Morphological evaluation of the conjunctiva and the trabecular meshwork incubated with Proline-3H.

It is well known that the trabecular meshwork is a complex structure in the shape of collagen and like-elastic fibers dipped in amorfous matrix. Previous researches have been showed that in the glaucoma disease there is a sclerosis in the lamellae of the trabecular meshwork and an increase in extracellular material. In order to add informations to complex and highly organized trabecular meshwork and its role in the glaucoma disease, 12 surgical specimens of trabecular meshwork and conjunctival tissue from patients suffering from chronic simple glaucoma and undergone medical therapy have been examined. The fragments have been immediately incubated with Proline 3H for 45 minutes; after this period they have been fixed and included. The results have been showed the presence of the fibroblast cells engaged to pick up radioactive Proline. The collagen synthesis has been happened in the trabecular meshwork and in this study there is not demonstration of collagenic material coming from surrounding structures.

Parathyroid function and bone metabolism in children with beta thalassaemia major: effects of sex steroid treatment.

OBJECTIVE: Data on parathyroid function in patients with homozygous beta-thalassaemia are discordant. Moreover, there is no report on the effects of sexual steroid treatment on bone metabolism in these patients. METHODS: Serum parathyroid hormone (PTH), calcitonin (CT) and osteocalcin (GLA protein) levels were measured in 121 patients. Thirty-three prepubertal subjects were treated for six months with sexual steroids. RESULTS AND CONCLUSIONS: Primary hypoparathyroidism was present in 3.3% of the patients. Osteocalcin levels were found to be lower in thalassaemic subjects than in controls, whereas CT values were similar. No effects of sexual steroid administration on plasmatic levels of osteocalcin were observed.

[Proposal for a dynamic study of the temporo-mandibular joint, using a computerized image analyzer]. / Proposta di uno studio dinamico dell'articolazione temporo-mandibolare, mediante l'uso di un analizzatore computerizzato di immagini.

With the aim to go deep into the knowledge of the morpho-functional anatomical characteristics of the temporo-mandibular joint in humans, a dynamic method of study by means of a computerized analyzer of images is suggested. The acquired advantages are the following: a) the accuracy of evaluation of the chosen morphometric parameters; b) the working speed, from which results: c) the possibility to increase adequately the number of cases and d) the possibility to easily investigate many parameters with a very high accuracy of the quantitative results. Both right and left temporo-mandibular joints of adult individuals aged from 18 to 53 have been studied utilizing lateral tomographies focused at 3.3 mm to the lateral surface of the condylar head. The evaluations were done both in the position of completely closed mouth and in extreme opening. From the barycentre of the condyle several straight lines were drawn according to the figure 2. The length of the segment a-b (distance of profiles of the condyle and mandibular fossa) were evaluated in all the lines counter-clockwise and the results submitted to a statistical analysis. The results furnish very good information on the normal or pathological anatomical characteristics, of the joint.

Interaction between morphine, an opioid agonist, and clonidine, an alpha-adrenergic agonist, on the regulation of anterior pituitary hormone secretion in normal male subjects.

In order to investigate the possible interaction between opioid system and noradrenergic system in the regulation of pituitary hormone secretion, the effects of morphine (an opioid agonist, 10 mg i. v.), clonidine (an alpha-adrenergic agonist, infusion of 0.3 mg in 15 minutes) and clonidine + morphine (infusion of the same dose of clonidine beginning 30 minutes before morphine 10 mg i.v.) on anterior pituitary hormone secretion were studied in six normal male volunteers. Morphine alone induced both an increase in TSH and PRL serum levels and a decrease in cortisol serum levels with no changes in GH serum levels. On the contrary clonidine was able to increase GH and TSH levels and to decrease cortisol levels; PRL secretion was not affected. As regards interaction between morphine and clonidine we observed that morphine-induced increase in PRL release was potentiated by clonidine pretreatment; as regards TSH secretion its increase was greater after the administration of the two drugs with respect to the effect of the single drugs. This study, in agreement with our previous data concerning LH secretion, confirms the important link between clonidine and opioid system in neuroendocrine function, too; the possible explanations of our data are discussed.

Evaluation of the effects induced by four opiate drugs, with different affinities to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and on cortisol secretion in normal men.

In order to ascertain the subtype(s) of opioid receptors involved in the control of pituitary function the effects of four different opiate drugs (morphine, pentazocine, nalorphine and buprenorphine) were studied in four groups of six normal male volunteers. Each of the drugs tested induced, with varying degrees, both a significant increase in PRL and a significant decrease in LH and cortisol. On the contrary TSH secretion was stimulated by buprenorphine and morphine only and GH by nalorphine only. FSH did not change significantly after administration of any drug. Taking into account the different affinities of the drugs used by us for the different opioid receptors, our data do not allow to demonstrate a well-defined correlation between subtypes of opioid receptors and the control of pituitary hormone secretion. The possible explanations of this fact are discussed.

Morphine-induced TSH release in normal and hypothyroid subjects.

The effects of morphine (10 mg i.v.), an opioid agonist, and of naloxone (10 mg i.v.), an opioid antagonist, on serum levels of TSH and PRL were studied in 7 hypothyroid patients and in 5 normal volunteers. Morphine administration induced a prompt, significant increase in serum TSH and PRL in all subjects. The degree of PRL release after morphine was similar in the two groups, while, as regards TSH, the increase was more evident in hypothyroid subjects. Pretreatment with naloxone (4 mg i.v. 5 min before morphine administration) blocked these effects in all subjects. In contrast, naloxone alone was not able to affect significantly TSH and PRL secretion. Moreover, in 5 other euthyroid volunteers, morphine significantly enhanced the response of TSH and PRL to TRH stimulation (200 micrograms i.v.). These data demonstrate that morphine exerts a stimulatory action on TSH and PRL secretion: the possible mode of action of this drug and the physiologic significance of these findings are discussed.

On the role of dopamine receptors in the naloxone-induced hormonal changes in man.

To assess the role of dopamine receptors in naloxone-induced hormonal changes, the effects of dopamine and metoclopramide on anterior pituitary hormone secretion were studied during the infusion of the opiate blocker in normal men. Naloxone stimulated LH and cortisol secretion in all subjects, whereas FSH, TSH, PRL, and GH did not change. The infusion of dopamine completely suppressed the naloxone-induced LH rise; on the contrary, metoclopramide failed to alter the magnitude of the increments in LH observed during the infusion of the opiate blocker. The cortisol response to naloxone remained unchanged during dopamine and metoclopramide infusion. Metoclopramide stimulated PRL and TSH release during naloxone treatment, whereas dopamine suppressed PRL and TSH secretion. The data do not suggest a participation of dopamine receptors in the naloxone-induced hormonal changes in man and confirm a suppressive effect of dopamine infusion on LH release in humans.

Muscarinic receptor blockade by pirenzepine: effect on prolactin secretion in man.

The effect of pirenzepine, a muscarinic receptor blocker which does not cross the blood brain barrier, on basal and TRH-stimulated prolactin (PRL) secretion in normal subjects was studied. Administration of 75 mg oral pirenzepine had no effects on prolactin levels in male subjects whereas it significantly reduced prolactin in females. No effect on TRH induced prolactin secretion was observed.

Effects of the H2 receptor antagonist ranitidine on anterior pituitary hormone secretion in man.

The effect of an i.v. bolus of the H2-receptor antagonist ranitidine 50, 100, 200 and 300 mg on serum levels of prolactin, TSH, GH, LH, FSH and cortisol was studied in 12 normal males. Ranitidine 200 and 300 mg significantly stimulated prolactin release without affecting any of the other hormones. Ranitidine 300 mg caused a rise in prolactin comparable to that observed following cimetidine 200 mg. The results show that ranitidine releases prolactin in man, but only when a large intravenous injection is given.

On the role of dopamine receptors in the central regulation of human TSH.

The effects of acute administration of haloperidol (4 mg im) and pimozide (4 mg orally) on TSH and Prl secretion were studied in normal and hypothyroid man. The TRH-induced TSH secretion before and after pre-medication with pimozide and domperidone, a peripheral dopamine (DA) blocker, was also evaluated in a group of normal subjects. Haloperidol and pimozide induced a marked increment in serum Prl; mean Prl levels were still significantly elevated 12 h following pimozide administration. A small but significant TSH increase was observed following haloperidol and pimozide in normal as well as hypothyroid subjects. Both domperidone and pimozide significantly enhanced TRH-induced TSH release. In another experiment 3 women with primary thyroid failure received an infusion of DA (4 micrograms/kg/min for 4 h) with and without domperidone administration. TSH and Prl levels were suppressed by DA, but the effect was completely abolished by domperidone. The results suggest that psychotrophic drugs, such as haloperidol and pimozide, can, like substituted benzamides, stimulate TSH release in man. Since domperidone and DA do not cross the blood-brain-barrier and domperidone significantly enhanced the TSH response to TRH, the data also support the hypothesis that human TSH is regulated by DA at the hypothalamus (median eminence) and/or pituitary level.

Opiate receptors and anterior pituitary hormone secretion in man. Effect of naloxone infusion.

The role of endogenous opioid receptors on anterior pituitary hormone secretion was evaluated by the administration of the opioid receptor antagonist naloxone. The infusion of naloxone (8 mg iv followed by 4mg/h for 3 h) did not alter basal growth hormone (GH), prolactin (Prl) and thyrotrophin (TSH) secretion but produced a significant rise in cortisol and gonadotrophins in normal man. The infusion of the opiate antagonist appeared to increase the rate and amplitude of luteinizing hormone (LH) pulsatility. Naloxone pre-medication (10 mg iv 30 min before testing) did not alter the pituitary response to TRH and LRH stimulation. These results demonstrate that naloxone can modify basal anterior pituitary hormone secretion and strongly suggest an endogenous opioid modulation of some of these hormones.

Effects of a Met-enkephalin analogue and naloxone infusion on anterior pituitary hormone secretion in acromegaly.

The effect of a long-acting analogue of Met-enkephalin (Damme) and naloxone on anterior pituitary hormone secretion has been investigated in 14 acromegalic patients. Damme produced a progressive fall in circulating LH and cortisol and stimulated prolactin release in normoprolactinaemic patients. Naloxone infusion significantly stimulated gonadotrophin and cortisol secretion without modifying basal prolactin release both in normo-and hyperprolactinamic patients. GH levels remained unchanged during naloxone and Damme infusion. The data suggest that endogenous opiate receptors do not play a major role in modulating GH hypersecretion in acromegaly.

Pituitary hormone secretion after inhibition of L-aromatic amino acid decarboxylase activity in man.

The effect of acute administration of 200 mg benserazide, an L-aromatic amino acid decarboxylase inhibitor, on pituitary hormone secretion in humans was studied. Benserazide induced in all subjects a quick and marked increment of serum prolactin (Prl) and TSH levels: at 180 min TSH and Prl levels were still significantly higher than the baseline values. Women with normal menstrual cycles showed a Prl response to benserazide which was significantly greater than that observed in post-menopausal women and men. In another experiment six normal men received 10 mg of domperidone, a peripheral dopamine receptor blocker. The hormonal changes induced by domperidone were comparable to those obtained with benserazide. Since domperidone and benserazide are thought not to cross the blood-brain barrier, these results suggest that dopamine regulates Prl and TSH secretion through extra blood-brain barrier structures.

Dopamine inhibits the naloxone induced gonadotrophin rise in man.

Twenty milligrams of the opiate receptor antagonist naloxone were infused over 3 h to five young male volunteers. Naloxone produced a significant rise in both LH and FSH, but did not affect serum prolactin levels. The infusion of dopamine (4 microgram . kg-1 . min-1) completely abolished the naloxone effect on gonadotrophin release. The results suggest a possible interaction between dopamine, opioid receptors and gonadotrophin secretion in man.

Domperidone, an extracerebral inhibitor of dopamine receptors, stimulates thyrotropin and prolactin release in man.

Domperidone, an extracerebral dopamine receptor antagonist, was given im to 12 normal subjects and to a group of patients with subclinical hypothyroidism to study its effect on PRL and TSH secretion. Domperidone induced in all subjects a quick and marked increment of serum PRL. At 180 min, the levels remained high. A small but significant increase of TSH was also observed in normal as well as in hypothyroid subjects. Since domperidone does not cross the blood-brain barrier, the hormonal changes observed may be mediated through the pituitary and median eminence, tissues which lie outside of the blood-brain barrier.

Inhibition of prolactin secretion by nomifensine in man.

Serum prolactin, TSH and GH levels were measured in thirty healthy volunteers in fasting conditions and following oral administration of 200 mg nomifensine. In addition, the effect of the drug on serum prolactin and TSH response to synthetic TRH was studied in twenty normal subjects. Inhibition of endogenous catecholamine reuptake by nomifensine significantly inhibited prolactin release whereas it had no effect on TSH and GH levels. Nomifensine administration had no appreciable effect on the TRH-induced release of TSH and prolactin.

TSH and prolactin stimulation by the decarboxylase inhibitor benserazide in primary hypothyroidism.

200 mg of the 4-aromatic amino acid decarboxylase inhibitor benserazide were administered orally to five patients with primary hypothyroidism. Benserazide induced a significant increase in prolactin and TSH plasma concentration in all subjects. Since the drug blocks the conversion of DOPA to dopamine, these hormonal changes may be due to a reduction in circulating and/or median eminence levels of dopamine.

Enhancement of insulin-induced prolactin secretion by fluoxetine in man.

Fluoxetine hydrochloride, a specific inhibitor of serotonin reuptake, was given orally to five adult males to study its effect on fasting and insulin-stimulated release of PRL. A 3-day course of fluoxetine (30 mg daily) had no demonstrable effect on fasting PRL levels. Fluoxetine significantly enhanced insulin-induced PRL release. These data suggest that serotoninergic pathways have little or no part in the control of spontaneous PRL secretion in man, whereas they may play a role in insulin-stimulated PRL release.

Effects of long-term treatment with metergoline in patients with idiopathic oligospermia.

The effect of metergoline, an ergoline derivative with antiserotonin as well as dopaminergic properties, was studied in forty-five male patients with idiopathic oligospermia. Metergoline treatment (6 mg daily for 5 months) had no demonstrable effect on spermatogenesis; moreover, it did not influence the serum levels of LH, FSH, testosterone and oestradiol although it significantly reduced prolactin levels. It is concluded that, in all likelihood, serotonin plays little or no part in the pathogenesis of idiopathic oligospermia and that pharmacological reduction of normal prolactin levels has no therapeutic effect on this disease.