Chronomics and chronobiology in health and disease (original) (raw)

Abstract

Chronobiology is a branch of science that objectively explores and quantifies mechanisms of biological time structure including important rhythmic manifestations of life right from molecular level of living being, from unicellular organism to complex organism such as human being. Genetics eventually leads to genomics, concurrently the study of biological variability i.e. chronobiology leads to chronomics.

Figures (6)

Fig 1: Variation within the physiological range can be resolved into meaningful information, including rhythms with frequencies covering 10 orders of magnitude, far beyond the circadian system and seasonal changes. Non-photic as well as photic influences of the sun have been genetically preserved in a set of photo- and magneto- periodicities from which much can be leamed. © Halberg or the true neart rate, but replacing tne nistorically useful homeostatic truisms by the dynamics end points of a variable in the biosphere and/or in its cosmos (Fig 1). Apart from providing a better understanding of the universe, common to both nuclear physics and chronobiology, perhaps one of the most challenging applications of chronobiology is that of improving the quality of health care of individuals, societies and environments while so reducing its cost by focusing on detecting and treating risk to prevent overt diseases again of societies, such as homicide and war, and of individuals, such as severe vascular disease or cancer. For such aims, chronomics offers the opportunity to refine the definition and assessment of health and broader normalicy positively and individually, rather than quantifying disease as a deviation from normalcy, negatively as the absence of disease and only for populations, as percent morbidity and mortality. Early time structure alternation indicates earlier risk elevation. Herein, we try to note the cost-effectiveness of using a database of vascular chronomes for severe disease prevention. Chronomics specifically resolves risks of stroke and other severe incapacitating diseases, higher than the risk associated with hypertension and other oncological and psychiatric disease risks.

Fig 1: Variation within the physiological range can be resolved into meaningful information, including rhythms with frequencies covering 10 orders of magnitude, far beyond the circadian system and seasonal changes. Non-photic as well as photic influences of the sun have been genetically preserved in a set of photo- and magneto- periodicities from which much can be leamed. © Halberg or the true neart rate, but replacing tne nistorically useful homeostatic truisms by the dynamics end points of a variable in the biosphere and/or in its cosmos (Fig 1). Apart from providing a better understanding of the universe, common to both nuclear physics and chronobiology, perhaps one of the most challenging applications of chronobiology is that of improving the quality of health care of individuals, societies and environments while so reducing its cost by focusing on detecting and treating risk to prevent overt diseases again of societies, such as homicide and war, and of individuals, such as severe vascular disease or cancer. For such aims, chronomics offers the opportunity to refine the definition and assessment of health and broader normalicy positively and individually, rather than quantifying disease as a deviation from normalcy, negatively as the absence of disease and only for populations, as percent morbidity and mortality. Early time structure alternation indicates earlier risk elevation. Herein, we try to note the cost-effectiveness of using a database of vascular chronomes for severe disease prevention. Chronomics specifically resolves risks of stroke and other severe incapacitating diseases, higher than the risk associated with hypertension and other oncological and psychiatric disease risks.

Chronomes of putative anti-and pro-oxidants should be mapped to explore their putative chronotherapeutic role as markers in cancer chronoprevention and management of established disease. Marker rhythm- guided individualized chronotherapy using cancer markers for the desired effect and host markers for the side effects remains in goal that has to be rendered cost effective (Fig 3). We are resuming marker rhythm guided cancer chronotherapy with kind cooperation of ProfM C Pantand Prof. M L B Bhattin Lucknow with University of Minnesota, USA (21). Furthermore, we are studying the chronomics of 7-day/24-hour BP/HR monitoring in health and disease in our population. We measure BP/HR notonly once and not only around the clock for 24-hours, but at half hourly intervals for 7-days. Moreover, we analyze not the fiction of a “true blood pressure”, but the chronome of this variable as it Fig 2 (b): Amplitude-map in gynecological malignancy vs health, showing non-zero circadian amplitude for malondialdehyde, an aspect desired from a putative cancer marker, also shown by other variables investigated in the human circulation

Chronomes of putative anti-and pro-oxidants should be mapped to explore their putative chronotherapeutic role as markers in cancer chronoprevention and management of established disease. Marker rhythm- guided individualized chronotherapy using cancer markers for the desired effect and host markers for the side effects remains in goal that has to be rendered cost effective (Fig 3). We are resuming marker rhythm guided cancer chronotherapy with kind cooperation of ProfM C Pantand Prof. M L B Bhattin Lucknow with University of Minnesota, USA (21). Furthermore, we are studying the chronomics of 7-day/24-hour BP/HR monitoring in health and disease in our population. We measure BP/HR notonly once and not only around the clock for 24-hours, but at half hourly intervals for 7-days. Moreover, we analyze not the fiction of a “true blood pressure”, but the chronome of this variable as it Fig 2 (b): Amplitude-map in gynecological malignancy vs health, showing non-zero circadian amplitude for malondialdehyde, an aspect desired from a putative cancer marker, also shown by other variables investigated in the human circulation

Fig 4: By the early detection of disease risk syndromes in the individual subject, countermeasures for primary prevention can be instituted. Such pre-habilitation in health can also complement rehabilitation in disease. As a major goal of health care, pre- habilitation could complementan across-the-board reduction of risk factors, implemented by changes in lifestyle or drugs. © Halberg Fig 3: Principles of chronoradiotherapy (top), evolved first to lower toxicity based on the discovery of susceptibility-resistance rhythms to a variety of stimuli; eventually, we aimed for the timing of best therapeutic efficiency, goals pursued in the laboratory first, to be followed by clinical studies of chronoradiotherapy, wherein oncostatic efficiency gained major focus. The final goal is the best temporal compromise between effectiveness and tolerance, as shown abstractly at the top of this figure on the right. At the bottom on the left, toxicity studies summarize a susceptibility rhythm to adriamycin with its uncertainty; in the middle, clinical studies with timing by peak tumor temperature show faster regression and doubling of 2-year disease free survival that remains to be tested further; the promise of circadian and circaseptan cancer marker rhythms is implied at the bottom on the right. © Halberg

Fig 4: By the early detection of disease risk syndromes in the individual subject, countermeasures for primary prevention can be instituted. Such pre-habilitation in health can also complement rehabilitation in disease. As a major goal of health care, pre- habilitation could complementan across-the-board reduction of risk factors, implemented by changes in lifestyle or drugs. © Halberg Fig 3: Principles of chronoradiotherapy (top), evolved first to lower toxicity based on the discovery of susceptibility-resistance rhythms to a variety of stimuli; eventually, we aimed for the timing of best therapeutic efficiency, goals pursued in the laboratory first, to be followed by clinical studies of chronoradiotherapy, wherein oncostatic efficiency gained major focus. The final goal is the best temporal compromise between effectiveness and tolerance, as shown abstractly at the top of this figure on the right. At the bottom on the left, toxicity studies summarize a susceptibility rhythm to adriamycin with its uncertainty; in the middle, clinical studies with timing by peak tumor temperature show faster regression and doubling of 2-year disease free survival that remains to be tested further; the promise of circadian and circaseptan cancer marker rhythms is implied at the bottom on the right. © Halberg

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References (24)

  1. Halberg F. Quo vadis basic and clinical chronobiology: promise for health maintenance. Am J Anat 1983; 168: 543-94.
  2. Halberg F, Halberg E. Chronopharmacology and further steps toward chronotherapy. In: Benet LZ, Massound N, Gambertoglio JG (eds): Pharmacokinetic Basis for Drug Treatment, Raven Press, New York, 1984; pp 221-48.
  3. Halberg F, Cornelissen G, Bakken E. Care giving merged with chronobiologic outcome assessment, research and education in health maintenance organizations. Prog Clin Biol Res 1990; 341B: 491-549.
  4. Halberg F, Cornelissen G, Wang Z, Wan C, Ulmer W, Katinas G, et al. Chronomics: Circadian and Circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond. J Exp Therapeutics Oncol 2003; 3: 223-60.
  5. Halberg F, Cornelissen G, Ulmer W, Blank M, Hrushesky W, Wood P, et al. Cancer, Chronomics III. Chronomics for cancer, ageing, melatonin and experimental therapeutics researchers. J Exp Therapeutics Oncol 2006; 6: 73-84.
  6. Cornelissen G, Halberg F, Schwartzkopff O, Katinas G, Johnson D, Otsuka K, et al. Editor's forward: What Gesell wished, Hellbrugge accomplished: Chronomics of child development. Neuroendocrinol Letters 2003; 24(S): 14-24.
  7. Halberg F, Cornelissen G, Regal P, Otsuka K, Wang ZR, Katinas GS, et al. Chronoastrobiology: Proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near decades, phylogenetic and ontogenetic memories. Biomed Pharmacother 2004: 58: S150-S186.
  8. Singh RK , Chansouria JPN , Udupa KN. Circadian periodicity of plasma cortisol (17-OHCS) levels in normal, traumatized, corticotrophin and dexamethasone treated rabbits. Ind J Med Res 1975; 63: 793-8.
  9. Singh RK, Nakra VK, Pandey HN, Arora SR. Studies of circadian periodicity of plasma, breast milk and urinary calcium in lactating Indian women. Trop Geogr Med 1984; 36: 345-9.
  10. Singh RK, Bansal A, Bansal SK, Rai SP. Circadian rhythms of common laboratory profiles in serum and urine of healthy Indians. Prog Clin Biol Res 1990; 341B: 559-66.
  11. Singh RK, Bansal A, Bansal SK, Singh AK, Mahdi AA. Circadian periodicity of urinary inhibitor of calcium oxalate crystallization in healthy Indians and renal stone formers. Eur Urol 1993; 24: 387-92.
  12. Singh R, Singh RK, Mahdi AA, Misra S, Rai SP, Singh D, et al. Studies of circadian periodicity of urinary corticoids in carcinoma of breast. In Vivo 1998; 12: 69-74.
  13. Singh R, Singh RK, Mahdi AA, Saxena SP, Cornelissen G, Halberg F. Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians. Life Sciences 2000; 66: 209-14.
  14. Singh RK, Chandra R, Narang RK, Singh SK, Katiyar SK, Singh RP, et al. Circadian variations of the absolute eosinophil count and serum histaminase activity in tropical pulmonary eosinophilia. Trop Georg Med 1987; 39: 49-52.
  15. Singh RK, Singh S, Saxena S, Narang RK. Studies on circadian periodicity of plasma 17-hydroxycorticoids in tropical pulmonary eosinophilia. Prog Clin Biol Res 1987; 227B: 285-94.
  16. Singh RK, Bansal A, Bansal SK. Studies on circadian periodicity of serum and urinary urate in healthy Indians and renal stone formers. Prog Clin Biol Res 1987; 227B: 305-13.
  17. Singh RK, Singh Y, Srivastava R. Circadian variations of serum urea concentrations in healthy Indians. Ind J Med Res 1990; 92(B): 257-60.
  18. Singh RK, Mahdi AA, Singh AK, Bansal SK, Wu J, Zhou S, et al. Circadian variation of circulating cholesterol components on vegetarian and omnivorous diets in healthy Indians. Ind J Clin Biochem 1992; 7: 185-92.
  19. Singh R, Singh RK, Mahdi AA, Kumar A, Tripathi AK, Rai R, et al. Circadian periodicity of plasma lipid peroxides and antioxidants as putative markers in gynecological malignancies. In Vivo 2003; 17: 593-600.
  20. Singh R, Singh RK, Tripathi AK, Cornelissen G, Schwartzkopff, Otsuka K, et al. Chronomics of circulating plasma lipid peroxides and antioxidant enzymes and other related molecules in cirrhosis of liver. Biomed Pharmacother 2005; 59: S228-S234.
  21. Bhatt MLB, Singh RK, Cornelissen G, Srivastava M, Rai G, Singh R, et al. Chronoradiotherapy guided by circadian rhythm in tumor temperature. In: Noninvasive Methods in Cardiology, Brno: Kongresove Centrum Brno1; ISBN 80- 86607-16-X; p. 19, 2005.
  22. Germaine C, Delcourt A, Toussaint G, Otsukla K, Watanabe Y, Siegelova J, et al. Opportunity of detecting pre- hypertension: worldwide data on blood pressure overswinging. Biomed Pharmacother 2005; 59: S152-S156.
  23. Halberg F, Cornelissen G, Otsuka K, Watanabe Y, Singh RB, Revilla M, et al. Home C-ABPM for preventive and curative health care and transdisciplinary science. World Heart J 2008; 1: 232-62.
  24. Singh R, Verma NS, Singh RK, Singh S, Singh RB, Singh Rajesh K, et al. Continued 7-day/24-hour monitoring required in (MESOR)-Hypertension and other VVDs (Vascular Variability Disorders). World Heart J 2008; 1: 311-23.