It has been generally accepted that the therapeutic effect of repeating hot spring bathing (base of balneotherapy) consists in alternation and normalization of diseased physiological functions of the body. Endocrine and neural functions act major rolls in these mechanisms. In the present paper, the effects of single bathing in hot and cold water and of long-term repetition of bathing were investigated from endocrinological stand-points. Increased secretion of plasma 11-OHCS was observed by body immersion in cold water (25°C) at 9AM and in hot water (42°C) at 9PM. No change of plasma level of this hormone was seen by cold stimulus at 9PM and heat stress by water immersion at 9AM. These results suggest that there are circadian difference of sensitivity in adrenocortical function to thermal stimuli by water immersion. Both plasma prolactin and renin activity increased by hot water immersion in contrast, cold stimulus caused the suppressive responses in both hormones. It can be postulated that other mechanism(s) than the sensitivity of endocrine gland may be involved in these responses.
In order to investigate the effect of long-term balneotherapy on endocrine function, the change in circadian rhythm of plasma 11-OHCS was measured at 1 week interval in hospitalized patients. In general, diminishing in the amplitude and lowering of peak value were observed 3-4 weeks after starting of balneotherapy. Plasma cortisol level was measured at 7AM everyday during hospitalization for 28 days. The results showed that the possible existence of circaseptan rhythm of cortisol secretion by balneotherapy. Daily fluctuation became smaller approximately 3 weeks after the begining of therapy.
Circadian rhythm of plasma cyclic AMP and cyclic GMP were measured to investigate the effect of balneotherapy on the state of autonomic nervous system. Although marked individual difference in the circadian rhythm of cyclic nucleotides was observed before balneotherapy, common and definite tendency of the rhythm was obtained approximately 4 weeks after starting of balneotherapy.
These results suggests that normalization effect of balneotherapy can be reached 3-4 weeks after starting of therapy from the view-point of endocrine and autonomic nervous functions.

The objective of this paper is to define the basis for the translational research and its knowledge framework in balneology aiming to approach the disease prevention. As a method to attain this objective, we advocate the knowledge framework that can bridge gene ontology (GO), balneologic ontology (BO), and clinical ontology (CO) virtually at a client site with three sided basic concepts as (1) the logically extended anatomical index from micro to macro, (2) the knowledge representation based on feature described logical conceptual unit, and (3) the EBM (Evidence Based Medicine) based quality evaluation of knowledge. As an result, the scheme and the prototype of the knowledge framework for the basic balneology was built. The logically extended anatomically hierarchical index could offer the seamless and logical continuity from genome to human/environment. The EBM based quality assessment enhanced the reliability of knowledge, and the knowledge representation based on the logical conceptual unit approach offered the unification of the different grain size knowledge.