Circaseptan (about-7-day) bioperiodicity--spontaneous and reactive--and the search for pacemakers.

A built-in (genetically determined) about-7-day (circaseptan) period comes to the fore as a desynchronized feature of human time structure in the urinary excretion of 17-ketosteroids by a clinical healthy man: during several years following an endocrine intervention (the self-administration of testosterone suppositories), a circaseptan rhythm (which during the preceding decade had revealed a period of precisely 7 days) deviated slightly, yet with statistical significance, from the environmental week. A second line of evidence for an intrinsic circaseptan component stems from the demonstration of statistically significant differences in timing of a circaseptan rhythm in springtail oviposition. A third line of evidence documents prominent circaseptan rhythmicity after the application of a single stimulus (devoid in itself of any circaseptan information). Such single stimulus induction, amplification and/or synchronization also documents the clinical and biologic importance of built-in circaseptan rhythms that were previously often misinterpreted as being purely reactive: a circaseptan spectral component is remarkably prominent in mammalian organ transplant rejection, both in the clinic and in the laboratory. In the latter case, in the absence of any weekly cycles in hospital routine, including treatment schedules, circaseptan components characterize the rejection of the rat kidney, pancreas and heart. Much additional information here reviewed reveals the occurrence of periods of about 7 days. Their implications for transplant and other chronoimmunology as well as biology in general, and their clinical applications in drug treatment, include the need to weld circaseptan timing to circadian timing and dosing. A dramatic documentation of this need stems from the circumstance that pretreatment for one week with the same total dose of the same substance (a polysaccharide - Lentinan) accelerates or retards cancerous growth (hence shortens or lengthens survival) as a function of interactive circaseptan and circadian rhythms.