Influences of sex and age on biological rhythms of serum lipids and lipoproteins

Background: Few studies have evaluated seasonal variations of biochemical parameters routinely analyzed in clinical laboratories. Rhythmic patterns for lipids and lipoproteins have been demonstrated and have been the object of research, mainly because of their demonstrated association with coronary artery disease. This study evaluated the occurrence of biological rhythms on serum lipids and lipoproteins and the effects of sex and age on the rhythms in a Brazilian hospital outpatient population. Methods: Retrospective laboratory study was carried out to evaluate the results of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglycerides (TG), from individuals registered at a university referral hospital over 8years. The studied population was composed of individuals of both sexes and all ages totaling 38,579 participants and 301,934 measurements. Statistical analyses were carried out using the SAS program and the temporal analysis used the Cosinor method. Results: TG rhythm was present only in females. All other parameters were equally rhythmic in both sexes. Regarding age, HDL-C presented rhythms in all age groups, but TC and LDL-C showed seasonality only for those > 13years, TG did not present rhythms in all age groups. Conclusion: Effects of sex and age on biological rhythms detected in TC, LDL-C and HDL-C should be considered a significant cause of pre-analytical variation in these laboratory tests. (C) 2009 Elsevier B.V. All rights reserved.

Rhythmic variations in pain, stiffness, and manual dexterity in hand osteoarthritis

Objective: To explore circadian variation in pain, stiffness, and manual dexterity inpatients with hand osteoarthritis (OA). Methods: Twenty one patients with hand OA, as defined by ACR criteria (17 women, four men, mean age 62.2 years, range 52-74 years) self rated pain and stiffness on separate 10 cm horizontal visual analogue scales and performed bead intubation coordinometry (BIC) six times each day (on waking up, at bedtime, and every four hours in between) for 10 consecutive days. Each series (using data with the trend removed if there was a significant trend) was analysed for circadian rhythmicity by a cosine. vector technique (single cosinor). With individual data expressed as the percentage of the mean, group rhythm characteristics at period 24 hours were summarised for each variable by population mean cosinor analysis. Results: Individual analyses identified significant circadian rhythms at pless than or equal to0.05 for pain (n=15/21), stiffness (n=16/20), and dexterity (n=18/21), and a significant circadian rhythm on a group basis was identified for pain (p=0.013), stiffness (p

The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

Seasonal variation of overall and cardiovascular mortality: a study in 19 countries from different geographic locations.

BACKGROUND: Cardiovascular diseases (CVD) mortality has been shown to follow a seasonal pattern. Several studies suggested several possible determinants of this pattern, including misclassification of causes of deaths. We aimed at assessing seasonality in overall, CVD, cancer and non-CVD/non-cancer mortality using data from 19 countries from different latitudes. METHODS AND FINDINGS: Monthly mortality data were compiled from 19 countries, amounting to over 54 million deaths. We calculated ratios of the observed to the expected numbers of deaths in the absence of a seasonal pattern. Seasonal variation (peak to nadir difference) for overall and cause-specific (CVD, cancer or non-CVD/non-cancer) mortality was analyzed using the cosinor function model. Mortality from overall, CVD and non-CVD/non-cancer showed a consistent seasonal pattern. In both hemispheres, the number of deaths was higher than expected in winter. In countries close to the Equator the seasonal pattern was considerably lower for mortality from any cause. For CVD mortality, the peak to nadir differences ranged from 0.185 to 0.466 in the Northern Hemisphere, from 0.087 to 0.108 near the Equator, and from 0.219 to 0.409 in the Southern Hemisphere. For cancer mortality, the seasonal variation was nonexistent in most countries. CONCLUSIONS: In countries with seasonal variation, mortality from overall, CVD and non-CVD/non-cancer show a seasonal pattern with mortality being higher in winter than in summer. Conversely, cancer mortality shows no substantial seasonality.

The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

Daily activity patterns of 2316 men and women from five countries differing in socioeconomic development.

Daily rhythmicity in the locomotor activity of laboratory animals has been studied in great detail for many decades, but the daily pattern of locomotor activity has not received as much attention in humans. We collected waist-worn accelerometer data from more than 2000 individuals from five countries differing in socioeconomic development and conducted a detailed analysis of human locomotor activity. Body mass index (BMI) was computed from height and weight. Individual activity records lasting 7 days were subjected to cosinor analysis to determine the parameters of the daily activity rhythm: mesor (mean level), amplitude (half the range of excursion), acrophase (time of the peak) and robustness (rhythm strength). The activity records of all individual participants exhibited statistically significant 24-h rhythmicity, with activity increasing noticeably a few hours after sunrise and dropping off around the time of sunset, with a peak at 1:42 pm on average. The acrophase of the daily rhythm was comparable in men and women in each country but varied by as much as 3 h from country to country. Quantification of the socioeconomic stages of the five countries yielded suggestive evidence that more developed countries have more obese residents, who are less active, and who are active later in the day than residents from less developed countries. These results provide a detailed characterization of the daily activity pattern of individual human beings and reveal similarities and differences among people from five countries differing in socioeconomic development.

Worker honeybee hemolymph lipid composition and synodic lunar cycle periodicities

The aim of the present investigation was to extend a previous study, showing a correlation of the variations of hemolymph carbohydrates with synodic lunar-like cycle and its circaseptan harmonics to worker honeybee hemolymph lipids. Hemolymph lipid concentrations of emerging worker imagos were analyzed in terms of one ideal synodic lunar cycle and processed by the cosinor method testing the null hypothesis versus the presence of 29.5-, 14.8- or 7.4-day periods in the data. A rhythmicity statistically compatible with a 29.5-day rhythm was observed for triacylglycerols and steroids as well as for body weight. A circadiseptan rhythm was determined for 1,3 diacylglycerols, while fatty acids and phospholipids exhibited a circaseptan rhythm. An agreement of peaks for triacylglycerols, steroids and body weight at the new moon, but not at the full moon, was noted with respect to trehalose and glucose circadiseptan rhythms. The latter moon-phase timing of peaks and nadirs, compared with that previously determined for trehalose and glucose, appeared to be identical to the circadiseptan rhythm and reciprocal for the circaseptan rhythms of 1,3 diacylglycerols. Reciprocal tendencies in circaseptans of trehalose and glucose on the one hand, and fatty acids and phospholipids on the other are indicated. The underlying causal nexus of these relationships is unknown

Low-cost automatic activity data recording system

We describe a low-cost, high quality device capable of monitoring indirect activity by detecting touch-release events on a conducting surface, i.e., the animal's cage cover. In addition to the detecting sensor itself, the system includes an IBM PC interface for prompt data storage. The hardware/software design, while serving for other purposes, is used to record the circadian activity rhythm pattern of rats with time in an automated computerized fashion using minimal cost computer equipment (IBM PC XT). Once the sensor detects a touch-release action of the rat in the upper portion of the cage, the interface sends a command to the PC which records the time (hours-minutes-seconds) when the activity occurred. As a result, the computer builds up several files (one per detector/sensor) containing a time list of all recorded events. Data can be visualized in terms of actograms, indicating the number of detections per hour, and analyzed by mathematical tools such as Fast Fourier Transform (FFT) or cosinor. In order to demonstrate method validation, an experiment was conducted on 8 Wistar rats under 12/12-h light/dark cycle conditions (lights on at 7:00 a.m.). Results show a biological validation of the method since it detected the presence of circadian activity rhythm patterns in the behavior of the rats

Daily birth numbers in Passo Fundo, South Brazil, 1997-1999: trends and periodicities

Between October 6, 1997 and April 30, 1999, 5011 births (mean: 8.76 per day) were registered in the city of Passo Fundo, South Brazil. The sequence of 572 daily birth numbers was not random (iteration test). Neyman distribution (m = ¥) showed the best fit. Clusters of days with higher birth numbers alternated with days with low numbers of births. Periodogram analysis revealed a significant periodicity of 6.98 days. The cosinor regression, testing 10 a priori supposed period lengths, found significant seasonality peaking in August-September and significantly highest birth numbers on Thursdays. Among the lunar and solar rotation cycles, the tropic lunar cycle and its 4th harmonic were most pronounced, in agreement with results concerning natality in Germany obtained by Svante Arrhenius in the 19th century. These findings confirm Derer-Halberg's concept of multiseptans. In addition to cycling, a significantly increasing linear trend with a daily increase of 0.0045 births was encountered. This documents a growth of the population in agreement with national statistical data.

Circadian rhythms in blood pressure in free-ranging three-toed sloths (Bradypus variegatus)

Blood pressure (BP) profiles were monitored in nine free-ranging sloths (Bradypus variegatus) by coupling one common carotid artery to a BP telemetry transmitter. Animals moved freely in an isolated and temperature-controlled room (24ºC) with 12/12-h artificial light-dark cycles and behaviors were observed during resting, eating and moving. Systolic (SBP) and diastolic (DBP) blood pressures were sampled for 1 min every 15 min for 24 h. BP rhythm over 24 h was analyzed by the cosinor method and the mesor, amplitude, acrophase and percent rhythm were calculated. A total of 764 measurements were made in the light cycle and 721 in the dark cycle. Twenty-four-hour values (mean ± SD) were obtained for SBP (121 ± 22 mmHg), DBP (86 ± 17 mmHg), mean BP (MBP, 98 ± 18 mmHg) and heart rate (73 ± 16 bpm). The SBP, DBP and MBP were significantly higher (unpaired Student t-test) during the light period (125 ± 21, 88 ± 15 and 100 ± 17 mmHg, respectively) than during the dark period (120 ± 21, 85 ± 17 and 97 ± 17 mmHg, respectively) and the acrophase occurred between 16:00 and 17:45 h. This circadian variation is similar to that observed in cats, dogs and marmosets. The BP decreased during "behavioral sleep" (MBP down from 110 ± 19 to 90 ± 19 mmHg at 21:00 to 8:00 h). Both feeding and moving induced an increase in MBP (96 ± 17 to 119 ± 17 mmHg at 17:00 h and 97 ± 19 to 105 ± 12 mmHg at 15:00 h, respectively). The results show that conscious sloths present biphasic circadian fluctuations in BP levels, which are higher during the light period and are mainly synchronized with feeding.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

We studied the effects of adverse conditions such as constant light (LL) on the circadian rhythm of malate (MDH, EC 1.1.1.37) and lactate (LDH, EC 1.1.1.27) dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28), anxiety-like behavior (elevated plus-maze test) at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark), LL (light from day 10 to 21 of pregnancy), and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy). LL offspring did not show circadian rhythms of MDH (N = 62) and LDH (N = 63) activities (cosinor and ANOVA-LSD Fisher). They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test), an increase in mounting (94.4%), intromission (94.5%) and ejaculation (56.6%) latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test) and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12) compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher), anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

Circadian variation with a diurnal bimodal profile on scent-marking behavior in captive common marmosets (callitrhix jacchus)

Scent-marking behavior is associated with different behavioral contexts in callitrichids, including signalizing a territory, location of feeding resources, and social rank. In marmosets and tamarins it is also associated with intersexual communication. Though it appears very important for the daily routine of the individuals, very few researchers have investigated distribution through the 24-h cycle. In a preliminary report, we described a preferential incidence of this behavior 2 h before nocturnal rest in families of common marmosets. We expand the data using 8 family groups (28 subjects), 8 fathers, 6 mothers, 8 nonreproductive adults (4 sons and 4 daughters), and 6 juvenile (3 sons and 3 daughters) offspring that we kept in outdoor cages under natural environmental conditions. We recorded the frequency of anogenital scent marking for each group during the light phase, twice a wk, for 4 consecutive wks, from March 1998 to September 1999. Cosinor test detected 24- and 8-h variations in 89.3% and 85.7% of the subjects, respectively, regardless of sex or reproductive status. The 8-h component is a consequence of the 2 peaks for the behavior, at the beginning and end of the light phase. Daily distribution of scent marking is similar to that others described previously for motor activity in marmosets. The coincident rhythmical patterns for both behaviors seem to be associated with feeding behavior, as described for callitrichids in free-ranging conditions, involving an increase in foraging activities early in the morning and shortly before nocturnal rest

Longitudinal study of daily variation of rats' behavior in the elevated plus-maze

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1) a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2) light/dark phases differences in EPM exploration were present at all developmental stages, (3) older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4) behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. (C) 2003 Elsevier B.V. All rights reserved.

Uric acid biorhythm, a feature of long-term variation in a clinical laboratory database

Background: The biorhythm of serum uric acid was evaluated in a large sample of a clinical laboratory database by spectral analysis and the influence of the gender and age on uric acid variability. Methods: Serum uric acid values were extracted from a large database of a clinical laboratory from May 2000 to August 2006. Outlier values were excluded from the analysis and the remaining data (n = 73,925) were grouped by gender and age ranges. Rhythm components were obtained by the Lomb Scargle method and Cosinor analysis. Results: Serum uric acid was higher in men than in women older than 13 years (p<0.05). Compared with 0-12 year group, uric acid increased in men but not in women older than 13 years (p<0.05). Circannual (12 months) and transyear (17 months) rhythm components were detected, but they were significant only in adult individuals (>26 years, p<0.05). Cosinor analysis showed that midline estimating statistic of rhythm (MESOR) values were higher in men (range: 353-368 mu mol/L) than in women (range: 240-278 mu mol/L; p<0.05), independent of the age and rhythm component. The extent of predictable change within a cycle, approximated by the double amplitude, represented up to 20% of the corresponding MESOR. Conclusions: Serum uric acid biorhythm is dependent on gender and age and it may have relevant influence on preanalytical variability of clinical laboratory results.

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

Abstract: Background: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions: The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms.