Role of the liver in the regulation of circadian rhythm of blood iron in rats]

In experiments with Wistar rats there was discovered statistically significant circadian rhythm of serum iron concentration reaching its maximum in the evening, minimum--early in the morning, and having an amplitude of at least 20% of the mesor. The reciprocal interrelations between circadian cycles of iron content in blood and liver were also found. The synchronization of blood iron level with lipid peroxidation products in membranous liver structures, as well as serum alanine aminotransferase activity, and their inversion with respect to the circadian rhythms of liver RES absorption ability and liver iron content are considered to be a proof of liver participation in regulation of iron exchange temporal organization in rats.     

Constant light influences the circadian oscillations of circulatory lipid peroxidation, antioxidants and some biochemical variables in rats

Temporal oscillations of circulatory thiobarbituric acid reactive substances (TBARS), antioxidants such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and glucose, cholesterol, total protein and aspartate transaminase (AST) were studied under LD (12:12 h) and constant light (LL) (500 lux) conditions after exposing the animal for 21 days. Advances in the acrophase of GSH, SOD, catalase, glucose, total protein and (AST) rhythms and delays in TBARS and cholesterol were found; amplitude and mesor values of these rhythms were found to be altered during constant light treatment. The above said circadian alterations during LL exposure may be due to (1) formation of photooxidants and stress mediated lipid peroxidation, suppression of melatonin (2) modulation of neuroendocrine and neurotransmitters rhythm (3) suppression of sleep - wake cycle (4) feeding and locomotion rhythm. The exact mechanism still remains to be explored and further research needed.     

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 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.     

Rhythmometry gauges treatment of mesor-hypertension in the seventh and eight decades of life

Autorhythmometry of blood pressure by an individual over an age-span of 67 to 72 years showed a strong circadian rhythm superimposed upon significant circaseptan and circannual rhythms. Automatic BP monitoring with an Arteriosonde throughout 24-hour spans on 4 separate occasions, before and during treatment, also indicated a prominent circadian BP rhythm and a treatment-related reduction in circadian mesor. The concept of a blood pressure mesor reference for the antimesor-hypertensive treatment constitutes a valuable guideline in the control of "familial" mesor-hypertension.     

The influence of short-term sedentary behavior on circadian rhythm of heart rate and heart rate variability

The notion that sedentary behavior is harmful to human health is widespread. Little is known about the short term influence of sedentary behavior on heart rate (HR) and heart rate variability (HRV) circadian rhythms. Therefore the purpose of the present study was to examine the influence of short term sedentary behavior on the circadian rhythms of HR and HRV using cosine periodic regression analysis. Sixteen healthy young students were included in a randomized crossover study. All subjects underwent 24-h ECG Holter monitoring in two different states of physical activity, an active condition (more than 15,000 steps per day) and a sedentary condition (less than 1,000 steps per day). Hourly mean values were calculated for HR and HRV, and then were evaluated using cosine periodic regression analysis. The circadian rhythm parameters, amplitude, mesor, and acrophase for HR and HRV variables were obtained. As a result, the significance of the circadian rhythm was confirmed for all variables in each condition. The measure of fit R2 value was decreased in sedentary condition. The amplitude of the sedentary condition was significantly smaller than that of the active condition with respect to HR (7.94 ± 1.91 bpm vs. 15.4 ± 3.93 bpm, p < 0.001), natural log of the high frequency measurement (lnHF) (0.38 ± 0.21 ms2 vs. 0.80 ± 0.28 ms2, p < 0.001), and low frequency/high frequency ratio (LF/HF) (0.75 ± 0.54 vs. 1.24 ± 0.69, p = 0.008). We found that sedentary behavior not only significantly lowered the amplitude of HR and HRV variables, but also might have led to weakness of the circadian rhythm of the HR and HRV variables.     

Circadian rhythms of urinary excretions of water and electrolytes in patients receiving total parenteral nutrition (TPN)

In order to determine whether the usual feeding pattern actually modifies the circadian rhythms of urinary excretion of water and electrolytes, we compared the circadian rhythm characteristics in patients receiving total parenteral nutrition (TPN group) with those in patients on an ordinary hospital diet (control group). Statistically significant circadian rhythms were detected in all of the urinary variables investigated herein by using the population mean-cosinor method in both groups. In addition, there were no statistically significant differences of the mesor, the %-amplitude and the acrophase between the two groups. These results suggest that the usual feeding pattern is not a main determinant in forming the circadian rhythm characteristics of human urinary variables.     

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.     

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.     

Influence of seasons on circadian rhythm of acid phosphatase and beta-acetyl-glucosaminidase activity in the mouse salivary gland and liver

Influence of seasons on circadian changes in acid phosphatase and beta-acetylglucosaminidase activity was studied in the liver and submandibular gland of sexually mature mice. Seasonal differences in circadian rhythm was found in both examined enzymes in both organs. These changes were independent from each other and each rhythm was differently subjected to seasonal changes. The lowest seasonal influence was observed in acid phosphatase in the salivary gland. Activity of the other enzymes changed in different degrees, having their acrophases at different times of the day and different rhythm intensity. The highest circadian activity changes measured by amplitude and mesor were observed in spring and summer whereas in the autumn and winter their activity had much weaker rhythms or even they disappeared completely. An attempt was made to explain the observed changes by changes in hormonal background and a certain kind of genetic memory pertaining to laboratory animals.     

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.     

Circadian Hematologic Time Structure in the Elderly

Twenty-three clinically healthy, diurnally active elderly subjects, 71 ± 5 years of age were studied over a 24-hr span (six samples). Complete blood counts and differential counts were done (Ortho ELT-8, Wright stained smears). The circadian rhythm parameters of the hematologic variables in the elderly subjects were compared with reference values obtained from a larger group of clinically healthy young adult and adult subjects studied independently. The data were analyzed by cosinor and the Bingham test. Circadian rhythms in the number of circulating formed elements in the peripheral blood persist in the aged. In comparison with the young adult, the elderly subjects show differences in the timing (phase advance) of the circadian rhythms in circulating neutrophil leukocytes and lymphocytes, a decrease in the circadian amplitude of circulating platelets, a decrease in circadian rhythm adjusted mean (mesor) in the red cell count, and in the neutrophil band forms.     

Locomotor Activity and Temperature Rhythms in Cirrhotic and Portal Hypertensive Rats

This study was performed to examine the circadian variations in body temperature and locomotor activity in two rat models of liver damage and portal-systemic collateralization, it is, cirrhosis by common bile duct ligature and portal vein ligation. Locomotor activity and temperature were measured telemetrically, and the degree of portal-systemic shunting was evaluated by the radioactive microsphere technique. In cirrhotic rats a significant increase in portal pressure and portal-systemic shunting occurred, with extensive liver damage and ascitis. These changes were accompanied by a derangement of the activity rhythm (decrease in total activity, night/day ratio and Qp) and an increase in the amplitude of the temperature rhythm. In portal vein-ligated rats, portal vein pressure and portal-systemic shunting increased significantly, with no changes in any of the rhythm parameters analyzed (total, diurnal and nocturnal activity pulses, night/day activity ratio and Qp for activity; mesor, amplitude and free-running period for temperature). The results indicate that liver dysfunction, and not merely portal hypertension or portal-systemic shunting, is the main factor affecting daily rhythms in cirrhotic rats.     

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.     

Locomotor Activity and Temperature Rhythms in Cirrhotic and Portal Hypertensive Rats

This study was performed to examine the circadian variations in body temperature and locomotor activity in two rat models of liver damage and portal-systemic collateralization, it is, cirrhosis by common bile duct ligature and portal vein ligation. Locomotor activity and temperature were measured telemetrically, and the degree of portal-systemic shunting was evaluated by the radioactive microsphere technique. In cirrhotic rats a significant increase in portal pressure and portal-systemic shunting occurred, with extensive liver damage and ascitis. These changes were accompanied by a derangement of the activity rhythm (decrease in total activity, night/day ratio and Qp) and an increase in the amplitude of the temperature rhythm. In portal vein-ligated rats, portal vein pressure and portal-systemic shunting increased significantly, with no changes in any of the rhythm parameters analyzed (total, diurnal and nocturnal activity pulses, night/day activity ratio and Qp for activity; mesor, amplitude and free-running period for temperature). The results indicate that liver dysfunction, and not merely portal hypertension or portal-systemic shunting, is the main factor affecting daily rhythms in cirrhotic rats.     

Features of the circadian rhythm of temperature of the skin at children of 8-9 years and young men and girls

Problem of the present work was studying age features circadian rhythm of temperature of a skin with application of a method "Termochron iButton". Day-night rhythm of a skin temperature at two age-grades was investigated: boys and girls of 8-9 years and young men and girls of 20-22 years. For this purpose monitoring temperature during 48 hours with an interval of registration 10 minutes has been lead. Are revealed authentic chronobiological differences: mesor temperatures above at girls, than at boys, and at young men, above, than at girls. Amplitude of a circadian rhythm is above at boys and at girls. Researches chronobiological parameters in the different terms of day have shown, that an average level of temperature at night below at all examinees. The amplitude at adult people in the different terms of day does not differ, while at children it above in the night term.     

Photoperiodic influences on ultradian rhythms of male siberian hamsters

Seasonal changes in mammalian physiology and behavior are proximately controlled by the annual variation in day length. Long summer and short winter day lengths markedly alter the amplitude of endogenous circadian rhythms and may affect ultradian oscillations, but the threshold photoperiods for inducing these changes are not known. We assessed the effects of short and intermediate day lengths and changes in reproductive physiology on circadian and ultradian rhythms of locomotor activity in Siberian hamsters. Males were maintained in a long photoperiod from birth (15 h light/day; 15 L) and transferred in adulthood to 1 of 7 experimental photoperiods ranging from 14 L to 9 L. Decreases in circadian rhythm (CR) robustness, mesor and amplitude were evident in photoperiods ≤14 L, as were delays in the timing of CR acrophase and expansion of nocturnal activity duration. Nocturnal ultradian rhythms (URs) were comparably prevalent in all day lengths, but 15 L markedly inhibited the expression of light-phase URs. The period (τ'), amplitude and complexity of URs increased in day lengths ≤13 L. Among hamsters that failed to undergo gonadal regression in short day lengths (nonresponders), τ' of the dark-phase UR was longer than in photoresponsive hamsters; in 13 L the incidence and amplitude of light-phase URs were greater in hamsters that did not undergo testicular regression. Day lengths as long as 14 L were sufficient to trigger changes in the waveform of CRs without affecting UR waveform. The transition from a long- to a short-day ultradian phenotype occurred for most UR components at day lengths of 12 L-13 L, thereby establishing different thresholds for CR and UR responses to day length. At the UR-threshold photoperiod of 13 L, differences in gonadal status were largely without effect on most UR parameters.     

RNAi of the circadian clock gene period disrupts the circadian rhythm but not the circatidal rhythm in the mangrove cricket

The clock mechanism for circatidal rhythm has long been controversial, and its molecular basis is completely unknown. The mangrove cricket, Apteronemobius asahinai, shows two rhythms simultaneously in its locomotor activity: a circatidal rhythm producing active and inactive phases as well as a circadian rhythm modifying the activity intensity of circatidal active phases. The role of the clock gene period (per), one of the key components of the circadian clock in insects, was investigated in the circadian and circatidal rhythms of A. asahinai using RNAi. After injection of double-stranded RNA of per, most crickets did not show the circadian modulation of activity but the circatidal rhythm persisted without a significant difference in the period from controls. Thus, per is functionally involved in the circadian rhythm but plays no role, or a less important role, in the circatidal rhythm. We conclude that the circatidal rhythm in A. asahinai is controlled by a circatidal clock whose molecular mechanism is different from that of the circadian clock.