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Biomedical subjects

F Carandente

Publications and source records attributed to F Carandente.

At least 55 records · Page 3Linked to original sources

Heart rate and extrasystolic arrhythmias in active subjects aged over 90. A chronobiological study.

We analyzed the circadian rhythm of heart rate (HR), of simple atrial premature beats (APB) and of simple ventricular premature beats (VPB) in very old subjects undergoing dynamic ECG for 24 h. The 18 subjects under study (11 women and 7 men) were aged 90 or more (mean +/- SD 92.3 +/- 2.3, range 90-98), did not complain of acute cardiac pathologies, were not taking any medication and were synchronized as to time schedules. The mean duration of DECG recording was of 23 h and 54 min. The collection of data concerning the hourly mean of HR (6 ten-sec samples taken every 10 min) and of the number/hour of APB and VPB was carried out manually. A significant rhythm (single cosinor) was detected for heart rate in 14 subjects out of 18 and in the group (population cosinor); it was also detected for APB (9 subjects out of 15) and for VPB (5 subjects out of 15) also by the single cosinor. It was not detected for the group (population cosinor). No significant correlations, either direct or inverted, were revealed between HR and premature beats. We demonstrate therefore that, even in very old subjects, the circadian rhythm of HR still exists as in younger subjects.

Aged↗

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↗

A chronomorphological structural model of rat thyroid gland.

Circadian rhythmicity of the structural morphometric model of thyroid has been studied in 36 Wistar rats kept in LD 12:12. The parameters evaluated are: a. the volume fraction occupied by: 1. follicle epithelium, 2. colloid, 3. interstitium at 6 time points in 24h; b. the follicle size distribution; c. the number of follicles per unit tissue volume. The circadian rhythms of mean follicular diameter and of follicular cavity mean diameter have been demonstrated (p less than 0.03 and p less than 0.01 respectively) and show overlapping acrophases of -120 degrees (-64 degrees/-176 degrees) and -108 degrees (-99 degrees/-116 degrees). The synchronization between rhythms, shown for mean follicular diameter and for follicular cavity mean diameter, suggests a rhythmical pulsation of the whole follicle, while the thickness of the follicular epithelium does not undergo a statistically significant periodic variation.

Animals↗

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↗

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↗

Antimicrobial agents as biological response modifiers (BRM) and chrono-immunomodulation: an emerging relationship.

Immune defense mechanisms play an essential protective role against infections caused by a wide array of pathogenic microorganisms. Although the growing number of the available antimicrobial agents has certainly improved the overall clinical outcome of such infections, antimicrobial therapy not rarely fails whenever the host's immune function is depressed. On the other hand, recently introduced therapeutic and diagnostic procedures (antineoplastic chemotherapy causing severe neutropenia and mucositis; organ transplantation requiring conditioning regimens; the widespread use of intravascular catheters and prosthetic devices; administration of adrenal corticosteroids and/or other immunosuppressive agents) have resulted in an unprecedented number of immunocompromised hosts. In addition, a variety of antibiotics have been found to display adverse effects on specific and non-specific immune functions, thus further impairing the already depressed immune system of the host. Antibiotic-mediated immunomodulation hence is explored with the introduction of a third-generation cephalosporin, namely cefodizime (CDZ), which has been shown to possess immunostimulating properties in preliminary in vitro and ex vivo studies as well as in a few experimental animal models. A chronoimmunopharmacological approach to CDZ-induced immunomodulation has been started by ourselves. The study, which is still in progress, includes patients with multiple myeloma (MM), selective IgA deficiency and chronic uremia, and matched healthy subjects. A number of immunological parameters are being assessed on blood samples drawn every 6h in the 24-h span prior to CDZ administration (a single 2 g daily dose i.v. for 6 days to the patients and for 4 days to healthy subjects), and in the 24h following the last CDZ injection. Healthy subjects and patients are randomly assigned to two groups, depending on whether they are given the antibiotic at 0800 or at 1800. Although a full evaluation of the results will be reported elsewhere, the group of MM now includes 24 patients. A circadian stage-dependent chronoimmunomodulating effect has been unequivocally shown for the monocytic chemotactic responsiveness to CDZ in MM. Immunostimulating 'side-effects' suggest that CDZ should possibly be regarded as a prototype antimicrobial agent for patients with impaired immune functions. Conceivably, a better knowledge of such properties will help synthesize new antibiotics with specific immunomodulating effects.

Adjuvants, Immunologic↗

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↗

Circadian rhythms of DNA content in brain and kidney: effects of environmental stimulation.

Male adult Wistar rats kept under natural lighting show circadian rhythms of DNA content and DNA synthesis in the cerebral cortex, cerebellum and kidney. In the cerebral cortex the acrophases of the 2 rhythms almost coincide during the dark period. On the other hand, in kidney, the acrophase of DNA synthesis is phase-advanced by about 14 h with respect to the acrophase of DNA content, which occurs in the dark span, as in the cerebral cortex. Comparable results were obtained in 5 week-old rats raised under artificial lighting conditions (LD 7:19) and exposed for a few days to sensory and social stimulation (an enriched sensory environment). At variance with the latter data, the circadian changes of DNA content and synthesis flattened out and were not statistically significant in the cerebral cortex of 5 week-old rats kept for a few days under conditions of sensory and social deprivation (an impoverished sensory environment). A similar effect occurred in kidney with regard to the rhythm of DNA content, while the circadian rhythm of DNA synthesis remained statistically significant but was phase-delayed by about 6h with respect to the corresponding rhythm occurring in the enriched environment. In sensory impoverished rats, MESOR values of kidney wet weight and DNA specific activity were significantly higher than in sensory enriched rats, while MESOR values of DNA content were significantly lower. The data demonstrate the striking dependence of the circadian variations of DNA content and synthesis on the nature of environmental stimulation.

Animals↗

Toward a chronoimmunomodulation by cefodizime in multiple myeloma and chronic uremia.

Nine healthy subjects, 19 patients with multiple myeloma (MM) and 21 patients with chronic uremia were given cefodizime (2 g i.v.) at 2 different timepoints either in the morning or in the evening for 5 to 7 consecutive days. The following immunological parameters were comparatively evaluated before and after cefodizime administration: rosette-forming cells (RFC%), T lymphocyte subpopulations, monocyte chemotaxis index (MCI) and granulocyte chemotaxis index (GCI). Independently of the time of drug administration, a circadian rhythm was clearly detected (90% CI) as regards RFC%, CD3, CD4, CD8, CD4/CD8 before and RFC%, CD3, CD4, CD8, GCI after therapy. In addition, in patients treated at 0800 cefodizime increased the MESOR of the MCI and, to a lesser extent, of the GCI. The chronoimmunomodulatory effects of cefodizime in patients with MM and chronic uremia are discussed.

Adjuvants, Immunologic↗

Dosing time and sex-related differences in the pharmacokinetics of cefodizime and in the circadian cortisol rhythm.

Two g cefodizime i.v. administration at 00:00, 06:00, 12:00 and 18:00 respectively, to 8 male and 8 female, young healthy volunteers, has shown: 1. a sex-related difference in both plasma (AUC) and total cumulative excretion of the agent with larger values in females than in males; 2. a dosing time-related difference in plasma (AUC) with the largest values for Rx at 00:00 and lowest for Rx at 18:00 in both males and females; 3. a dosing time-related difference in urinary concentration of cefodizime with largest values for Rx at 06:00 and lowest for Rx at 12:00. These urinary changes were highly correlated with changes in AUC for each dosing time; 4. no dosing time-related changes were observed for plasma T1/2 as well as cumulative urinary excretion of cefodizime; 5. curve patterns of plasma cortisol had similar aspects for both control and Rx at 00:00 with no sex-related differences. Curve patterns differed from control for other dosing times (p less than 0.005 to p less than 0.001 with ANOVA tests).

Adult↗

Mesor-hypertension: hints by chronobiologists.

Circadian systems are intermodulated by networks of specialized neural, hormonal and cellular functions, with time structures that are interdependent. In cardiovascular pathophysiology, circadian and ultradian rhythms of clinical interest have been demonstrated. Cardiac output, heart rate, arterial pressure and blood volume are the best known. Systolic and diastolic blood pressure and heart rate have circadian patterns in health and therefore arterial pressure cannot be evaluated by a single measurement during a 24-h span. With correct monitoring for at least 48-h it is possible to detect the mesor-hypertension and the possible amplitude-hypertension that precedes the mesor-hypertension. Prolonged elevation of blood pressure can cause irreparable harm to sensitive tissues. To quantify the damage, the concept of hyperbaric impact has been introduced. This is a measure of the excess load exerted upon the arterial walls. Studies of the beta-blocker penbutolol with correct automatic monitoring have shown the persistence of the physiological circadian variation in the cardiovascular parameters during penbutolol administration. The so-called elimination of the circadian rhythm in blood pressure, which would not really be desirable, was not seen in any of our patients, whose cardiovascular parameters were monitored continuously, day and night, while taking penbutolol. The amplitudes of the rhythms were always prominent. A phase shift, a delay of about 100 degrees, was demonstrated in the heart rate of one 63-year-old mesor-normotensive woman.

Blood Pressure↗

Circadian temporal structure evaluated by automatic monitoring.

A few aspects of the circadian time structure were evaluated in a young healthy woman, with a special reference to arterial pressure and body temperature. Both parameters were estimated by the use of automatic equipments. The present study evidences the importance and the advantages of autorhythmometry (which should be applied in every instance, but can not be omitted when measuring arterial pressure) and automatic monitoring (which warrants an excellent reproducibility of measurements).

Adult↗

Evaluation of circadian, circaseptan, and circannual periodicity of attempted suicides.

A retrospective investigation has been carried out on the incidence of attempted suicides registered at the Fatebenefratelli Hospital in Milano, during the span from June 27, 1978 to November 11, 1980. On a total of 451 cases, the age, sex, hour, day of the week and date of the attempted suicide have been recorded for each single case. The cosinor analysis for tau = 24 h has shown that a circadian periodicity is statistically significant both for the total of men (phi =-265 degrees +/- 17) and for the total women (phi =-285 degrees +/- 13), with p less than 0.01. The maximum incidence occurs during the later afternoon (approximately between 1700 and 1900). The results are similar to those obtained for the younger subjects only (up to 22 years), while for the following range of age, (22 to 40 years), and after 40 years, the rhythm is not so well demonstrable. As regards the circaseptan rhythm, it is quite evident for women, both up to 22 years (maximum incidence on Friday) and between 23 years and 40 years (maximum incidence Thursday), and from 40 years onwards, but it is not demonstrable for men. A circannual rhythm is demonstrable, on the contrary, both for men and women: the maximum incidence is in May for men and in February for women.

Adolescent↗

Circadian temporal structure in psoriasis.

The unknown etiopathogenesis of psoriasis and its often unpredictable course, in spite of actual treatment, suggest the search of parameters correlated with the disease that could help to better define and treat these patients. The altered cell turnover of the psoriatic epidermis leads to hypothesize a disturbance or at least a modification of the cellular rhythm of the skin. In order to prove alterations of the circadian temporal structure in psoriasis, we have studied some easily detectable variables, registered at 3-h intervals, in both psoriatic and in healthy control subjects. The control subjects presented statistically significant circadian rhythms of oral temperature, arterial blood pressure, pulse, electrolytes, 17KS, 17-OHCS and uricemia. In the psoriatic group, only a few of these variables present a clearly reproducible circadian rhythm. Moreover these rhythms, when they are demonstrable in the patients, do not show the same circadian acrophases of the control subjects and they are also desynchronized inside the group itself. The alteration in these circadian urinary and haematic rhythms implies that in psoriasis not only the skin is involved: all the circadian structure seems to be perturbed and the cause of the disease should mot be searched only in the epidermis.

17-Hydroxycorticosteroids↗