SEASONAL VARIATION IN THE EFFECT OF A FIXED DOSE OF HEPARIN ON ACTIVATED CLOTTING TIME IN PATIENTS PREPARED FOR OPEN-HEART SURGERY *

We investigated the effect of an injected bolus of 5 mg kg^- heparin at one circadian stage (08:30 to 11:00) on blood coagulation during different months of the year. Activated clotting times (ACTs) were assessed before and 5 min after heparin dosing to ensure extracorporeal circulation during open-heart surgery. The ACT data of 1083 presumably day-active Turkish patients (816 men and 267 women, mostly older than 46 years) who underwent coronary bypass surgery between 08:30 and 11:00 in the years from 1994 to 1997 were analyzed for annual rhythmicity. The ACT values obtained just before and 5 min after heparinization were subjected to cosinor analysis using a 365.25-day period to assess seasonality in basal ACT level and heparin effect. A small-amplitude annual rhythm with a wintertime peak was documented in the morning ACT in the group of 1083 patients. Rhythms of similar magnitude and staging were also detected in heparin effect on ACT in the 1083 patients and in subgroups categorized by gender. Circannual rhythmicity in the heparin effect on ACT was also documented in the elderly (≥ 45 years old), but not young (18-45 years old) patients. The annual mean effect of heparin on the ACT was statistically significantly greater in younger than older patients. The relatively low-amplitude circannual rhythm in heparin effect on ACT (∼10% of the annual mean) is not viewed as being meaningful in patient preparation for bypass surgery for the 5 mg kg^-1 level of heparin dosing. (Chronobiology International, 18(5), 865-873, 2001)     

LIGHT AT NIGHT ALTERS THE PARAMETERS OF THE ECLOSION RHYTHM IN A TROPICAL FRUIT FLY,DROSOPHILA JAMBULINA

We investigated the effects of natural light at night (LAN) in the field and artificial LAN in the laboratory on the circadian rhythm of pupal eclosion in a tropical wild type strain of Drosophila jambulina captured at Galle, Sri Lanka (6.1^oN, 80.2^oE). The influence of natural LAN, varying in intensity from 0.004 lux (starlight intensity) to 0.45 lux (moonlight intensity), on the entrainment pattern of the circadian rhythm of eclosion at 25^o?±?0.5^oC was examined by subjecting the mixed-aged pupae to natural cycles of light and darkness at the breeding site of this strain in the field. The eclosion peak was ～2?h prior to sunrise, and the 24?h rhythmicity was the most robust. Effects of artificial LAN at 25^o?±?0.5^oC were determined in the laboratory by subjecting pupae to LD 12:12 cycles in which the light intensity of the photophase was 500 lux in all LD cycles, while that of the scotophase was either 0 lux (complete darkness, DD), 0.5, 5, or 50 lux. In the 0 lux LAN condition (i.e., the control experiment), the eclosion peak was ～2?h after lights-on, and the 24?h eclosion rhythm was not as strong as in the 0.5 lux LAN condition. The entrainment pattern in 0.5 lux LAN was strikingly similar to that in the field, as the 0.5 lux LAN condition is comparable to the full moonlight intensity in the tropics. LAN at 0.5 lux dramatically altered both parameters of entrainment, as the eclosion peak was advanced by ～4?h and the 24?h eclosion rhythm was better than that of the control experiment. LAN at 5 lux, however, resulted in a weak eclosion rhythm that peaked in the subjective forenoon. Interestingly, the 50 lux LAN condition rendered the eclosion events unambiguously arrhythmic. After-effects of LAN on the period (τ) of the free-running rhythm and the nature of eclosion rhythm were also determined in DD by a single LD 12:12 to DD transfer. After-effects of the LAN intensity were observed on both the τ and nature of the eclosion rhythm in all four experiments. Pupae raised in 0.5 lux LAN exhibited the shortest τ (20.6?±?0.2?h, N?=?11 for this and subsequent values) and the most robust rhythm, while pupae raised in 50 lux LAN had the longest τ (29.5?±?0.2?h) and weakest rhythm in DD. Thus, these results demonstrate the intensity of LAN, varying from 0 to 50 lux, profoundly influences the parameters of entrainment as well as free-running rhythmicity of D. jambulina. Moreover, the observed arrhythmicity in LD 12:12 cycles caused by the 50 lux LAN condition appeared to be the masking effect of relatively bright light at night, as the LD 12:12 to DD transfer restored the rhythmicity, although it was rather weak. (Author correspondence: drdsjoshi08@gmail.com)     

Evaluation of chronopharmacodynamics of indomethacin by the kaolin-induced pain model in mice

We previously showed that the kaolin-induced writhe reaction exhibits 24h variation with a peak at the end of the resting period (14:00-18:00h) in mice maintained under light from 07:00 to 19:00h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.5 mg/kg) was given orally to mice at 02:00, 08:00, 14:00, or 20:00h, and the suppressive effect on kaolin-induced writhing was determined after each timed dosing. After dosing at 08:00h, indomethacin remarkably reduced the number of writhes during the critical span of 14:00-18:00h—the time when writhing reaction was greatest during the 24h, while the suppressive effect of the medicine after dosing at the other clock times was relatively small. These data suggest the analgesic effect of indomethacin in mice with the kaolin-induced writhing is greater after dosing in the early resting period, which is similar to that reported in patients with nocturnal pain. The kaolin-induced pain mouse model seems to be useful for the chronopharmacodynamic evaluation of analgesic agents.     

MORNING-EVENING ADMINISTRATION TIME DIFFERENCES IN DIGOXIN KINETICS IN HEALTHY YOUNG SUBJECTS

Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration C_max; T_max, the time to reach C_max; area under plasma concentration curve AUC; and elimination half-time T_1/2 of digoxin were determined. T_max was statistically significantly shorter (54 min) following 08:00 dosing compared to 20:00 dosing (96 min). Although the C_max was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except T_max exhibited administration time dependency. (Chronobiology International, 18(5), 841-849, 2001)     

MAXIMAL POWER,BUT NOT FATIGABILITY,IS GREATER DURING REPEATED SPRINTS PERFORMED IN THE AFTERNOON

The present study was designed to investigate if the suggested greater fatigability during repeated exercise in the afternoon, compared to the morning, represents a true time-of-day effect on fatigability or a consequence of a higher initial power. In a counterbalanced order, eight subjects performed a repeated-sprint test [10?×?(6 s of maximal cycling sprint?+?30 s of rest)] on three different occasions between: 08:00–10:00, 17:00–19:00, and 17:00-19:00?h controlled (17:00–19:00?h_cont, i.e., initial power controlled to be the same as the two first sprints of the 08:00–10:00?h trial). Power output was significantly (p?<?0.05) higher for sprints 1, 2, and 3 in the afternoon than in the morning (e.g., sprint 1: 23.3 ±1 versus 21.2 ±1 W·kg^?1), but power decrement for the 10 sprints was also higher in the afternoon. Based on the following observations, we conclude that this higher power decrement is a consequence of the higher initial power output in the afternoon. First, there was no difference in power during the final five sprints (e.g., 20.4 ±1 versus 19.7 ±1 W·kg^?1 for sprint 10 in the afternoon and morning, respectively). Second, the greater decrement in the afternoon was no longer present when participants were producing the same initial power output in the afternoon as in the morning. Third, electromyographic activity of the vastus lateralis decreased during the exercise (p?<?0.05), but without a time-of-day effect. (Author correspondence: sebastien.racinais@aspetar.com)     

Evaluation of Chronopharmacodynamics of Indomethacin by the Kaolin-Induced Pain Model in Mice

We previously showed that the kaolin-induced writhe reaction exhibits 24h variation with a peak at the end of the resting period (14:00–18:00h) in mice maintained under light from 07:00 to 19:00h. In this study, we used this model to evaluate the administration-time-dependent (chronopharmacodynamic) effect of indomethacin. Indomethacin (0.5 mg/kg) was given orally to mice at 02:00, 08:00, 14:00, or 20:00h, and the suppressive effect on kaolin-induced writhing was determined after each timed dosing. After dosing at 08:00h, indomethacin remarkably reduced the number of writhes during the critical span of 14:00–18:00h—the time when writhing reaction was greatest during the 24h, while the suppressive effect of the medicine after dosing at the other clock times was relatively small. These data suggest the analgesic effect of indomethacin in mice with the kaolin-induced writhing is greater after dosing in the early resting period, which is similar to that reported in patients with nocturnal pain. The kaolin-induced pain mouse model seems to be useful for the chronopharmacodynamic evaluation of analgesic agents.     

GENDER DIFFERENCES IN DIURNAL VARIATIONS OF SUBJECTIVE ACTIVATION AND MOOD

This article evaluates the influence of gender on diurnal and postlunch period variations in subjective activation and mood. This topic is not often addressed in the literature; particularly, little attention has been paid to how biological rhythms might bias research results. We studied 40 university student volunteers (20 men, 20 women) aged 18 to 23 years old (X = 20.23, SD = 1.03); they responded to questions on eight unipolar visual analog scales every hour from 08:00 to 21:00. Gender differences were observed in both diurnal and postlunch variations for scales of positive activation (alertness, vigor); sleepiness, however, was only sensitive to diurnal variation, and weariness was sensitive only to a postlunch effect. Women displayed a morning- type pattern, with their optimal moment (11:00) coming 2h earlier than for men, and their activation ratings ranged more widely. The only mood scale that showed differences related to gender was that of happiness, for which women had a higher diurnal mean, a diurnal peak 2h earlier, and a less-intense postlunch effect. Endogenous control of rhythmic pattern appears to be less intense in women, probably due to the coexistence of circamensual rhythmicity, although environmental or sociocultural influences may play a modulating role. Chronopsychological gender differences in affective states should be studied further given the implication they have for the prevention and treatment of mood disorders. (Chronobiology International, 18(3), 491–502, 2001)     

MORNING-EVENING ADMINISTRATION TIME DIFFERENCES IN DIGOXIN KINETICS IN HEALTHY YOUNG SUBJECTS

Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration C_max; T_max, the time to reach C_max; area under plasma concentration curve AUC; and elimination half-time T_1/2 of digoxin were determined. T_max was statistically significantly shorter (54 min) following 08:00 dosing compared to 20:00 dosing (96 min). Although the C_max was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except T_max exhibited administration time dependency. (Chronobiology International, 18(5), 841–849, 2001)     

Extremely low frequency magnetic field exposure modulates the diurnal rhythm of the pain threshold in mice

The aim of this study was to determine whether exposure to extremely low frequency magnetic field (ELF-MF) affects the normal diurnal rhythm of the pain threshold in mice. Pain thresholds were evaluated in mice using the hot plate test. A significant increase of pain threshold during night was observed compared to that during day. This rhythm was attenuated by both constant exposure to light (LL) and constant exposure to darkness (DD) for 5 days. Under DD exposure, the diurnal rhythm in pain threshold was restored when mice were exposed to ELF-MF (60 Hz, 1.5 mT for 12 h daily, from 08:00 to 20:00 h) for 5 days. The diurnal rhythm was not reversed under dark with reversed ELF-MF cycle (exposure to 1.5 mT from 20:00 to 08:00 h, next day) for 5 days, although pain threshold in the ELF-MF exposed period of night was slightly decreased. The diurnal rhythm of melatonin analgesic effect related to pain threshold was also observed under DD by the exposure of ELF-MF for 5 days, but not for 5 nights. The present results suggest that ELF-MF may participate in the diurnal rhythm of pain threshold by acting on the system that is associated with environmental light-dark cycle.     

Glucocorticoid effects on the diurnal rhythm of circulating leptin levels

It is known that circulating leptin shows diurnal variation with a nocturnal rise; however, the mechanisms generating this rhythm have not been fully elucidated. Glucocorticoids are a potent stimulator of leptin secretion, and there is a reciprocal relationship between circulating leptin and glucocorticoid levels. We hypothesized that glucocorticoids could modulate the diurnal rhythm of circulating leptin. We therefore explored the diurnal variation of leptin under situations in which subjects showed no or some shift of glucocorticoid diurnal rhythm, such as prednisolone-administered humans, and adrenalectomized and corticosterone-replaced (ADX+B) rats. The peak level of plasma cortisol immunoreactivity was shifted from early morning to noon by prednisolone administration. The nocturnal increment of plasma leptin in prednisolone-administered patients (71.2 +/- 14.2% from 08:00 h value) was significantly greater than that in normal volunteers (12.2 +/- 7.5% from 08:00 h value), but the timing of nadir and the peak of plasma leptin was not shifted. In normal rats, the plasma concentration of leptin showed the diurnal rhythm with the bottom at 16:00 h and the top between midnight and early morning. The amplitude of leptin diurnal rhythm was significantly reduced in ADX+B rats (08:00 h: 3.0 +/- 0.2, 16:00 h: 2.7 +/- 0.2, 00:00 h; 3.7 +/- 0.2 ng/ml) compared with sham operated rats (08:00 h: 3.0 +/- 0.2, 16:00 h 2.2 +/- 0.2, 00:00 h: 4.7 +/- 0.4 ng/ml); but ADX+B rats still retained similar timing of nadir and the peak of plasma leptin as observed in sham rats. These results indicate that glucocorticoids enhance the amplitude of leptin diurnal rhythm, and are consistent with previous findings showing that glucocorticoids increase leptin secretion. Glucocorticoids appear to play modulatory, but not essential roles in generating leptin diurnal rhythm.     

Atrial natriuretic peptide-renin-aldosterone system in cirrhosis of the liver: circadian study

Plasma levels of immunoreactive atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone (PA) were measured for an entire day at 6:00 am, 8:00 am, 12:00 pm, 6:00 pm, 8:00 pm, and 12:00 am in 6 healthy subjects, in 10 patients with compensated cirrhosis of the liver, and in 10 cirrhotics with ascites. The subjects, after synchronized standard life conditions lasting for 6 days were held in a clinostatic position during the study. The data were analyzed by the "cosinor" method. The results show significant circadian rhythms for the three biological variables in healthy subjects. In the compensated cirrhotic group, a circadian rhythm was detected only for PA. No rhythm was demonstrated in the ascitic patients. These data suggest that in cirrhosis of the liver, great variations in secretion rhythmicity for PRA and ANP are present, while maintaining the intrinsic PA rhythmicity, which is lost in patients with ascites. This progressive derangement in PA circadian rhythm in the ANP-PRA-PA system can be considered as an index of evolution in the natural history of cirrhosis of the liver.     

秦岭羚牛春夏季昼夜活动节律与时间分配

1996年4~8月,在陕西省佛坪自然保护区内采用无线电遥测技术对4只秦岭羚牛（Budorcas taxicolor bedfordi）的活动规律进行了研究。春夏季羚牛的活动规律以白昼活动为主。羚牛每昼夜有69.95+11.06%的时间处于活动状态（n=40）,其中76.77%的活动时间是在日出后到日落前的白昼。白昼有3个活动高峰期,分别出现在06:00~08:00、10：00~12：00、18：00~20：00 3个时间段。在夜间羚牛只有1个活动高峰期,通常出现在24：00至次日凌晨01：00的时间段。野外观察证实,羚牛白昼的3个活动高峰期与羚牛群体活跃采食的时间吻合。羚牛的昼夜活动节律的形成与变化,可能会受到诸如光照、温度、雨等气候条件的影响。每天的黎明阶段（06：00~07：00）及黄昏阶段（18：30~19：30）是羚牛活动最频繁的时候,平均活动率在90%以上。大雨期间羚牛常常站立或卧地休息。此外,羚牛昼夜活动节律和时间分配方面的差异在年龄上也有所体现。     

Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy humans

Neuro-endocrine hormone secretion is characterized by circadian rhythmicity. Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak in the morning, determining the circadian rhythm of cortisol secretion, TRH and TSH show circadian variations with higher levels at night. Thyroxine levels do not change with clear circadian rhythmicity. In this paper we have considered a possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were determined in blood samples obtained every four hours for 24 hours from ten healthy males, aged 36-51 years. We correlated hormone serum levels at each sampling time and evaluated the presence of circadian rhythmicity of hormone secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated negatively with FT4, TSH correlated positively with TRH, TRH correlated positively with FT4 and melatonin correlated positively with TSH. In the resting phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin correlated negatively with FT4, TSH correlated negatively with FT4, cortisol correlated positively with FT4 and TSH correlated positively with TRH. A clear circadian rhythm was validated for the time-qualified changes of melatonin and TSH secretion (with acrophase during the night), for cortisol serum levels (with acrophase in the morning), but not for TRH and FT4 serum level changes. In conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by cortisol and melatonin serum levels and by their circadian rhythmicity of variation.     

Seasonal rhythms of "acute phase proteins" in humans

"Acute phase proteins" comprise a group of proteins whose concentrations increase or decrease by at least 25% after a damaging stimulus (burn, trauma, tissue damage, etc.) or during inflammation. We investigated the seasonal variation in the concentrations of several acute phase proteins--alpha1-antichymotrypsin (ACT), alpha1-acid glycoprotein (AGP), transferrin (Tf), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cp), antitrypsin (AT), and haptoglobin (Hp). Blood samples were collected from 15 healthy volunteers, who were subjected to the seasonal changes in illumination, were drawn at 08:00 h every 3 months (August, November, January/February, March/April, June/July). With the exception of Hp, all acute phase proteins showed an annual rhythm (ANOVA; p < 0.01). Lowest concentrations occurred in the winter months (November through February), with the exception of Tf, which was oppositely phased.     

EFFECT OF CHRONIC HYPERPROLACTINEMIA ON DAILY CHANGES OF GLUTAMATE AND ASPARTATE CONCENTRATIONS IN THE MEDIAN EMINENCE AND DIFFERENT HYPOTHALAMIC AREAS OF MALE RATS

The 24h changes of glutamate (GLU) and aspartate (ASP) werestudied in the median eminence (ME) and hypothalamic areas. It was analyzedwhether prolactin may change their daily patterns. The hypothalamic concentrationof these amino acids was measured by high-performance liquid chromatography(HPLC) with fluorometric detection. Plasma prolactin levels increased overthe 24h light-dark cycle after pituitary grafting compared to controls, andits circadian rhythm was disrupted. In controls, aspartate and glutamate inthe hypothalamic areas studied followed a specific daily variation or showedno rhythmicity. In the median eminence, hyperprolactinemia seem to phase advancethe aspartate or glutamate peaks from 16:00 to 12:00. In the mediobasal hypothalamus,hyperprolactinemia altered daily changes of aspartate and significantly decreasedits concentration. Also, it seems to delay the nocturnal glutamate peak comparedto controls. In the posterior hypothalamus, hyperprolactinemia did not changeaspartate and glutamate concentrations and their daily changes, although itincreased the glutamine concentration. These data show the existence of 24hchanges of amino acid concentration in three of the hypothalamic regions studied.Increased plasma prolactin levels differentially affected these patterns dependingon the hypothalamic area analyzed. (ChronobiologyInternational, 17(5), 631–643, 2000)     

DIURNAL VARIATION IN THE P300 COMPONENT OF HUMAN COGNITIVE EVENT-RELATED POTENTIAL

Diurnal variation in the P300 component of the human cognitive event-related potential (ERP) was examined. The P300 component is considered to be a measure of neuroelectric activity related to cognitive functions such as attention allocation and information processing. Nine diurnally active healthy male subjects whose sleep-wake rhythms were synchronized prior to the experiment were studied. The P300 components oral temperature, heart rate, left- and right-hand grip strength, reaction time, subjectively rated sleepiness, attention level, and fatigue were measured at 08:00, 11:00, 14:00, 17:00, and 20:00. Significant diurnal variations in P300 latency, P300 amplitude, oral temperature, heart rate, left- and right-hand grip strength, subjectively rated sleepiness, and attention level were observed. The P300 latency at 08:00 was significantly longer than at 11:00, 17:00, and 20:00, while the P300 amplitude at 08:00 was significantly greater than at 17:00 and 20:00. The P300 latency was correlated positively with subjectively rated sleepiness and negatively correlated with subjectively rated attention level. These results suggest the existence of diurnal variation in human cognitive functions. (Chronobiology International, 17(5), 669–678, 2000)     

Relative bioavailability of copper in a copper-lysine complex or copper sulfate for ruminants as affected by feeding regimen

An experiment was conducted with 40 crossbred wether lambs to compare the relative bioavailability of Cu from a Cu-lysine complex with that from Cu sulfate under two feeding regimens. Liver biopsy samples were collected by a laparotomy technique and lambs were given 12 days to recover and adapt to individual pens. Lambs were fed either a control basal diet (9.8 mg kg⁻¹ Cu dry matter (DM) basis) or basal supplemented with 180 mg kg⁻¹ Cu as either reagent grade CuSO₄ · 5H₂O or a feed-grade Cu-lysine complex. There were 12 lambs fed control diet and 14 lambs fed each Cu-supplemented diet. Half of the lambs given each diet were fed 1.0 kg of their respective diet once daily at 08:00 h. The remaining half were fed 1.0 kg in equal portions (166 g) six times during a 24 h period at 04:00 h, 08:00 h, 12:00 h, 16:00 h, 20:00 h and 24:00 h. Lambs were fed experimental diets for 10 days, then killed and livers removed for Cu analysis. Lambs fed once daily accumulated more (P < 0.05) Cu in liver than those fed every 4 h. There was no Cu source × feeding regimen interaction (P > 0.10). Based on multiple linear regression slope ratio of log₁₀ transformed final liver Cu concentration on total intake of Cu (mg day⁻¹) with the initial liver biopsy Cu concentration as a covariate, bioavailability of Cu from Cu-lysine relative to Cu sulfate was 93.4% (P > 0.05) for combined feeding regimens.     

Melatonin concentrations in patients with large goiter before and after surgery

OBJECTIVES: Surgical removal of a very large goiter may traumatize adjacent anatomical structures. The manipulations that involve superior cervical ganglia may alter melatonin secretion. To test this hypothesis we decided to study diurnal serum melatonin profiles in patients with a very large goiter before and after the surgery. MATERIAL AND METHODS:The study was performed on 10 women (mean age-46.5+/-1.6 years; mean+/-SEM; range 39-54 years) with very large non-toxic nodular goiter (mean thyroid volume-125.8+/-25.9 cm (3); mean+/-SEM; range 82.6-326.7 cm(3)). Diurnal serum melatonin profiles were estimated two days before the operation and 10 days after the surgery. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: Nocturnal serum melatonin concentrations (at 24, 02, and 04 hours) were significantly higher after the surgery than before the operation. CONCLUSIONS: Very large goiter may compress the superior cervical ganglia altering indirectly the melatonin synthesis. It cannot be excluded, however, that the presence of the large goiter in some other way affects melatonin secretion.     

Diurnal variation in gait characteristics and transition speed

The aim of this study was to investigate the effect of time-of-day on Preferred Transition Speed (PTS) and spatiotemporal organization of walking and running movements. Twelve active male subjects participated in the study (age: 27.2?±?4.9 years; height: 177.9?±?5.4?cm; body mass: 75.9?±?5.86?kg). First, PTS was determined at 08:00?h and 18:00?h. The mean of the two PTS recorded at the two times-of-day tested was used as a reference (PTS_m). Then, subjects were asked to walk and run on a treadmill at three imposed speeds (PTS_m, PTS_m?+?0.3?m.s^?1, and PTS_m???0.3?m.s^?1) at 08:00?h and 18:00?h. Mean stride length, temporal stride, spatial stride variability, and temporal stride variability were used for gait analysis. The PTS observed at 08:00?h (2.10?±?0.17?m.s^?1) tends to be lower (p?=?0.077) than that recorded at 18:00?h (2.14?±?0.19?m.s^?1). Stride lengths recorded while walking (p?=?0.038) and running (p?=?0.041) were shorter at 08:00?h than 18:00?h. No time-of-day effect was observed for stride frequency during walking and running trials. When walking, spatial stride variability (p?=?0.020) and temporal stride variability (p?=?0.028) were lower at 08:00?h than at 18:00?h. When running, no diurnal variation of spatial stride variability or temporal stride variability was detected.     

Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.