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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2006; 27(4): 445-452 PubMed PMID: 16891997 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Aging:immunology, Antioxidants:metabolism, Carcinogens:pharmacology, Circadian Rhythm:immunology, Female, Flow Cytometry, Granulocytes:drug effects, Humans, Infant, Newborn, Male, Middle Aged, Monocytes:drug effects, Oxidat.   

OBJECTIVES: In the present paper the circadian variation and age differences in human leukocyte reactive oxygen species (ROS) levels and plasma total antioxidant status were studied. Different ROS levels could influence disease during ageing and at different times of the day/night.

METHODS: Unstimulated and stimulated (12-O-tetradecanoyl-phorbol-13-acetate (TPA) blood samples were analysed by flow cytometry using dihydroethidium (DHE) and dihydrorhodamine 123 (DHR) as probes. 60 healthy individuals were divided into five equal groups ((I) 1-2 days post partum, (II) 20 +/- 2 years, (III) 40 +/- 2 years, (IV) 60 +/- 2 years and (V) 80 +/- 2 years) and 6 healthy volunteers were followed with blood samples at 3 hour intervals for 24 hours.

RESULTS: We observed a significant peak of ROS levels in both monocytes and granulocytes at 6 pm and 3 am using DHE as probe. DHR showed in principle the same pattern. The monocytes (unstimulated and stimulated) and unstimulated granulocytes of the newborn group showed higher ROS values than all the other groups, whereas the groups of adults did not differ from each other. The plasma total antioxidant status was significantly higher in the newborn group and showed no circadian variation.

CONCLUSIONS: The present data show that there is a circadian variation of ROS production in leukocytes that might possibly influence the occurrence of cardiovascular incidents like myocardial infarction. No increase in ROS production was found in healthy elderly compared to younger individuals. The increased ROS levels and antioxidant status of newborns might influence neonate immunity and play a part in cell signalling and development....

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Controlled Clinical Trial 2006; 27(3): 373-380 PubMed PMID: 16816833 Citation  Keywords:  Bottle Feeding, Chronobiology Phenomena:physiology, Circadian Rhythm:physiology, Double-Blind Method, Feeding Behavior:physiology, Female, Humans, Infant, Infant Formula:pharmacology, Infant Nutritional Physiological Phenomena, Infant, Newborn, Male, Nucl.   

: On the basis of the circadian nutritional variations present in breast milk, and of the implications for the sleep/wake cycle of the nutrients present in infant formula milks, we designed a formula milk nutritionally dissociated into a Day/Night composition. The goal was to improve the bottle-fed infant's sleep/wake circadian rhythm. A total of 21 infants aged 4-20 weeks with sleeping difficulties were enrolled in the three-week duration study. The sleep analysis was performed using an actimeter (Actiwatch) placed on an ankle of each infant to uninterruptedly record movements during the three weeks. The dissociated Day milk, designed to be administered from 06:00 to 18:00, contained low levels of tryptophan (1.5g/100g protein) and carbohydrates, high levels of proteins, and the nucleotides Cytidine 5 monophosphate, Guanosine 5 monophosphate and Inosine 5 monophosphate. The dissociated Night milk, designed to be administered from 18.00 to 06.00, contained high levels of tryptophan (3.4g/100g protein) and carbohydrates, low levels of protein, and the nucleotides Adenosine 5 monophosphate and Uridine 5 monophosphate. Three different milk-feeding experiments were performed in a double-blind procedure covering three weeks. In week 1 (control), the infants received both by day and by night a standard formula milk; in week 2 (inverse control), they received the dissociated milk inversely (Night/Day instead of Day/Night); and in week 3, they received the Day/Night dissociated formula concordant with the formula design. When the infants were receiving the Day/Night dissociated milk in concordance with their environment, they showed improvement in all the nocturnal sleep parameters analyzed: total hours of sleep, sleep efficiency, minutes of nocturnal immobility, nocturnal awakenings, and sleep latency. In conclusion, the use of a chronobiologically adjusted infant formula milk seems to be effective in improving the consolidation of the circadian sleep/wake cycle in bottle-fed infants....

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Comparative Study 2006; 27(3): 359-364 PubMed PMID: 16816831 Citation  Keywords:  Adult, Analysis of Variance, Circadian Rhythm:physiology, Estradiol:blood, Female, Follicular Phase:blood, Humans, Linear Models, Luteinizing Hormone:blood, Ovulation:blood, Periodicity, Progesterone:blood, Reference Values, Substance P:blood,.   

OBJECTIVES: In order to determine the exact pattern of plasma Substance P (SP) concentration during the LH preovulatory surge and the functional correlates which could exist between plasma SP, LH, 17 beta-estradiol (E2) and Progesterone, we performed a detailed analysis of changes in plasma SP concentration, during the critical phases of the LH preovulatory surge in the Human.

METHODS: The experimental study was performed in 21 women between the ages of 26 and 35 years. For each subject, blood samples were taken every 15 min, between 07:00 a.m. and 09:00 a.m. for 3 consecutive days when E2 plasma values reached at last 125 pg/ml. Then, each subject, according to the mean LH value of each day, was classified into one of the following groups: 1) the day before the day of the ascending phase, 2) the day of the ascending phase, 3) The day of the LH surge, 4) the day of the descending phase, 5) the day after the day of the descending phase.

RESULTS: Mean SP plasma values for the day of the LH peak, the day of the descending phase and the day after the day of the descending phase were all significantly higher than the values of the day of the ascending phase. Overall, there was an almost linear increase for plasma SP values between the day before the day of the ascending phase and the day after the day of the descending phase Also,this linear increase in plasma SP concentration exhibited a positive correlation (p = 0.016) with plasma progesterone concentrations which also started to increase on the day of the ascending phase of the LH surge.

CONCLUSIONS: Taken together with previous results which have shown that the administration of a SP antagonist reduces both the amplitude and the duration of the preovulatory LH surge in the monkey, the increase in plasma SP concentrations, possibly driven by the rise in serum progesterone concentration, which take place at the time of the preovulatory LH surge, is certainly an important element of the Hypothalamo-Pituitary-Gonadal interactive network necessary for the full development of the preovulatory LH surge in the Human....

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Journal Article 2006; 27(1-2): 35-52 PubMed PMID: 16648818 Citation  Keywords:  Animals, Antioxidants, Blindness:epidemiology, Carcinogens:toxicity, Circadian Rhythm:physiology, Environmental Pollution:adverse effects, Humans, Light, Melatonin:physiology, Neoplasms:epidemiology, Reproduction:physiology, Risk,.   

: At present, light pollution (exposure to light-at-night) both in the form of occupational exposure during night work and as a personal choice and life style, is experienced by numerous night-active members of our society. Disruption of the circadian rhythms induced by light pollution has been associated with cancer in humans. There are epidemiological evidences of increased breast and colon cancer risk in shift workers. An inhibition of the pineal gland function with exposure to the constant light (LL) regimen promoted carcinogenesis whereas the light deprivation inhibits the carcinogenesis. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the LL regimen. These observations might lead to use melatonin for cancer prevention in groups of humans at risk of light pollution....

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Journal Article 2006; 27(1-2): 157-161 PubMed PMID: 16648812 Citation  Keywords:  Animals, Cattle, Craniocerebral Trauma:metabolism, Female, Hemorrhage:metabolism, Hypothalamus:metabolism, Immunohistochemistry, Male, Radioimmunoassay, Rest:physiology, Sex Characteristics, Stress, Psychological:metabolism, Vasopressins:blood,.   

OBJECTIVES: This study investigates antidiuretic hormone (ADH) plasma concentration in bulls and heifers at rest, after transportation stress, trauma and massive hyper-acute hemorrhage at slaughter, with special attention to differences between sexes. We also quantified ADH concentration in the ADH-producing hypothalamic area.

SETTING AND DESIGN: The study was carried out on animals at the abattoir, exploiting the routinely procedure of slaughtering to obtain the experimental stressful conditions. The control group was represented by a group of animals matched for breed, age and gender.

RESULTS: ADH plasma values suggest that transportation stress has little or no effect in heifers in contrast to bulls. In both sexes ADH release increases after open head trauma due to stunning prior to slaughter. Hemorrhagic hyper-acute stress caused by bleeding induces a rapid hundredfold rise of ADH plasma concentration that becomes diergic (physiologically different between sexes), with males showing far higher values. Females show a higher ADH concentration in the hypothalamus.

MAIN FINDING: This study points out a difference in ADH output between bulls and heifers under conditions of severe hemorrhagic stress, as produced by severing of the neck vessels at slaughtering.

CONCLUSION: Extreme stress unmasks endocrine differences in bovine ADH release that may be relevant only during specific circumstances, such as fighting....

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Clinical Trial 2005; 26(6): 657-661 PubMed PMID: 16380706 Citation  Keywords:  Bottle Feeding, Breast Feeding, Circadian Rhythm:physiology, Female, Humans, Infant, Infant, Newborn, Male, Melatonin:analogs & derivatives, Milk, Human:metabolism, Reference Values, Sleep:physiology, Statistics, Nonparametric, Tryptophan:metabolism,.   

INTRODUCTION: The hormone melatonin regulates the sleep and this pineal hormone is synthesized in the organism from the amino acid tryptophan. It is known that breast-fed babies have better sleep patterns and a better entrained sleep/wake cycle than bottle-fed babies (adapted formula).

OBJECTIVE: To compare the circadian rhythm of 6-sulfatoxymelatonin (aMT6s)--the metabolite of melatonin excreted in the urine--in urine of bottle-fed and breast-fed children, and relate it to the circadian rhythm of tryptophan in breast milk, also evaluating the possible effects on the baby's night-time rest.

METHODS: 16 infants of 12 weeks of age were studied, divided into two groups depending on their exclusively natural or artificial feeding. The circadian rhythm of 6-sulfatoxymelatonin in urine was measured for the two groups of infants and for the breast-feeding mothers. In the breast milk, the circadian rhythm of the amino acid tryptophan was measured. The rest of the infants was tested by wrist actimeters for a week and the sleep parameters of the infants were measured and evaluated.

RESULTS: The tryptophan in the breast milk presented a circadian rhythm with acrophase at around 03:00. This affected the 6-sulfatoxymelatonin circadian rhythm with acrophase at 06:00 in the breast-fed infants, and also promoted nocturnal sleep. Assumed sleep, actual sleep, and sleep efficiency were significantly increased in the breast fed infants with respect the formula fed infants.

CONCLUSION: A temporal relationship was observed between the circadian rhythm of 6-sulfatoxymelatonin of the exclusively breast-fed babies and that of tryptophan in the mother's milk. Acting this amino acid as a zeitgeber entrainment of the biological rhythms in the breast-fed infant....

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Clinical Trial 2005; 26(6): 811-814 PubMed PMID: 16380700 Citation  Keywords:  Acromegaly:blood, Adult, Cardiovascular Diseases:complications, Female, Glucose Tolerance Test, Growth Hormone:blood, Homocysteine:blood, Humans, Hyperhomocysteinemia:blood, Male, Middle Aged, Risk Factors, Statistics, Nonparametric,.   

: Acromegaly is associated with a two to three-fold increase in mortality related predominantly to cardiovascular disease. The excess mortality is associated most closely with higher levels of growth hormone (GH). Survival in acromegaly may be normalized to a control age-matched rate by controlling GH levels; in particular, GH levels less than 2.5 ng/mL are associated with survival rates equal to those of the general population. Hyperhomocysteinemia has also been recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with acromegaly. Eighteen acromegaly patients (7 male, 11 female, mean age 42.8 +/- 11.0 years) in our endocrine clinic consented to having the following tests performed: complete blood count (CBC), thyroid hormones, folic acid, vitamin B12, plasma homocysteine levels, uric acid, fibrinogen, CRP, fasting glucose, insulin, C-peptide, total serum cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, GH, insulin-like growth factor-1 (IGF-1) and GH levels after an oral glucose tolerance test (OGTT). By history, fourteen had macroadenomas and four had microadenomas; eight had hypertension; two had glucose intolerance, and four had diabetes. Fifteen had had transsphenoidal or transfrontal surgery: two had been cured, but 13 others were taking long-acting octreotide. Five patients had undergone radiotherapy and the acromegaly in two was treated primarily with long-acting octreotide. CBC, thyroid hormone, folic acid, and vit B12 levels were normal in all patients. We divided the patients into two groups according to mean GH levels after an OGTT: Group 1 (GH<2.5 ng/mL, n=10), and Group 2 (GH<2.5 ng/mL, n=8). Comparison of the two groups using Mann-Whitney U testing revealed statistically significant lower levels in Group 1 of the following parameters: GH (1.91 +/- 0.90 vs. 8.58 +/- 5.55 ng/mL, p=0.002), IGF-1 (338.30 +/- 217.90 vs. 509.60 +/- 293.58 ng/dL, p=0.06), GH after an OGTT (1.42 +/- 0.81 vs. 9.01 +/- 4.53 ng/mL, p=0.001), plasma homocysteine (12.85 +/- 4.47 vs. 18.20 +/- 4.99 micromol/L, p=0.05), total cholesterol (164.0 +/- 20.81 vs. 188.0 +/- 22.26 mg/dL, p=0.05) and LDL cholesterol (81.0 +/- 9.64 vs. 116.70 +/- 13.03 mg/dl, p=0.01). Differences between the other parameters were not significantly different. Acromegaly patients with high GH levels after an OGTT have much higher levels of homocysteine than patients with lower GH levels. The role of elevated homocysteine levels as an independent cardiovascular risk factor in the mortality of acromegaly patients should be determined in future studies....

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