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Journal Article 2002; 23(Suppl 1): 118-121 PubMed PMID: 12019364 Citation  Keywords:  Animals, Free Radical Scavengers, Humans, Melatonin:adverse effects, Sleep Wake Disorders:drug therapy,.   

: Report of the round table conference summarizing the International Symposium on "Melatonin: Clinical Significance and Therapeutic Applications" is presented in this article. Some sleep disorders and circadian rhythm disturbances are the widely accepted indications for melatonin treatment. However, other possibilities for use of melatonin in the therapy should be also taken into account, including a co-treatment in cancer patients and free radical-related diseases. All aspects of the possible therapeutic use of melatonin as well as its safety, dosage, side effects and contraindications are discussed herein based on the round table conference and they are presented in this paper....

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Journal Article 2002; 23(Suppl 1): 111-117 PubMed PMID: 12019363 Citation  Keywords:  Adrenergic Fibers:metabolism, Adrenergic alpha-2 Receptor Agonists, Adrenergic alpha-2 Receptor Antagonists, Adrenergic alpha-Agonists:pharmacology, Adrenergic alpha-Antagonists:pharmacology, Animals, Female, Homeostasis, In Vitro Techniques, Norepinephri.   

BACKGROUND: Norepinephrine is the main neurotransmitter controlling melatonin secretion in the mammalian pineal gland. Presynaptic autoregulation of norepinephrine release from the sympathetic nerve fibers in the pineal gland is poorly known.

METHODS: Uptake and depolarization-evoked release of (3)H-norepinephrine were investigated in vitro using pieces of the pig pineals. Specific antagonists and agonists of alpha(2)-adrenoceptors were employed for the characterization of alpha(2)-adrenoceptors involved in the autoregulation of depolarization-evoked release of norepinephrine in the pig pineal.

RESULTS: The level of neuronal uptake of norepinephrine in the pig pineal was 3.5+/-0.9 pmol/h/mg of wet tissue and represented about 77% of the total tissue radioactivity. Potassium ions at concentration of 60 mM significantly evoked tritium release. This effect was abolished in the absence of extracellular Ca(2+) and was diminished in the presence of Cd(2+). Antagonists of alpha(2)-adrenoceptors increased depolarization evoked tritium release. The order of its potency (based on pED(30)) was rauwolscine > phentolamine > BRL 44408 > WB 4101> RS 79948 = yohimbine > prazosin > imiloxan. alpha(2)-agonists decreased K(+) evoked release of tritium with the order of potency: UK14,304 > norepinephrine = guanfacine > oxymetazoline.

CONCLUSION: The processes of neuronal uptake and depolarization-evoked release of norepinephrine from the sympathetic nerve endings in the pig pineal gland have been demonstrated. The studies with the use of adrenergic antagonists and agonists indicate that the sympathetic nerve fibers in the pig pineal gland possess functional presynaptic alpha(2)-adrenoceptors, which are involved in norepinephrine release inhibition. Due to the pharmacological properties these receptors closely resemble the subtype alpha(2A)....

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Journal Article 2002; 23(Suppl 1): 104-109 PubMed PMID: 12019362 Citation  Keywords:  Alkaline Phosphatase:metabolism, Animals, Biomarkers, Bone and Bones:metabolism, Collagen:metabolism, Female, Melatonin:pharmacology, Osteoporosis:metabolism, Ovariectomy, Pineal Gland:physiology, Rats, Rats, Wistar,.   

BACKGROUND AND OBJECTIVES: There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.

METHODS: The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).

RESULTS: The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.

CONCLUSION: Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy....

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Clinical Trial 2002; 23(Suppl 1): 97-102 PubMed PMID: 12019361 Citation  Keywords:  Adult, Blood Pressure:physiology, Circadian Rhythm:physiology, Creatinine:urine, Disease Progression, Female, Humans, Kidney Failure, Chronic:blood, Male, Melatonin:blood, Middle Aged, Urea:metabolism,.   

OBJECTIVES: In spite of broad interest, intensive studies on function of melatonin have not yielded much information about relationships between this hormone and kidneys in health, and particularity, in disease. Very little is known about the circadian plasma melatonin concentrations in patients with chronic renal failure (CRF). There are only a few studies dealing with melatonin concentrations in renal diseases, mainly performed in hemodialyzed patients with end-stage renal disease (ESRD). Moreover, the most melatonin assays were performed during the daytime, and the results are conflicting. Therefore, the aim of the present study was to determine the circadian melatonin profiles in patients with different stages of CRF.

MATERIAL AND METHODS: Twenty four patients (13 males and 11 females) with CRF aged 35 to 58 years (mean+/-SEM: 47.0+/-1.6 years) were included in the study. Patients were divided into two groups: group 1 -- patients with compensated CRF (serum creatinine: 2.0-5.0 mg/dL), group 2 -- patients with ESRD (serum creatinine: > 8,0 mg/dL). The control group consisted of 20 healthy volunteers (10 males and 10 females) aged 35 to 55 years (mean+/-SEM: 46.0+/-1.5 years) checked not to have renal failure [serum creatinine: 0.8-1.4 mg/dL], and matched according to sex and age. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, and 08:00 h. Melatonin concentration was measured by enzyme immunoassay.

RESULTS: In both groups of patients with chronic renal failure, i.e. in patients with compensated disease and in patients with end-stage renal disease melatonin nocturnal concentrations were significantly lower then those in healthy volunteers. Moreover, in patients with compensated renal failure also day-time melatonin concentrations were significantly depressed. Area under curve was significantly lower in both groups of patients in comparison with the control group.

CONCLUSIONS: The mechanism of depressed melatonin concentrations in CRF observed in our study remains unclear. However, it seems possible that decline in melatonin levels is due to impairment in adrenergic function that occurs in CRF. Because the studies on the melatonin secretion in CRF bring about conflicting results, the relationship between renal diseases and melatonin secretion needs further investigations....

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Journal Article 2002; 23(Suppl 1): 88-91 PubMed PMID: 12019359 Citation  Keywords:  Adult, Blood Pressure:drug effects, Circadian Rhythm:physiology, Clinical Trials as Topic, Electromagnetic Fields:adverse effects, Heart Rate:drug effects, Humans, Male, Melatonin:analogs & derivatives, Telephone,.   

OBJECTIVES: It is quite likely that non-visible electromagnetic fields (EMF) may affect melatonin production. Some studies confirmed this hypothesis and showed that extremely low EMF altered pineal function in animals and humans. Thus, it is reasonable to suppose that EMF emitted by cellular phones may also influence secretion of melatonin. The present study sought to evaluate possible effect of the exposure to EMF emitted by cellular phone on 6-hydroxymelatonin sulfate (6-OHMS) excretion, which reflects melatonin levels in blood.

MATERIAL AND METHODS: The examined group consisted of 9 healthy males aged 19-29 years. The experiment was performed under controlled conditions (the light intensity-50 lx till midnight and 0 lx during night). Each person was examined twice: on a day without exposure (control day, C-day) and on a day with continuous exposure (60 min. exposure from cellular phone, frequency 900 MHz, pulsed with 217 Hz, pulse with 576 micros, SAR 1.23 W/kg, E-day). From 7 p.m. to 8 p.m. they used a cellular phone. The subjects did not know which day was E-day, and which was C-day. From 8 p.m. till midnight the subjects listened to music and than they slept till 7 a.m. next day. Urine samples were collected at 7 p.m., at midnight, and at 7 a.m. in the same way in C-day as in E-day. Sample were frozen for later ELISA analysis of 6-OHMS. The 6-OHMS ELISA kit from Immuno-Biological Laboratories (Hamburg) was used for measurement of 6-OHMS. The data were analysed using Wilcoxon matched-pairs signed-ranks test for each subject and for the whole group. We compared 6-OHMS level on the E-day and on the C-day separately for 3 time-points - 7 p.m., midnight, 7 a.m.

RESULTS: Mean 6-OHMS level in both experiments did not differ significantly for any of the respective time points. Circadian variations of 6-OHMS level were detected in all subjects.

CONCLUSIONS: The results of our investigation has demonstrated that EMF emitted by cellular phones has no distinct influence on the melatonin level....

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Journal Article 2002; 23(Suppl 1): 84-87 PubMed PMID: 12019358 Citation  Keywords:  Animals, Anticarcinogenic Agents:pharmacology, Electromagnetic Fields:adverse effects, Humans, Melatonin:pharmacology, Neoplasms:epidemiology,.   

: There is public health concern raised by epidemiological studies indicating that extremely low frequency electric and magnetic fields generated by electric power distribution systems in the environment may be hazardous. Possible carcinogenic effects of magnetic field in combination with suggested oncostatic action of melatonin lead to the hypothesis that the primary effects of electric and magnetic fields exposure is a reduction of melatonin synthesis which, in turn, may promote cancer growth. In this review the data on the influence of magnetic fields on melatonin synthesis, both in the animals and humans, are briefly presented and discussed....

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Journal Article 2002; 23(Suppl 1): 73-78 PubMed PMID: 12019356 Citation  Keywords:  Animals, Antioxidants:metabolism, Humans, Melatonin:physiology, Pineal Gland:drug effects, Thyroid Gland:growth & development, Thyroid Hormones:pharmacology,.   

: This review briefly summarizes the published data on relationships observed between melatonin - the main pineal hormone, and the thyroid gland. The prevailing part of the survey is devoted to thyroid growth processes and function. A large experimental evidence exists suggesting the inhibitory action of melatonin on thyroid growth and function; this effect has been revealed by using different experimental models: by chronic and short-term melatonin administration in vivo, by light restriction, which is known to increase the activity of the pineal gland, by pinealectomy, etc., as well as by employing the in vitro conditions. Thus, much information has been accumulated, indicating - in experimental conditions - a mutual relationship between the pineal gland and the thyroid. The confirmation of these relations in clinical studies in humans meets numerous difficulties, resulting - among others - from the fact that, nowadays, human beings, as well as certain animal species, used in experimental studies, have been living far away from their natural and original habitat. It makes almost impossible to compare the results obtained in particular studies performed in different species, on the pineal-thyroid interrelationship....

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Journal Article 2002; 23(Suppl 1): 67-72 PubMed PMID: 12019355 Citation  Keywords:  Animals, Antioxidants:pharmacology, Cell Division:drug effects, Cell Membrane:drug effects, Cells, Cultured, Chickens:physiology, Colforsin:pharmacology, Cyclic AMP:metabolism, Lymphocytes:drug effects, Male, Melatonin:pharmacology, Phytohemagglutinins:ph.   

OBJECTIVES: Time-dependent melatonin effects on chicken lymphocyte proliferation in vitro and the involvement of cAMP in melatonin signal transduction were examined.

MATERIALS AND METHODS: Splenocytes and peripheral blood mononuclear cells (PBMC) were cultured in vitro in the presence of melatonin, phytohemagglutinin, luzindole, dibutyrylcAMP (dbcAMP), forskolin and vasoactive intestine peptide (VIP). Proliferation was measured by [(3)H]-thymidine incorporation in cultures carried out for 24, 36, 48 and 72 h. Cyclic AMP formation was assessed by radioimmunoassay in cells incubated for 30 min. or 24 h.

RESULTS: Melatonin stimulated the spontaneous proliferation in short-term (36 and 48 h) splenocyte cultures and had no effect in 72 h cultures. It inhibited mitogen-stimulated proliferation already in 24 h cultures and this effect was observed regardless of the time of the culture. Both melatonin effects were antagonized by luzindole - membrane-bound melatonin receptor antagonist. Forskolin and dbcAMP caused a significant inhibition of proliferation of splenocytes and PBMC cultured for 24 or 72 h, respectively. Melatonin inhibited the cAMP formation (30 min. of incubation) stimulated by adenosine cyclase activators - forskolin and VIP, but added alone failed to affect the cAMP concentration. In mitogen-stimulated splenocytes cultured for 24 h Mel caused an increase in cAMP correlated with the inhibition of cell proliferation.

CONCLUSIONS: Melatonin effects on chicken splenocytes appears time- and activation-dependent: in short-term cultures it stimulates spontaneous and inhibits mitogen-activated proliferation, probably via membrane-bound, luzindole-sensitive melatonin receptors. Incubation with melatonin for 30 min. inhibits cAMP formation, but in 24 h cultures it increases cAMP concentration leading to inhibition of proliferation....

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