A blood plasma inhibitor is responsible for circadian changes in rat renal Na,K-ATPase activity

Rhythmic changes in activity following a circadian schedule have been described for several enzymes. The possibility of circadian changes in Na,K-ATPase activity was studied in homogenates of rat kidney cortex cells. Male Sprague-Dawley rats were kept on a schedule of 12h light (06:00-18:00 h) and 12 h darkness (18:00-06:00 h) for 2 weeks. At the end of the conditioning period, one rat was killed every 2 h, until completion of a 24 h cycle. Outermost kidney cortex slices were prepared, homogenized and assayed for Na,K-ATPase activity. The whole procedure was repeated six times. Na,K-ATPase activity shows an important oscillation (2 cycles/24 h). Peak activities were detected at 09:00 and 21:00 h, whereas the lowest activities were detected at 15:00 and 01:00-03:00 h. The highest activity was 40+/-3 nmoles Pi mg protein(-1)min(-1) (09:00 h), and the lowest was 79+/-3 nmoles Pi mg protein(-1)min(-1) (15:00 h). The amount of the Na+-stimulated phosphorylated intermediate is the same for the 09:00 h and 15:00 h homogenates. Preincubation of 09:00 h kidney cortex homogenates with blood plasma drawn from rats at either 03:00 h or 15:00 h, significantly inhibited their Na,K-ATPase activity. This inhibition was not seen when the preincubation was carried out with either 09:00 h or 21:00 h blood plasma. The striking oscillation (2 cycles/24 h) of the Na,K-ATPase activity of rat kidney cortex cells is ascribed to the presence of an endogenous inhibitor in blood plasma.     

The effect of diets on different factors involved in the duration of resistance to low temperature in rats

Cold resistance of male Sprague Dawley rats (300 g) fed a laboratory chow (P) or a semi-purified diet (T4F or H) for 14 days was evaluated by the degree of hypothermia developed under unrestrained conditions at –18°C or under restraint at +6°C or +1°C. Cold tests were started either at 09:00 h, 14:00 h or 23:00 h. Rats fed a semi-purified diet were more resistant to cold than P-fed rats in winter and summer but not in spring or fall. Cold resistance followed a circadian cycle, being very high at 23:00 h, very low at 14:00 h and in between at 09:00 h. The higher resistance to cold of rats on semi-purified diets coincided with a higher liver glycogen reserve throughout the day and a higher production of corticosterone in stressful conditons than in rats on P diet. However, unrelated diurnal cycles of cold resistance and liver glycogen, absence of hypoglycemia and maintenance of a high level of blood corticosterone in hypothermic rats fed P or semi-purified diets indicate that cold resistance is not limited by glycogen availability in liver or glucose and corticosterone in blood respectively. The lower fecal lactobacilli content found in rats fed a semi-purified diet supports the hypothesis that heat producing organs of these animals may have to compete with a smaller bacterial population in their small intestine for essential nutrients than the P-fed rats which could be a factor in their greater degree of cold resistance.NRCC # 17311     

Orcadian Rhythm in the Torque Developed by Elbow Flexors During Isometric Contraction Effect of Sampling Schedules

Time-dependent changes in elbow flexion torque have been documented according to two different sampling schedules. Seven physical education students took part in the first series of experiments, and 7 other similar subjects in the second. In both sets of experiments, the subjects performed isometric contractions: maximal and submaximal at 90° in the first experiments and maximal at different angular positions in the second. After a 30-minute rest period, the torque developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00h on the day of the experiment. These subjects remained in the laboratory for 24h. In the second series of experiments, the torque developed was measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00h over the subsequent 6 days with only one test session per day. In this case, there was an interval of 20h between two successive test sessions. In the first experiment, a significant time-of-day effect was observed for the torque of the elbow flexors under isometric conditions with an acrophase at 17:58h. The 24h normalized mean score was 92.85% with an amplitude of 7.63% of the daily mean. In the second series of experiments, there was evidence of a circadian rhythm in the torque developed by the elbow flexors at every angle position, especially at 90°, the angle investigated in the first set of experiments. The peak torque was calculated to have occurred at 17:55h. The amplitude of the rhythm was equal to 6.99% of the daily mean. There were no statistically significant differences in the characteristics of the circadian rhythm observed between the two experimental designs. We concluded that an experiment extending over several days could be employed to evaluate circadian rhythms in muscular activity reliably. (Chronobiology International, 14(3), 287–294, 1997)     

Gender differences in morningness-eveningness preference

Morningness-eveningness preference (morning-, intermediate-, evening-type) or circadian typology is the individual difference that most clearly explains the variations in the rhythmic expression of biological or behavioral patterns. The aim of this study was to analyze gender difference in morningness-eveningness preference using the Horne and Ostberg questionnaire in the largest university student population selected so far (N = 2135), with an age range 18-30 yr. Morningness-eveningness questionnaire (MEQ) score distribution closely correlated to the normal curve (range 17-78, mean = 48.25; SD = 10.11), with 338 (15.84%) morning-types, 1273 (59.62%) intermediate-types, and 524 (24.54%) evening-types. The men and women differed significantly in their mean scores (p < 0.0001) and distribution per circadian typology (p < 0.00001), with the men presenting a more pronounced eveningness preference. Three factors were identified by factor analysis: time of greatest efficiency (I), sleep time/sleep phase (II), awakening time/sleep inertia (III). The MEQ items sensitive to gender differences were essentially those included in factor I and factor II. The results are discussed in relation to recent models of circadian regulation of the sleep-wake cycle.     

Sex Difference in Sleep‐Time Preference and Sleep Need: A Cross‐Sectional Survey among Italian Pre‐Adolescents,Adolescents, and Adults

The aim of this study was to examine sex differences in sleep‐time preference by age among Italian pre‐adolescents, adolescents, and adults. The final sample consisted of 8,972 participants (5,367 females and 3,605 males) from 10 to 87 yrs of age. To assess preferred sleep habits, we considered the answers to the open‐ended questions of the Morningness‐Eveningness Questionnaire (MEQ). In agreement with previous studies, we found that sleep‐time preference started to shift toward eveningness from the age of 13 yrs. Females reached their peak in eveningness earlier (about 17 yrs of age) than males (about 21 yrs of age). Thereafter, the ideal sleep‐time preference advanced in men and women with increasing age. Females presented a more significant advanced sleep phase than males only during the years when sexual hormones are typically active. Moreover, females reported a longer ideal sleep duration than males across all age groups examined, except in over 55 yrs one. (Author correspondence: vincenzo.natale@unibo.it)     

Light/dark patterns of interleukin-6 in relation to the pineal hormone melatonin in patients with acute myocardial infarction

AIMS: Atherosclerosis is a chronic disease that, from its origin to its ultimate complications, involves inflammatory cells, inflammatory proteins, and inflammatory responses from vascular cells. It has been demonstrated that cytokine activities are under neuroendocrine control, in part exerted by the pineal gland through the circadian secretion of its main product melatonin. Melatonin is mainly released during the night, but the precise relationship between melatonin and the light/dark rhythm of interleukin-6 in patients with acute myocardial infarction is still unclear. METHODS AND RESULTS: The study included 60 patients diagnosed with acute myocardial infarction and 60 healthy volunteers whose venous blood samples were collected at 09:00 h (light period) and 02:00 h (dark period). Our results demonstrate that interleukin-6 concentrations presented a light/dark pattern with mean serum concentrations being higher in the acute myocardial infarction group than in the control group (101.26 +/- 13.43 and 52.67 +/- 7.73 pg/ml at 02:00 h, 41.93 +/- 5.90 and 22.98 +/- 4.49 pg/ml at 09:00 h, respectively, p < 0.05). Differences in the day/night changes in melatonin levels in control subjects (48.19 +/- 7.82 at 02:00 h, 14.51+/- 2.36 at 09:00 h, pg/ml) and acute myocardial infarction patients (25.97 +/- 3.90 at 02:00 h, 12.29 +/- 4.01 at 09:00 h, pg/ml) (p < 0.05) were a result of a reduced nocturnal elevation of melatonin in the acute myocardial infarction group. CONCLUSIONS: The current findings suggest that the circadian secretion of melatonin may be responsible at least in part for light/dark variations of endogenous interleukin-6 production in patients with acute myocardial infarction. In this study, the melatonin seems to have an anti-inflammatory effect.     

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, epsilon = 0.383; and F(7,175) = 8.01, p < 0.001, epsilon = 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.     

Timing Light Treatment for Eastward and Westward Travel Preparation

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9±8.2 yrs (mean±SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6±6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0±7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p?<?.028) and B (p?<?0.004). Experiment 2 showed significant phase advances in conditions A (p?<?0.018) and B (p?<?0.003) but not C (p?<?0.23), relative to condition D. In Experiment 3, only condition B (p?<?0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R²?=?0.94) provided a partial phase-response curve with maximum advance at approximately 9–11 h and maximum delay at approximately 5–6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).     

Chronopharmacological Study of an Antimicrobial Agent,Norfloxacin, in the Rat

Circadian rhythms in physiological processes may affect pharmacological actions of drugs. The purpose of this study was to determine whether pharmacokinetics or acute lethality (LD 50) of norfloxacin, exhibited circadian rhythmicity. Female Sprague- Dawley prepuberal rats (weight 115.8 ± 10.2 g) synchronized with a 12-h-light/ 12-h-dark cycle (lights on 7:00h) were used throughout the study. Norfloxacin pharmacokinetics after intraperitoneal administration at 4:00, 10:00, 16:00 and 22:00h was characterized. Intraperitoneal norfloxacin LD 50 was administered at 2:00, 6:00, 10:00, 14:00, 18:00 and 22:00 h. Pharmacokinetic parameters and lethality percentages were analyzed by the cosinor method for the presence of circadian rhythmicity. The results showed evidence of circadian rhythmicity for norfloxacin k abs, t ½abs, t max, MRT abs, Cl t /f and AUC. Absorption was higher when the drug was administered during the rest (16:00 h) period, meanwhile elimination was higher when administered during the activity (22:00 h) period. No rhythmicity was determined for norfloxacin lethality. It is concluded that, in this study, time of administration modifies the pharmacokinetics of norfloxacin.     

Circadian variation of carrageenan-paw edema in the rat

The circadian variation of carrageenan (carr)-induced paw edema was studied in sham-operated and adrenalectomized rats. The edema was produced by carr injection into the plantar tissue at 03:00, 09:00, 15:00 and 20:00 hr. In sham-operated rats the rate of appearance of maximal edema was much faster in the evening than in the morning: at 20:00 hr, it was obtained 2 hours after carr injection while at 09:00 hr it took 4 hours. At 03:00 and 15:00 hr, maximal edema was found respectively 2.5 and 4 hours after carr. In adrenalectomized rats, maximal edema at 4 hours of investigation was always larger than in sham-operated animals but the rate of appearance of edema did not change throughout the day as it was obtained 3 hours after carr administration. At 09:00 and 20:00 hr injection of hydrocortisone (HC) to adrenalectomized rats produce the same dose-dependent effect on the rate of formation of edema. However, to reproduce in adrenalectomized animals the rates of formation of edema similar to those obtained in sham-operated rats, an injection of 18 mg/kg HC was required at 09:00 hr while less than 2 mg/kg was needed at 20:00 hr. The results suggest that the circadian rhythm of carr edema is related to circadian variation in the corticosteroid system.     

Orcadian Variation in Amikacin Clearance and Its Effects on Efficacy and Toxicity in Mice with and Without Immunosuppression

A once-daily dosage regimen has been recently recommended in the use of aminoglycoside antibiotics since they induce a postantibiotic effect. In choosing this regimen, one must determine the most appropriate time of day for administration of the drug. We investigated the effects of the timing of amikacin (AMK) administration on the kinetics, the efficacy against intraperitoneal infection with Pseudomonas aeruginosa, and the toxicity of AMK in mice with and without immijnosuppression. We found circadian variations in the kinetics, efficacy, and toxicity of the drug in mice. Male and female ICR mice, which were housed under a light-dark (12:12 h) cycle with free food and water intake, were injected subcutaneously with AMK sulfate 50 mg/kg body wt. There was a circadian variation in AMK clearance for both sexes with the maximum value in the dark phase and the minimum in the light phase after a single administration. When AMK 500 mg/kg/day was repeatedly administered once daily for 30 days, higher toxicity was demonstrated in mice injected with the drug at the time of day with lower AMK clearance, although no difference was demonstrated in the toxicity between the two time points with different AMK clearance when AMK 1,500 mg/kg was administered in a single dose. The ED₅₀ of AMK to cure the infected mice in the midlight phase (13:00 h) with lower clearance was significantly lower than that in the middark phase (01:00 h) with higher clearance. In contrast, the ED₅₀ in the early light phase (09:00 h) was significantly lower than that in the early dark phase (21:00 h), although AMK clearance was not different between these two different time points. In mice premedicated with cyclophosphamide to suppress immune functions, the difference in the ED₅₀ of AMK was still demonstrated between 13:00 and 01:00 h, but not between 09:00 and 21:00 h. The present study shows not only that there were circadian variations in both AMK clearance and toxicity after repeated administration, but also that there was a circadian variation in the efficacy of AMK in mice infected with P. aeruginosa. These results suggest that the timing of drug administration should be considered in pharmacotherapy with AMK and that the most appropriate time of administration in mice and nocturnal animals may be in the midlight (resting) phase. They also suggest that the ED₅₀ of AMK. against P. aeniginosa infection may be influenced not only by the circadian variation in pharmacokinetics but also by the variations in immune systems suppressed by cyclophosphamide.     

Circadian response of annual weeds to glyphosate and glufosinate

Five field experiments were conducted in 1998 and 1999 in Minnesota to examine the influence of time of day efficacy of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [2-amino-4-(hydroxymethyl-phosphinyl)butanoic acid] applications on the control of annual weeds. Each experiment was designed to be a randomized complete block with four replications using plot sizes of 3×9 m. Glyphosate and glufosinate were applied at rates of 0.421 kg ae/ha and 0.292 kg ai/ha, respectively, with and without an additional adjuvant that consisted of 20% nonionic surfactant and 80% ammonium sulfate. All treatments were applied with water at 94 L/ha. Times of day for the application of herbicide were 06:00h, 09:00h, 12:00h, 15:00h, 18:00h, 21:00h, and 24:00h. Efficacy was evaluated 14 d after application by visual ratings. At 14 d, a circadian response to each herbicide was found, with greatest annual weed control observed with an application occurring between 09:00h and 18:00h and significantly less weed control observed with an application at 06:00h, 21:00h, or 24:00h. The addition of an adjuvant to both herbicides increased overall efficacy, but did not overcome the rhythmic time of day effect. Results of the multiple regression analysis showed that after environmental temperature, time of day was the second most important predictor of percent weed kill. Thus, circadian timing of herbicide application significantly influenced weed control with both glyphosate and glufosinate.     

Circadian response of annual weeds to glyphosate and glufosinate

Five field experiments were conducted in 1998 and 1999 in Minnesota to examine the influence of time of day efficacy of glyphosate [N-(phosphonomethyl)glycine] and glufosinate [2-amino-4-(hydroxymethyl-phosphinyl)butanoic acid] applications on the control of annual weeds. Each experiment was designed to be a randomized complete block with four replications using plot sizes of 3×9 m. Glyphosate and glufosinate were applied at rates of 0.421 kg ae/ha and 0.292 kg ai/ha, respectively, with and without an additional adjuvant that consisted of 20% nonionic surfactant and 80% ammonium sulfate. All treatments were applied with water at 94 L/ha. Times of day for the application of herbicide were 06:00h, 09:00h, 12:00h, 15:00h, 18:00h, 21:00h, and 24:00h. Efficacy was evaluated 14 d after application by visual ratings. At 14 d, a circadian response to each herbicide was found, with greatest annual weed control observed with an application occurring between 09:00h and 18:00h and significantly less weed control observed with an application at 06:00h, 21:00h, or 24:00h. The addition of an adjuvant to both herbicides increased overall efficacy, but did not overcome the rhythmic time of day effect. Results of the multiple regression analysis showed that after environmental temperature, time of day was the second most important predictor of percent weed kill. Thus, circadian timing of herbicide application significantly influenced weed control with both glyphosate and glufosinate.     

The relationship between chronotype,sleep disturbance,severity of fibromyalgia,and quality of life in patients with fibromyalgia

ABSTRACT

Patients with fibromyalgia (FM) report high levels of sleep disturbance and chronic diffuse musculoskeletal pain. These patients experience diminished quality of life (QoL) due to pain and other comorbidities. Chronotype preferences have been suggested as a potential factor connecting increased severity of FM, sleep disturbances, and poor overall QoL. The present study is the first study examining the possible association between chronotype preferences, sleep disturbance, severity of FM, and QoL in patients with FM.

One hundred drug-free patients diagnosed with FM participated in this cross-sectional study. Of them, 79 (79%) were females and 21 (21%) were males. The mean age was 41.65 ± 9.17 years (range: 21–62 years). The severity of FM symptoms, chronotype preferences, and QoL was evaluated using the Fibromyalgia Impact Questionnaire (FIQ), Morningness-Eveningness Questionnaire (MEQ), and World Health Organization Questionnaire on Quality of Life: Short Form (WHOQOL-BREF). The participants’ anxiety/depressive symptoms and sleep problems were assessed using the Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI).

The participants were classified according to their MEQ scores as evening type (score: 16–41), neither type (score: 42–58), and morning type (score: 59–86). It was found that there were significant differences in the FIQ score between the three groups (p < .001). It was determined that the total PSQI score was significantly higher in the evening type than the other two types (p < .05). It was found that there were significant differences in the general health, physical health, psychological, and environmental domain scores of the WHOQOL-BREF between the three groups (p < .05). It was detected that there were significant correlations between MEQ scores, WHOQOL-BREF subscale scores, FIQ scores, HADS-A and HADS-D scores, and PSQI scores. According to hierarchical regression analysis, eveningness preference explained an additional 21.9% of the variation in FM severity, thereby causing a statistically significant change in R-squared.

Our results indicated that eveningness preference was directly related to increased FM symptom severity and poorer QoL. Based on these findings, neglecting to take chronotype preference into account may not result in optimal response to standard treatment for some patients with FM.     

Administration-time differences in the pharmacokinetics of gentamicin intravenously delivered to human beings

Administration-time differences of gentamicin pharmacokinetics were studied by crossover design after a single intravenous administration of gentamicin (80 mg) to 10 human subjects at 09:00 (morning time) and 22:00 (nighttime). The profiles of serum gentamicin concentration showed a significant statistical difference between 09:00 and 22:00, suggesting circadian variations of pharmacokinetic behaviors. A significant circadian rhythm of pharmacokinetic parameters as a function of time of day was noted in human subjects, showing lower total body clearance Clt and higher serum area under the curve (AUC) when given at nighttime. The half-life t1/2 was shorter in the morning (2.82 h +/- 0.43 h) when compared to the nighttime (2.97 h +/- 0.36 h), but the difference was not statistically significant. The AUC was significantly greater in the morning (23.4 +/- 3.84 micrograms-h/mL) than that in the nighttime (26.3 +/- 5.79 micrograms-h/mL) (p < .05), most likely because the Clt was significantly higher when gentamicin was given in the morning (3.51 +/- 0.57 L/h) versus in the nighttime (3.18 +/- 0.65 L/h). Although the volume of distribution Vd decreased when given at nighttime, it was independent of the dosing time. From this study, there was an administration-time difference of gentamicin pharmacokinetics in human beings. The optimized dosing regimen of gentamicin can be decided by considering circadian rhythm and rest-activity routine so that minimized toxicity and effective therapy are established for patients. The current findings also can be applied to other drugs with circadian rhythms of pharmacokinetics and narrow therapeutic windows in clinical chronotherapeutics.     

Orcadian Variation in Amikacin Clearance and Its Effects on Efficacy and Toxicity in Mice with and Without Immunosuppression

A once-daily dosage regimen has been recently recommended in the use of aminoglycoside antibiotics since they induce a postantibiotic effect. In choosing this regimen, one must determine the most appropriate time of day for administration of the drug. We investigated the effects of the timing of amikacin (AMK) administration on the kinetics, the efficacy against intraperitoneal infection with Pseudomonas aeruginosa, and the toxicity of AMK in mice with and without immijnosuppression. We found circadian variations in the kinetics, efficacy, and toxicity of the drug in mice. Male and female ICR mice, which were housed under a light-dark (12:12 h) cycle with free food and water intake, were injected subcutaneously with AMK sulfate 50 mg/kg body wt. There was a circadian variation in AMK clearance for both sexes with the maximum value in the dark phase and the minimum in the light phase after a single administration. When AMK 500 mg/kg/day was repeatedly administered once daily for 30 days, higher toxicity was demonstrated in mice injected with the drug at the time of day with lower AMK clearance, although no difference was demonstrated in the toxicity between the two time points with different AMK clearance when AMK 1,500 mg/kg was administered in a single dose. The ED₅₀ of AMK to cure the infected mice in the midlight phase (13:00 h) with lower clearance was significantly lower than that in the middark phase (01:00 h) with higher clearance. In contrast, the ED₅₀ in the early light phase (09:00 h) was significantly lower than that in the early dark phase (21:00 h), although AMK clearance was not different between these two different time points. In mice premedicated with cyclophosphamide to suppress immune functions, the difference in the ED₅₀ of AMK was still demonstrated between 13:00 and 01:00 h, but not between 09:00 and 21:00 h. The present study shows not only that there were circadian variations in both AMK clearance and toxicity after repeated administration, but also that there was a circadian variation in the efficacy of AMK in mice infected with P. aeruginosa. These results suggest that the timing of drug administration should be considered in pharmacotherapy with AMK and that the most appropriate time of administration in mice and nocturnal animals may be in the midlight (resting) phase. They also suggest that the ED₅₀ of AMK. against P. aeniginosa infection may be influenced not only by the circadian variation in pharmacokinetics but also by the variations in immune systems suppressed by cyclophosphamide.     

Circadian phase preference in college students: relationships with psychological functioning and academics

The current study offers a comprehensive assessment of psychosocial functioning and academic performance in relation to circadian phase preference in a US sample of undergraduate college students (N?=?838), aged 17-26 (M?=?19.78, SD?=?1.89). Women had greater morning preference than men, and seniors had greater morning preference than freshmen. Circadian phase preference, fatigue, perceived stress, depression, anxiety, and substance use were assessed cross-sectionally and grade point average (GPA) was assessed prospectively. Evening phase preference was related to higher levels of fatigue, alcohol and caffeine use, and worse academic performance than morning or intermediate phase preferences.     

Phase relationships between sleep-wake cycle and underlying circadian rhythms in Morningness-Eveningness

A shorter phase angle between habitual wake time and underlying circadian rhythms has been reported in evening types (E types) compared to morning-types (M types). In this study, phase angles were compared between 12 E types and 12 M types to verify if this difference was observed when the sleep schedule was relatively free from external social constraints. Subjects were selected according to their Morningness-Eveningness Questionnaire score (MEQ score). There were 6 men and 6 women in each group (ages 19-34 years), and all had a habitual sleep duration between 7 and 9 h. Sleep schedule was recorded by actigraphy and averaged over 7 days. Circadian phase was estimated by the hour of temperature minimum (T(min)) in a 26-h recording and by the timing of the onset of melatonin secretion (dim-light melatonin onset [DLMO]) measured in saliva samples. Phase angles were defined as the interval between phase markers and averaged wake time. Results showed that, in the present experimental conditions, phase angles were very similar in the 2 groups of subjects. However, results confirmed the previously reported correlation between phase and phase angle, showing that a later circadian phase was associated with a shorter phase angle. Gender comparisons showed that for a same MEQ score, women had an earlier DLMO and a longer phase angle between DLMO and wake time. Despite a significant difference in the averaged circadian phases between E-type and M-type groups, there was an overlap in the circadian phases of the subjects of the 2 groups. Further comparisons were made between the 2 circadian types, separately for the subgroups with overlapping or nonoverlapping circadian phases. In both subgroups, the significant difference between MEQ scores, bedtimes, and wake times were maintained in the expected direction. In the subgroup with nonoverlapping circadian phases, phase angles were shorter in E-type subjects, in accordance with previous studies. However, in the overlapping subgroup, phase angles were significantly longer in E types compared to M types. Results suggest that the morningness-eveningness preference identified by the MEQ score refers to 2 distinct mechanisms, 1 associated with a difference in circadian period and phase of entrainment and the other associated with chronobiological aspects of sleep regulation.