The pineal hormone melatonin in hematology and its potential efficacy in the treatment of thrombocytopenia.

Recent experimental studies suggested that hematopoietic cell proliferation and differentiation are under a neuroendocrine control and that they change in relation to the 24-hour period. Moreover, it has been shown that the pineal hormone melatonin (MLT) plays a role in mediating the influence of the psychoendocrine system and of the lighting conditions on the hematopoiesis. Finally, MLT has appeared to regulate hematopoietic cell growth by influencing apoptosis-related mechanisms. In particular, preliminary studies have shown that the pineal hormone MLT may determine some benefits in blood cell disorders, mainly platelet diseases. On this basis, a pilot phase II study of MLT therapy was performed in patients suffering from persistent thrombocytopenia due to different causes. The study included 14 patients, and thrombocytopenia was due to bone metastatic involvement in 5, hypersplenism in 3, myelodysplastic syndrome in 3, DIC in 1, genetic factors in 1, and Werlhof's disease in the last case. MLT was given orally at 20 mg/day in the evening for 2 months. No MLT-related toxicity occurred. A normalization of platelet number was achieved in 8/14 (57%), and platelet mean number significantly increased on MLT therapy. This preliminary study would suggest that MLT may be effective in the treatment of thrombocytopenia due to different reasons, for which no effective standard therapy is available.

The clinical significance of melatonin serum determination in oncological patients and its correlations with GH and PRL blood levels.

In order to investigate the pineal function and its relation with the hypophysis in human neoplasms, melatonin and GH serum levels were determined in 63 patients, 42 affected by solid tumours and 21 by lymphoma or leukaemia. In women with breast cancer PRL was also measured. Melatonin, GH and PRL were evaluated in 52 healthy subjects acting as controls. The oncological patients showed significantly higher mean melatonin serum levels than the control subjects. Mean melatonin values were lower in patients with solid tumours who had metastases, than in cases without metastases. Chemotherapy caused an evident decrease in melatonin levels. Surgery was followed by a fall in melatonin in patients without metastases. Mean GH serum levels observed in oncological patients were similar to those in control subjects and were not influenced by therapy. PRL levels were within the normal range in women suffering from breast cancer.

Effect of an acute injection of melatonin on the basal secretion of hypophyseal hormones in prepubertal and pubertal healthy subjects.

It is well known that the pineal gland can modulate the secretion of pituitary hormones. Melatonin, the main hormone produced by the pineal gland, acts at the hypothalamic site, whereas hypophyseal sensitivity to melatonin seems to change with age. To investigate the influence of pubertal development on the role of the pineal gland in the regulation of the secretion of pituitary hormones, FSH, LH, Prl, TSH and GH responses to melatonin were evaluated in a group of 9 prepubertal and 10 pubertal healthy subjects of both sexes. Melatonin was given im at a dose of 0.2 mg/kg body weight at 3 p.m. Venous blood samples were drawn -20, 0, 20, 40, 60, 90, 120, 180 and 240 min, after melatonin injection. According to the same experimental protocol, venous blood samples were collected during a saline infusion on a separate occasion. FSH, LH, Prl, TSH and GH plasma levels were measured with RIA. In pubertal subjects, a significant rise in the mean Prl levels was seen 90 min after melatonin as compared with those during saline infusion. The Prl melatonin response area was significantly lower in prepubertal treated subjects and significantly higher in pubertal ones compared with the respective controls. The mean GH values showed a significant decrease 120 min after melatonin only in prepubertal subjects; no significant variations were seen in 8 of 10 pubertal subjects, whereas in the last 2 a marked increase was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of melatonin on PRL secretion during different photoperiods of the day in prepubertal and pubertal healthy subjects.

The effect of melatonin on PRL secretion has not been established yet. In an attempt to establish whether PRL response to melatonin changes in relation to the photoperiods of the day and pubertal maturation, we evaluated PRL plasma levels after melatonin administration in 19 prepubertal and pubertal healthy subjects of both sexes in two different periods of the day: in the morning, when the sensitivity to melatonin is low, and in the afternoon, when the responsiveness to melatonin is higher. Melatonin was given im at a dose of 0.2 mg/kg BW PRL plasma levels were determined with double antibody RIA method. When melatonin was administered in the morning, all pubertal subjects and 7 of 9 prepubertal ones showed no significant variation of PRL levels; a significant decrease was observed in the other 2 prepubertal subjects. On the contrary, when melatonin was given in the afternoon, a significant increase in PRL plasma levels was seen in all pubertal subjects; no significant changes were found in 6 prepubertal ones, while in the other 3 a marked decrease could be observed. The results reveal that the response of PRL to melatonin depends upon the times of day of administration and on pubertal development.

[Effect of the simultaneous action of melatonin and ADP in megakaryocytes in vitro. -IV-]. / Effetti dell'azione simultanea della melatonina (MLT) e dell'ADP sui megacariociti in vitro. -IV-.

Simultaneous addition of ADP plus Melatonin induces apparent emission of platelets by rat's megacariocyte in vitro.

[Determination of taste threshold]. / Sulla determinazione della soglia gustativa.

A linear inverse relation links the HCl solution molarity to both the absolute HCl solution intake, and the ratio of the HCl solution to the total fluid intake. The last algebraic relation allows the taste threshold to be estimated.

[Peripheral and central factors which modify the taste threshold]. / Fattori periferici e centrali atti a modificare la soglia gustativa.

Several anatomical, physiological and behavioral factors have part in changing the values of the detection threshold, among which the reflexly secreted oral fluid. The HCl molar concentration appears to be a hyperbolic function of preference (= taste solution/water ratio); the empirical formula of the function makes the HCl molar concentration to be known, at which the same voll. of water and taste solution are drunk, i.e. the taste threshold.

[The action of melatonin (MLT) on platelet metabolism in vitro.-II-]. / Azione della melatonina (MLT) sulla piastrinogenesi in vitro.-II-.

Melatonin induces an apparent platelets emission by rat's megakaryocytes in vitro.

[The effect of ADP on platelet metabolism in vitro.-III-]. / Azione dell'ADP sulla piastrinogenesi in vitro.-III-.

ADP induces an apparent platelets protrusion by rat's megakaryocytes in vitro.

[In vitro studies on megakaryocytes.-I-]. / Contributo alle tecniche di studio in vitro dei megacariociti.-I-.

Normal rat's recent bone marrow has been suspended in an isoionic, oxygenated, warmed solution; platelets production by megakaryocytes has never been verified.