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Editorial 2002; 23(4): 271-272 PubMed PMID: 12195223 Citation  Keywords:  Humans, Neuroendocrinology:trends, Periodicals as Topic:trends,.   

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Journal Article 2002; 23(Suppl 2): 52-56 PubMed PMID: 12163849 Citation  Keywords:  Animals, Darkness, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:physiopathology, Photoperiod, Pineal Gland:physiology,.   

: Over the past few years, we have shown that the surge of melatonin in the circulation during darkness represents a potent oncostatic signal to tissue-isolated rat hepatoma 7288CTC, which is an ER+ adenocarcinoma of the liver. This oncostatic effect occurs via a melatonin receptor-mediated suppression of tumor cAMP production that leads to a suppression of the tumor uptake of linoleic acid (LA), an essential fatty acid with substantial oncogenic properties. The ability of LA to promote cancer progression is accomplished by its intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which amplifies the activity of the epidermal growth factor receptor/mitogen-activated protein kinase pathway leading to cell proliferation. By blocking tumor LA uptake, melatonin effectively blocks the production of 13-HODE and thus, markedly attenuates tumor growth. A similar effect of melatonin is observed in tissue-isolated, ER+ MCF-7 human breast cancer xenografts and nitrosomethylurea (NMU)-induced rat mammary cancers. When male rats bearing tissue-isolated hepatomas are exposed either to constant bright light (300 lux) or dim light (0.25 lux) during the dark phase of a 12L:12D photoperiod, the latency to onset was significantly reduced while the growth of tumors was markedly increased over a 4 wk period as compared with control tumors in 12L:12D-exposed rats. In constant light- and dim light during darkness-exposed rats, melatonin levels were completely suppressed while tumor growth, LA uptake and 13-HODE production were markedly increased. Similar results were obtained in constant bright light-exposed female rats bearing tissue-isolated NMU-induced mammary cancers or MCF-7 human breast cancer xenografts. To date, these studies provide the most definitive experimental evidence that light exposure during darkness increases the risk of cancer progression via elimination of the nocturnal melatonin signal and its suppression of tumor LA uptake and metabolism to 13-HODE....

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Journal Article 2002; 23(Suppl 2): 28-36 PubMed PMID: 12163845 Citation  Keywords:  Animals, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:etiology, Photoperiod, Pineal Gland:physiology,.   

: The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen....

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Comparative Study 2002; 23(3): 249-254 PubMed PMID: 12080287 Citation  Keywords:  Animals, Body Temperature, Brain Ischemia:pathology, Infarction, Middle Cerebral Artery:drug therapy, Male, Neuropeptides:pharmacology, Neuroprotective Agents:pharmacology, Pituitary Adenylate Cyclase-Activating Polypeptide, Rats, Rats, Wistar, Vasoactive.   

OBJECTIVES: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) belong to the same peptide family, and both neuropeptides have been shown to exert in vitro and in vivo neurotrophic and neuroprotective effects. The aim of the present study was to investigate and compare the protective effects of PACAP and VIP in permanent focal cerebral ischemia in rats. The effect on the progression of the cerebral infarct was also studied.

METHOD: Male rats were injected 450 pmol PACAP or VIP dissolved in physiological saline intracerebroventricularly, preceding the occlusion of the middle cerebral artery. Control animals received vehicle treatment. Permanent focal ischemia was induced by the intraluminal filament occlusion of the middle cerebral artery. Animals were sacrificed 12 or 24 hours after the onset of ischemia, and infarcted brain areas were determined by staining bran sections with triphenyl-tetrazolium chloride.

RESULTS: Twelve hours after ischemia, the infarcted brain volume resulted to be 14.8% in the control group, 15.3% in the VIP-treated group and 5.8% in the PACAP-treated animals. Twenty-four hours after middle cerebral artery occlusion, the infarcted brain volumes were 21.5%, 20.7% and 14.3% in the control, VIP and PACAP-treated animals, respectively.

CONCLUSION: Our results provide further evidence for the neuroprotective effects of PACAP38 as given in form of a preischemic bolus. It slows down the progression of the evolution of the infarct and reduces the final infarct size. In contrast, a related peptide, VIP, does not have neuroprotective effects under the same experimental conditions....

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Clinical Trial 2002; 23(3): 213-217 PubMed PMID: 12080281 Citation  Keywords:  Adult, Body Temperature:drug effects, Circadian Rhythm:drug effects, Humans, Male, Melatonin:blood, Pineal Gland:drug effects, Pyridoxine:administration & dosage, Sleep:drug effects,.   

OBJECTIVES: To determine pineal response to pyridoxine in normal men.

MATERIAL AND METHODS: Twelve healthy men were given orally pyridoxine (100 mg) or placebo at 1700h. Serum melatonin levels were determined every 30 minutes with simultaneous measurement of core body temperature between 1700h to 0300h. Polysomnographic sleep recordings were performed between 1800h to 2000h.

RESULTS: Serum melatonin levels after both placebo and pyridoxine showed a nocturnal rise occurring at 22:10+/-1:22h and 22:24+/-1:09h, respectively. The melatonin onset, peak, mean and area under the curve (AUC) values after pyridoxine (3.2+/-1.6 pg/ml, 47.2+/-22.6 pg/ml, 31.5+/-11.0 pg/ml and 173.5+/-138.4 pg/ml x min, respectively) were similar to the values after placebo administration (4.7+/-1.6 pg/ml, 53.9+/-26.0 pg/ml, 37.2+/-2.8 pg/ml and 205.3+/-137.8 pg/ml x min, respectively). CBT revealed a significant nocturnal decline but without significant difference between pyridoxine and placebo. Sleep amount and architecture were similar after the two treatments.

CONCLUSIONS: In adult man, the oral administration of 100 mg-pyridoxine during the evening hours has no effect on melatonin secretion nor does it alter CBT or sleep quality....

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Journal Article 2002; 23(Suppl 1): 24-29 PubMed PMID: 12019348 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Humans, Melatonin:pharmacology, Neoplasms:drug therapy, Neoplasms, Experimental:drug therapy,.   

: The paper presents the data concerning the in vivo effects of melatonin on experimentally-induced tumors in animals and the in vitro effects on animal and human tumor cells. The majority of experimental tumors responded to the melatonin treatment with growth inhibition. However, some negative or opposite results (i.e. stimulation of tumor instead of inhibition) were also reported. Some of the negative results can be attributed to the improper timing of melatonin administration. Melatonin was also shown to inhibit the growth of several animal and human tumor cell lines in vitro. On the basis of these experiments, a hypothesis of the oncostatic action of melatonin was put forward. The mechanism of the postulated action is complex and probably includes: 1) modulation of the endocrine system; 2) modulation of the immune system; 3) the direct oncostatic action of melatonin on tumor cells. The latter includes the recently discovered anti-oxidative action which probably plays an important role in the countering the DNA damage during the radiation challenge or the exposure to chemical carcinogens. It also includes the antiproliferative and pro-apoptotic effects exerted via melatonin receptors expressed by tumor cells. The involvement of the membrane melatonin receptors is mainly assumed. However, the recent data from our and other laboratories suggest also the involvement of RZR/ROR receptors (the putative melatonin nuclear receptors) in both melatonin-induced proliferation inhibition and apoptosis....

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Journal Article 2002; 23(2): 170-187 PubMed PMID: 12011804 Citation  Keywords:  Authorship, Humans, Neuroendocrinology:trends, Neuroimmunomodulation, Periodicals as Topic:trends,.   

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Journal Article 2002; 23(2): 161-167 PubMed PMID: 12011803 Citation  Keywords:  Analgesics, Opioid:pharmacology, Animals, Behavior, Animal:drug effects, Chickens, Dose-Response Relationship, Drug, Female, Immune System:drug effects, Irritants, Leukocyte Count, Leukocytes:cytology, Male, Morphine:pharmacology, Peritoneum:cytology, Per.   

BACKGROUND: Morphine exerts immunomodulatory effects dependent on several factors including species and parameter examined. The aim of this study was to assess the influence of morphine on experimental peritonitis and leukocyte activity in young chickens of both sexes.

METHODS: Peritonitis was elicited by intraperitoneal injection of thioglycollate (TG) alone or supplemented with morphine; additional chicken groups were injected with morphine alone. Morphine-treated birds (with or without elicited peritonitis) were pretreated with naltrexone, an antagonist of opioid receptors. Control groups were intact or PBS-injected. At specific postinjection intervals peritoneal leukocytes (PTL) were obtained by flushing the peritoneal cavity, counted and used for in vitro assays of activity (respiratory burst). Vascular permeability was measured using Evans blue solution.

RESULTS: Inflammatory reaction and morphine influence were gender-dependent: the extent of TG-induced peritonitis was higher in males and it was additionally stimulated by morphine. This pro-inflammatory effect of morphine was not seen in females. PTL collected from morphine-treated chickens of both sexes exhibited a stronger nitroblue tetrazolium reduction than in non-treated birds and this effect was antagonized by naltrexone.

CONCLUSIONS: The effect of morphine on peritonitis in chickens appears different to that in other vertebrate species, although the mechanism(s) of its influence on leukocyte activity are similar....

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