Search PubMed⌕ Search

Biomedical subjects

A Angeli

Publications and source records attributed to A Angeli.

At least 235 records · Page 13Linked to original sources

Similarity of the nocturnal profile of serum melatonin at early puberty and early adulthood.

In the present study we determined the nocturnal profile of serum melatonin (MT) concentrations in 10 short normal children at Tanner stage I-II of pubertal development (12.5-14.9 yrs) and in 6 young adults (24-29 yrs). Blood was collected every 30 min from 00(00) to 06(00). We did not find any significant difference in the nocturnal profile of serum MT, as gauged by the comparison of MT concentrations at any time-point tested as well as of the transverse means (84.2 +/- 36.0 pg/ml [M +/- SD] in the children vs 78.7 +/- 10.8 pg/ml in the adults). Mean serum melatonin concentration was not correlated to sex hormone concentration or body surface area. Our findings do not support the view that MT concentrations fall at the beginning of pubertal development and that changes in body size may be the reason for age-dependent changes of serum MT concentrations.

Adolescent↗

Circadian rhythm of urinary 17-hydroxycorticosteroids during metyrapone-induced ACTH release in normal subjects.

The circadian rhythm of urinary 17-OHCS was studied in nine normal subjects before and after oral metyrapone administration (750 mg every 4 hrs over a period of 24 hrs). The test was carried out twice in each subject with a shift of 12 hrs in the time of first administration (0800-test and 2000-test). For data from serial measurements of steroid metabolites on urine collected at 2-h intervals, the least squares fit of a 24-h cosine curve allowed the demonstration of a rhythm both in control conditions and during the 48-h span following metyrapone administration. Circadian acrophases were substantially similar. Total urinary 17-OHCS output in the first 24-h day following metyrapone was higher in the 2000-test as compared with the 0800-test (P less than .001). Conversely, in the second 24-h day, higher values were obtained in the 0800-test (P less than .025). The combined 48-h exretion, however, was identical in the two groups. The results suggest a time-limited action of metyrapone upon the pituitary-adrenal axis, since the increased excretion of 17-OHCS seems essentially accounted for by an exaggerated impulsive phase of ACTH secretion during the early morning hours.

17-Hydroxycorticosteroids↗

Rhythms in the ovulatory cycle. 3rd: Cortisol and dehydroepiandrosterone sulphate (DHEA-S).

The circadian profiles of cortisol and dehydroepiandrosterone sulphate (DHEA-S) were analyzed in a homogeneous group of 15 young normally cycling women, at 4 times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan variations of the same hormones were also evaluated. Population-mean cosinor analysis allowed the demonstration of a highly significant circadian periodicity for both variables in any of the 4 stages of the menstrual cycle; on the other hand, the same computation failed to demonstrate a significant circatrigintan periodicity. In each of the stages considered, the circadian acrophase of DHEA-S was delayed in comparison to that of cortisol, being located in the early afternoon hours. The demonstration of a clear-cut circadian oscillation in serum DHEA-S prompts studies on possible chrono-abnormalities of the steroid production in women with hyperandrogenic diseases.

Adult↗

24-hour profiles of blood pressure and heart rate in Cushing's syndrome. Evidence for differential control of cardiovascular variables by glucocorticoids.

We monitored the circadian profile of cortisol, systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) in 33 normotensive subjects aged 20-40 years, 20 normotensive subjects aged 40-60, 32 patients with essential hypertension and 13 patients with Cushing's syndrome (6 pituitary adenomas, 5 adrenal adenomas and 2 adrenal carcinomas). All controls and patients underwent serial blood drawings at 4-h intervals during the 24-h cycle. BP and HR were recorded every 30 min by an automatic, room-restricted instrument. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry) to quantify rhythm parameters such as the MESOR (rhythm-adjusted average), amplitude (difference between maximum and MESOR) and acrophase (timing of the crest of the rhythm). Both the control and essential hypertensive subjects showed a BP and HR circadian profile characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: p less than 0.001). The chronobiological analysis did not reveal any significant difference between healthy young and aged subjects. BP rhythmicity was disrupted in patients affected by Cushing's syndrome, whereas the 24-h oscillation of HR was preserved (p less than 0.001). Patients with pituitary-dependent Cushing's syndrome had higher BP levels than adrenal-dependent subjects (p less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.

Adenoma↗

Rhythms in the ovulatory cycle. 2nd: LH, FSH, estradiol and progesterone.

The circadian profiles of LH, FSH, estradiol and progesterone were compared in a homogeneous group of 15 young normally cycling women, at 4 well characterized times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan profiles of the same hormones were also evaluated. Population-mean cosinor analysis failed to demonstrate a circadian periodicity of LH in any of the 4 stages of the menstrual cycle; a circadian rhythm for FSH was present only in the 2 luteal phases (EL, LL); the same type of rhythmicity was present for estradiol only in the late luteal stage; on the contrary, a highly significant circadian rhythm of progesterone was present in each of the 4 menstrual stages considered (EF, LF, EL and LL). Population-mean cosinor analysis showed a highly significant circatrigintan periodicity of LH and FSH with the acrophases respectively between -109 degrees and -181 degrees and between -74 degrees and -125 degrees. Circatrigintan rhythmicity was also present for estradiol (acrophases between -161 degrees and -245 degrees) and progesterone (acrophases between -246 degrees and -296 degrees).

Adult↗

Rhythms in the ovulatory cycle. 1st: Prolactin. Chronobiological Research Group on Synthetic Peptides in Medicine.

Circadian and circatrigintan profiles of prolactin (PRL) in young normally cycling women at 4 well characterized times of the ovulatory cycle have been compared. Circadian patterns of PRL (collected at 2-h intervals for 24h at each phase selected) change during the 4 phases, being higher in the luteal phase. In a consistent percentage of individuals, serum PRL rises notably during the night; in one half of the subjects a peak is located also in the afternoon or early evening. The statistically significant circatrigintan rhythm of PRL shows the acrophase approximately in the mid-luteal phase.

Adult↗

Effects of exogenous melatonin on human pituitary and adrenal secretions. Hormonal responses to specific stimuli after acute administration of different doses at two opposite circadian stages in men.

We evaluated the effect of an acute oral administration of 2 dosages (100 and 1 mg) of melatonin (MT) vs placebo (PL) on pituitary release of LH, FSH, TSH and PRL after GnRH + TRH and on the adrenocortical release of cortisol, aldosterone and progesterone after ACTH in healthy adult males. We carried out a double blind study on 6 volunteers in winter-early spring, at 2 opposite phases of the circadian cycle: 08(00) and 20(00). Injection of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms of the synthetic analogue ACTH 1-17, alsactide) was performed 1 h after MT or PL ingestion. The measurement of plasma MT levels confirmed its effective gastrointestinal absorption after both doses. The hormonal patterns were superimposable after MT and PL. A higher response of FSH, PRL, cortisol and aldosterone was observed in the evening vs morning protocols independently of previous treatment (MT or PL). Our data demonstrate that the acute oral administration of 2 different doses of MT at 2 opposite circadian stages is ineffective as to the modification of a variety of pituitary and adrenocortical responses in human male subjects. The circadian chronosusceptibility of pituitary and adrenocortical cells to specific stimuli deserves interest to future investigation.

Adrenal Cortex Hormones↗

Progress in chronophysiology of peptide hormones with emphasis on clinical application of analogues.

It is now established that peptide hormones are among the most versatile substances involved in intercellular communications. By substitution of one or more natural aminoacids, numerous peptide analogues have been synthesized with increased duration of action and potency with respect to endogenous hormones. Most of these effects are programmable as a function of dose and timing of administration. Not surprisingly, the chronobiological use of hormone-related peptides may represent a valuable tool providing new approaches to diagnosis and therapy of different disease states. One pertinent example of the applicability of peptide analogues refers to a new short chain ACTH analogue (ACTH 1-17; Synchrodyn) that has been proved useful to reset or preset the rhythmic ordering of a number of functions and to provide, furthermore, information about specific pathogenetic mechanisms and/or subtle alterations of the adrenal function. A large body of evidence indicates that the same concepts apply to most actions of the gonadotropin-releasing hormone (LH-RH) related analogues. The efficacy of the so-called low-dose pulsatile LH-RH therapy in the management of hypogonadotropic hypogonadism and of some forms of infertility seems now established. The use of potent analogues is providing new approaches to the heretofore unsuccessful therapies in a number of disease conditions. In this light, chronoendocrinology and biotechnology have to be mutually supporting. Novel clinical applications are expected from the emerging use of portable instrumentation designed to record endogenous data and/or to deliver drugs according to a temporal program.

Adrenocorticotropic Hormone↗

Circadian rhythm of the angiotensin converting enzyme (ACE) activity in serum of healthy adult subjects.

Angiotensin converting enzyme (ACE) activity was measured in the peripheral serum of 10 healthy, diurnally-active and nocturnally-resting adult subjects (5 women and 5 men). Blood was drawn serially at 4-h intervals throughout a 24-h cycle with the subjects hospitalized and synchronized. They were not kept in recumbency. Data were evaluated by conventional statistical analysis and by single- and population mean- cosinor procedures. A low-amplitude circadian rhythm was statistically validated for the group. Acrophase was located in the afternoon, at about 1630. The recognition that ACE activity oscillates physiologically in the peripheral blood according to a circadian rhythm may serve to amplify the clinical use of ACE measurements.

Adult↗

Alsactide: ACTH-agonist for use in microdoses in brain-adrenal and other feedsidewards.

An increasing number of ACTH-related peptides have been isolated and/or chemically synthesized. In addition to the multiplicity of molecules, there is experimental evidence for multiple target cells and multiple receptors, and hence for different biological activities. The heptadecapeptide analogue alsactide (ACTH 1-17: Synchrodyn) has a C-terminal amide group (butylamide) and the substitution of beta-alanine for serine in position 1 and of lysine for arginine in position 17. These modifications account for enhanced biological activity and uniquely demonstrated chronopharmacological properties. In adult healthy men, the tailoring of dosage and timing of peptide administration was successful in a selective and transient stimulation of glucocorticoid secretion, without a change in the plasma concentrations of aldosterone and testosterone. The dose of 10 micrograms alsactide injected subcutaneously at awakening is proposed for clinical application with the aim of enhancing cortisol secretion in diurnally active subjects. It is noteworthy that injection of even much higher doses for several days at this particular circadian stage did not elicit detectable antibodies to the peptide in more than 200 patients. Restoring or reinforcing the circadian ordering of bioperiodicities correlated with the adrenocortical cycle can thus be achieved as a result of a time-specified therapy with an ACTH-agonist analogue. The results of studies in experimental animals and of preliminary trials in human beings have emphasized the value of alsactide as the first chronizer-peptide in clinical medicine. Its use in the dosage here proposed is expected to be beneficial for preventing deterioration of the circadian system in the elderly, for enhancing psycho-physical performances, and for gaining compliance with regard to chronic disease as well as tolerance to a number of potentially damaging xenobiotics.

Adrenal Glands↗

Multifrequency rhythms of immunological functions.

Chrono-immunological functions are reviewed starting from the first studies on circadian variations in the count of circulating blood eosinophils to the most recent studies on lymphocyte subpopulation periodicities. Serum Ig levels, complement components, plaque forming cells, phagocytosis, autologous mixed lymphocyte reactions, have also been demonstrated to be circadian periodic. Transplant immunology is also known to show circadian and circa septan periodicities in the rejection of transplanted organs. Rhythms of susceptibility to a series of allergens and bronchial asthma symptoms characterize chronobiology in allergy. A periodic pattern is a common finding in the recurrence of the symptoms in rheumatoid arthritis. Finally, the beginnings of chrono-immunotherapy of experimental and human tumors are briefly reviewed. The conclusion that can be drawn from this short overview is that the demonstration of the periodicity in such a big number of variables in health and the modifications of the relevant parameters in disease, emphasize the importance of the predictable, since periodic, part of the variations that can be shown by the immunological findings.

Animals↗

Circannual rhythmicities of cortisol levels in the peripheral plasma of healthy subjects.

Seasonal variations of endocrine function have been extensively studied both in rodents and in man. However, only few studies have attempted to concomitantly evaluate and compare circadian and circannual components by inferential rhythmometric procedures. We have examined [9] circadian profiles (single cosinor: P less than 0.01) of plasma cortisol obtained from samples drawn at 4-h intervals in healthy adult subjects of both sexes (71 males, 120 females, aged 20-54 years) along a 7-year span, from 1974 to 1980. All subjects were routine synchronized. Circulating cortisol was measured by a competitive protein-binding technique and expressed as microgram/dl; intra-assay coefficient of variation was always less than 5%. Both conventional and rhythmometric analysis were used to evaluate seasonal differences of mesor, amplitude and acrophase. The population-mean cosinor analyses revealed statistically significant differences as a function of the time of the year in both the circadian amplitude and acrophase. Examining data year by year revealed in 5 out of 7 annual cycles an apparent tendency to a delayed acrophase and to a reduced amplitude with advancing months towards winter. No significant changes in mesor values were found. Further fitting to a 365.25-day cosine curve of circadian parameters available for different months of an 'average' year yielded significant circannual rhythmicity for acrophase and amplitude; crest-value resulted in spring and autumn, respectively. Our data extend previous observations and are consistent with the existence of circannual variations in plasma cortisol levels in the human. In Italian people, cortisol secretion is conceivably higher in cold months; seasonal changes, on the other hand, appear to be of minor entity of at least as inferred by transverse sampling on a relatively large population. Effects of lighting regimen and of other climatological variables upon the adrenal cycle have to be considered.

Adult↗

Circadian and circaseptan rhythmicities in corticosteroid-binding globulin (CBG) binding activity of human milk.

It has been demonstrated that human milk contains a corticosteroid-binding globulin (CBG, transcortin) which is very similar to that isolated from plasma. It is agreed, moreover, that the cortisol environment of the breast is important for the synthesis of major milk proteins. It was of interest, therefore, to investigate whether milk transcortin exhibits circadian variations in the binding activity as does the plasma counterpart. Twelve lactating women, aged 23-35 years, collected specimens of milk just before feeding at different times of the 24-h cycle for 3 consecutive days in the first week of lactation. Six women extended milk collection for at least a 28-days span in the first 2 months of lactation. To obtain whey, milk was centrifuged in cellulose nitrate tubes at 105,000 g for 30 min at 4 degrees C. Specific cortisol binding activity of CBG was measured by an adsorption technique and data were expressed as a function of protein content. Cortisol levels in milk were measured by radioimmunoassay. Rhythmometric analyses (single- and mean-cosinor procedures) yielded detection of a significant circadian rhythm in 'apparent specific binding activity' for cortisol (ASBA-F) whereas no significant oscillation was found as far as milk cortisol concentrations were concerned. Mean acrophase of the CBG-binding activity in milk was located in the evening, lagging behind the corresponding activity in serum by approximately 8 h. A circaseptan rhythmicity in milk binding activity was also present in our longitudinal series at a high level of significance. These results provide evidence that CBG binding activity in human milk has a clear circadian rhythm in the face of ecchronic milk cortisol concentrations. Phase-shift with regard to the rhythm of the plasma counterpart may be accounted for by processes of milk accumulation before nursing The significance of circadian and circaseptan variations in specific cortisol (and other steroids) binding in milk awaits further investigation.

Circadian Rhythm↗