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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 163 records · Page 9Linked to original sources
PubMed1989

Circadian and ultradian characteristics of plasma growth hormone in children with normal and short stature.

Circadian and ultradian variations characterize plasma growth hormone (GH) in 40 boys and 10 girls of short stature, and 15 boys and girls of normal stature, 6-14 yr of age, living on a diurnal waking (approximately 07:00 to approximately 22.00), nocturnal resting routine. Blood was drawn at about 3-h intervals during a 24-h span and serum stored frozen at -60 degrees C until radioimmunoassay for GH concentration. A linear least-squares spectrum analysis of those data reveals the anticipated statistically significant circadian rhythm as the principal spectral feature for all groups. Prominent components with a period of 12 h were also found for the groups of short boys and short girls, and of 8 h for short boys. A parameter comparison indicates similar circadian characteristics between short and normal children, whether one compares boys (p = .52, .30 and .84 for comparison of rhythm-adjusted means (M), amplituedes (A) and acrophases (phi), respectively), girls (p = .65, .37 and .92), or all children (p = .53, .31 and .87). These results notwithstanding, studies of GH responses to GH-releasing hormone in children with short stature and healthy controls should be extended to evaluate any possible difference in terms of gender and circadian or ultradian timing.

Adolescent↗
PubMed1989

Chronobiology, growth hormone and healthy and malignant growth.

Chronobiology, the computer-aided science (logos) of life (bios) in time (chronos), provides novel concepts, tools and facts for those concerned with mitosis, growth and growth hormone (GH). GH concentrations in human plasma demonstrate a statistically significant circadian rhythm on a 6h as well as on a 24h rest-activity cycle. On a 24h routine of light (L) and darkness (D), alternating at 12h intervals, and in continuous D, circadian mitotic rhythms in mice persist as a feature of growth or regeneration. A circadian cell cycle commences with an increase in phospholipid labeling, followed by an increase in cytoplasmic RNA formation, preceding, in regular sequences, an increase in nuclear DNA formation and the next mitotic peak in those cells that are dividing in a growing or regenerating (reversibly "post-mitotic') rodent liver. About 5-day (presumably estral) and about 7-day (circaseptan) components as well as circadians are resolved as a spectrum of mitotic rhythms in rodent cornea. The effects of hormones such as GH or a synthetic ACTH analogue, ACTH 1-17, depend upon the circadian cell cycle stages when the agent is administered. No effect or statistically significant effect can be the result only of 1) the timing of a fixed dose of GH or 2) of the timing of the samples taken to investigate any effect. For both the timing of administration and the assessment of effects, a multifrequency spectrum of rhythms, if taken into account, can provide (in lieu of a considerable and often formidable source of variation) a new critical dimension of growth and development.

Adolescent↗
PubMed1988

Circadian and circannual rhythms of several enzymes of lysosomal origin in human plasma.

The circadian and circannual group rhythms in the plasma concentrations of the following lysosomal enzymes were studied in women and men: beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, beta-D-glucosidase, beta-D-galactosidase, alpha-D-galactosidase, alpha-L-fucosidase and alpha-D-mannosidase. The circadian rhythm was detected in all the tested enzymes of women, and only in alpha-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase and beta-D-N-acetylglucosaminidase of men. A statistically significant difference between genders in the circadian rhythm was exhibited by beta-D-galactosidase, beta-D-glucosidase, beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase and alpha-L-fucosidase. A circannual rhythm was detected in all the tested enzymes, with the exception of beta-D-glucuronidase and beta-D-N-acetylglucosaminidase, without any statistically significant difference between genders. The group rhythms of some of the enzymes (alpha-D-galactosidase, beta-D-glucosidase, beta-D-galactosidase) showed similar values of both circadian and circannual acrophases, suggesting that they may be subjected as a group to the same chronobiological coordination. The chronobiological rhythms of lysosomal enzymes were different from those of lactate dehydrogenase and alpha 1-antitrypsin, indicating that these rhythms are not merely reflecting fluctuations of the water content of plasma. No in-phase relationship was observed between the circadian and circannual rhythms of plasma cortisol and those of the tested lysosomal enzymes, excluding a direct chronobiological relationship between this hormone and lysosomal enzymes.

Acetylglucosaminidase↗
PubMed1988

Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men.

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs--blood pressure (systolic, diastolic, pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components--albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components--calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed for serum Ca, cholesterol, Cl, CO2, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically significant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Circadian stage-dependent effect of ACTH and melatonin on protein synthesis by rat adrenal cells.

The objective of the present study was to determine the circadian effects of melatonin and two different ACTH preparations: a synthetic heptadecapeptide with adrenocorticotrophic action (Synchrodyn 1-17, HOE 433) and a natural ACTH (Acthar, Armour). Both ACTH preparations acted in a circadian stage-dependent fashion affecting the MESOR and the amplitude of total protein synthesis of rat adrenal cells. The results also indicated interaction of melatonin with the rhythmic action of ACTH. We conclude that circadian adrenocortical organization also modulates protein synthesis.

Adrenal Glands↗
PubMed1988

[Blood levels of dehydroepiandrosterone sulfate (DHEA-S) and the risk of breast cancer].

In North American women at low or high risk of developing breast cancer, as assessed by an epidemiologic questionnaire, the plasma concentration of dehydroepiandrosterone sulfate shows a statistically significant circannual variation. In adolescents, in all seasons, circulating dehydroepiandrosterone sulfate is a classifier of the risk of developing breast cancer, a relatively low concentration of this hormone being associated with an increased risk.

Adolescent↗
PubMed1987

Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain.

The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.

Adrenal Glands↗
PubMed1987

Circadian rhythm of gastric acid secretion in active duodenal ulcer: chronobiological statistical characteristics and comparison of acid secretory and plasma gastrin patterns with healthy subjects and postvagotomy and pyloroplasty patients.

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.

Adult↗
PubMed1987

The gerontological decline of the renin-aldosterone system: a chronobiological approach extended to essential hypertension.

The circadian (about 24-hr) oscillating function of the renin-angiotensin-aldosterone system (RAAS) was investigated as a function of age in clinically healthy participants and in essential hypertensive patients. A peculiar age-related decline in the RAAS circadian mesor (rhythm-adjusted mean) and amplitude (variability from mesor) was found in the essential hypertensive patients. This finding suggests a nonphysiologic evolution in the tonic (24-hr mean level) as well as phasic (oscillating amplitude) circadian activity of the RAAS with increasing age. A relative hyperreninemic aldosteronism characterized the aged essential hypertensive patients.

Adolescent↗
PubMed1987

Effects of a mild and prolonged restriction in sodium or food intake on the circadian rhythm of aldosterone and related variables.

The effect of a mild reduction in dietary sodium intake (-30 mEq/24 hr) and body weight (-2 kg/2 months) on circadian rhythms of urinary aldosterone (UA), sodium (UNa), potassium (UK), creatinine (UC) and volume (UV) have been investigated in nine clinically healthy subjects. The mild reduction in dietary sodium is associated with: (1) a decrease in the 24-hr excretion rate of UNa, UK and UV, and an increased mesor of UA and UC; (2) a lowered extent of the circadian variation for UNa, UK, UV and a greater amplitude for UA and UC (3) a later crest in the temporal phase for UK, UA, UC, an earlier phasic wave for UNa. The mild reduction in calorie intake resulting in a body weight loss is associated with a more pronounced decrease in the 24-hr excretion rate of UNa and UK, and in the extent of circadian fluctuation for UNa. Peculiar events are: (1) the decreased 24-hr excretion rate for UA, and the increased mesor for UV; (2) the extent variability increased for UV, decreased for UC. Such effect may have a practical resonance for heuristic physiology since the role of dietary sodium and food intake has been better clarified. Dietary sodium and food can be regarded as 'chronomodulatory agents' for the adrenal cortex since their adrenotropic influence is extended to the tonic as well as phasic secretion of aldosterone.

Adult↗
PubMed1987

Autometrically and automatically monitored, iatrogenous, inhalant-decongestant-associated high blood pressure quantified by rhythmometry.

Blood pressure and heart rate were oscillometrically monitored with an automatic Nippon Colin instrument (Komaki, Japan) and were also self-measured by a 20-year-old man treated with an inhalant-decongestant containing an adrenergic and a corticosteroid analog. The subject also collected 24-hr urines for aldosterone determination. An elevation of urinary aldosterone excretion was observed compared to the usual value range of a peer group. After removal of the drug, urinary aldosterone dropped as did urinary potassium, whereas plasma potassium rose. Chronobiologic serial sections, carried out to follow the time course of blood pressure and heart rate, showed decreasing trends in MESOR after discontinuance of treatment. A decrease in the hyperbaric index, a measure of blood pressure excess over 24 hr, was also observed. Another subject treated with the same and a third treated with a similar inhalant-decongestant, who also monitored their blood pressures automatically and/or with self-measurements, showed similar effects: a decrease in blood pressure after removal of treatment and an increase in blood pressure when (for testing only) treatment was briefly resumed.

Adult↗
PubMed1987

Chronobiologic dynamics of delta 5-3 beta-hydroxysteroids and glucocorticoids in rat brain and plasma and human plasma.

While a different timing of circadian rhythms does not necessarily demonstrate the operation of independent mechanisms, it is one step in the isolation of separate interacting rhythmic factors underlying the dynamics of all life. With this step in mind, circadian rhythms are quantified in rat plasma and brain for corticosterone (B), pregnenolone (P), and dehydroepiandrosterone (D) by the rejection of the zero-amplitude assumption with the single cosinor method, from data obtained every 3 hr for 24 hr on groups of three male Sprague-Dawley rats, 11-12 weeks of age. The rats were killed; steroids were extracted from brain and plasma and were radioimmunoassayed. In relation to the acrophase (phi) of B, the phi of P in brain (P = 0.035) and of D in plasma (P = 0.0012) preceded the phi of B. By contrast, in clinically healthy women, the phi of plasma dehydroepiandrosterone sulfate (DHEA-S) lags behind that of cortisol (F), on the average by 6 hr 28 min. Such a lag is also seen in men. A species difference in the time relations of delta 5-3 beta-hydroxysteroids vs. glucocorticoids in plasma is obvious (P less than 0.01). A difference in time relations of human circulating D, DHEA-S, and F between schizophrenic and clinically healthy men renders the time relations of glucocorticosteroids and delta 5-3 beta-hydroxysteroids in brain particularly interesting, as do relations of an egocentric and expansive personality to the rhythm characteristics of DHEA-S. The fact that the acrophases for some of the steroids investigated in brain and plasma, respectively, are differently timed is in keeping with the assumption that they involve partly different mechanisms, even if differences in the metabolic handling of different steroids also remain to be investigated.

Animals↗
PubMed1987

Circatrigintan hormonal and skin surface temperature rhythms following hysterectomy.

Starting 2.5 weeks after removal of her uterus, but not of her ovaries, a 34-year-old, clinically healthy woman contributed a daily blood sample at 0900 and measured her skin surface temperature on her right breast above the nipple and just below the right breast daily for the ensuing 2 months. In aliquots of serum stored frozen, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined in the United States; these hormones and prolactin, estradiol (E2), progesterone, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), cortisol, triiodothyronine (T3), free thyroxine (T4), and free testosterone were determined in Italy. Hormonal data were analyzed by least-squares rhythmometry with and without the data obtained around the FSH-LH surge, to assess any circatrigintan variation. Technically, there is good agreement between the rhythm characteristics of the series of determinations made in Italy and the United States. A circatrigintan rhythm is thus quantified for LH, FSH, prolactin, E2, progesterone, and testosterone. Analyses of the differential skin surface temperature (DST) between the two sites were carried out to examine the usefulness of this variable as a marker rhythm for a noninvasive assessment of the time of ovulation. Features as prominent as the LH and FSH surge, which would render the noninvasive assessment of ovulation time more reliable, were not found in the DST of the subject under the conditions examined, even if a circatrigintan component is demonstrable for DST and some of the hormones examined after hysterectomy.

Adult↗
PubMed1987

Rhythmic pineal-hypophyseal-adrenal intermodulations ex vivo.

To assess circadian and circaseptan rhythmic intermodulation, female mice, kept on regimens of 12 hr light (L) alternating with 12 hr of darkness (D) (LD 12:12) were sampled for 1-13 days at six circadian stages. Pineals were removed and homogenized with 0.9% NaCl. Adenohypophyses were bisected and incubated in Krebs-Ringer buffer (KRb) and/or with 10(-7) M melatonin (Mt). Adrenals were bisected and incubated with KRb, with 10(-7) M Mt, with 0.05 IU of ACTH 1-17 (Sy; Hoechst, Italy), or with Sy + 0.025 ml of the aqueous pineal homogenate (APH). ACTH and prolactin (PRL) in adenohypophysis incubation fluid were determined by radioimmunoassay (RIA), and corticosterone in adrenal incubation fluid was determined by RIA or by a fluorometric method. By this chronobiologic approach, time series were collected systematically in the search for predictable variability. Once these series reveal an algorithmically formulatable pattern, with a waveform validated by inferential statistical means, they are graded in terms of complexity as alpha, beta, gamma, and delta rhythms. Spontaneously (alpha-) rhythmic along the 24-h scale is the corticosterone produced by bisected adrenal glands incubated with KRb only, and the Mt content of the APH, in keeping with earlier work. Reactively (beta-) rhythmic is the response, again along the 24-hr scale, of the adrenal to Sy or Mt and the response of the anterior pituitary to Mt at different circadian times. Modulatory (gamma and delta) rhythms characterize the Mt effect on the (beta-rhythmic) adrenal stimulation by Sy. Chronomodulations thus emerge as more or less complete sequences of a decrease, no effect and/or increase; or, rather, as an attenuation, no effect and/or amplification by the pineal, of the pituitary effect upon the adrenal. Linear least-squares rhythmometry, mostly single cosinors, describes and quantifies circadian (alpha, beta, and gamma) and infradian (delta) rhythms in the original series and in the differences in responses [beta - alpha] and [gamma - beta] (P less than 0.001 in each case). These spontaneous alpha, response beta, modulatory gamma, and frequency-divided delta rhythms reveal a collateral neuroendocrine hierarchy, characterized by the pineal feedsideward phenomenon, as a feature of interactions recurring with circadian and infradian frequencies.

Adrenocorticotropic Hormone↗
PubMed1987

Circadian-infradian intermodulation of corneal epithelial mitoses in adult female rats.

An infradian modulation with a 5-day period characterizes corneal mitoses in adult female inbred Lewis rats. The animals had been standardized, two per cage, with Purina Chow and deionized water freely available at 24 +/- 1 degree C and approximately 50% relative humidity, on six different sequences of light (L) alternating every 12 hr with darkness (D). The LD 12:12 regimen was staggered by approximately 4hr in the six environments to approximate, by sampling within 1 hr, sampling over a 24-hr LD span. Bedding was changed 3 days before each day of killing. During each of 8 consecutive days, one rat from each environment was anesthetized with ether and the eyeballs were removed. Mitotic indices, computed separately for each eye, were analyzed by linear and nonlinear least-squares analyses. For a prominent circadian component of mitotic activity, the 95% confidence interval (CI) extended from 23.84 to 24.85 hr, with a point estimate of 24.32 hr; for a second component of 117 hr, the Cl extended from 90 to 163 hr. Whether the approximate 5-day infradian rhythm is of ovarian or other origin is a problem for further study.

Animals↗