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Actigraphy is the reference objective method to measure circadian rhythmicity. One simpler subjective approach to assess the circadian typology is the Morningness-Eveningness Questionnaire (MEQ) by Horne and Ostberg. In this study, we compared the MEQ score against the actigraphy-based circadian parameters MESOR, amplitude and acrophase in a sample of 54 students of the University of Milan in Northern Italy. MEQ and the acrophase resulted strongly and inversely associated (r = -0.84, p < 0.0001), and their relationship exhibited a clear-cut linear trend. We thus used linear regression to develop an equation enabling us to predict the value of the acrophase from the MEQ score. The parameters of the regression model were precisely estimated, with the slope of the regression line being significantly different from 0 (p < 0.0001). The best-fit linear equation was: acrophase (min) = 1238.7-5.49·MEQ, indicating that each additional point in the MEQ score corresponded to a shortening of the acrophase of approximately 5 min. The coefficient of determination, R2, was 0.70. The residuals were evenly distributed and did not show any systematic pattern, thus indicating that the linear model yielded a good, balanced prediction of the acrophase throughout the range of the MEQ score. In particular, the model was able to accurately predict the mean values of the acrophase in the three chronotypes (Morning-, Neither-, and Evening-types) in which the study subjects were categorized. Both the confidence and prediction limits associated to the regression line were calculated, thus providing an assessment of the uncertainty associated with the prediction of the model. In particular, the size of the two-sided prediction limits for the acrophase was about ±100 min in the midrange of the MEQ score. Finally, k-fold cross-validation showed that both the model's predictive ability on new data and the model's stability to changes in the data set used for parameter estimation were good. In conclusion, the actigraphy-based acrophase can be predicted using the MEQ score in a population of college students of North Italy.

The influence of the chronotype on the sleep quality in male collegiate soccer players in response to acute high intensity interval training (HIIT) performed at two different times of day was evaluated. The sleep quality was poorer in the morning-type than in the evening-type players after the evening HIIT session, whereas no significant changes in the sleep quality of the two chronotypes after the morning HIIT session was observed. The results suggest that an athlete's chronotype should be taken into account when scheduling training sessions and to promote faster recovery processes.

Strenuous exercise affects immune system and stimulates the synthesis of pro-inflammatory cytokines, including interleukin 6 (IL-6) and the anti-inflammatory cytokines, mainly interleukin 10 (IL-10). IL-6 and IL-10 fluctuations can influence sleep quality. Many genetic tracts influence the immune system response to exercise. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs1799752) is one of the most investigated genetic variants correlated to the physical performance and immune system. The aim of this study was to evaluate: (a) the response to an exhaustive strength exercise in terms of IL-6 and IL-10 expression in relation to ACE polymorphisms; and (b) the sleep behavior in response to an exhaustive strength exercise in relation to ACE polymorphisms. All participants were subjected to the following procedures: (a) genotyping of ACE polymorphism, (b) assay cytokine expression (IL-6 and IL-10) pre- and post-exhaustive exercise, and (c) evaluation of sleep parameters pre- and post-exhaustive exercise by actigraphy. We showed that after the exhaustive exercise: (a) the ACE I/I, I/D, and D/D genotypes underwent an increase in IL-6 expression (p

Hypotheses. Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. Study design. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. Methods. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. Results. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Conclusion. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

Insulin may affect breast cancer (BC) risk and prognosis. Exercise reduces insulin in obese BC survivors. We designed a randomised controlled trial to test the effect of an aerobic exercise intervention (AEI) on insulin parameters and body composition in non-obese BC women without insulin resistance. Thirty-eight BC women were randomised into an intervention group (IG = 18) or control group (CG = 20). IG participated in a structured AEI for 3 months, while CG received only the Word Cancer Research Fund/American Institute Cancer Research (WCRF/AICR) recommendation to be physically active. Fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index, metabolic parameters and body composition were collected at baseline and after the AEI. IG reduced insulin and HOMA-IR index by 15% and 14%, while CG increased these parameters (+12% and +16%). Insulin changed differently over time in the two randomised groups (pinteraction = .04). The between-group differences in the change of insulin (IG = -1.2 μU/ml versus CG = +0.8 μU/ml) and HOMA-IR index (IG = -0.26 versus CG = +0.25) were respectively significant (p = .04) and non-significant (p = .06). IG significantly improved lower limb muscle mass in comparison with CG (p = .03). A structured AEI may improve insulin, HOMA-IR index and body composition in non-obese BC survivors without insulin resistance.

Studies on the molecular clockwork during aging have been hitherto addressed to core clock genes. These previous investigations indicate that circadian profiles of core clock gene expression at an advanced age are relatively preserved in the master circadian pacemaker and the hypothalamic suprachiasmatic nucleus (SCN), and relatively impaired in peripheral tissues. It remains to be clarified whether the effects of aging are confined to the primary loop of core clock genes, or also involve secondary clock loop components, including Rev-erbα and the clock-controlled genes Dbp and Dec1. Using quantitative real-time RT-PCR, we here report a comparative analysis of the circadian expression of canonical core clock genes (Per1, Per2, Cry1, Cry2, Clock and Bmal1) and non-core clock genes (Rev-erbα, Dbp and Dec1) in the SCN, liver, and heart of 3month-old vs 22month-old mice. The results indicate that circadian clock gene expression is significantly modified in the SCN and peripheral oscillators of aged mice. These changes are not only highly tissue-specific, but also involve different clock gene loops. In particular, we here report changes of secondary clock loop components in the SCN, changes of the primary clock loop in the liver, and minor changes of clock gene expression in the heart of aged mice. The present findings outline a track to further understanding of the role of primary and secondary clock loop components and their crosstalk in the impairment of circadian output which characterizes aging.

Vitale, JA, Caumo, A, Roveda, E, Montaruli, A, La Torre, A, Battaglini, CL, and Carandente, F. Physical attributes and NFL Combine performance tests between Italian National League and American football players: a comparative study. J Strength Cond Res 30(10): 2802-2808, 2016-The purpose of this study was to examine anthropometric measurements and the results of a battery of performance tests administered during the National Football League (NFL) Combine between American football players who were declared eligible to participate in the NFL Combine and football players of a top Italian team (Rhinos Milan). Participants (N = 50) were categorized by position into 1 of 3 groups based on playing position: skill players (SP) included wide receivers, cornerbacks, free safeties, strong safeties, and running backs; big skill players (BSP) consisted of fullbacks, linebackers, tight ends, and defensive ends; lineman (LM) included centers, offensive guards, offensive tackles, and defensive tackles. A 1-way analysis of variance followed by the Tukey-Kramer post hoc test was used for comparisons between Italian players by playing position. Ninety-five percent CIs were used for comparisons between American and Italian football for the NFL Combine performance tests. Significant differences for all the variables between the 3 playing categories were observed among the Italian players; LM had higher anthropometric and body composition values than SP (p < 0.001) and BSP (p < 0.001), whereas LM performed significantly worse in the physical tests, except for the 225-lb bench press test when compared with SP (p < 0.002). American football players presented significantly higher anthropometric values and test performance scores when compared with Italian players. Administrators of professional football teams in Italy need to improve the player's physical attributes, so the gap that currently exists between American and Italian players can be reduced, which could significantly improve the quality of American football in Italy.

Dear Editor,We have recently shown that the score yielded by the Morning-Evening Questionnaire (MEQ) (Horne & Ostberg, 1976) can be used to predict the acrophase measured by actigraphy in a sample ...

Shift work schedules, intensive physical exercise late in the day, psychological stress, or a busy lifestyle might induce disorders of the circadian structure, which can affect health on both the physiological and neurobehavioral levels. Rest–activity rhythm is strongly connected with an organism’s circadian structure, and irregular sleep–wake patterns can lead to a disruption of entrainment, resulting in physiological and neurobehavioral dysfunction. Shift nurses are often subject to disturbances in the quality and duration of their sleep, raising the possibility of negative impacts on their health and their patients' safety. Researchers have used actigraphy in a number of studies to assess sleep patterns. Because of the close connection between sleep and circadian structure, it may be useful to extend the evaluation of actigraphy data to the analysis of the rest–activity rhythm with rhythmometric procedures to provide a better understanding of possible sleep disorders in relation to entrainment. Actigraphy is an easy and reliable way to study these rhythms and identify possible circadian-rhythm disorders. In this article, the authors discuss methodological issues concerning the evaluation of the rest–activity rhythm, with a focus on actigraphy.

Child and adolescent obesity currently affects at least 10-25% of the paediatric population in most developed countries. The BMI value is one of the most appropriate method of defining obesity and has a strong association with body fatness and health risk. Two main environmental factors, nutrition and physical activity, could influence paediatric obesity development. This paper studies the relationship between sedentariness, snack and soft drink intake and overweight or obesity in children. 1194 primary school children (age 8-10) participated in the study. For all the subjects we measured the anthropometric data to calculate the BMI. The overweight and obesity prevalence was estimated using age-specific BMI cutoffs. A questionaire was also submitted to all the children by a single interviewer to obtain data about: a) Weekly Physical Activity, b) Weekly Sedentary Activity, c) Alimentary Style. Spearman rank correlation and the Student’s t-test were used. The data demonstrated that 23.2% of the children is overweight and the 4.8% obese. BMI is inversely correlated to the physical activity, while there is positive correlation between BMI and number of double portions. Statistically significant positive correlation is present among eating snacks and hours of sedentariness, while there is a negative correlation between physical activity and TV hours. Physical activity in the childhood could be an important tool to prevent obesity development and adult-onset chronic diseases. It is important to encourage an active lifestyle in order to reduce sedentariness. (Biol.Sport 26:349-367, 2009)

A pilot study was conducted to describe the reaction to lack of daylight and different training times of circadian rhythms and sleep in a subject arriving in Alta (Northern Norway) from Milan (Italy) in the darkness period. Monitoring sessions by heart rate (HR) monitor and actigraph were performed after four conditions: MS1, no training in Italy; MS2, no training in Alta (lack of daylight); MS3, evening training in Alta; and MS4, morning training in Alta. Midline Estimating Statistic Of Rhythm (MESOR) for activity was lower in MS2 than in MS1, MS3 and MS4, and decreased progressively for HR. Acrophases were advanced in MS2 and MS4 compared to MS1 and MS3 for both activity and HR. Sleep Efficiency was higher in MS2, MS3 and MS4 compared to MS1, coinciding with low values in the Mean Activity Score and Movement and Fragmentation Index. It could be seen that lack of daylight induced a decrease of the activity state in the subject, advancing the acrophase and leading to increased sleep. After the exercise sessions the activity state of the subject increased and the circadian structure was influenced according to the time at which the training was performed.

The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness-eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey-Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal-Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (χ(2) with p = 0.011) and the photoperiod at birth (χ(2) with p 0.05). Though the MESOR and amplitude of the activity levels were not different among the three chronotypes, the acrophases compared by the ANOVA post-hoc test were significantly different (p 0.001). The ANOVA post-hoc test revealed the presence of a significant difference (p 0.001) between the M-types (14:32 h) and E-types (16:53 h). There was also a significant interaction between the chronotype and four sleep parameters: Sleep end, Assumed Sleep, Immobility Time and Sleep Efficiency. Sleep Efficiency showed the same patterns as did Assumed Sleep and Immobility Time: the Sleep Efficiency of the E-types was poorer than that of the M- and N-types during weekdays (77.9% ± 7.0 versus 84.1% ± 4.9 and 84.1% ± 5.2) but was similar to that measured in the M- and N-types during the weekend. Sleep Latency and Movement and Fragmentation Index were not different among the three chronotypes and did not change on the weekend compared with weekdays. This study highlights two key findings: first, we observed that the circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during "free days" on the weekend.

On the basis of the circadian oscillations of the rat’s exocrine pancreatic function and previous reports on concomitant ultrastructural changes in the pancreatic tissue, we analysed stereologically the circadian rhythmicity in the structure of this organ. Twenty-four male Wistar rats, four and a half months old, were singly housed two months before the experiment in a lighting regimen LD=12:12, constant environmental temperature and relative humidity, with food and water ad libitum. The experiment was performed in winter. The rats were randomly divided into 6 balanced groups and killed under ether anesthesia at 6 equidistant time points in 24 hours. The pancreatic tissue was fixed in glutaraldehyde and osmium and embedded in Epon. 1 µm thick sections were examined by light microscopy for the evaluation by stereological methods of: a) volume fractions of the different parenchymal components of the exocrine pancreas; b) surface fractions of acinar cell faces; c) size distribution of acinar cell nuclei, the...

We wish to show that cardiologic variability can be examined with benefit by the concepts and computer methods of chronobiology, the science (logos) of life's (bios) time (chronos) structure. From heart rate data in a recent article, 1 dynamic end points are obtained to quantify health. 2 On a group basis, when conventional end points applied to 2 sets of electrocardiographic records fail to separate for sudden adult death, chronobiologic end points already do so. 2 Novel information not obtained by conventional location or dispersion indexes 3 can be provided by the computation of the circadian and other amplitudes. 4 Beyond sudden death after myocardial infarction, the importance of these amplitudes has been demonstrated in several additional cases of cardiologie interest 2 : (1) the amplitudes of several rhythmic components of systolic or diastolic blood pressure separate groups of human newborns with a positive versus negative family history of high blood pressure or cardiovascular diseases, or both, when the mean based on the same data does not do so; (2) in children ≥9 years old, the circadian amplitude and acrophase of blood pressure, but not the mean, separate groups at low or high risk of developing high blood pressure later in life; (3) at 15 years of age, the circadian amplitude of diastolic blood pressure, but not the mean, correlates with the thickness of the interventricular septum of the heart.

Circadian rhythmicity of the structural morphometric model of rat endocrine pancreas has been studied in 24 Wistar female rats, four months old, kept in LD 12:12. The following parameters were evaluated: the volume fractions of nucleus and cytoplasm of exocrine cells, the size distribution and number in unit tissue volume of acinar cell nuclei, the mean nuclear diameter, the shape coefficient of glandular acini (that is the ratio acinar area/perimeter2 which indicates the shifting of structures from circularity). A statistically significant circadian rhythm was demonstrated for the shape coefficient of glandular acini. Results obtained in the present experiment are compared with data recorded in a previous study.

Objective : To compare the 24-hour blood pressure (BP) pattern in physiologic pregnancy, pregnancy-induced hypertension, preeclampsia, and chronic hypertension. Methods : We investigated four groups of women with singleton pregnancy: 73 controls, 48 patients with pregnancy-induced hypertension, 38 with preeclampsia, and 53 with mild to moderate chronic hypertension. The 24-hour BP monitoring was performed longitudinally in controls and in patients with chronic hypertension, and at the time of diagnosis in those with pregnancy-induced hypertension or preeclampsia. Results : Nineteen thousand eight hundred seventy-two BP measurements were analyzed. In controls, the mean values of BP indices were lower than those first reported in non-pregnant women, and the acrophase was always localized in the first part of the afternoon. In pregnancy-induced hypertension and especially in preeclampsia, besides the obvious quantitative increase in BP, circadian BP oscillations were less pronounced than in controls, and the severity of hypertension seemed to favor the loss of diurnal rhythm. Conversely, in chronic hypertension, circadian oscillations were the same as in controls. Conclusion : Standardized 24-hour BP monitoring during pregnancy allows quantitative and qualitative evaluations of the hypertensive status. However, if such a technique is used routinely in every clinical setting, we should establish specific thresholds of normality for pregnancy.

A fluorescein isothiocyanate (FITC) reference standard for quantitative microfluorometry is described. This standard has been used to quantify the fluorescence intensity emitted by IgM membrane receptors of normal human peripheral blood lymphocytes.

Neutrophil chemotaxis in ten subjects with psoriasis was evaluated in vivo by the quantitative skin-window technique using autologous serum and in vitro using a modified Boyden technique. The in vitro chemotaxis values of the psoriatics were significantly lower (P less than 0.01) than those of healthy controls. When measured in vivo, however, we found that, after 9, 12, and 24 h, the values of the migrating polymorphonuclear leukocytes (PMNL) of psoriasis patients were only slightly and non-significantly lower than normal values. Analysing the in vivo chemotaxis data by a chronobiological method, we demonstrated statistically significant circadian rhythms in nine of the ten psoriasis patients. In seven of the patients, we found that the population had a significant rhythm, with the acrophase at -328 degrees. Our in vitro and in vivo values are in agreement with previously published values. However, there was a definite circadian rhythm of migration that we could not demonstrate in normal controls. We consider that our data reveal a significant and important difference between neutrophil chemotaxis in vivo in normal subjects and that in patients with psoriasis.

Alteration of electrical function in mammalian gastric mucosa is considered as an indicator of gastric barrier rupture. Measurements of transmucosal potential difference (PD) and electrical resistance (R) have documented such alterations to a variety of mucosal damaging agents. This study was designed to test whether the rat gastric mucosa exhibits circadian rhythms in acid secretion and electrical function and whether the damage produced by a mucosal acting agent (butyric acid) is also circadian-stage dependent. Mucosa was isolated from the gastric body of male rats standardized from birth to a light-dark regimen. Circadian rhythms of acid secretion and PD and R with acrophases during the dark hours were documented. Administration of butyric acid produced circadian-stage dependent damage with an acrophase also during the dark-phase span. Thus, in this experimental model, measurements of electrical function represented a poor index of gastric mucosal susceptibility to damaging agents. The authors discuss the possibility that rhythms other than those related to electrical function may better define mucosal vulnerability to ulcerogenesis.

In studying many diseases we meet with periodic phenomena. The appearance of some symptoms and the relevant remissions often have a cyclic pattern. The temporal structure of living organisms is at the root of these phenomena: the correct intermodulation, in terms of time, of the biological variables, realizes the conditions of well being. If the harmony between the biological rhythms is disturbed for some reason, the subjects find themselves in the state of proneness to disease or of overt disease. To evaluate this different situation it is necessary to follow the biological phenomena during the time and estimate, with correct statistical methods, the periodicity, the relevant parameters and the ratios. So research has to be completed with a sufficient number of measurements of pertinent variables and of the variables to be utilized as marker rhythms. For this purpose, autorhythmometry and automatic monitoring can help greatly. Evaluation of the parameters and ratios between the biological rhythms pertinent to the studied disease and marker rhythms constitute the ground on which the discussion and conclusions of the research have to be founded.En étudiant beaucoup de pathologies on rencontre des phénomènes périodiques. L'apparition de certains symptômes et les rémissions relatives ont souvent un charactère cyclique. A’ la base de ces phénomènes il y a la structure temporelle des organismes vivants: la correcte intermodulation des rythmes biologiques entre eux, réalise la condition de bien-être. Lorsque l'harmonie entre ces rythmes est troublée pour n'importe quelle raison, on se trouve dans les conditions de la prédisposition à la maladie ou bien à la maladie déclarée. Pour évaluer ces situations différentes il est nécessaire de suivre les phénomènes biologiques dans le temps et de choisir les méthodes statistiques les plus appropriées pour examiner la périodicité, les paramètres s'y afférant et les rapports. Les recherches doivent donc se baser sur un nombre suffisant de mesures des variables pertinentes et des variables à utiliser comme des rythmes guide. L'emploi de l'autorythmométrie et de la rythmométrie automatique peut être d'une grande utilité. L'évaluation des paramètres et des rapports des rythmes biologiques concernant la pathologie étudiée et des rythmes guide représent le matériel sur lequel baser la discussion et les conclusions de la recherche.Nello studio di molte forme patologiche ci si imbatte in fenomeni periodici. La comparsa di talune sintomatologie e le relative remissioni hanno sovente carattere ciclico. Alla base di questi fenomeni è la struttura temporale degli organismi viventi: la corretta intermodulazione, in termini temporali, delle variabili biologiche tra loro, realizza la condizione di benessere. Quando l'armonia tra i ritmi biologici viene turbata, per qualsiasi ragione, ci si trova nelle condizioni di predisposizione alla malattia od alla malattia conclamata. Per valutare queste diverse situazioni è necessario seguire nel tempo i fenomeni biologici e valutarne con le corrette metodiche statistiche la periodicità, i relativi parametri ed i rapporti. Le ricerche in tal senso devono essere corredate da un sufficiente numero di misurazioni delle variabili interessate e di variabili da utilizzare come ritmi marker. L'utilizzo di autoritmometria e di ritmometria automatica possono essere di grande aiuto. La valutazione dei parametri e dei rapporti dei ritmi biologici pertinenti la patologia studiata e dei ritmi guida costituisce il materiale su cui fondare la discussione e le conclusioni della ricerca.

Selected methods for the study of biologic time series are reviewed and their relative merits are discussed in the light of underlying assumptions. Their potential applications are exemplified in several fields of biology and medicine. The monitoring of environmental integrity, notably of pollution, is investigated. The need for specifying optimal sampling requirements is underlined. An individualized and time-qualified definition of health by the establishment of reference intervals is required for increasingly rational individualized program for the prevention and/or treatment of disease. With these reference intervals and rhythm characteristics available, one can better interpret with single samples or time series an increased risk of a certain disease or the inception of the disease. For all of these aims the monitoring of environmental and/or personal marker rhythms is essential--to obtain large data bases from which information can be more easily derived for monitoring personal health, to recognize risk as well as to diagnose disease early and to optimize treatment by timing according to rhythms.

A microfluorometric ‘numerical’ scale for serum ANA evaluation is described. ANA content of sera from patients with autoimmune liver disease is evaluated by this scale.

The heptadecapeptide ACTH 1-17 is the analogue of corticotropin with beta-alanine in position 1, lysine instead of 17-arginine and a basic amide instead of 18 arginine-amide. These modifications give enhanced biological activity and longer duration of the action. Several researchers investigated the acute effect of the analogue after administration at different time points along the 24 h cycle, and discovered that glucocorticoid and mineralocorticoid responses are dissociated in terms of doses and timing. Cortisol and urinary 17 OH-CS rise more after morning injections whereas for aldosterone the maximum effect was noted at 14(00). The most interesting finding that concerns ACTH 1-17 is the chronizing effect. ACTH 1-17 can be a chronizer because its administration resets, for instance, the toleration to antimitotic drugs, to a more convenient time. At clinical level, a group of researchers studied, in some case correctly from a chronobiological point of view, the effect of the ACTH 1-17 on patients and on healthy subjects. It is useful to remember the concept of hierarchies of rhythms: each different periodic function is regulated or, better, intermodulated by a network of other periodic variables of the same organ or of other organs and systems. So the necessity of large samplings to evidentiate periodic phenomena, and the utility of investigating pertinent marker rhythms significantly correlated with those to be studied are evident. Autorhythmometry and automatic monitoring can help very much on this purpose.

Administration of glucocorticoids is effective and necessary in various diseases, but the appearance of side effects may compromise its results. Timing as well as dosing designed to obtain, for the highest number of patients, maximal beneficial effects with minimal undesired effects, is particularly pertinent to long-term corticosteroid therapy, in view of the rhythms exhibited by the endogenous secretion of adrenal cortical and coordinating hormones, primarily ACTH. In experimental animals, properly-timed circadian treatment can be preferred to alternate-day treatment for avoiding certain side effects. To secure the desired effect each day rather than only on alternate days, a chronobiologically correct corticosteroid therapy seeks the best compromise between timing for most of the desired and least of the undesired effects. This was the aim in the design of a chronopluricorticoid drug, with the time specification on its label. The clinical use of this preparation allowed the inferential statistical demonstration of a rhythmic circadian organization maintained during therapy, while the pharmacological results gained were similar to those obtained by the conventional administration of larger doses of corticoids.