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Biomedical subjects

B Claustrat

Publications and source records attributed to B Claustrat.

At least 73 records · Page 4Linked to original sources

Concanavalin-A-bound and -unbound prolactin in normal and hyperprolactinaemic rats.

Concanavalin-A (Con-A)-bound and -unbound forms of prolactin were studied in female Wistar-Furth rats, both normal and with hyperprolactinaemia induced by treatment with oestrogen or a prolactinoma graft. In normal rats, Con-A-bound prolactin was the major circulating form (more than 50%) and a minor pituitary component (less than 10%), essentially as 25 kDa prolactin. In oestrogen-treated rats, plasma prolactin levels were 100-fold higher and pituitary weight was fivefold higher than in the controls, but total pituitary prolactin content was unmodified. Under oestrogen, Con-A-bound prolactin represented about one-third of the total hormone levels in the plasma and less than 10% in the pituitary. In the pituitary, bound prolactin was found essentially as 25 kDa and unbound prolactin as 22, 30 and 40-45 kDa. A similar increase in plasma prolactin levels was induced 6 months after the graft of a prolactinoma. Pituitary weights and total pituitary prolactin contents were slightly decreased. Plasma and pituitary Con-A-bound prolactin levels were similar to those observed in oestrogen-treated rats. On the other hand, unbound prolactin was only present as a 22 kDa monomer. In the tumour, Con-A-bound prolactin (essentially as 25 kDa prolactin) represented one-third of the total hormone level and unbound prolactin was composed of the 22 and 45 kDa forms, this latter form being partially transformed into 22 kDa by heating.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PET and plasma pharmacokinetic studies after bolus intravenous administration of [11C]melatonin in humans.

A human PET study was performed with carbon-11 labelled melatonin in a healthy volunteer. Plasma pharmacokinetics of melatonin and 6-sulfatoxymelatonin were simultaneously determined using radioimmunoassay. Analysis of tracer kinetics showed maximum activity in the brain 8.5 min following injection, which was different from the curve observed for the plasma radioactivity (maximum at 3.5 min). The results confirmed that melatonin readily crosses the blood-brain barrier and that 6-sulfatoxymelatonin is the main plasma metabolite. The distribution of tracer as a function of time in this study failed to reveal any specific binding.

Adult↗

Direct radioimmunoassay of 6-sulfatoxymelatonin in plasma with use of an iodinated tracer.

We describe here a direct a radioimmunoassay (RIA) for the determination of 6-sulfatoxymelatonin (aMT6s) in plasma, with iodinated aMT6s as tracer. The aMT6s antiserum was raised in rabbit by immunization with a bovine serum albumin conjugate, giving negligible cross-reactivities for related compounds. The low limit of detection (15 pmol/L) allowed a direct assay that required only a 100-microL plasma sample. Dilutions of plasma and of synthetic aMT6s gave the same parallel response in the RIA. A preliminary study showed a circadian variation in healthy volunteers, with mean concentrations ranging from 52 (at 1600-2100 h) to 378 pmol/L (at 0400 h), whereas this rhythm was abolished in pinealomectomized patients. After administration of melatonin orally, or by infusion, the aMT6s concentrations in plasma concorded with previous data on aMT6s production and pharmacokinetics, with aMT6s being cleared from plasma more slowly than melatonin. This assay should have practical application in the development of new pharmaceutical formulations that minimize the hepatic metabolism of melatonin.

Adult↗

Spontaneous prolactin transplantable tumor in the Wistar/Furth rat (SMtTW): a new animal model of human prolactinoma.

Two spontaneous prolactinomas, removed from 28-mo-old female Wistar/Furth rats, were grafted by serial passages under the kidney capsule and the skin in 117 females of the same consanguineous strain. The hosts, aged between 2 and 10 mo, were free of estrogen treatment. These transplantable tumors, named SMtTW1 and SMtTW2, were studied until the fifth serial passage. The percentage of success was 100% under the kidney capsule and 20% under the skin. From the radioimmunoassays of prolactin (PRL), growth hormone, and adrenocorticotropic hormone and the immunocytochemical results, the tumors secrete PRL only. The PRL tumoral secretion was detected after 3 to 5 mo of graft; at 8 mo, mean plasma PRL values reached 5150 ng/ml (normal value, 15.2 ng/ml). Plasma growth hormone and adrenocorticotropic hormone values remained normal. Like the primary tumors, the grafted tumors were benign, grew slowly, and were sparsely granulated well-differentiated prolactinomas with exocytosis. They remained identical during the first serial passages. The secretion and the growth of SMtTW2 were inhibited by bromocriptine. In the light of our knowledge of the human prolactinoma, the spontaneous transplantable prolactinoma of the rat may be considered to be an animal model closer to the human pathology than the estrogen-induced "tumors" and the induced transplantable tumors. It is easier to use than the spontaneous prolactinoma of the rat.

Animals↗

Brain autoradiographic study in the golden hamster after intracarotid injection of [14C]melatonin.

The distribution of [14C]melatonin [( 14C]MT) after systemic injection was studied in the plasma and brain of golden hamsters. Thin-layer chromatographic analysis indicated that the radioactivity of the biological samples taken at two different times following the injection of label was exclusively associated with [14C]MT. Representative autoradiograms revealed a heterogeneous localization of [14C]MT in the grey matter. Two min after injection, the highest regional values were found in the hippocampus, caudate-putamen, medial thalamus and choroid plexuses. Lower radioactive concentrations were observed in the cingulate and frontoparietal cortex, anterior thalamus, inferior colliculus, dorsolateral geniculate nucleus, lateral and medial hypothalamus and amygdala. Fifteen min after injection, a significant level of radioactivity remained in the hippocampus, caudate-putamen, ventral thalamus and hypothalamus area. The heterogeneous distribution and the partial retention of [14C]MT in the brain are compatible with the existence of specific brain binding sites for this hormone.

Animals↗

Pharmacokinetics of melatonin in man after intravenous infusion and bolus injection.

The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished was investigated after the i.v. infusion--once during the night and once during the day. The clearance of melatonin from blood showed a biexponential decay. The pharmacokinetic parameters in the two studies were similar, except for the disappearance rate constant beta and the apparent volume of distribution at steady-state (Vss). Supplementary peaks or troughs were superimposed on the plateau and the falling part of the profile. They were not due to stimulation of endogenous secretion, because they were also seen in the pinealomectomized patient. During the melatonin infusion, the plasma hormone level reached a steady-state after 60 and 120 min, and when it was equal to the nocturnal level. The infusion regime may be valuable in replacing blunted hormonal secretion in disease states.

Adult↗

A graphical and statistical method for investigation of time series in chronobiology according to the cosinor procedure.

The mathematical and statistical analysis of biological time series is complex. In view of the necessity to deal with non equidistant data to analyse biological variables, preference is often given to the "cosinor procedure". We propose here a graphical and statistical assistance program for single or multiple cosinor procedure applicable to time series in chronobiology. This program investigates whether a cosine function or a mixture of cosine functions describe the experimental data adequately. The computer program is illustrated on data which have been published in a preceding paper.

Chronobiology Phenomena↗

Effects of a new prolactin inhibitor, CV 205-502, in the treatment of human macroprolactinomas.

The effects of a new PRL inhibitor, CV 205-502 (CV), on human macroprolactinomas were studied in nine patients according to a prospective protocol. Five patients had undergone surgery leaving tumor remnants and persistent hyperprolactinemia. The four others were de novo patients, two of whom had received short term treatment with Parlodel. Plasma PRL levels ranged from 235-6050 micrograms/L before treatment. The doses of CV used in this trial ranged from 0.075-0.600 mg. Plasma PRL normalized in eight of the nine patients during treatment with CV. The time to normalize varied from 2 weeks to 9 months, and the doses from 0.075-0.450 mg. A tumor volume reduction of more than 50% was obtained in all four patients who had not been operated on before CV treatment. Only one of the five patients with postoperative tumor remnants had no reduction in tumor size. The drug was generally well tolerated, and no patient interrupted the treatment. Slight and short-lasting gastrointestinal symptoms were noted in several patients, and a single episode of fainting occurred in one patient when the drug was not taken at bedtime as instructed. A noticeable and persistent weight loss with anorexia was noted in two patients. Since CV 205-502, administered in a single daily dose, has tolerable side-effects and is effective in reducing PRL secretion and tumor size, it can be considered to be a useful treatment for macroprolactinomas.

Adult↗

[Normal and tumorous human gonadotropic cells].

Gonadotropic cells are scattered in the anterior and tuberal lobes and make up 10 to 20% of the anterior pituitary cells. Having a morphofunctional plasticity, they secrete FSH and LH, most often simultaneously. These hormones are stored together in the granulations. In addition, under the action of regulating factors, especially GnRH, the cells can secrete one hormone or the other, or even the alpha subunit. Gonadotropic adenomas range third in frequency among operated pituitary adenomas (12% in our series). The diagnosis is based on the presence of at least 5% of immunoreactive cells with specific antibodies to gonadotropic hormones. These adenomas are distributed into 3 major types: FSH-LH adenoma, the most frequent one, FSH adenoma and alpha-subunit adenoma. The LH adenoma and the beta FSH and beta LH adenomas are very rare. Tumoral gonadotropic cells lose their morphofunctional differentiation. They also lose, to an extent varying according to the cases, their control mechanisms as well as their capacity of synthesis and excretion of both subunits. The alpha subunit, the oldest one in ontogeny, remains the most often and longest-secreted substance. There is a continuum from the gonadotropic adenoma with high plasma gonadotropins levels to the non-functioning adenoma.

Adenoma↗

The effects of melatonin and pinealectomy upon local cerebral glucose utilization in awake unrestrained rats are restricted to a few specific regions.

The effects of the infusion of melatonin (MT) and/or of pinealectomy upon glucose utilization in anatomically discrete regions of the brain of freely moving rats have been studied by the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose technique. The experiments were made from 14.00 to 16.00 h, when MT is normally not secreted by the pineal gland, in order to compare the local cerebral glucose utilization (LCGU) response to MT from animals with long-term (pinealectomized) or short-term (pineal intact) absence of MT secretion. The majority of the 98 brain areas examined showed no change in LCGU after MT administration and/or pinealectomy. Pinealectomy increased the LCGU in the median mammillary nucleus only, whereas following MT administration, an increase in LCGU was observed in 3 cerebral regions of intact rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexus of the third ventricle) and in 5 cerebral regions of pinealectomized rats (paraventricular nucleus of the hypothalamus, nucleus of the solitary tract, choroid plexuses of the lateral ventricles, third and fourth ventricles). Except for the choroid plexuses of the fourth ventricle, there was no difference in LCGU response to MT between pinealectomized and intact animals. This does not favor the hypothesis of receptor supersensitivity under the conditions of this experiment. Our results suggest that the hypothalamus, nucleus of the solitary tract and choroid plexuses represent a neural substrate through which MT could influence the activity of the central nervous system when administered at a low dose under near-physiological conditions.

Animals↗

Intraoperative glucose infusion and blood lactate: endocrine and metabolic relationships during abdominal aortic surgery.

The hypothesis that increased intraoperative blood lactate depends both on intraoperative glucose supply and inadequate tissue oxygenation occurring during surgery was tested in anesthetized patients undergoing infrarenal abdominal aortic surgery. Twenty surgical patients received either Ringer's solution or 5% glucose solution for intraoperative volume loading. Arterial blood lactate, arterial glucose, hemodynamic variables, insulin, glucagon, cortisol, epinephrine, and norepinephrine were determined preoperatively and intraoperatively. There were no significant changes in hemodynamic values, glucagon, norepinephrine, and epinephrine compared with control values in both groups. Oxygen consumption decreased only during aortic clamping. Cortisol and lactate increased significantly 10 min after aortic clamping until the end in both groups. Glucose 5% solution infusion resulted in significantly greater blood lactate accumulation and significantly greater blood glucose and insulin levels, whereas there were no changes in the patients receiving Ringer's solution. From control until aortic clamping, lactate and glucose were significantly correlated with each other in both groups; after aortic clamping until the end of the procedure, the correlation remained constant in patients in the Ringer's group, whereas no relationship could be demonstrated in those in the glucose group. The authors conclude that intraoperative glucose administration increases intraoperative blood lactate and that blood lactate accumulation depends both on glucose supply and tissue oxygen deficit. Furthermore, none of the hemodynamic metabolic and endocrine factors were reliable for assessing tissue perfusion and metabolic demands during surgery.

Anesthesia, General↗

Nocturnal plasma melatonin levels in migraine: a preliminary report.

We determined by radioimmunoassay plasma melatonin levels on blood samples drawn at 11 p.m. in migraine patients and control subjects. Ninety-three cephalalgic outpatients (75 females, 18 males) were compared to a control group (24 females, 22 males) matched according to age. Patients were divided into subgroups presenting common migraine (n = 38); ophthalmic migraine (n = 12); and tension headache associated with ophthalmic or common migraine (n = 24), and associated depressive status (n = 19). Statistical analysis revealed a decrease in plasma melatonin levels for the entire migraine population, compared to the control one, and a heterogeneity in both controls and patients; this heterogeneity was found mainly in the depressive and tension headache subgroups. When the migraine population--from which the depressive patients were excluded--was divided into male and female subgroups, a decrease in plasma melatonin levels was observed only for the female subgroups. Results are discussed with reference to the role of the pineal gland in the synchronization of the organism with the environmental conditions.

Adult↗

Failure of N-(2,4-dinitrophenyl)-5-methoxytryptamine (a putative melatonin antagonist) and of N-(3,5-dinitrophenyl)-5-methoxytryptamine to prevent the effects of injections of melatonin in the late afternoon on testicular activity of the golden hamster.

Daily injections of 10 micrograms melatonin in the late afternoon into male golden hamsters kept under a long photoperiod (14 h light: 10 h darkness) and at low ambient temperature 6 +/- 1 degrees C) induced a complete gonadal atrophy after 4 weeks. When administered under the same conditions at doses of 25 micrograms, neither N-(3,5-dinitrophenyl)-5-methoxytryptamine or N-(2,4-dinitrophenyl)-5-methoxytryptamine, a putative melatonin antagonist termed ML-23 in the literature, showed any effect on testicular activity. Moreover, these two drugs were also unable to prevent melatonin-induced gonadal atrophy when injected 30 min before melatonin. The results demonstrate that in the golden hamster and in the present experimental conditions, these drugs do not have the melatonin-antagonistic properties as described in the rat.

5-Methoxytryptamine↗

Regulation of melatonin secretion in a photoreceptive pineal organ: an in vitro study in the pike.

The pineal organ (or pineal) of a teleost fish, the pike, contains typical (cone-like) and modified photoreceptor cells. Both are involved in indole metabolism, including melatonin production. How photoperiod controls melatonin biosynthesis in organs containing mainly photoreceptor cells, remains unclarified. To tackle this question we have used cultured pike pineal organs to investigate the variations in (1) the activity of the arylalkylamine-N-acetyltransferase (NAT), which is involved in the biosynthesis of melatonin, in static culture and (2) melatonin release in a perifusion system. Serum melatonin was also quantified in pike kept under a 24 hr light/dark (LD) cycle. Under LD conditions, NAT activity, melatonin release, and serum melatonin levels were high during the scotophase and low during the photophase. High-amplitude rhythms in NAT activity and melatonin release were maintained during three 24 hr cycles in constant darkness and a low-amplitude rhythm of NAT persisted in constant illumination. Midnight illumination induced a dramatic decrease of NAT activity and melatonin release. Darkness at midday did not induce a rise of the melatonin release, which occurred only at the onset of the subjective scotophase. From the present data it is strongly suggested that the pineal of the pike contains a circadian oscillator--synchronized by the photoperiod--which generates the rhythms of NAT activity and of melatonin release. Melatonin release, which reflects the rhythmic activity of NAT, might largely contribute to the melatonin circulating levels. The circadian oscillations observed under constant conditions suggest that the oscillator might behave differently in the pike, compared with intrapineal oscillators of 2 other species (lizard and chicken) under investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Melatonin production in organ cultured chicken pineal: modulation by adenosine and its analogs.

The effects of adenosine, of its non-metabolizable analogs, and of compounds related to its metabolism, were investigated in the photosensitive chicken pineal, maintained in static culture or in superfusion. Stimulation or inhibition of melatonin production was obtained, depending on the experimental conditions tested. Endogenous adenosine is involved in the regulation of the melatonin output. The effects of the nucleoside might depend on the balance between its intra- and extracellular pools; (re)uptake mechanisms are most probably involved. It is suggested that cell surface receptors mediate adenosine effects, but intracellular actions (P-site, transmethylation pathways) are not excluded. This investigation is a breakthrough in the field of pineal physiology which offers new perspectives in the study of the control of melatonin production.

2-Chloroadenosine↗

Pineal and circulating melatonin rhythms in the box turtle, Terrapene carolina triunguis: effect of photoperiod, light pulse, and environmental temperature.

Pineal and circulating melatonin concentrations have been measured throughout the 24-hr cycle in the box turtle, Terrapene carolina triunguis, under different conditions of photoperiod and temperature. An obvious effect of photoperiod on the duration of the night rise of pineal and circulating melatonin is observed; the period of elevated melatonin is 4.30 hr in long photoperiod (18L:6D) and 11.00 hr in short photoperiod (8L:16D). A single pulse of 1 hr illumination beginning 1.30 hr after the onset of darkness, in a 16L:8D cycle, has no effect on pineal or circulating melatonin levels. A clear effect of environmental temperature on the amplitude of the day-night rhythm of melatonin production is observed. A possible role of the pineal of poikilotherms in the transduction of several environmental factors, via the daily pattern of melatonin secretion, is hypothesized.

Animals↗