones in the rabbit.

1. Electrical stimulation of the central nucleus of the amygdala in the urethane or alpha-chloralose anaesthetized rabbit evokes a bradycardia with a rapid onset and a concomitant fall in arterial blood pressure. 2. Extracellular neuronal activity was recorded in the ipsilateral nucleus tractus solitarius and dorsal vagal nucleus whilst stimulating the ipsilateral central nucleus of the amygdala, the aortic and vagus nerves. 3. A total of 213 neurones were activated by stimulation of at least one of these inputs. 93 of these neurones received a marked excitatory input from the central nucleus with a wide range of latencies (2-100 ms). 50 of these cells also received inputs from either the aortic or vagus nerves, or both. 4. The activity of 42 vagal preganglionic neurones was recorded in the dorsal vagal nucleus of which 22 had properties typical of cardioinhibitory neurones. 9 of these vagal motoneurones received inputs from the central nucleus with latencies between 2 and 100 ms. Of these, 5 had physiological properties indicating they were cardio-inhibitory neurones. 5. We conclude that neurones in the nucleus tractus solitarius and dorsal vagal nucleus can be influenced by descending inputs arising from the central nucleus of the amygdala. Some of these neurones are also likely to be influenced by afferents innervating the thoracic viscera and arterial baroreceptors. The implications of these observations on the role of forebrain-brain-stem interactions in cardiovascular control are discussed.

Action Potentials↗

Zinc may play a role in the regulation of thyrotropin function.

We studied the in vitro and in vivo influence of physiologically relevant zinc concentrations on the thyrotropin function both at the pituitary and hypothalamic level. Zinc gluconate (Zn Glu) concentrations from 5 to 100 microM decreased basal TSH release from anterior pituitary gland in vitro, but did not affect TSH-stimulated release by TRH, cAMP or high K+ concentrations. Zn Glu altered neither the basal nor stimulated production of TRH by hypothalami in vitro. In vivo brain third ventricle injection of Zn Glu decreased serum TSH 30-60 min after injection. The ability of physiological concentrations of zinc to influence TSH secretion both in vitro and in vivo suggest that this trace element might be involved in the regulation of thyrotropin function.

8-Bromo Cyclic Adenosine Monophosphate↗

Post-synaptic activity evoked in the nucleus tractus solitarius by carotid sinus and aortic nerve afferents in the cat.

Post-synaptic responses evoked in neurones of the nucleus tractus solitarius by electrical stimulation of the carotid sinus, aortic and vagal nerves, alone or in combination, have been studied in anaesthetized cats using both extracellular and intracellular recording techniques. A total of 292 neurones received an input from at least one of the three nerves tested. The activity of the large majority of these cells (249) could only be shown to be altered by stimulation of one of these nerves and in 222 of these cases this was an excitatory response. These responses showed the expected post-synaptic characteristics including temporal summation and, in intracellular records, a summation of evoked excitatory post-synaptic potentials (e.p.s.p.s). The minimum latency to onset of these responses was variable, both for individual cells and for the population as a whole and varied within the range 2-124 ms. In a small number of cells (twenty-seven), the input was purely inhibitory in nature. In neurones showing a tonic discharge this produced a decrease in the rate of firing. This influence was most marked in intracellular records where membrane hyperpolarizations were noted. Again, the latency to onset was variable, in the range 4-27 ms. Convergent inputs from two or more of the nerves were identified in forty-three neurones. The effects of these were always excitatory. They could be observed both as a facilitation of spike activity recorded extracellularly and as summation of subliminally evoked e.p.s.p.s recorded intracellularly. On the basis of threshold voltages and latency to onset, the afferents to these neurones are indistinguishable from those providing an exclusive input. It can be concluded that at least some of the neurones in the nucleus tractus solitarius and its vicinity receive inputs from more than one source. The implications of these observations on the role of this brain-stem area in cardiorespiratory reflexes is discussed.

Action Potentials↗

Multispectral analysis of magnetic resonance images.

Magnetic resonance (MR) imaging systems produce spatial distribution estimates of proton density, relaxation time, and flow, in a two dimensional matrix form that is analogous to that of the image data obtained from multispectral imaging satellites. Advanced NASA satellite image processing offers sophisticated multispectral analysis of MR images. Spin echo and inversion recovery pulse sequence images were entered in a digital format compatible with satellite images and accurately registered pixel by pixel. Signatures of each tissue class were automatically determined using both supervised and unsupervised classification. Overall tissue classification was obtained in the form of a theme map. In MR images of the brain, for example, the classes included CSF, gray matter, white matter, subcutaneous fat, muscle, and bone. These methods provide an efficient means of identifying subtle relationships in a multi-image MR study.

Basal Ganglia Diseases↗

Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males.

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.

Adult↗

Excitatory effects of iontophoretically applied substance P on neurons in the nucleus tractus solitarius of the cat: lack of interaction with opiates and opioids.

The effects of iontophoretically applied substance P (SP), (D-Pro2, D-Trp7,9)-SP and (D-Pro4, D-Trp7,9,10)-SP were studied on neurons identified by their histological location in the nucleus tractus solitarius (NTS), their response to vagal or carotid sinus nerve stimulation and eventually their functional correlation with the central respiratory drive. Potent and consistent excitatory effects of SP were found supporting its role as a putative excitatory transmitter in the NTS. The effects of SP and L-glutamate (Glu) were differentiated by the relative insensitivity of SP-induced excitations to levorphanol and Met-enkephalin.

Animals↗

Metabolic alterations induced by chronic heat exposure in the rat: the involvement of thyroid function.

The effects of chronic exposure to high environmental temperature (34 degrees C) on T4 production rate, food-intake, growth-rate and resting metabolic rate were investigated in adult male rats. This study was designed to examine the extent of variations and possible relationships between these parameters. As compared to control rats of the same body weight kept at 25 degrees C, rats exposed to 34 degrees C for 3-4 weeks exhibited a retarded growth-rate: 2.3 vs 4.0 g/day, a reduced food-intake: 15.2 vs 23.2 g/day, a decreased T4 production-rate: 1.8 vs 2.7 micrograms/day and a decreased oxygen consumption: 4.0 vs 5.4 ml/min. Heat-exposure altered the 4 parameters to a similar extent. T4 supplementation (3 micrograms/day) which induced a decrease in plasma TSH concentration, did not restore a normal growth-rate in heat-exposed rats. The decreased food-intake of the heat-exposed rats was not associated with any significant changes in the daily pattern of variations of liver glycogen content, or in the mean daily levels of blood glucose or insulin. The ratio T3 to rT3 in plasma was not altered by chronic heat exposure. When rats which had been chronically exposed to heat (25 days at 34 degrees C) were exposed to 25 degrees C, growth-rate, food-intake and oxygen consumption rapidly increased to control values whereas the rate of T4 production remained low. It is concluded that (1) a decrease in thyroid hormone economy is not directly involved in the alterations of growth and energy expenditure in rats chronically exposed to heat, (2) heat exposure does not lead to the establishment of a fasted state resulting from a large reduction in voluntary food intake, (3) metabolic alterations induced by heat exposure are rapidly and completely reversible upon decreasing the environmental temperature.

Animals↗

Evidence for a monosynaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory beta neurones.

The synaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory neurones within a region ventral to the tractus solitarius was determined using intracellular recording and spike triggered averaging techniques. When the vagus nerve was stimulated at intensities eliciting a Hering-Breuer reflex, the difference in mean latency between centrally recorded action potentials of slowly adapting pulmonary stretch receptor afferents and e.p.s.p.s of inspiratory beta neurones was 0.2 ms. This difference is indicative of a monosynaptic connection. Extracellular single unit spikes of slowly adapting pulmonary stretch receptors recorded from the nodose ganglion were used to trigger the averaging of synaptic noise recorded from inspiratory neurones. A prominent wave of synaptic depolarization was observed in all inspiratory beta neurones even when a small number of sweeps were averaged. This depolarization was absent from inspiratory alpha neurones. The shape indices of these depolarizations are consistent with a monosynaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory beta neurones. In addition, the data raise the possibility that this connection is multiple and distributed.

Animals↗

A chronobiological study of melatonin, cortisol growth hormone and prolactin secretion in cluster headache.

The temporal organization of plasma melatonin, cortisol, growth hormone (GH) and prolactin secretion was examined in healthy rested controls and in patients suffering from episodic cluster headache. Eleven patients with typical cluster headache (10 men, 1 female) and 8 male controls were studied over a 24-h period: blood was collected at 2-h intervals during the day and at 1-h intervals at night. Plasma melatonin, cortisol, GH and prolactin levels were determined by radioimmunoassay. Most of the cluster headache patients showed a decrease in nocturnal melatonin secretion and the melatonin rhythm was even completely abolished in one patient. Chronobiological analysis of the cluster headache patients' 24-h plasma melatonin profile showed a significant decrease in amplitude and mesor: these were 58.7 pg/ml and 34.4 pg/ml respectively in control subjects, versus 18.7 pg/ml and 17.6 pg/ml for the patients. In addition, patients showed a significant phase-advance in their melatonin rhythm. For cortisol, the rhythm appeared slightly blunted in the cluster headache group and was significantly phase-advanced. The plasma prolactin profile showed no significant alteration, but for plasma GH the nocturnal peak was advanced in some patients; in the absence of sleep recording, however, no conclusion could be drawn. Results from this study suggest a neuroendocrine dysregulation in cluster headache in the endogenous clock which controls the pineal rhythmicity.

Adult↗

The central projections of carotid baroreceptors and chemoreceptors in the cat: a neurophysiological study.

The medullary projections of afferent neurons with cell bodies in the petrosal ganglion have been investigated using an antidromic mapping technique. Of the ninety-three units studied, fifty-eight were shown to have patterns of discharge indicating that they were baroreceptors and thirty-five showed responses to stimuli indicating that they were arterial chemoreceptors. Twelve baroreceptor and thirteen chemoreceptor afferents had sufficiently stable unitary discharges to permit a detailed estimation of some of their central projections using stimulation through monopolar tungsten micro-electrodes to evoke antidromic spikes. In order to estimate their pattern of projection, depth-threshold contours for each penetration through the dorsomedial medulla and the values of antidromic latency were considered. Baroreceptor afferent fibres with myelinated (six units) and non-myelinated (six units) axons showed similar patterns of central projection. All could be activated from the ipsilateral nucleus of the tractus solitarius (n.t.s.), most often from its lateral divisions rostral to the obex. The dorsolateral and dorsomedial portions of the n.t.s. were most often innervated, with the commissural subnucleus receiving an innervation in seven of the twelve neurones studied. Stimulation of the ventrolateral subnucleus was effective in activating two afferent fibres whilst stimulation of the ventral subnucleus was effective in only one case. All chemoreceptor afferent fibres had calculated conduction velocities less than 4 m/s and all were activated from the dorsomedial and medial subnuclei of the ipsilateral n.t.s. In twelve of the thirteen neurones investigated in detail there was evidence of an innervation of the commissural nucleus both at the level of the obex and behind it. In three cases this extended into the contralateral portion of the commissural nucleus. In four cases a sparse innervation of the lateral subnucleus, comprising its dorsolateral aspects, was seen. The potential significance of these distinctive patterns of projection of arterial baroreceptors and chemoreceptors is discussed in relation to cardiovascular and respiratory control.

Action Potentials↗

Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat.

The respiratory modulation of the activity of vagal cardio-inhibitory neurones of the nucleus ambiguus of the cat has been investigated by electrophysiological and neuropharmacological techniques. All twenty-four vagal efferent neurones studied had axons with conduction velocities indicative of B fibres and projected to the right cardiac branches of the vagus. Their spontaneous or DL-homocysteic acid (DLH)-evoked activity showed a marked reduction during the phase of inspiration and all showed signs of receiving a baroreceptor input. Ionophoretic application of DLH always excited cardiac vagal motoneurones (c.v.m.s). Application of acetylcholine to these same cells provoked a decrease in firing rate in twelve of the fifteen neurones tested. In ten of these twelve cells simultaneous application of atropine antagonized the effect of acetylcholine. Atropine applied alone enhanced neuronal firing, particularly in inspiration. Stable intracellular recordings have been made from two c.v.m.s. These were inhibited during inspiration. Input resistance fell markedly during inspiration and injection of chloride reversed this wave of hyperpolarization to a wave of depolarization indicating that this resulted from chloride-mediated inhibitory post-synaptic potentials (i.p.s.p.s). These c.v.m.s were activated during Stage I expiration, and showed a weak and variable wave of inhibition in Stage II expiration. Pulse-rhythmic depolarizing potentials were reduced in their amplitudes during the periods of decreased neurone input resistance. It is concluded that c.v.m.s receive an excitatory input during post-inspiration and a powerful inhibitory synaptic input during inspiration. The implications of these observations for the physiology of cardiorespiratory reflexes are discussed.

Acetylcholine↗

Processing of afferent inputs in cardiovascular control.

The present report describes the use of an antidromic mapping technique to define the extent and localisation of the afferent projections of the arterial baroreceptors and chemoreceptors to the medulla oblongata. There are distinct differences in their pattern of projection: baroreceptors project primarily laterally, chemoreceptors medially, to regions which are also innervated by lung stretch afferents. Baroreceptors, however, do project to medial regions of the nucleus tractus solitarius and the significance of these patterns of projection is discussed in relation to the respiratory modifications of the performance of the baroreceptor reflex. The diencephalic control of transmission of the baroreceptor reflex is also discussed in the light of the marked innervation that the nucleus tractus solitarius receives from cell groups in the diencephalon.

Afferent Pathways↗

A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression.

The temporal organization of plasma melatonin and cortisol secretion was examined in healthy rested controls and in depressed patients: 11 patients suffering from a primary affective disorder (10 female, 1 male) and 8 male controls were studied over a 24-hr period; blood was collected at 2-hr intervals during the day at 1-hr intervals at night. Plasma melatonin and cortisol levels were determined by radioimmunoassay. In addition, melatonin was determined in plasma sampled at 3 AM in older male controls (n = 8) and in females (n = 10) at ovulation. The controls showed low or undetectable (less than 5 pg/ml) diurnal plasma melatonin levels and a very marked nocturnal rhythm (acrophase: 2.27 AM, mesor: 34.4 pg/ml, amplitude: 58.7 pg/ml). For the three control groups, no significant difference was observed in the nocturnal melatonin peak at 3 AM. The depressed patients also showed a significant melatonin rhythm but with lower amplitude (14.5 pg/ml) and mesor (19.1 pg/ml). The latter rhythm was not significantly phase-advanced with respect to the controls (acrophase at 1.18 and 2.34 AM, respectively). In 9 of the 11 patients, nocturnal melatonin secretion was less marked and frequently associated with hypercortisolemia. An additional episodic melatonin secretion was observed in the late afternoon in only two patients. In depressed patients, there was an increase in the mean cortisol secretion level (mesor at 13.6 micrograms/100 ml against 9.1 micrograms/100 ml in the controls), but the amplitude and the acrophase were not significantly modified. These data are discussed in terms of both the hypothalamus-pituitary-adrenal-epiphysis and aminergic abnormalities.

Adult↗

Role of GABA in the control of thyrotropin secretion in the rat.

Various doses of GABA from 0.25 to 5 mumol injected into the third ventricle decrease serum TSH rapidly. The same effect was observed with GABOB (10 mumol), the hydroxylated form of GABA. The inhibitory effect of both of these drugs was prevented by picrotoxin injection (1 microgram). Peripheral injection of GABAergic drugs such as GABOB or AOAA also decreased serum TSH. In vitro, the addition of GABA (from 6.7 . 10(-6) to 6.7 . 10(-4) M) to the incubation medium of hemi-anterior pituitary did not modify the liberation of TSH. To test the physiological role of GABA in the regulation of thyrotropin function the circadian TSH rhythm was used as a model. Both GABAergic inhibitors, picrotoxin (10 microgram/kg b.w.) as well as semicarbazide (150 mg/kg b.w.), induced an increase of the low basal nocturnal level of TSH (centered on the 02.00 h time point) without altering the diurnal peak of TSH. We conclude that GABA has an inhibitory effect on central thyrotropin control via an inhibition of TRH release from the hypothalamus and might be, at least partly, responsible for the low nocturnal levels of serum TSH observed during the circadian physiological rhythm.

Animals↗