Daily variations of plasma sex hormone-binding globulin binding capacity, testosterone and luteinizing hormone concentrations in healthy rested adult males

In this study the daily variations of plasma sex hormone-binding globulin (SHBG) binding capacity were measured together with plasma testosterone and luteinizing hormone (LH) concentrations in 7 healthy rested adult males. Plasma SHBG-binding capacity demonstrated a significant circadian rhythm (acrophase = 2.06 p.m.; mesor = 0.35 +/- 0.6 ng testosterone bound/100 ml; amplitude = 17% of the mesor). Plasma testosterone also showed a circadian rhythm (acrophase = 7.02 a.m.; mesor = 4.38 +/- 0.67 ng/ml; amplitude = 18% of the mesor). The free testosterone index (or the ratio between plasma testosterone and SHBG-binding capacity) was not correlated with plasma LH levels. In our hands this last parameter did not vary according to a circadian pattern. These data are discussed in terms of a feedback mechanism controlling the pituitary-testis axis regulation.     

Toward a chronophysiology of circulating aldosterone

The physiology of aldosterone secretion has been prominently investigated by homeostatic studies on the levels of the steroid in plasma and/or urine. Aldosterone secretion is, however, arranged in a rhythmic fashion along the 24-hr cycle. The dynamics of aldosterone should thus be reanalyzed chronobiologically in order to gain further insight into the physiology of the hormone. Such a revisitation has been performed in the present study on four groups of clinically healthy volunteers categorized according to sex and age. Aldosterone has been assayed in the plasma of systemic venous blood six times a day (0600, 0800, 1200, 1800, 2000, 0000) in different conditions of physical activity and sodium intake. Time-qualified data have been analyzed by the single-cosinor method and then summarized by the population-mean cosinor procedure to quantify the circadian rhythms in their properties (mesor, amplitude, acrophase). Differences in rhythmometric parameters have been tested by a multivariate analysis for vectorial units. (Hotelling's T2 test). Cosinor analysis indicates that the dynamics of circulating aldosterone substantially changes in relation to posture. The habit of having a routine of diurnal activity leads the circadian rhythm of aldosterone to delay its acrophase from morning to afternoon. The postural shift of acrophase is essentially accompanied by an elevation in the 24-hr mean level. The restriction of salt intake is associated with an increase in mesor; the temporal localization of the circadian crest shows, however, a very high stability. Sex is not characterized by significant differences in the 24-hr patterns of aldosterone in the sense that young males and females show substantially identical time-qualified curves and circadian parameters. Increasing age until the seventh decade in life is responsible for changes mainly in 24-hr mean levels with a slight modification in amplitude. Such a chronophysiology for circulating aldosterone related to the motor-rest schedule, sodium intake, sex, and age, is of interest not only to heuristic but also to practical approaches in clinical medicine.     

Photo-reversal of the circadian rhythm in the proliferative activity of the mouse small intestine

Mice (C57Bl) were placed for 35 days in a room with reversed light cycle; lights came on at 1800 hours and off at 0600 hours. At six hour intervals throughout the day three mice were injected with tritiated thymidine and sacrificed 30 minutes later. Crypts were dissected for radioautography and determination of disintegrations per minute per crypt, the number of cells in mitosis and the number of cells synthesizing DNA was determined. The results reported clearly demonstrate reversal of the circadian rhythm in the parameters tested.     

Postnatal development of TRH and TSH rhythms in the rat

We previously observed that under a 12-hour light/12-hour dark schedule (lights off at 19.00 h), adult male Sprague-Dawley rats showed a circadian rhythm for serum thyroid-stimulating hormone (TSH) with a zenith near midday. In the present work, the ontogenesis of serum TSH rhythm was determined as well as pituitary TSH variations. In addition, hypothalamic and blood TRH were measured in these rats aged 15, 25, 40 and 70 days when sacrificed. As from the first age studied (15 days), a hypothalamic thyrotropin-releasing hormone (TRH) circadian rhythm was present. The mesor and the amplitude of this hypothalamic TRH rhythm increased while the rats were growing up, in contrast with the decrease observed for these parameters as far as blood TRH circadian rhythm is concerned. The time of the acrophase moved from 17.32 h in the 15-day-old rats to 13.57 h in the 70-day-old rats, being constantly in phase opposition with the blood TRH acrophase. The low amplitude pituitary TSH circadian rhythm detected in the young rat disappeared in the adult while, in contrast, the serum TSH rhythm became consistent to reach the well-characterized circadian midday peak in the 70-day-old rats.     

Circadian Rhythms of Histatin 1, Histatin 3, Histatin 5, Statherin and Uric Acid in Whole Human Saliva Secretion

The circadian rhythms of histatins 1, 3, 5, of statherin and uric acid were investigated in whole human saliva. Histatins showed a rhythm approximately synchronous with salivary flow rate (acrophase around 5 pm), the higher amplitude pertaining to histatin 1 (about 50% of the mesor). Uric acid showed a large rhythm asynchronous with flow rate and histatin concentrations (4.4 ± 1.4 am). Statherin did not show a significant circadian rhythm on five of six volunteers. This finding confirms that the secretion route of statherin is different from that of histatins.     

Protective effect of atorvastatin on circadian regulation of liver marker enzymes and redox status in hyperlipidemic rats

Hyperlipidemia was induced in rats by administering 2% cholesterol, 20% coconut oil, and 0.125% cholic acid for 10 weeks. Atorvastatin (0.8 mg/kg b.w.) was administered orally to rats together with high-fat diet for 10 weeks. At the end of the experimental period, the circadian characteristics (acrophase, amplitude, and mesor) of liver marker enzymes (aspartate aminotransferase and alanine transferase), lipid peroxidation products (thiobarbituric acid reactive substances (TBARS), and antioxidants (superoxide dismutase, catalase, reduced glutathione, and glutathione peroxidase) were analyzed. Circadian characteristics (mesor, amplitude, and acrophase) of liver marker enzymes, TBARS, and antioxidants were altered in high-fat diet-induced rats, and the diminished amplitude along with decreased mesor levels of antioxidants were observed in high-fat diet-induced rats. Further, oral administration of atorvastatin to high-fat diet-induced rats showed the normalized mesor, amplitude, and acrophase. These findings suggest that the antihyperlipidemic potential of atorvastatin could modulate the circadian patterns of liver marker enzymes and redox status in hyperlipidemic rats.     

Circadian temperature rhythm of laboratory swine

The circadian temperature rhythm (CTR) profile holds promise for monitoring the domestic pig's responses to stress and illness. In the present study we quantified the CTR profile of nine growing-finishing swine using a time-series, small-group design. Temperature was monitored using a probe implanted in the ear for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed singly in pens. The dominant period of the temperature data was estimated with the autocorrelation function and then used in standard cosinor analysis to compute the amplitude (half of the distance between the highest and lowest value within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the cosine maximum). To examine the effect of procedural stress on CTR, we compared data from the first 3 days with those from subsequent days. Eight of the nine (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h, amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower (P = 0.03) during the first 3 days after instrumentation than during subsequent days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as reflected in attenuated CTR amplitude during the first 3 days after instrumentation; and 3) CTR adaptation to stress appears to occur over time.     

Regulation of the 24h body temperature rhythm of women in luteal phase: role of gonadal steroids and prostaglandins

An investigation into whether the rise in the 24h body temperature rhythm observed in the luteal menstrual phase is antagonized by the administration of prostaglandin synthesis inhibitors has been made. Intravaginal body temperature was monitored continuously for 24h, once in the follicular and twice in the luteal phase. In the luteal phase, women were studied both without and with the simultaneous administration of a prostaglandin synthesis inhibitor (lysine acetylsalicylate; 1.8 g every 6 h orally). The progesterone/estradiol ratio (measured at 17:00h each day) was related to mesor (r = 0.825; P < 0.001), acrophase (r = 0.682; P < 0.02), and amplitude (r = -0.731; P < 0.001) of the 24h body temperature rhythm. Luteal phase elevation of the progesterone/estradiol ratio was associated with a 0.32 +/- 0.07 degrees C increase in mesor (P < 0.01), a 0.11 +/- 0.02 degrees C decrease in amplitude (P < 0.001), and a 34.8 +/- 11.6 min delay in acrophase (P < 0.03) of the 24h body temperature rhythm. Prostaglandin synthesis inhibitors did not counteract these modifications. The present data shows that the modifications of the circadian parameters of the 24h body temperature rhythm observed during the luteal phase of the menstrual cycle are strictly related to modifications of the progesterone/estradiol ratio, and presumably independent of prostaglandin synthesis.     

The Time-Course of Mouse Liver Regeneration after Carbon Tetrachloride Injury is Influenced by Orcadian Rhythms

Male NM jnice received 50 nmol CC14 i.p. at 1800,2400,0600 or 1200 and the changes in regenerative DNA synthesis (incorporation of 3H-thymidine into DNA and labelling index) and mitotic rate were determined. The time-course of regeneration varied with the time of CC14 injection; when CC14 was injected at 0600 or 1200 biphasic patterns were observed, and when CC14 was injected at 2400 or 1800 single wide peaks were seen. Independently of time of CC14 injection, the DNA synthesis peaked at 2400, the acrophase of the circadian rhythm. Consequent to the DNA synthesis peaks, a similar pattern, 6 hr delayed, was observed for the mitotic rate values. The most pronounced synchronization was seen with CC14 injected at 1200.     

The Time-Course of Mouse Liver Regeneration after Carbon Tetrachloride Injury is Influenced by Orcadian Rhythms

Male NM jnice received 50 nmol CC14 i.p. at 1800,2400,0600 or 1200 and the changes in regenerative DNA synthesis (incorporation of 3H-thymidine into DNA and labelling index) and mitotic rate were determined. The time-course of regeneration varied with the time of CC14 injection; when CC14 was injected at 0600 or 1200 biphasic patterns were observed, and when CC14 was injected at 2400 or 1800 single wide peaks were seen. Independently of time of CC14 injection, the DNA synthesis peaked at 2400, the acrophase of the circadian rhythm. Consequent to the DNA synthesis peaks, a similar pattern, 6 hr delayed, was observed for the mitotic rate values. The most pronounced synchronization was seen with CC14 injected at 1200.     

Suprachiasmatic nucleus and circadian core temperature rhythm in the rat

Core temperature was telemetered from 26 singly-housed adult male inbred Fischer rats standardized in an ambient temperature of 24 ± 1°C, in light from 0600–1800 alternating with darkness (L:D 12:12), with food and water freely available. The rats were operated upon first for bilateral electrolytic lesioning of the suprachiasmatic nucleus (SCN) or by a sham-operation, which consisted of an inserted electrode which neither penetrated into the SCN area nor was activated to produce a lesion. Next, a temperature sensor was implanted intraperitoneally. The telemetered data obtained at 10-min intervals from each rat were analyzed by the least-squares fit of certain trial periods (cosinor methods). A circadian population rhythm persisted in the SCN-lesioned rats which sustained destruction of both SCN (P < 0.01). The amplitude of the circadian temperature rhythm was attenuated(P < 0.01) and the rhythm's acrophase advanced (P < 0.05) from mid-dark to a time near the transition from light to darkness. Unilateral lesions of the suprachiasmatic nuclei altered the circadain amplitude but not the phasing.     

Role of Sleep Restriction in Daily Rhythms of Expression of Hypothalamic Core Clock Genes in Mice

Lack of sleep time is a menace to modern people, and it leads to chronic diseases and mental illnesses. Circadian processes control sleep, but little is known about how sleep affects the circadian system. Therefore, we performed a 28-day sleep restriction (SR) treatment in mice. Sleep restriction disrupted the clock genes’ circadian rhythm. The circadian rhythms of the Cry1 and Per1/2/3 genes disappeared. The acrophase of the clock genes (Bmal1, Clock, Rev-erbα, and Rorβ) that still had a circadian rhythm was advanced, while the acrophase of negative clock gene Cry2 was delayed. Clock genes’ upstream signals ERK and EIFs also had circadian rhythm disorders. Accompanied by changes in the central oscillator, the plasma output signal (melatonin, corticosterone, IL-6, and TNF-α) had an advanced acrophase. While the melatonin mesor was decreased, the corticosterone, IL-6, and TNF-α mesor was increased. Our results indicated that chronic sleep loss could disrupt the circadian rhythm of the central clock through ERK and EIFs and affect the output signal downstream of the core biological clock.     

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 forserum 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 signficiant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase. For the group as a whole, a statistically significant advance in acrophase was observed in serum transaminase, while a statistically significant delay in acrophase was observed for serum A/G ratio, globulin, glucose, potassium, protein, sodium and for urinary magnesium. Statistically significant by sign test, but not by cosinor, was a numerical mesor increase for urinary urea clearance, a numerical decrease in mesor for urinary zinc; a numerical amplitude decrease for serum cholesterol; and a numerical delay in acrophase for oral temperature and serum cholesterol, CO², and globulin in all men examined. Only mesor changes in serum cholesterol and urinary Ca/Mg were positively correlated with the change in body size over the 10-year span between studies.

From a circadian chronobiologic perspective, the immense amount of data uniquely reviewed in this report across a 10-year span in seven healthy individuals serves a useful beginning to the study of the effects of normal aging upon commonly measured physiologic and biochemical variables and, more importantly, upon the circadian rhythm characteristics of these variables. A great deal of supposition about what happens to the mesor, amplitude and acrophase of an individual's circadian rhythms in a variety of endpoints has been based upon transverse studies of short duration and relatively few longterm studies. The further accumulation of data such as presented here and similar long-term longitudinal time series can have no adequate substitute for truly understanding whether reproducible age-related changes in circadian rhythms occur as individuals age.

With these qualifications and with the further qualification that the timing of our observations within the aging process (mid-20's and mid-30's) may be suboptimal for conclusions about aging, very interesting trends definitely appear worth comment. There is some evidence in these data that the flattening of circadian rhythms may really accompany advancing age. In grouped data, this fall in amplitude may be secondary to an isolated fall in predictable swing around the mesor or a combination of this and increased variability of the acrophase with or without amplitude changes. The data are not robust enough to be sure of the relative contribution of these two components. In any event, the circadian amplitude of each and every physiologic variable studied demonstrated a tendency to fall between the mid-20's and mid- 30's. This tendency toward a flattening of circadian variability is also a very prominent property of many of the serum chemistries which were measured. The circadian patterns of excretion of substances in the urine change much less between the mid-20's and mid-30's in our subjects. These findings may indicate a separate effect of aging especially upon metabolic hepatic variables and upon nephrologic circadian rhythms. Cardiovascular rhythms seem to change more in parallel with hepatic metabolic rhythms in contradistinction to the kidney-related serum and urinary rhythms.

Further, ongoing statistical analyses may hopefully turn up interesting and relevant cross-correlations among the individual data themselves in each study year and between the 10-year span, as well as with rhythm (mesor, amplitude and acrophase) and other physiologic characteristics of each subject. Planned re-observation of what happens to the circadian time structure of these seven individuals in their mid-40's will prove invaluable to further sorting out of the effects of aging upon circadian time structure.     

Circadian Rhythm of Liver Parameters (Cellular Structures, Mitotic Activity, Glycogen and Lipids in Liver and Serum) During Three Consecutive Cycles in Phenobarbital-Treated Rats

The circadian rhythm of gastric content, serum alkaline phosphatase (alk.P.), serum lipids, body weight (wt), relative (rel.) liver wt, cellular structures (by light- and electron-microscopy), mitotic activity of hepatocytes, glycogen content, protein and lipids in liver was studied in 180 male Sprague-Dawley rats orally treated at 0830-1030 with 50 mg/kg phenobarbital (PB) for 7 days. Thereafter, five PB-treated males and five controls each were studied at 4-hr intervals at 0600, 1000, 1400, 1800, 2200 and 0200 on 3 consecutive days. The lighting schedule in the colony was 12:12 = light/dark (light from 0600 to 1800). Following the rhythm of gastric emptying, the rel. liver wt showed a clear circadian rhythm with a peak at 0800. The rel. liver wt was raised in PB-treated rats at all times of the day. The circadian rhythm of cellular structures was closely related to the hepatic glycogen content which exhibited a clear rhythm with the peak also at 0800, but lowered values were found in PB-treated rats. The mitotic activity of hepatocytes was significantly increased in PB-treated rats but displayed the same circadian rhythm as controls with peaks at noon and troughs at midnight. The well-known hypertrophy of the smooth endoplasmic reticulum in PB-treated rats was not found at 0600, but was fully developed at 1400 and 2200. PB-treatment increased significantly the liver content of cholesterol, triglycerides and phospholipids. Liver cholesterol showed a clear circadian rhythm with peaks at 1800. No rhythm of liver protein, triglycerides and phospholipids was observed. In serum, levels of cholesterol were significantly elevated, those of triglycerides and alk.P. significantly lowered, while those of phospholipids were not affected by the treatment. The three serum lipids, alk.P. and beta-lipoprotein exhibited a clear circadian rhythm, while serum glucose and non-esterified fatty acids did not.     

Circadian Rhythm of Liver Parameters (Cellular Structures,Mitotic Activity,Glycogen and Lipids in Liver and Serum) During Three Consecutive Cycles in Phenobarbital-Treated Rats

The circadian rhythm of gastric content, serum alkaline phosphatase (alk.P.), serum lipids, body weight (wt), relative (rel.) liver wt, cellular structures (by light- and electron-microscopy), mitotic activity of hepatocytes, glycogen content, protein and lipids in liver was studied in 180 male Sprague-Dawley rats orally treated at 0830-1030 with 50 mg/kg phenobarbital (PB) for 7 days. Thereafter, five PB-treated males and five controls each were studied at 4-hr intervals at 0600, 1000, 1400, 1800, 2200 and 0200 on 3 consecutive days. The lighting schedule in the colony was 12:12 = light/dark (light from 0600 to 1800). Following the rhythm of gastric emptying, the rel. liver wt showed a clear circadian rhythm with a peak at 0800. The rel. liver wt was raised in PB-treated rats at all times of the day. The circadian rhythm of cellular structures was closely related to the hepatic glycogen content which exhibited a clear rhythm with the peak also at 0800, but lowered values were found in PB-treated rats. The mitotic activity of hepatocytes was significantly increased in PB-treated rats but displayed the same circadian rhythm as controls with peaks at noon and troughs at midnight. The well-known hypertrophy of the smooth endoplasmic reticulum in PB-treated rats was not found at 0600, but was fully developed at 1400 and 2200. PB-treatment increased significantly the liver content of cholesterol, triglycerides and phospholipids. Liver cholesterol showed a clear circadian rhythm with peaks at 1800. No rhythm of liver protein, triglycerides and phospholipids was observed. In serum, levels of cholesterol were significantly elevated, those of triglycerides and alk.P. significantly lowered, while those of phospholipids were not affected by the treatment. The three serum lipids, alk.P. and beta-lipoprotein exhibited a clear circadian rhythm, while serum glucose and non-esterified fatty acids did not.     

Circadian regulation gene polymorphisms are associated with sleep disruption and duration,and circadian phase and rhythm in adults with HIV

Genes involved in circadian regulation, such as circadian locomotor output cycles kaput [CLOCK], cryptochrome [CRY1] and period [PER], have been associated with sleep outcomes in prior animal and human research. However, it is unclear whether polymorphisms in these genes are associated with the sleep disturbances commonly experienced by adults living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thus, the purpose of this study was to describe polymorphisms in selected circadian genes that are associated with sleep duration or disruption as well as the sleep–wake rhythm strength and phase timing among adults living with HIV/AIDS. A convenience sample of 289 adults with HIV/AIDS was recruited from HIV clinics and community sites in the San Francisco Bay Area. A wrist actigraph was worn for 72?h on weekdays to estimate sleep duration or total sleep time (TST), sleep disruption or percentage of wake after sleep onset (WASO) and several circadian rhythm parameters: mesor, amplitude, the ratio of mesor to amplitude (circadian quotient), and 24-h autocorrelation. Circadian phase measures included clock time for peak activity (acrophase) from actigraphy movement data, and bed time and final wake time from actigraphy and self-report. Genotyping was conducted for polymorphisms in five candidate genes involved in circadian regulation: CLOCK, CRY1, PER1, PER2 and PER3. Demographic and clinical variables were evaluated as potential covariates. Interactions between genotype and HIV variables (i.e. viral load, years since HIV diagnosis) were also evaluated. Controlling for potentially confounding variables (e.g. race, gender, CD4+ T-cell count, waist circumference, medication use, smoking and depressive symptoms), CLOCK was associated with WASO, 24-h autocorrelation and objectively-measured bed time; CRY1 was associated with circadian quotient; PER1 was associated with mesor and self-reported habitual wake time; PER2 was associated with TST, mesor, circadian quotient, 24-h autocorrelation and bed and wake times; PER3 was associated with amplitude, 24-h autocorrelation, acrophase and bed and wake times. Most of the observed associations involved a significant interaction between genotype and HIV. In this chronic illness population, polymorphisms in several circadian genes were associated with measures of sleep disruption and timing. These findings extend the evidence for an association between genetic variability in circadian regulation and sleep outcomes to include the sleep–wake patterns experienced by adults living with HIV/AIDS. These results provide direction for future intervention research related to circadian sleep–wake behavior patterns.     

Plasma Corticosterone, Motor Activity and Metabolic Circadian Patterns in Streptozotocin-Induced Diabetic Rats

Experiments were conducted in male rats to study the effects of streptozotocin-induced diabetes on circadian rhythms of (a) plasma corticosterone concentrations; (b) motor activity; and (c) metabolic patterns. Animals were entrained to LD cycles of 12: 12 hr and fed ad libitum.

A daily rhythm of plasma corticosterone concentrations was found in controls animals with peak levels at 2400 hr and low values during the remaining hours. This rhythm was statistically confirmed by the cosinor method and had an amplitude of 3.37μg/100 ml and the acrophase at 100 hr. A loss of the normal circadian variation was observed in diabetic animals, with a nadir at the onset of light period and high values throughout the remaining hours; cosinor analysis of these data showed no circadian rhythm, delete and a higher mean level than controls.

As expected, normal rats presented most of their motor activity during the dark period with 80+ of total daily activity; the cosinor method demonstrated a circadian rhythm with an amplitude of 60+ of the mean level and the acrophase at 0852 hr. Both diabetic and control rats showed a similar activity during the light phase, but diabetic animals had less activity than controls during the night and their percentage of total daily activity was similar in both phases of the LD cycle (50+ for each one). With the cosinor method we were able to show the persistence of a circadian rhythm in the motor activity of diabetic rats, but with a mesor and amplitude lower than in controls (amplitude rested at 60+ of the mean level) and its acrophase advanced to 0148 hr.

The metabolic activity pattern of diabetic rats also changed: whereas controls showed a greater metabolic activity during the night (70+ food; 82+ water; 54+ urine; 67+ faeces), diabetics did not show differences between both phases of the LD cycle. Water ingested and urine excreted by the diabetic group were higher than normal during light and dark periods; food consumed and faeces excreted were higher than controls only in the light phase.

These data suggest that alterations in circadian rhythms of plasma corticosterone and motor activity are consecutive to the loss of the feeding circadian pattern, due to polyphagia and polydipsia showed by these animals, which need to extend intakes during the light and dark phases.     

Rhythms in human bone marrow and blood cells

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.     

Serum angiotensin-converting enzyme activity in pre-eclamptic pregnancy: evidence for a relative hypermesorACEemia

The circadian rhythm of serum angiotensin-converting enzyme (ACE) activity was investigated in pregnant women with normal and pre-eclamptic gestation. The chronobiological approach was able to document the occurrence of a circadian rhythm for serum ACE activity in normal pregnancy. Such a rhythm is characterized by a decreased mesor and amplitude and a shifted crest. The circadian rhythm for serum ACE activity was not detectable in pre-eclamptic pregnancy. Such an abrogation is accompanied by a negligible decrease of mesor suggesting the occurrence of a relative hyperACEemia. This disorder could play a role in pregnancy-induced hypertension.     

Circadian rhythm changes in core temperature over the menstrual cycle: method for noninvasive monitoring

The purpose of this study was to determine whether core temperature (T(c)) telemetry could be used in ambulatory women to track changes in the circadian T(c) rhythm during different phases of the menstrual cycle and, more specifically, to detect impending ovulation. T(c) was measured in four women who ingested a series of disposable temperature sensors. Data were collected each minute for 2-7 days and analyzed in 36-h segments by automated cosinor analysis to determine the mesor (mean temperature), amplitude, period, acrophase (time of peak temperature), and predicted circadian minimum core temperature (T(c-min)) for each cycle. The T(c) mesor was higher (P < or = 0.001) in the luteal (L) phase (37.39 +/-0.13 degrees C) and lower in the preovulatory (P) phase (36.91 +/-0.11 degrees C) compared with the follicular (F) phase (37.08 +/-0.13 degrees C). The predicted T(c-min) was also greater in L (37.06 +/- 0.14 degrees C) than in menses (M; 36.69 +/- 0.13 degrees C), F (36. 6 +/- 0.16 degrees C), and P (36.38 +/- 0.08 degrees C) (P < or = 0. 0001). During P, the predicted T(c-min) was significantly decreased compared with M and F (P < or = 0.0001). The amplitude of the T(c) rhythm was significantly reduced in L compared with all other phases (P < or = 0.005). Neither the period nor acrophase was affected by menstrual cycle phase in ambulatory subjects. The use of an ingestible temperature sensor in conjunction with fast and accurate cosinor analysis provides a noninvasive method to mark menstrual phases, including the critical preovulatory period.