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Journal Article 2002; 23(3): 239-242 PubMed PMID: 12080285 Citation  Keywords:  Adenocarcinoma:metabolism, Aged, Circadian Rhythm, Colorectal Neoplasms:metabolism, Female, Humans, Male, Melatonin:blood, Middle Aged, Radioimmunoassay,.   

OBJECTIVE: The aim of the study was pineal gland function assessment on the base of daily rhythm study and mean daily melatonin (MEL) concentrations in serum in patients with colorectal carcinoma.

MATERIAL AND METHODS: Studies were performed in 12 women at the age of 63.17+/-5.90 years and 21 men aged 58.95+/-11.32 years with large intestine adenocarcinoma. The control group consisted of 28 healthy volunteers at comparable age. During the circadian study blood samples for the measurement of melatonin (MEL) were collected every 4 hours during 12 h. MEL concentrations were assessed with the use of RIA methods. Statistical analysis of circadian rhythms of MEL was carried out with the use of cosinor method according to Halberg.

RESULTS: Existence of daily rhythm of MEL secretion was shown in all studied groups. A significant decrease of amplitude of rhythm and secretion of MEL at nocturnal hours in comparison with the control group was shown in the group of women with large intestine carcinoma. A significant decrease of mesor value and amplitude of MEL rhythm as a consequence of decrease of MEL secretion at nocturnal and morning hours was observed in the group of ill men.

CONCLUSIONS: Decrease in melatonin circadian rhythm amplitude as a consequence of its lowered nocturnal secretion occurred in all patients with colorectal carcinoma. Abnormalities in daily rhythm of melatonin secretion were more intensified in men with large intestine carcinoma, which leads to suppression of mean daily hormone concentration....

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Journal Article 2002; 23(3): 226-230 PubMed PMID: 12080283 Citation  Keywords:  Adult, Aged, Brain:physiopathology, Cognition, Diabetes Mellitus, Type 2:physiopathology, Diabetic Retinopathy:physiopathology, Event-Related Potentials, P300, Female, Humans, Hypoglycemia:physiopathology, Male, Middle Aged,.   

OBJECTIVES: The purpose of this study was to evaluate the ERP P300 in non insulin dependent diabetes mellitus (NIDDM) patients without cognitive impairment and the relationship with clinical variables, the presence of retinopathy and previous hypoglycemic episodes.

METHODS: NIDDM patients (N=44) without evidence of cognitive impairment and controls (N=17) were studied clinically and with ancillary exams and the ERPs P300 were recorded. Patients were examined clinically and with the Folstein Mini-Mental Examination (MMSE) for cognitive function and all patients showed a score higher than 26 (maximal value=30). Previous hypoglycemia was evaluated through a questionnaire establishing the number of episodes and the symptoms of hypoglycemia in a scale scoring from zero to 15.

RESULTS: ERP P300 latencies were significantly higher in NIDDM patients than in controls (p<0.03). ERP P300 measures were significantly related to age (Pearson, p<0.01) and not to metabolic variables, disease duration or the presence of retinopathy. Severity of hypoglycemia was not associated to ERP P300 latency.

CONCLUSIONS: Our study supports the evidence that NIDDM patients, without signs of nervous system involvement, have ERP P300 alterations and this is not related to retinopathy, metabolic variables or previous hypoglycemic episodes. Chronic hyperglycemia may alter brain glucose transport and increase tolerance to hypoglycemia effects in the nervous system....

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Journal Article 2002; 23(3): 219-225 PubMed PMID: 12080282 Citation  Keywords:  Acute Disease:psychology, Adult, Age Factors, Birth Weight, Cognition, Cross-Sectional Studies, Female, Humans, Male, Models, Psychological, Neuroimmunomodulation, Predictive Value of Tests, Retrospective Studies,.   

BACKGROUND: The Barker Hypothesis suggests that an unfavourable uterine environment can have the effect of programming the body for disease later in life. Research indicates a bidirectional relationship between thought and biochemical reactions, that may be influenced by early programming. Reports suggest that 25% of variance in birthweight is a result of foetal environment and that the health and cognitive deficits do not just affect those with an officially low birthweight.

OBJECTIVE: This study investigates the influence of birthweight on cognition and minor illness in adults.

METHODS: This is a retrospective, cross sectional design with an opportunity sample of 75 adults. Participants whose birthweight ranged from 2.5 kg to 4.88 kg, completed a symptom check list and general self-efficacy scale, reporting on the previous month.

RESULTS: Analysis of variance indicates that those with higher birthweight have fewer minor illness symptom days and higher general self-efficacy. Regression analysis indicates that birthweight is significantly predictive of levels of minor illness and general self-efficacy.

CONCLUSION: From the findings of this and previous studies, it is possible to infer vertical coactions between foetal environment and immuno competence. It is suggested that birthweight is an early predictor of levels of a cognitive mediator and minor illness. Data were applied to an equilibrium model to represent the relationship in terms of Gottlieb's concept of horizontal and vertical coactions....

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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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Clinical Trial 2002; 23(Suppl 1): 17-19 PubMed PMID: 12019346 Citation  Keywords:  Aged, Aged, 80 and over, Antioxidants:pharmacology, Blood Cell Count, Dehydroepiandrosterone Sulfate:blood, Estradiol:blood, Female, Humans, Hydrocortisone:blood, Melatonin:pharmacology, Pilot Projects, Sleep:drug effects, Sleep Wake Disorders:drug therap.   

OBJECTIVES: The role of melatonin is aging is still under debate. Therefore, an open pilot study on the effects of melatonin administration on some sleep parameters, routine hematological and biochemical parameters, and concentrations of hormones was performed in elderly women.

SUBJECTS AND METHODS: The study was performed on 14 women (volunteers), aged from 64 to 80 years (mean age 71+/-4.6 years). Melatonin (2 mg daily at 19:00 h) was administered during 6 months. Before and after melatonin treatment the peripheral venous blood samples were taken in the morning (approx. at 08:00 h) after the overnight fast. The total blood count, glucose, total cholesterol, LDL, HDL, and triglycerides were estimated by routine laboratory methods. The serum concentrations of the following hormones were determined: 17-beta-estradiol, dehydroepiandrosterone sulfate (DHEAS), cortisol, and somatomedin C (IGF-I). Additionally, before and after 6 months of melatonin therapy the investigated subjects answered to a questionnaire dealing with sleep parameters and self-estimation of general health status.

RESULTS: In 35.7% of investigated subjects an improvement in general sleep quality and in such sleep parameters as sleep initiation, sleep latency, number of awakenings episodes, wake time after sleep onset, was observed. A significant decrease of estradiol concentrations was observed after 6 months of the melatonin treatment in comparison to initial levels. IGF-I was found to be slightly but significantly increased after the 6 months melatonin therapy. Cortisol levels did not change significantly, during the melatonin treatment. DHEAS concentrations increased after melatonin therapy. Moreover, a tendency towards a higher DHEAS/cortisol ratio was found after 6 months of treatment. Melatonin treatment did not influence significantly either the parameters of total blood count or glucose and serum lipids levels.

CONCLUSIONS: On the basis of this preliminary open study it seems that melatonin administration may be beneficial for elderly subjects....

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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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