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Biomedical subjects

D Esposti

Publications and source records attributed to D Esposti.

36 records · Page 2Linked to original sources

Relation between lymphocyte subpopulations and pineal function in patients with early or metastatic cancer.

It has been demonstrated that melatonin and other pineal hormones play a role in the neuroendocrine control of immunity. Anomalies of both pineal and immune functions have been reported in cancer. Pineal and lymphocyte functions, however, have never been simultaneously evaluated in oncologic patients. This preliminary study was carried out in order to analyze the melatonin-lymphocyte relationship in human neoplasms. In a first investigation, we evaluated melatonin serum levels and lymphocyte subpopulations on venous blood samples collected during the morning from 46 healthy controls and from 27 cancer patients, 13 of whom had metastases, while the other 14 were without metastases. Moreover, melatonin levels were high in 10 oncological patients and within the normal range in the other 17 cases. B lymphocyte (B), total T lymphocyte (T3), T helper/inducer (T4) and T suppressor/cytotoxic (T8) mean percentages and T4/T8 mean ratios did not significantly differ, either between patients with high and normal melatonin levels, or between metastatic and nonmetastatic cancer patients. In a second study, we evaluated the effects of a prolonged treatment with melatonin (20 mg/daily intramuscularly at 3:00 p.m. for 2 months) on 8 patients with advanced cancer, in whom conventional antitumor therapies had failed. Mean percentages of B, T3, T4, T8 lymphocytes and T4/T8 mean ratios were not significantly different before or after melatonin treatment. In only one patient did the T4/T8 ratio decrease after therapy; in this case only, a stabilization of the disease was obtained, while in all 7 other patients the neoplastic disease progressed also during melatonin treatment, even if an evident improvement of the performance status was seen as it was in most cases. These results seem to exclude that melatonin may influence lymphocyte functions in cancer. Longitudinal studies and further data, however, will be needed to clarify this question.

Adult↗

[First seconds after acute experimental ischemic: changes in isovolumic contraction and relaxation].

The purpose of this study was to answer the following questions: 1) are isovolumic contraction and relaxation affected in a different way by LAD occlusion? 2) Does proximal and distal LAD coronary occlusion induce different changes in isovolumic contraction and relaxation? In 22 pigs, LAD coronary artery was dissected free right after the first or third diagonal branch and occluded by ligation. The following variables were evaluated: left ventricular systolic and end-diastolic pressure; peak - and + dP/dt, mean arterial and pulmonary pressure. All our data were obtained in the first minute following the occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Clinical study of melatonin in untreatable advanced cancer patients.

It is known that the pineal gland has some antitumor activity. Melatonin, its most important hormone, has been shown to inhibit tumor growth in vivo and in vitro. Moreover, some investigations have demonstrated an altered melatonin secretion in cancer patients. Despite these interesting data, clinical trials have never been carried out to evaluate the effects of melatonin on human neoplasms. The aim of this study was to draw some preliminary conclusions on melatonin therapy in advanced human neoplasms. Nineteen patients suffering from advanced solid tumors, which did not respond to standard therapies, entered the study. Performance status (PS) was 20 or less in 9 cases, and more than 20 in the other 10. Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period with lower doses in patients who had a remission, a stabilization of disease or an improvement in PS. Among patients with a PS higher than 20, a partial response was achieved in one case with cancer of the pancreas; moreover, 5 of 10 had stable disease, but the other 4 cases had a progression; an evident improvement of PS was obtained in 6 of the 10 cases. In contrast, among patients with a very poor PS, 7 of 9 died within the first 2 months of therapy. This preliminary study would suggest that melatonin may be of some value in treating cancer patients in whom standard antitumor therapies have failed, particularly in improving their PS and quality of life.

Adult↗

Correlation between changes in prolactin and melatonin serum levels after radical mastectomy.

Both prolactin (PRL) and melatonin (MLT) (the most important pineal hormone) have been shown to play a role in regulating breast cancer growth. The present study was carried out to investigate the relationship between PRL and MLT secretions in human breast cancer. Twenty-four women with breast cancer, at clinical stage T1-2 N0-2 M0, were evaluated before and after radical mastectomy. As controls, 14 women who underwent surgery for reasons other than neoplastic disease were included in the study. PRL and MLT serum levels were measured by RIA before and 15 days after surgery. There were no significant differences in mean PRL serum levels between patients and controls; mean MLT serum values were significantly higher in patients than in controls. In no control subject was PRL affected by surgery. In contrast, 13/24 breast cancer women showed high PRL levels after mastectomy; the PRL rise induced by surgery was significantly higher in patients without axillary node involvement. MLT was not affected by mastectomy in 13 patients, whereas it was enhanced in 5 women and decreased in the last 6 cases. No significant correlation was seen between PRL and MLT changes induced by mastectomy. The present study shows that radical mastectomy influences PRL and MLT secretions, however, its clinical significance remains to be established.

Adult↗

Acute effects of various chemotherapeutic combinations on hypophyseal and pineal hormone secretions in cancer patients.

It is known that prolonged therapy with cytotoxic drugs may affect the endocrine system. The present study was carried out to establish whether administration of chemotherapeutic drugs acutely influences hypophyseal and pineal activities. Nineteen patients affected by solid tumors were included in the study, 5 of whom were treated with CMF, 4 with FEC, 4 with CEV, and 6 with CDDP. Cytotoxic drugs were intravenously administered. Venous blood samples were collected at zero time and at 30, 60, 120 and 180 min after drug administration. On a separate occasion, venous blood samples were drawn during a saline infusion only. In each sample FSH, LH, GH, PRL, TSH, cortisol, melatonin and beta-endorphin were determined by the RIA method. The only significant changes observed in this study were a rise in PRL and a decrease in beta-endorphin after CDDP administration. Melatonin was enhanced after CDDP and CMF, and cortisol decreased after CMF and FEC, but their variations were not statistically significant with respect to those seen during saline infusion.

Adult↗

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.

Adolescent↗

A clinical study of the pineal gland activity in oncologic patients.

It has been known for many years that the pineal gland is involved in regulating tumor growth. In order to evaluate the functional activity of the pineal gland in neoplastic diseases, melatonin serum levels and its light/dark rhythm have been determined with the RIA method in patients affected by various forms of tumor. Irrespectively of the type of the tumor and of its localization, existence of two subpopulations has been observed within the oncologic patients, the former with normal levels of melatonin, and the latter with high ones. The light/dark rhythm of melatonin was anomalous in some cases. An evident decrease of serum melatonin values was seen after chemotherapy. It might be interesting to establish whether melatonin levels may conditionate the prognosis of patients with cancer.

Adolescent↗

A clinical study on the relationship between the pineal gland and the opioid system.

Recent reports point to a link between the pineal gland and the opioid system. In order to investigate this relationship, two separate studies were performed on humans. Beta-endorphin plasma levels were determined after melatonin administration (0.2 mg/kg b.w. i.m. at 2 p.m.). Melatonin serum values were evaluated after administration of FK 33-824, a met-enkephalin analogue (0.3 mg i.v. infusion at 9 a.m.). A significant decrease of beta-endorphin plasma levels was observed 120 minutes after melatonin injection. Melatonin release was stimulated by FK 33-824, with a peak at 30 minutes. The present results provide evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland. However, further studies will be required to clarify the relationship between the opioid system and the pineal gland.

Adolescent↗

Ceftriaxone therapy in otolaryngological and pulmonary infections.

The efficacy of ceftriaxone, 1 g given intramuscularly once daily, was evaluated in 38 patients with pneumonia (n = 11), pulmonary empyema (n = 2), bronchitis (n = 4), tonsillitis (n = 9), sinusitis (n = 7), and otitis (n = 5). Causative organisms were Streptococcus pneumoniae (n = 11), viridans type streptococcus (n = 1), Haemophilus influenzae (n = 6), group A streptococcus (n = 10), Staphylococcus aureus (n = 3), Klebsiella pneumoniae (n = 2), Pseudomonas aeruginosa (n = 1), Escherichia coli (n = 2), Proteus mirabilis (n = 1), and Proteus vulgaris (n = 1). Sterilization of infected foci was obtained in 89.4% of those treated, with clinical recovery in 86.8%. The ceftriaxone regimen was well tolerated.

Adolescent↗

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)

Adolescent↗

Effects of cephacetrile on reproduction cycle.

The research of possible effects of cephacetrile (Celospor) on the reproductive function was carried out on two animal species, rats and rabbits. The animals were divided into experimental groups, each treated subcutaneously with different amounts of cephacetrile (50, 100 and 500 mg/kg/die), control group receiving physiological solution. Effects of the preparation on fertility and post-natal growth in rats were analyzed, and trials were performed to test perinatal toxicity and teratogenesis in rabbits. From the observation of the experimental data collected it can be assumed that cephacetrile, administered subcutaneously in the given doses--1, 2 and 10 times, respectively, higher than the maximum therapeutic dose advisable--does not alter fertility, gestation and post-natal development of term foetuses of rats and fertility and gestation of rabbits.

Animals↗

Differentiated distribution of norfloxacin in the medullary-cortical part of the kidney in man.

Norfloxacin administered orally in a single dose of 400 mg, rapidly reaches high levels in the renal tissues, and provides an effective therapeutic action against sensitive pathogen germs. Twelve hours after administration, the drug is still detectable in the renal tissue; particularly, it was evidenced a positive tropism in the medullary part of renal parenchyma, where they were found norfloxacin levels far higher than those of cortical parts.

Female↗

A horseradish peroxidase study of afferent projections to nucleus reticularis thalami in the cat.

Afferent projections from both the reticular formation and the thalamic relay nuclei to nucleus reticularis thalami (R) were studied using the HRP technique. Injections were performed in different regions of the nucleus. Numerous labelled cells were found ipsilaterally in i) the lateral geniculate nucleus (GL) following HRP injections in dorsolateral regions of R and in ii) the ventrobasal complex (VB) following HRP injections in the ventral regions. No labelling of brain stem reticular structures was ever found. These results provide evidence for a direct projections from the VB and GL nuclei to R. The functional meaning of these data is discussed in relation with previous anatomical and neurophysiological findings. The hypothesis of a significant role of R in feedback circuits modulating sensory information seems to be supported.

Afferent Pathways↗

Melatonin involvement in immunity and cancer.

The most studied endocrine product of the pineal gland, melatonin, has been reported to be involved in the feedback between neuroendocrine and immune functions and to exert oncostatic action, at least in certain experimental conditions. Melatonin seems to be an integral part of the immune system, by exerting direct and/or indirect stimulatory effects on both cellular and humoral immunity. Likewise, an antitumor activity of melatonin has been shown in several experimental models in vivo and in vitro. The means by which melatonin exerts its effects on immunity and neoplastic growth have not been elucidated. The different putative mechanisms of action of melatonin investigated so far are here briefly discussed.

Adjuvants, Immunologic↗

Melatonin influences human balance.

In order to evaluate a possible correlation between melatonin, the cerebellum and, consequently, human balance, a double-blind pilot study was performed in 5 subjects with random administration of different doses of melatonin. Before and 1 h after a single administration, a complete otoneurological examination was performed. This first pilot study revealed that melatonin had effects on human equilibrium although these effects were not dosage related and were different in individual subjects. On the basis of these results, a second study was performed. Fourteen healthy volunteers were investigated before and 1 h after administration of a single dose of 10 mg melatonin. The otoneurological examination was restricted to the evaluation of: horizontal saccades, horizontal sinusoidal smooth pursuit, eyes open, eyes closed and head retroflexed static posturography. All subjects showed a decrease in posturographic performances, especially in the simplest test (eyes open) and half of them (6 out of 13) showed also impairment of eye movements. These results confirm the role of melatonin in the control of sensorimotor performances, and the cerebellar receptors might be correlated with the control of human balance.

Adult↗

Ultradian chronomodulation by melatonin of a Placebo effect upon human killer cell activity.

The effect of melatonin injection evaluated earlier with respect to placebo-treated controls is reevaluated, also with reference to spontaneous changes in natural killer cell activity. This effect consists, first, of stimulation of natural killer cell activity over and above any changes brought about by placebo (saline). After 6 h, the melatonin effect appears to be an inhibition as compared to values from placebo-treated subjects, or no effect as compared to values from untreated subjects. In this case, amplification and attenuation of the placebo effect by melatonin are found within the relatively short span of 1/4 of a day, rather than within a day or a week. An ultradian 'feed-sideward' by melatonin may be aligned with the corresponding previously reported circadian and infradian chronomodulation.

Activity Cycles↗