Preface

Chronobiology is the science investigating and objectively quantifying the mechanisms of the biological time structure, including the rhythmic manifestations of life. The disturbance of the temporal structure of the living organism leads to disturbed harmony between biological rhythms and the rhythm of the external environment often resulting in a cyclic course of various diseases.

A general view of the importance of chronobiology can be seen in the chapter "Time structure of the functional organization of living systems" by Mohammad Rayees Dar and Abdul Roof Rather. The authors describe the reality that there is a temporal biological system in living organisms that controls, synchronizes, and coordinates all body systems to external rhythmic changes. The authors present examples from everyday physiology and clinical medicine, where rhythmic phenomena can be encountered, as well as the meaning, perspectives, and representation of chronobiology in all scientific biological disciplines. More detailed issues of control of circadian rhythms are discussed in the chapter "Light-dependent regulation of circadian clocks in vertebrates" by Junko et al., where the authors analyze cellularclock regulation in mammals and point out the specifics of cellular-clock regulation in zebrafish (direct synchronization of peripheral cellular clocks in addition to central cellular clocks by light).

In the cardiovascular system, practically all measurable functions exhibit circadian oscillations. The importance of dosing of antihypertensive drugs over time is receiving increased attention. The authors Narsingh Verma et al. in the chapter "Blood pressure variability and its clinical implications" discuss this problem in more detail and point to the fact that this type of therapy may be important because of the greater incidence of cardiovascular events in the early morning hours, in association with increases in blood pressure, heart rate, cardiac ischemia, enhanced platelet aggregability, and plasma catecholamines. Also important are the facts about dippers and nondippers and their relationship to other cardiovascular diseases whose predominance is in the early morning hours. The clinical physiology of children and older people refers to the differences that arise during ontogenesis in the endocrine system that in turn affects physiological functions. The authors Sheveleva et al. in the chapter "Circadian rhythm of blood pressure in children and adolescents" express the idea that formation of the circadian organization of the vegetative mechanisms that underlie the formation of daily arterial pressure profile probably depend on age.

Jarczok et al. in "Circadian rhythms of the autonomic nervous system—scientific implication and practical implementation" discuss the practical application of circadian heart rate variability (HRV) patterns, for example, at different risk states and diseases, including depression, where reduced HRV parameters and circadian rhythm disorders have been reported. The inflammatory reflex is a physiological mechanism through which the vagus nerve regulates immune function. In the chapter, there are a few examples confirming that 24-hour measurement of HRV may be a practical tool in prevention. This statement is supported by examples with intact chronobiology and then examples with clear disorders. Finally, it is emphasized

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Integration of Chronobiological Concepts for NSCLC Management *by Christian Focan, Anne-Catherine Davin, Maryam Bourhaba* 

that although HRV evaluation is not disease specific, it can be a tool for monitoring overall health, e.g. before and after treatment, and serve as a tool for demonstrating the patient's physiological responses to its specific environmental stimuli. Hence, HRV seems to be a suitable psychosomatic marker.

Focan et al. in the chapter "Integration of chronobiological concepts for NSCLC management?" point to the importance of biological rhythms regarding carcinogenesis and molecular biology in animal or human situations. Results support clearly the hypothesis that circadian rhythm disruption plays an important role in lung tumorogenesis, as well as a link between circadian epigenetic regulation and cancer development. These findings also suggest that circadian disruption induces the progression of malignant tumors via a WNT signaling pathway in models involving tumor cells similar to those encountered in human nonsmall cell lung carcinoma (NSCLC). Experimental and clinical data consider taking into account the temporal dimension ("circadian") for the prevention and management of NSCLC. This type of observation illustrates that the circadian system is involved in the protection and restoration of tumor cells.

In the chapter "Impact of shift work on sleep problems, hormonal changes, and features of metabolic syndrome in industrial workers" Fadia Zyada addresses and describes the results of several authors who compared the levels of individual hormones in night shift workers and in morning and afternoon shift workers, in relation to sleep problems and features of metabolic syndrome, such as body mass index (BMI), type II diabetes, and cardiovascular problems. The overview of the results is interesting because it is concluded that night shift is the only independent predictor for hormone imbalance for shift workers rather than BMI, type II diabetes, cardiovascular problems, disturbed sleep, and sleep problems.

Circadian disruption may occur, and may be the result of a phase shifts in the oscillation of the circadian and activity-controlled physiological processes, or can be induced by factors related to periodic inputs: low contrast between day and night synchronizing signals; zeitgebers with different periods or unusual phasing; orzeitgeber shifts (jet lag syndrome, shift work). It can also be induced by factors related to oscillators: the uncoupling between the different oscillators inside the suprachiasmatic nucleus, the uncoupling between the central and peripheral oscillators, or clock gene functional alterations. This chronobiological pathology can be induced by factors related to outputs: for example, nocturnal melatonin suppression or loss of cortisol rhythmicity. Many pathological states can be promoted or impaired as a consequence of circadian disruption. This book includes chapters on recent research not only in the field of normal human chronobiology but also in experimental and clinical medicine.

> **Pavol Švorc** Department of Physiology, Medical Faculty Safarik's University, Kosice, Slovak Republic

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Section 1

Introduction

Section 1 Introduction

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**1. Introduction**

systems of organisms.

oscillations with cycles of environment.

**2. Biological rhythms and homeostasis**

ing scheme may be regarded as representative.

Introductory Chapter:

Biological Time Structure

Chronobiology - The Science of

Both humans and most animal species on our planet are exposed to regular alternations of light and darkness, with a constant periodicity of 24 h throughout their lifetime. This regular alternation of light and dark affects not only human biological systems but also the social organization of behavior. Processes occurring in the human organism, which are dependent on the periodic alteration and alternation of environmental factors, potentially affect the blind and those employed in shift work and "nocturnal types," whose habits deviate from the usual mode of most individuals. The mode of alternating light and darkness is different at the equator, behind the polar circles, and also at transitions across multiple time zones. The effect of such light modes is manifested in periodic changes in several physiological functions and biological rhythms exhibited at every level of life—in single cells, tissues, organs, and, ultimately, physiological

Changes in the external environment, such as those of the weather or atmospheric conditions, can be **unpredictable**; therefore, organisms need systems that directly respond to changing environments. However, there are also **predictable** changes, which are the result of specific planetary movements such as the day-night cycle (rotation of the earth on its axis), the cycle of the moon (cycle of the moon around the earth), or annual cycles (cycle of the earth around the sun). For these predicable changes, organisms have specific mechanisms that generate endogenous biological rhythms corresponding directly to certain periodicities in the environment. They are not directly dependent on the rhythmicities of environment but only use the periodic information from the environment to synchronize biological

Biological rhythms are sequences of events that are repeated over time in the same manner and with the same interval; in other words, they are predictable in time. Biorhythms of organisms are the result of adaptation to changes in the environment, which is highly variable and exhibits variation in many factors. Chronobiology is the science investigating and objectively quantifying the mechanisms of biological time structure, including the rhythmic manifestations of life. Because medicine is, in large part, based on homeostatic principles, the follow-

## **Chapter 1**
