Responses of the Steroid Circadian System to Alcohol in Humans: Importance of the Time and Duration of Intake

Reports provide conflicting data about the effects of alcohol consumption on the hormonal system. Any study of these effects must control for a number of variables, including sex, alcohol status (alcoholic addiction vs. non-addiction), medical status (malnutrition, liver disease), and conditions of alcohol exposure, including an acute or continuous pattern of intake. The latter appears to be an especially critical factor in interpreting these effects. The authors therefore conducted a trial with a circadian design in which alcohol was administered repeatedly and regularly over a 26 h period for a total dose of 256 g. Because this protocol involves continuous alcohol administration, it is similar to administration among alcoholics and thus sheds new light on alcohol's effect on hormone secretion. Using healthy volunteers rather than alcoholics, however, prevents any confounding due to liver disorders and nutritional deficiencies, and thus makes it possible to focus on the direct role of alcohol in hormonal modifications. In these conditions, the continuous administration of alcohol did not affect cortisol secretion, but serum testosterone levels were significantly higher at all time points during the alcohol session than at the corresponding time points during the control session. These data are not consistent with previously reported findings for the relation between alcohol and both cortisol and testosterone, because in the current experiment the action of ethanol on steroid secretion should involve the circadian clock more than the hormonal system itself.     

Time-of-Day Effect on Cardiac Responses to Progressive Exercise

This study was designed to examine time-of-day effects on markers of cardiac functional capacity during a standard progressive cycle exercise test. Fourteen healthy, untrained young males (mean?±?SD: 17.9?±?0.7 yrs of age) performed identical maximal cycle tests in the morning (08:00–11:00?h) and late afternoon (16:00–19:00?h) in random order. Cardiac variables were measured at rest, submaximal exercise, and maximal exercise by standard echocardiographic techniques. No differences in morning and afternoon testing values at rest or during exercise were observed for oxygen uptake, heart rate, cardiac output, or markers of systolic and diastolic myocardial function. Values at peak exercise for Vo₂ at morning and afternoon testing were 3.20?±?0.49 and 3.24?±?0.55?L min^?1, respectively, for heart rate 190?±?11 and 188?±?15?bpm, and for cardiac output 19.5?±?2.8 and 19.8?±?3.5?L min^?1. Coefficients of variation for morning and afternoon values for these variables were similar to those previously published for test-retest reproducibility. This study failed to demonstrate evidence for significant time-of-day variation in Vo₂max or cardiac function during standard progressive exercise testing in adolescent males. (Author correspondence: thomas.rowland@bhs.org)     

Circadian and Circannual Rhythms of Hormonal Variables in Elderly Men and Women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Circadian rhythm characteristics of serum cortisol and dehydroepiandrosterone sulfate in healthy Chinese men aged 30 to 60 years. A cross-sectional study

The relation of adrenal function and aging has been the subject of intense interest in recent years. The circadian variations of plasma cortisol have been described in Caucasians, but little information is available on such hormone variations among the Chinese population, especially its changes with age. This study was, therefore, designed to examine the effects of age on the circadian variations of serum cortisol, dehydroepiandrosterone sulfate (DHEAS) and the molar ratio of cortisol/DHEAS in Chinese men, stratified by 10-year age-groups (i.e. men in their 30-60s, aged from 31 to 63 years old). Circadian variations of serum cortisol and DHEAS were documented at 2-h intervals from 8:00 to 22:00 and hourly from 22:00 to 8:00 in 26 healthy Chinese men. We found that the serum levels of both hormones showed a statistically significant circadian rhythmicity in all age-groups. The circadian pattern of serum cortisol was characterized by peaks (04:00-06:00) and troughs (18:00-24:00) occurring approximately 2h earlier than those usually reported in Caucasians. Aging did not significantly influence serum cortisol concentrations, but serum DHEAS levels declined significantly with age: subjects in their 60s had significantly lower levels, and their cortisol/DHEAS molar ratios were significantly higher than those in the younger age-groups.     

Circadian Rhythms of Circulating NK Cells in Healthy and Human Immunodeficiency Virus-Infected Men

Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3^? CD16⁺, CD3^?CD57⁺, and CD2⁺CD3^?. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchro-nizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.     

Does Circadian and Seasonal Variation in Occurrence of Acute Aortic Dissection Influence in‐Hospital Outcomes?

The risk of acute aortic dissection (AAD) exhibits chronobiological variations with peak onset in the morning and in winter. However, it is not known whether the time of day or season of the year of the AAD affects clinical outcomes. We studied 1,032 patients enrolled in the International Registry of Acute Aortic Dissection from January 1997 to December 2001. For circadian and seasonal analysis, the time and date of symptom onset were available for 741 and 1,007 patients, respectively, and were grouped into four 6 h periods (morning, afternoon, evening, and night) and four seasons (winter, spring, summer, and autumn). The χ² test for goodness of fit was used to evaluate non‐uniformity of the time of day and time of year for critical in‐hospital clinical events, including death. While highest incidence of AAD occurred in the morning and winter, clinical events (including mortality) were similar during the four different periods of the 24 h (χ²=1.9, p=0.60) and seasonal (χ²=1.2, p=0.75) periods.     

Acute metabolic,hormonal, and psychological responses to strength training with superimposed EMS at the beginning and the end of a 6 week training period

Objectives:The aim was to determine metabolic and hormonal responses to strength training with or without superimposed electromyostimulation (EMS) at the beginning and the end of a 6 week training period.Methods:20 strength trained subjects were randomly assigned to two groups. The first group (S) performed 4 sets of back squats with a constantly adjusted additional load of their individual 10 repetition maximum (10 RM) twice a week over 6 weeks. The second group (S+E) did the same training program with superimposed EMS on leg and trunk muscles. Physiological responses were determined before and after the first (TS 1) and the last training session (TS 12).Results:No significant differences of hormonal responses could be observed between groups and TSs. However, small to large effects on metabolism occurred between groups and TSs. Delayed onset muscle soreness (DOMS) was significantly higher 48h after TS 1 for S+E.Conclusions:Despite a higher DOMS after S+E, there is no acute effect of superimposed EMS on hormonal response to exhaustive resistance exercise. We suggest that, because of the high resistance during 10 RM bouts, most of the muscle fibers are already activated and superimposed EMS only activates few additional muscle fibers.     

The Use of Salivary Steroids to Monitor Circadian Rhythmicity on Expeditions in the Arctic

The circadian variation in salivary Cortisol concentration was investigated in four men during a traverse on foot, of the Greenland ice cap and of salivary Cortisol and testosterone on a summer expedition to Spitzbergen. In both instances circadian rhythmicity was demonstrated both before leaving the U.K. and throughout the expedition. The acrophase of the rhythms followed the changes in activity patterns on both expeditions although there was a dissociation between the Cortisol and testosterone following an acute 8 hr phase shift in Spitzbergen. The mesor of Cortisol in both instances tended to be higher than in the U.K. but the difference was never statistically significant. This work demonstrates the feasibility of using salivary steroid concentrations to investigate their circadian rhythmicity in circumstances where frequent blood sampling would be precluded.     

Circadian Variation in Cortisol Reactivity to an Acute Stressor

To investigate the role of the circadian pacemaker in cortisol reactivity to a cold pressor challenge, 26 diurnally subjects participated in a constant‐routine protocol and were divided into two groups. Group 1 started immediately after a monitored sleep period at 09:00 h, while group 2 started 12 h later. After 2 h of adaptation, a cold pressor test was presented every 3 h. The cortisol response was assessed by means of saliva samples that were taken before and after the test. The pretest samples were considered to be base‐rate measures and base‐rate values as subtracted from post‐test values were considered as reactivity measures. Both measures showed distinct Time‐of‐Day variations (respectively: F_7,168 = 16.92, p < 0.001, ε = 0.383; and F_7,175 = 8.01, p < 0.001, ε = 0.523). These findings are interpreted as evidence for the existence of an endogenous circadian periodicity underlying the sensitivity of the hypothalamus–pituitary–adrenal (HPA)‐axis to acute stress.     

The Relation of Shift Work Tolerance to the Circadian Adjustment

The amplitude and phasing of circadian rhythms are under discussion as possible predictors of tolerance to night work. In a field study, subjective sleepiness and oral temperature of 147 female nurses were measured at 2-hour intervals during a period with one morning shift and two consecutive night shifts. The nurses also filled out a questionnaire. Two types of tolerance indices were constructed: The “health index” was based on questions referring to general fatigue, gastrointestinal symptoms, and sleep disturbances, and the “sleepiness index” on the actual subjective ratings of sleepiness. According to the health index, the group with good tolerance had a larger circadian amplitude of the oral temperature rhythm on the day of the morning shift than the group with poor tolerance. However, with regard to the sleepiness index, the corresponding difference between the groups with good or poor tolerance was not significant. The data did not confirm the hypothesis that predicts a quick adjustment of the circadian rhythm when the circadian amplitude is small before the change to night work. The contradictory results found in this and in other studies do not yet permit prediction of tolerance to night work.     

Impact of a Single Bout of Aerobic Exercise on Regional Brain Perfusion and Activation Responses in Healthy Young Adults

Purpose

Despite the generally accepted view that aerobic exercise can have positive effects on brain health, few studies have measured brain responses to exercise over a short time span. The purpose of this study was to examine the impact within one hour of a single bout of exercise on brain perfusion and neuronal activation.

Methods

Healthy adults (n = 16; age range: 20–35 yrs) were scanned using Magnetic Resonance Imaging (MRI) before and after 20 minutes of exercise at 70% of their age-predicted maximal heart rate. Pseudo-continuous arterial spin labeling (pcASL) was used to measure absolute cerebral blood flow (CBF) prior to exercise (pre) and at 10 min (post-10) and 40 min (post-40) post-exercise. Blood oxygenation level dependent (BOLD) functional MRI (fMRI) was performed pre and post-exercise to characterize activation differences related to a go/no-go reaction time task.

Results

Compared to pre-exercise levels, grey matter CBF was 11% (±9%) lower at post-10 (P<0.0004) and not different at post-40 (P = 0.12), while global WM CBF was increased at both time points post-exercise (P<0.0006). Regionally, the hippocampus and insula showed a decrease in perfusion in ROI-analysis at post-10 (P<0.005, FDR corrected), whereas voxel-wise analysis identified elevated perfusion in the left medial postcentral gyrus at post-40 compared to pre (p_corrected = 0.05). BOLD activations were consistent between sessions, however, the left parietal operculum showed reduced BOLD activation after exercise.

Conclusion

This study provides preliminary evidence of regionalized brain effects associated with a single bout of aerobic exercise. The observed acute cerebrovascular responses may provide some insight into the brain’s ability to change in relation to chronic interventions.     

Circadian and seasonal variation of the body temperature of sheep in a tropical environment

Nychthemeral and annual rhythms of the rectal temperature were determined for Corriedale sheep in a tropical climate. The minimum rectal temperature averaged 39.55° C at 0500 hours in summer, and 38.87° C at 0600 hours in winter. The maximum was 40.03° C in summer (1700 hours) and 39.33° C in winter (1830 hours). Annual cycle of the rectal temperature showed a minimum in July and maximum in December.     

Circadian Variability of Cystatin C,Creatinine, and Glomerular Filtration Rate (GFR) in Healthy Men during Normal Sleep and after an Acute Shift of Sleep

The estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease and for the treatment of patients with medications that are eliminated by the kidneys. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of GFR. However, there is limited information on the circadian variation of cystatin C and estimated GFR using cystatin C (eGFR_CystC) or “The Modification of Diet in Renal Disease Study” (MDRD) (eGFR_MDRD) equations. We studied the circadian variation of cystatin C and creatinine during night‐ and day‐sleep conditions in seven healthy volunteers. Serum samples were collected every hour (48 samples per individual) to evaluate the effect of different sampling times on the test results. The median intra‐individual coefficients of variations for the studied markers were 4.2% for creatinine, 4.7% for eGFR_MDRD, 5.5% for cystatin C, and 7.7% for eGFR_CystC. Neither cystatin C nor creatinine differed significantly between the night‐ and day‐sleep conditions. Cystatin C differed significantly with time of day (p=.0003), but this was not the case for creatinine (p=.11). The circadian variation of cystatin C was minor. Small but significant increases in creatinine values and a decrease of eGFR_MDRD were observed after food intake. Thus, cystatin C and creatinine sampling does not have to be restricted to specific times of the day.     

Increased Stearoyl-CoA Desaturase Index and Triglyceride Content in the Liver of Rats after a Single Bout of Swimming Exercise

Up-regulation of stearoyl-CoA desaturase (SCD) is closely related to improved insulin resistance. We investigated whether the SCD indices in tissues were influenced by a single-endurance exercise and low content of dietary medium-chain fatty acid (FA). Wistar rats were fed a long-chain (S) or medium- and long-chain FA (M) diet for 2 weeks. At the end of the experiment, the rats were further assigned to two sub-groups (sedentary, Sed; exercise, Ex). These groups were defined as S-Sed, S-Ex, M-Sed, and M-Ex. The rats in the exercise groups were subjected to swimming exercise for 4 h, and tissue samples were obtained. The exercise significantly increased the triglyceride (TG) content and SCD index only in the liver. In contrast, no such changes were apparent by intake of the M diet. A single bout of endurance exercise increased the hepatic TG content and SCD index which might be effective in protecting against insulin resistance.     

The Effects of Circadian Rhythmicity and Time‐Awake on a Simple Motor Task

The aim of the study was to assess if a simple motor task, one that required muscle contractions well below maximum, showed evidence of circadian changes and time‐awake. The task consisted of using a larger counter to flick a number of smaller counters to land as near as possible to the center of a target. The closer a counter landed next to the center of the target, the higher the score obtained. Two distances from the target were used (long and short), and 20 counters were flicked at each distance. The task was performed by 72 diurnally active healthy participants at six test sessions distributed every 4 h throughout the day (08:00 h, 12:00 h, … , 04:00 h), so covering a circadian cycle. When performing the sessions, subjects had been awake for about 1, 4, … , 20 h. Before each test session, sublingual temperature was measured, and estimates of the individual's fatigue and alertness were made. Clear normally phased circadian rhythms (p<0.0001) in oral temperature and alertness with mean peak time (i.e., acrophases of 17.2 h and 15.9 h, respectively) and fatigue (i.e., mean acrophase of 3.4 h) were detected. The total scores for both the long and short distances also showed circadian rhythms that peaked slightly before the temperature rhythm (by 2.31±0.91 h and 1.77±0.77 h, mean±SE, respectively), and the number of occasions that the target was missed altogether showed rhythms that were in anti‐phase (mean acrophases=3.8 h and 4.1 h for the long and short distances, respectively) to that of total scores (mean acrophases=16.0 h and 15.2 h for the long and short distances, respectively). With the long and, particularly, short distances, there were generally significant correlations (r<0.0005) between both the measures of accuracy (total score and number of misses) and body temperature and time‐awake. The accuracy of performance at this task seems to show circadian and time‐awake effects, and so makes it of potential value in protocols where repetitive measurements during the course of a day are required.     

Circadian Variation in the Onset of Acute Cerebral Ischemia: Ethiopathogenetic Correlates in 80 Patients Given Angiography

In a continuous series of 80 acute ischemic hemispheric strokes, the onset of symptoms was between 6:01 a.m. and noon in 45% of cases, between noon and 6:00 p.m. in 22.5%, between 6:Ol p.m. and midnight in 31.25%, and between midnight and 6:00 a.m. in 1.25% (p < 0.0001). By means ofangiography and computerized tomography, and by detection of arterial and cardiac sources of emboli, four stroke subtypes were identified. Embolic and thrombotic strokes had their most frequent onset between 6:01 a.m. and noon (45% and 71%, respectively), whereas strokes of unknown origin and lacunar strokes were randomly distributed between 6:01 p.m. and midnight. The morning activation of the catecholaminergic system can account for this pattern of circadian onset of ischemic stroke.     

Influence of Time of Day on Body Temperature,Heart Rate,Arterial Pressure,and Other Biological Variables in Horses during Incremental Exercise

We examined the response to exercise of selected physiological variables in horses performing the identical routine for eight days, in the morning (a.m.) or in the afternoon (p.m.). Heart rate (HR), systolic and diastolic blood pressure (BP), and body temperature (BT) were all consistently greater in the p.m. For BP and BT, the absolute increase above the a.m. values was the same at rest and during exercise. For HR, the absolute increase was greater during exercise, but the percent increase was the same as during rest. During exercise, blood glucose decreased, while blood lactate and skin temperature increased; these changes were the same during the a.m. and p.m. sessions. We conclude that there is no indication in horses of a difference in the responses of HR, BP, and BT to exercise between the a.m. and p.m. The circadian oscillations, however, alter the absolute values of these variables both at rest and during exercise, raising the possibility that the safety margins against hyperthermia and hypertension may decrease during p.m. exercise.     

Circadian Time Structure of Cardiovascular Characteristics in Human Pregnancy

Conventional time-unspecified single measurements of blood pressure and heart rate may be misleading because they may be influenced, among other factors, by the patient's emotional state, position, diet, and external stimuli. All of these effects depend on the stages of a (mathematical) spectrum of rhythms and trends with age. The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) chronobiologic data processing, assesses early cardiovascular disease risk, e.g., in pregnancy. We have used this approach to quantify changes in 24-h synchronized (circadian) characteristics of cardiovascular variables in two consecutive pregnancies of a clinically healthy woman. Blood pressure and heart rate were automatically monitored, with few interruptions, at I-h intervals, each time for at least 48 consecutive h, and for a total of 76 days of monitoring in each pregnancy. Circadian parameters of those circulatory variables were computed for each single day of measurement by the least-squares fit of a 24-h cosine curve. Regression analysis of parameters thus obtained revealed patterns of variation of circadian-rhythm-adjusted means and amplitudes with gestational age. In both pregnancies, the predictable variability of the circadian-rhythm-adjusted mean of blood pressure can be approximated by a second-order polynomial model on gestational age: a steady linear decrease in systolic, diastolic, and mean arterial blood pressure up to the 22nd week of pregnancy is followed by an increase in blood pressure up to the day of delivery. This longitudinal study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure and heart rate and also allows the establishment of prediction and confidence limits for cardiovascular parameters in a healthy pregnancy.     

Circadian Time Structure of Cardiovascular Characteristics in Human Pregnancy

Conventional time-unspecified single measurements of blood pressure and heart rate may be misleading because they may be influenced, among other factors, by the patient's emotional state, position, diet, and external stimuli. All of these effects depend on the stages of a (mathematical) spectrum of rhythms and trends with age. The evaluation of predictable variability in blood pressure and heart rate by (a) the use of fully ambulatory devices, and (b) chronobiologic data processing, assesses early cardiovascular disease risk, e.g., in pregnancy. We have used this approach to quantify changes in 24-h synchronized (circadian) characteristics of cardiovascular variables in two consecutive pregnancies of a clinically healthy woman. Blood pressure and heart rate were automatically monitored, with few interruptions, at I-h intervals, each time for at least 48 consecutive h, and for a total of 76 days of monitoring in each pregnancy. Circadian parameters of those circulatory variables were computed for each single day of measurement by the least-squares fit of a 24-h cosine curve. Regression analysis of parameters thus obtained revealed patterns of variation of circadian-rhythm-adjusted means and amplitudes with gestational age. In both pregnancies, the predictable variability of the circadian-rhythm-adjusted mean of blood pressure can be approximated by a second-order polynomial model on gestational age: a steady linear decrease in systolic, diastolic, and mean arterial blood pressure up to the 22nd week of pregnancy is followed by an increase in blood pressure up to the day of delivery. This longitudinal study confirms and extends to ambulatory everyday life conditions the predictable pregnancy-associated variability in blood pressure and heart rate and also allows the establishment of prediction and confidence limits for cardiovascular parameters in a healthy pregnancy.     

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

We tested the hypothesis that the capuchin monkey adrenal (Cebus apella) gland has oscillatory properties that are independent of adrenocorticotropic hormone (ACTH) by exploring under ACTH suppression by dexamethasone: (i) maintenance of a circadian rhythm of plasma cortisol and (ii) clock time dependency of plasma cortisol response to exogenous ACTH. The capuchin monkey had a clear ACTH and plasma cortisol rhythm. Dexamethasone treatment resulted in low non-rhythmic ACTH levels and decreased cortisol to 1/10 of control values; nevertheless, the circadian rhythm of plasma cortisol persisted. We found that cortisol response to exogenous ACTH was clock time-dependent. The maximal response to ACTH occurred at the acrophase of the cortisol rhythm (0800 h). These results suggest that the capuchin monkey adrenal cortex may possess intrinsic oscillatory properties that participate in the circadian rhythm of adrenal cortisol secretion and in the circadian cortisol response to ACTH.