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Biomedical subjects

D Lakatua

Publications and source records attributed to D Lakatua.

28 records · Page 2Linked to original sources

Human mesor-hypertensive chronorisk.

Twelve endocrine variables in blood from a small number of clinically healthy adult women were sampled systematically around the clock and the seasons. Pattern discrimination methods singled out certain hormone values in certain seasons as classifiers for a high vs low risk of developing diseases associated with a high blood pressure. Further evidence in support of such classifiers is obtained on data from adolescent, menstrually cycling young adults and post-menopausal women, here analyzed as pool of series, with the scope of the data from any one age group greatly extended by a resampling procedure, namely, by bootstrapping. This mathematical approach was carried out on data series around the clock and seasons on several hormones as well as systolic and diastolic blood pressure. Classifier roles were strongly supported for plasma aldosterone and thyroid stimulating hormone, originally by an analysis of variance and, in the case of aldosterone, by circannual cosinor analysis and by numerical resampling. Circannual bootstrapping, a procedure recommended for broad routine use as a safeguard for hypothesis testing, was also done for plasma cortisol, dehydro-epi-androsterone sulfate and prolactin, variables for which (parametric) analyses of variance and cosinors did not reveal any difference between groups at high and low cardiovascular risk. In these instances, bootstrapping results are tentative and await further analyses. Results show the ability of circannual bootstrapping to detect outliers. Identification of classifiers provides cost-effective endocrine checks complementing the targeted automatic monitoring of blood pressure. Circannual indices for risk evaluation are, however, costly in several ways since it takes at least a year and quite a few samples to estimate them reliably. Accordingly, we also extended the scope of previous results by the application of an added procedure for circadian bootstrapping. With circadian as well as circannual bootstrapping, we here illustrate a major potential component of a system of chrono-engineering for health maintenance. This system should start with focus on the newborn. The results on adults here analyzed are likely to be more prominent in the neonate, to the extent that they are genetic in origin, yet amenable to modification by the extra-uterine environment.

Adolescent↗

Circadian rhythm of beta-endorphin in the plasma of clinically healthy subjects and in patients with adrenocortical disorders.

Immunoreactive beta-endorphin was determined in the plasma of 37 elderly subjects (73 +/- 7 years of age), in 3 young or young adult subjects without adrenal disease, in 4 women with clinical adrenogenital syndrome, in 1 man with Cushing's disease. Immunoreactive beta-endorphin in plasma was measured by radioimmunoassay in six samples of each subject collected at 4-hour intervals over a 24-hour span. The observation of a circadian rhythm in circulating immunoreactive beta-endorphin with highest values during the late night and early morning hours is extended to elderly subjects in the 8th decade. The beta-endorphin plasma concentrations in the few clinically healthy young adult subjects studied fell within the same range. The circadian variation of the group of elderly subjects was used as reference in the clinical evaluation of plasma beta-endorphin concentrations in patients with pituitary-adrenocortical disorders. The need for circadian rhythm qualified reference values is shown by the observation of the circadian variations of circulating immunoreactive beta-endorphins in the patients with adrenogenital syndrome and Cushing's disease in whom abnormalities in the concentration of circulating beta-endorphin were found at certain circadian stages but not at others.

Adolescent↗

Chronosynergistic effects of lighting schedule-shift and cefodizime on plasmacytoma growth and host survival time.

Lighting regimen shifts can modify the effects of cefodizime, for the purpose of a chronoimmunomodulation. Two experiments were carried out on male and female LOU rats inoculated subcutaneously with plasmacytoma cells. Some rats were kept on their original LD12:12 regimen, whereas others, after tumor implantation, were subjected every second day to 6-h shifts, instituted, in alternation, as advance or delay. Daily treatment with cefodizime or placebo started when, overall, about 50% of the animals had developed a palpable tumor. A subgroup of animals contributed daily smears for the determination of the estrus cycle and further provided core temperature and activity data by telemetry. In Experiment I, the repeated shifting of the LD regimen was associated with survival time prolongation (p less than 0.05), irrespective of drug administration. Moreover, in those (female) rats repeatedly exposed to shifts of the lighting schedule, cefodizime was found to prolong survival time (p less than 0.05). The effects of cefodizime vs placebo on survival time were found to be circadian stage-dependent. In Experiment II, differing from Experiment I in the initial conditions before the institution of the shifts, cefodizime treatment was associated with a prolongation of survival time of the female rats kept on a fixed LD12:12 regimen. Both male and female rats again showed a circadian stage-dependence of the cefodizime effect. These results suggest that interactions between synchronizers of rhythms (such as shifts of the lighting regimen, the latter simulating the daily routine) and immunomodulating agents such as cefodizime may be optimized to improve treatment strategies against cancer and other diseases.

Animals↗

Chronobiologic observations of calcium and magnesium in the elderly.

Sixty-two elderly men (average age 75 +/- 6 yrs) and 85 elderly women (average age 79 +/- 8 yrs) institutionalized at Berceni Clinical Hospital, Bucharest, Romania, were investigated over a 24 hour span, some of them repeatedly, leading to a total of 269 profiles. The subjects were studied in 12 subgroups spread over all four seasons. Total serum calcium, inorganic phosphate, total protein, albumin and urinary calcium and magnesium were determined. Circadian rhythms were found in all variables. There were statistically significant phase differences between serum calcium, total protein and serum albumin speaking against the serum protein rhythm (or circadian variations in hydration) being responsible for the circadian rhythm in total serum calcium. There are phase differences between the elderly (and young) subjects studied in Romania and several series reported from Germany and the USA. Circadian and circannual variations were found for urinary calcium and magnesium excretion, with maximum in fall and low values during summer. The peak excretion thus follows, rather than coincides, with the time of maximum sun exposure. The elderly subjects studied in Romania show a relatively low circadian (24-hour) mean calcium excretion, and the circadian acrophase in the elderly occurs during the night hours in keeping with the acrophase shift found in elderly subjects in urine volume and other electrolytes.

Aged↗

Circadian rhythm in plasma immunoreactive somatomedin-C in children.

Fifteen boys and 27 girls, 11 +/- 2 years of age were studied over a single 24-hour span during the month of June. Statistically significant circadian rhythms of plasma immunoreactive somatomedin-C (SM-C) concentration, immunoreactive growth hormone (hGH) and cortisol concentration were found, which show marked differences in timing. The highest values of somatomedin-C occurred in the early evening hours (acrophase 19:08) in contrast to growth hormone which showed its peak values during the night and cortisol, which peaked in the morning hours. These observations are of interest for the physiologic regulation of somatomedin-C as well as for the clinical evaluation of plasma immunoreactive somatomedin-C concentrations, and for studies of the response of somatomedin-C to hormonal and/or pharmacologic manipulation.

Adolescent↗

Differences in the circadian rhythm parameters of urinary free epinephrine, norepinephrine and dopamine between children and elderly subjects.

The circadian rhythm in the urinary excretion of free epinephrine, norepinephrine and dopamine was studied in 60 elderly men and 83 women, 77 +/- 8 years of age, in a total of 260 24-hour profiles and in 63 boys and 81 girls, 11 +/- 1.5 years of age, in 144 24-hour profiles. The circadian mesor of all these compounds was increased in the children over that in the elderly subjects while the acrophase remained unchanged in spite of a phase shift of the acrophase of the urine excretion of the elderly in the night hours. The differences in functional state of the sympathetic and adreno-medullary function (and/or response) between children and elderly subjects may have clinical implications.

Aged↗

Time-varying effects in mice and rats of several synthetic ACTH preparations.

Circadian stage-dependent effects characterize synthetic ACTH 1-17 preparation (HOE 433 = Synchrodyn 1-17), tested in mice and rats, with reference notably to corticosterone and aldosterone production in vitro and to the behavior of rhythms in these two corticoids as an aspect of the adrenal cortical pacemaker of the circadian system. The possibility to advance or delay the rhythm in serum corticosterone by ACTH 1-17 also is demonstrated, as is a differential behavior of the circadian rhythm in serum aldosterone. Differences in timing of circadian corticosterone and aldosterone responses also are described and await further scrutiny for ultradian and infradian (notably circannual) modulation.

Adrenocorticotropic Hormone↗

Circadian-stage-specified effects of a synthetic short chain ACTH-1-17 (HOE 433) on blood leukocytes and corticosterone secretion in mice.

A synthetic short chain ACTH, ACTH-1-17 (HOE 433 = Synchrodyn 1-17), beta-ala1, lys17 corticotropin (1-17)heptadecapeptide-4-N-butylamide, was tested for activity at the anticipated circadian stage of highest adrenal corticosterone responsiveness (22-HALO) in BALB/c mice. Statistically significant dose-response relations were demonstrated both in vitro (corticosterone production by adrenals incubated in Krebs-Ringer solution) and in vivo (increases in the serum corticosterone concentration). Leukocyte counts in mice injected with this ACTH showed statistically significant decreases (as compared to controls) for all kinds of cells except the neutrophil and medium-sized lymphocyte.

Adrenocorticotropic Hormone↗

Circadian time structure of endocrine and biochemical parameters in adult onset (type II) diabetic patients.

Forty-one endocrine and biochemical serum parameters were studied over a 24-hour span with 6 samples at 4-hour intervals in 20 non-insulin dependent (Type II) diabetics and in 20 non-diabetic subjects matched for sex, age, height and weight. Circadian rhythms were verified by cosinor analysis. Group-synchronized circadian rhythms were detected in diabetic and non-diabetic subjects with no statistically significant difference in any of the rhythm parameters (rhythm adjusted mean, amplitude and acrophase) in: Aldosterone, cortisol, insulin, 17-OH progesterone, prolactin, testosterone, TSH, and in serum albumin, creatine phosphokinase (CPK), serum iron, inorganic phosphate and total protein. Statistically significant (p less than .05) circadian rhythms in both groups with a difference in some parameters between the diabetic and the non-diabetic subjects, which were verified by the Bingham Test (p less than .05) were found with a difference in the mesor in cholesterol, glucose, urea nitrogen (BUN), in the amplitude in C-peptide and in the acrophase in triglycerides, globulin and reverse T3 (rT3). Statistically significant circadian rhythms were detected as a group phenomenon for the diabetics only in progesterone, free and total T4, chloride, calcium, bilirubin and LDH and in the non-diabetic subjects only in ACTH, LH, total T3, alkaline phosphatase, uric acid and potassium. In the remainder of the functions studied, a circadian rhythm was detectable with statistical significance by cosinor analysis as a group phenomenon neither in the diabetics nor in the matched non-diabetic controls (DHEA-S, estradiol, FSH, GH, glucagon, free T3, sodium, GOT and gamma GT). In the absence of a detectable circadian rhythm as group phenomenon, the circadian mean was different between the diabetics and the non-diabetic subjects in sodium, chloride and calcium which were higher in the diabetic patients and serum LDH which was lower. In a comparison of endocrine determinations in the two groups, the circadian mean or mesor in T3 was lower in the diabetics and ACTH higher, without corresponding changes in TSH or in corticosteroids. The circadian time structure of Type II diabetic patients thus seems to be very similar to that seen in non-diabetic subjects of the same sex, age, weight and height. The minor differences found in some rhythm parameters will have to be confirmed or excluded in larger numbers of subjects. The higher circadian mean ACTH concentrations without change in steroid rhythm parameters observed in this group is interesting but will also require confirmation.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗