Assignment of islet cell antibody titres and selection of subjects for IDDM prevention trials.
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Antibody Affinity↗
Biomedical subjects
M Puig-Domingo
Publications and source records attributed to M Puig-Domingo.
Role of melatonin in health and disease.
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Adult↗
Utility of 99mTc-sestamibi scintigraphy as a first-line imaging procedure in the preoperative evaluation of hyperparathyroidism.
OBJECTIVE: The use of preoperative imaging in patients with hyperparathyroidism remains controversial. Many of the available techniques are insufficiently sensitive and specific to justify their routine use. We have evaluated the sensitivity and specificity of 99mTc-sestamibi scintigraphy in the management of patients with different forms of hyperparathyroidism. DESIGN: Preoperative imaging evaluation was carried out by scintigraphic detection of pathological parathyroid glands using 99mTc-sestamibi as a radiotracer; confirmation of scan findings was obtained surgically. PATIENTS: A group of 25 patients with primary (n = 21) or secondary (n = 4) hyperparathyroidism were studied. All were considered for surgical treatment. MEASUREMENTS: In all cases parathyroid imaging was carried out by 99mTc-sestamibi scintigraphy together with at least one other imaging technique which included CT-scan, ultrasonography, MRI or 201TI/99mTc subtraction scintigraphy. Blood tests included measurements of total calcium and PTH. RESULTS: 99mTc-sestamibi scintigraphy correctly localized 20 out of 21 adenomas, giving a sensitivity of 95.2%, markedly higher than that obtained with the other imaging techniques (ultrasonography 75%, 201TI/99mTc subtraction scintigraphy 57.1%, CT-scan 41.7% and MRI 33%). Of a total of 17 glands identified surgically as hyperplastic and confirmed by pathological examination, 99mTc-sestamibi scintigraphy showed a positive image in 10, corresponding always to the larger abnormal glands (sensitivity 58.8%, higher than that observed with the other techniques). No false positive images were obtained with 99mTc-sestamibi. All the ectopic adenomas (n = 3) were identified preoperatively, which contributed significantly to the surgical approach. CONCLUSION: In patients with hyperparathyroidism, 99mTc-sestamibi scintigraphy may be used as the single imaging technique as it shows a very high sensitivity and specificity in the preoperative localization of pathological parathyroid glands; the benefit of localizing parathyroid tissue prior to surgery in cases of ectopic adenomas clearly indicates that when an imaging procedure is required, this technique may be of great help in the management of hyperparathyroidism.
Adolescent↗
In vivo and in vitro flow cytometry comparative analysis of somatostatin-positive cells in the pineal gland of the neonatal rat.
Flow cytometry was used for comparative in vivo and in vitro analysis of cell populations staining positively for somatostatin. Experiments were carried out with pineals obtained from neonatal, 8- and 15-day-old rats. Pineal cells were obtained by dispersion with collagenase and then processed in a flow cytometer or maintained in culture for 1 or 2 weeks. Identification of somatostatin-immunopositive cell populations was performed using a polyclonal somatostatin antibody and confirmed by indirect immunostaining of cytospun smears with the avidin-biotin-peroxidase method. In vivo, the percentage of somatostatin-positive cells was 60.6 +/- 4% in neonatal pineals and declined to 22.2 +/- 11% in 15-day-old animals (p < 0.04). The density of peptide immunostaining decreased in 8-day-old animals but recovered to the neonate levels in 15 day-old animals; homogeneity in the immunopositive population increased with age. Maintenance in culture for 1 week resulted in an increase in positive somatostatin staining in animals of 8 and 15 days with no changes in neonates; however, after 2 weeks of culture, the percent of immunopositive cells decreased from 53.3 +/- 6 to 12.2 +/- 4% in the older animals and remained unchanged in neonates. We conclude that somatostatin is found in pinealocytes and shows a declining pattern during the perinatal period; this probably implies that the peptide plays a paracrine role important for cell differentiation in these young animals, since maximal cellularity and a high mitotic index occur within the first 3 days of life, and pineal cell differentiation is completed before the end of the third week of extrauterine life.
Age Factors↗
Dopaminergic resistance in a case of invasive macroprolactinoma.
Invasive prolactinoma is a relatively infrequent variety of macroprolactinoma characterized by a fast and aggressive growth, with infiltration to adjacent structures, and whose management is frequently difficult. We present the case of a fatal invasive macroprolactinoma in whom resistance to different dopaminergic drugs developed.
Combined Modality Therapy↗
Expression of somatostatin in rat pineal cells in culture.
The expression of somatostatin mRNA was investigated in rat pineal cells after 1 week in culture, using reverse transcription of mRNA into cDNA and the polymerase chain reaction. The positive expression in cultured pineal cells demonstrates the capacity of this gland to synthesize somatostatin in denervated cells. Thus, apart from the neural origin of pineal somatostatin, which has been described in detail in the bovine species, a parenchymal source is demonstrated.
Animals↗
Brief report: melatonin-related hypogonadotropic hypogonadism.
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Adult↗
Outcome and long-term effects of pregnancy in women with hyperprolactinaemia.
Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long-acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way.
Adenoma↗
Computerized tomography versus magnetic resonance imaging: a comparative study in hypothalamic-pituitary and parasellar pathology.
OBJECTIVE: We wished to analyse the relative value of computerized tomography and magnetic resonance in patients referred for evaluation of pituitary and parasellar lesions. DESIGN: We performed a separate evaluation by two independent neuroradiologists of computerized tomography and magnetic resonance images ordered numerically and anonymously, with no clinical data available. PATIENTS: We studied 40 patients submitted for hypothalamic-pituitary study; 31 were carried out preoperatively, of which histological confirmation later became available in 14. The remaining nine patients were evaluated postoperatively. MEASUREMENTS: Over 40 parameters relating to the bony margins, cavernous sinuses, carotid arteries, optic chiasm, suprasellar cisterns, pituitary, pituitary stalk and extension of the lesion were evaluated. These reports were compared with the initial ones offered when the scans were ordered, and with the final diagnosis. RESULTS: Concordance between initial computerized tomography and magnetic resonance was observed in 27 cases (67.5%); among the discordant cases computerized tomography showed the lesion in two, magnetic resonance in 10, while in the remaining case reported to harbour a microadenoma on computerized tomography the differential diagnosis between a true TSH-secreting microadenoma and pituitary resistance to thyroid hormones is still unclear. Both neuroradiologists coincided in their reports in 32 patients (80%); when the initial report was compared with those of the neuroradiologists, concordance was observed with at least one of them in 34 instances (85%). Discordant results were observed principally in microadenomas secreting ACTH or PRL and in delayed puberty. In the eight patients with Cushing's disease (histologically confirmed in six) magnetic resonance was positive in five and computerized tomography in two; the abnormal image correctly identified the side of the lesion at surgery. CONCLUSIONS: In patients referred for evaluation of Cushing's syndrome or hyperprolactinaemia (due to microadenomas) or after surgery, magnetic resonance is clearly preferable to computerized tomography. In macroadenomas both scans are equally diagnostic but magnetic resonance offers more information on pituitary morphology and neighbouring structures. Nevertheless, there are cases in which the results of computerized tomography and magnetic resonance will complement each other, since different parameters are analysed with each examination and discordant results are encountered.
Adenoma↗
Immunoreactive somatostatin diurnal rhythms in rat pineal, retina and harderian gland: effects of sex, season, continuous darkness and estrous cycle.
Diurnal profiles of the content of immunoreactive somatostatin (IRS) in the male and female rat pineal, Harderian gland and retina have been studied. Supplementary experiments have been performed to elucidate a possible effect of infradian cycles, namely estrous and seasonal cycles, and continuous dark on IRS concentration. Results demonstrate that the IRS content in the rat pineal gland, Harderian gland and retina is submitted to diurnal variations, but not under all studied conditions. A sexual dimorphism exists between male and female animals: male rats showed higher IRS content in pineal (103.8 +/- 4.7 vs 32.3 +/- 1.8 pg IRS/gland), but lower in retina (1,362.1 +/- 82.7 vs 2,176 +/- 102.2 +/- pg IRS/mg of protein) and Harderian gland (10.3 +/- 0.8 vs 30.6 +/- 3.5 pg IRS/mg of protein). Additionally, seasonal differences appeared: in male and female animals pineal IRS content was lower in spring than in November. This decrease also appeared in female retina IRS concentration. Estrous cycle did not seem to change IRS content in the three studied tissues. Finally, pineal IRS rhythm persisted after continuous dark for a week. These results demonstrate, in the rat, sexual differences in the IRS content of the various tissues studied and suggest a physiological role for somatostatin, possibly related to seasonal adaptation.
Animals↗
Episodic nyctohemeral secretion of melatonin in adult humans: lack of relation with LH pulsatile pattern.
The concentration of melatonin and LH were determined in plasma samples obtained at 10-min intervals during 4 h of darkness (00.00-04.00 h) from 4 normal women, age 23-27 years, in the early follicular phase of the menstrual cycle and in 6 normal men, age 23-31 years. Additionally, melatonin concentration was determined in samples obtained from the men at 10-min intervals for 4 h during the day (10.00-14.00 h). A pulsatile pattern of melatonin secretion was found for all the subjects during darkness. There was no significant difference between women and men as to the number of pulses (2.8 +/- 0.5 vs 5.2 +/- 1.0 per h), amplitude of pulses (51.3 +/- 28 vs 27.2 +/- 6 ng/l), concentration per 4 h (32.5 +/- 13 vs 31.0 +/- 5 ng/l), or apparent half-life of melatonin (19.3 +/- 2.3 vs 15.3 +/- 7.5 min). The mean amplitude of the melatonin pulse correlated (r = 0.863, p less than 0.001) with the mean melatonin concentration per 4 h. A pulsatile LH secretion pattern was found for the 10 subjects and did not correlate significantly with the melatonin secretion pattern. The results are consistent with an independent signal for the demonstrated nyctohemeral pulsatile melatonin and LH secretions.
Adult↗
Activation of cerebrocortical type II 5'-deiodinase activity in Syrian hamsters kept under short photoperiod and reduced ambient temperature.
Cerebrocortical type II thyroxine 5'-deiodinase (5'-D II) was studied in the Syrian hamster. Animals maintained in 14 hr light/day and 20 degrees C ambient temperature and then subjected to acute cold exposure (4 degrees C) for 4 hours did not exhibit changes in cortical 5'-D II activity. Prolonged exposure of hamsters to natural autumnal short photoperiods and reduced ambient temperatures for 8 weeks increased cortical 5'-D II activity compared to hamsters maintained inside under controlled long photoperiod (14:10 LD) and temperature (20 +/- 2 degrees C) conditions. Animal given subcutaneous implants of melatonin and exposed to the natural autumnal condition for 8 weeks exhibited a greater increase in the cortical 5'-D II activity than that in hamsters with blank pellets kept under the same conditions of reduced photoperiod and temperature. Type II 5'-deiodinase activity was not affected by treatment with 6-methoxy-2-benzoxazolinone (6-MBOA), a compound with a chemical structure related to melatonin. All animals maintained outdoors in the natural photoperiod and temperature conditions had depressed circulating thyroxine (T4) and elevated triiodothyronine (T3) concentrations; neither implants of melatonin nor 6-MBOA affected these thyroid hormone levels. It is concluded that serum T4 is depressed and cerebrocortical 5'-D II activity is stimulated despite the elevation of T3 levels in this autumnal condition. These responses, unlike classic pineal-mediated responses to environmental changes, are not blocked by subcutaneous implants of melatonin. However, chronic administration of melatonin might augment the cortical 5'-D II response to low serum T4 or some other component of the autumnal condition.
Animals↗
Regional distribution of immunoreactive somatostatin in the bovine pineal gland.
Regional distribution of immunoreactive somatostatin (IRS) and melatonin were investigated in the bovine pineal gland. The total IRS and melatonin content ranged from 0.26 to 2.28 pmol, and from 19.4 to 42.7 pmol, respectively, per bovine pineal. Reverse phase liquid chromatography of pineal extracts demonstrated that more than 90% of IRS coeluted with synthetic somatostatin-14 and somatostatin-28. While the IRS content was shown to vary considerably throughout the gland, with a constant and marked maximal concentration at the proximal end of the pineal, the maximal melatonin concentration appeared in the central part of the gland, coinciding with the total protein distribution. The existence of the highest levels of pineal IRS near the habenular commissure, where the afferent fibers of the central pinealopetal innervation enter the gland, suggests that pineal somatostatin may be, at least in part, of neural origin.
Animals↗
Enhanced circadian rhythm of melatonin in anorexia nervosa.
Plasma melatonin circadian profiles were investigated in a group of 4 patients with anorexia nervosa and 4 healthy regularly cycling women. There were no differences in the mean age of both groups, whereas the anorexia nervosa patients had lower mean body weight (37.8 +/- 2.0 vs 57.0 +/- 4.9 kg) and body mass index (13.9 +/- 1.1 vs 20.8 +/- 2.0). Samples were collected every 2 h and plasma melatonin was measured by using a RIA with an iodinated tracer. Anorexia nervosa patients exhibited higher diurnal (60.7 +/- 1.8 vs 25.4 +/- 1.72 pmol/l, P less than 0.02) and nocturnal (419.2 +/- 37.4 vs 108.0 +/- 33.6 pmol/l), P less than 0.001) mean plasma melatonin concentrations. There were no differences in the time peak for nocturnal melatonin secretion in both groups, detected at 02.00 h. In anorexia nervosa, the melatonin circadian profile paralleled that observed in the control group, indicating that the increased melatonin values for anorexia nervosa were probably due to an enhanced secretory pineal function rather than an impaired melatonin metabolism. These results suggest a participation of the pineal gland in the pathophysiology of anorexia nervosa.
Adolescent↗
Melatonin specifically stimulates type-II thyroxine 5'-deiodination in brown adipose tissue of Syrian hamsters.
The response of type-II thyroxine 5'-deiodinase (5'-DII) to melatonin treatment was studied in the Syrian hamster. Male hamsters were treated for 15 days with a s.c. pellet containing melatonin, and 5'-DII activity in brown adipose tissue, anterior pituitary gland, Harderian gland and pineal gland was measured using a radioenzymatic technique. Melatonin-treated animals exhibited enhanced 5'-DII activity restricted to brown adipose tissue; the increase was threefold above the values measured in the control group. Serum concentrations of thyroid hormones were unaffected by melatonin treatment. We conclude that the stimulatory effect of melatonin on type-II thyroxine 5'-deiodination is specifically directed to the isoenzyme located in brown adipose tissue and is not accompanied by changes in serum thyroid hormones.
Adipose Tissue, Brown↗
Differential responses of rat pineal thyroxine type II 5'-deiodinase and N-acetyltransferase activities to either light exposure, isoproterenol, phenylephrine, or propranolol.
1. Compared to pineal N-acetyl transferase (NAT) activity, which exhibited a dramatic drop following acute light exposure at night, nocturnal rat pineal thyroxine type II 5'-deiodinase (5'-D) activity was minimally influenced by the same light exposure. The injection of cycloheximide, a potent inhibitor of protein synthesis, although it did curtail the rise in NAT activity for at least 2 hr, did not elicit decreases in the activities of either 5'-D or NAT enzymes. Propranolol, a beta-adrenergic blocker, either delayed the continued nocturnal rise in 5'-D activity when injected at 0000 hr or slightly enhanced the fall in 5'-D activity when injected at 0200 hr. These results suggest that interruption of the synthesis of proteins is responsible for the slow deterioration of 5'-D activity induced by either light or propranolol. 2. The slight fall in 5'-D activity induced by light at night was prevented by isoproterenol; phenylephrine, however, did not prevent the fall and the effect of isoproterenol + phenylephrine was similar to that obtained with isoproterenol alone. On the other hand, the light-inhibited NAT activity recovered after the injection of isoproterenol; phenylephrine did not elicit any effect, but the injection of both isoproterenol and phenylephrine simultaneously caused a greater NAT response than that induced by isoproterenol alone. 3. When injected during the day, phenylephrine had no effect on either pineal 5'-D or NAT activities; however, the injection of either isoproterenol alone or isoproterenol + phenylephrine elicited 5-fold and 10-fold increases in nocturnal, light-suppressed 5'-D and NAT activities, respectively. During the day, phenylephrine did not potentiate the effects of isoproterenol on NAT activity as it did at night. When the effects of isoproterenol on the 5'-D activity were compared to rats exposed to light during the day and at night, the activity of 5'-D reached a higher level at night than during the day.
Animals↗
Melatonin and 6-methoxy-2-benzoxazolinone (6-MBOA) alter the response of the male Syrian hamster to natural photoperiod.
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Animals↗
Neither the pituitary gland nor the sympathetic nervous system is responsible for eliciting the large drop in elevated rat pineal melatonin levels due to swimming.
Since the pineal gland is an end organ of the sympathetic nervous system, stress might increase the synthesis of its hormone, melatonin. The stress of a 10 min swim, which elicits a marked rise in circulating catecholamines, causes a dramatic depression of high pineal melatonin levels at night within 15 min after swimming onset. N-acetyltransferase (NAT) activity is unaffected by the treatment at 15 or 30 min after swimming onset. Within 90 min after initiation of a 15 min swim, high nighttime pineal melatonin levels are restored while NAT values remain elevated. The swimming-induced reduction in high pineal melatonin levels is not influenced by either hypophysectomy, superior cervical ganglionectomy, prazosin (alpha 1-adrenergic receptor blocker) pretreatment, yohimbine (alpha 2-adrenergic receptor blocker) pretreatment, or reserpine (amine depletor) pretreatment. These results indicate that neither hormones secreted from the pituitary gland nor catecholamines secreted from the sympathetic nerves are involved in eliciting the dramatic reduction in elevated pineal melatonin levels in the rat.
Animals↗