High Dilution Effects on Cells and Integrated Systems

The following sections are included:

• PREFACE

• CONTENTS

Basic research on high dilution effects started with homeopathic therapy. So many models have been tested that we have tried to classify them according to the general concept of regulation. Firstly, succussed dilutions must be separated from unsuccussed very low doses from a physical point of view. This leads us to discuss the validity of the controls in high dilution research. Then, following a classification according to regulating effects, one can consider that some research in the field of “homeopathic research” can be relevant to cybernetic regulation and, in some cases, very low dose effects can be described as cybernetic regulatory signals. Hormetic models and application of the Arndt-Schultz law are based on the identity principle and are related to variations of concentration. They are presented and differentiated from the self recovery process which exists as a function of time. By using unsuccussed molecular and succussed non-molecular dilutions, the hormetic model supports a learning process which must be related to informative concepts. Starting from this primary level of informative process and by comparison with the phylogenic evolution of the immune system as an informative system, we can elaborate a progressive information organisation of the high dilution effects. Endogenous molecules have a specific regulatory function while highly diluted exogenous molecules will only be informative in the framework of the similia principle.

The following sections are included:

• Introduction

• The Arndt-Schultz Law

• Hormoligosis

• Possible Mechanisms

• Longevity Hormesis

• Discussion

• References

In 1956, the experiments on insertion of synthetic inhibitors of radical reactions to animals were pioneered. The model of peroxidation of membrane lipids was constructed. In 1957-1965, it was found that non-toxic synthetic inhibitors of radical reactions (antioxidants) are biologically active substances. It was shown that the antioxidants decrease the rate of free-radical peroxidation processes in membrane lipids and interact with natural antioxidants in lipids…

The following sections are included:

• Effects of very high dilutions in vegetal models (table 2)

• Effects of metal very high dilutions in animal models (table 3)

• Effects of metal very high dilutions in in vitro cellular models (table 4)

• GENERAL CONCLUSION

• REFERENCE

The following sections are included:

• Introduction

• Main Part

• Acknowledgements

• References

The aim of our studies is to understand the stimulation of self-recovery processes at the cellular level by compounds which are applied according to the similia-principle. In order to induce self-recovery, cells are exposed to mildly damaging conditions. In our research a non-lethal concentration of sodium arsenite or a mild heat shock was used which induces the so-called heat shock- or stress response. This response includes the synthesis of a specific class of proteins (the heat shock proteins or stress proteins), the stimulation of proliferation, and the development of tolerance. Based on several lines of experimental evidence, we have proposed that self-recovery can be evaluated in terms of the development of tolerance and the enhanced production of heat shock proteins. With respect to the aim of our studies, it is of interest to determine whether, after an exposure to a damaging condition, cells can be stimulated in their development of tolerance and the production of heat shock proteins, by stressor doses that are not effective in undamaged (control) cells. In the present paper, we summarize the experimental evidence, in which it was shown that moderate stressor conditions (such as sublethal temperature elevation or arsenite concentration) transiently stimulate cell proliferation. Furthermore, it will be shown that these conditons were not only able to stimulate growth, but also induced the development of tolerance. Then, the evidence is summarized which indicates that the hsps can be used as a molecular parameter for cellular recovery. Finally, the experiments are described which were performed to study the effect of low doses of arsenite as well as of mild heat shock temperatures on the synthesis of hsps and on the development of tolerance in arsenite- and in heat shock-sensitized cell cultures. Along this line we offer an explanation for the capacity of low doses to stimulate molecular processes that are essential for self-recovery.

The concept of coherence in biological systems is introduced and related to electromagnetic theory, energetics and the dimensions of systems, and to bio-information. The phenomenon of coherence in water is considered with its thresholds and limits. This is related to the properties of water “memory”.

The effect of a remedy cannot be traced back to the active substance alone. There is also an intricate connexion with the degree of dilution, e.g., in water, and the way the dilution has been produced. To get more insight, a global model of water has been developped. It consists of several levels which are associated with different degrees of dilution. In the present paper, this relation is made more precise, and some new conclusions are drawn.

The following sections are included:

• INTRODUCTION

• EXPERIMENTAL RESULTS

• GENERAL DISCUSSION

• ACKNOWLEDGMENTS

• REFERENCES

The following sections are included:

• Introduction

• Results

• Discussion

• References

Low degree centesimal dilution, 5 CH, and high degree centesimal dilution, 30 CH, have been prepared, starting from tincture of Chamomilla (Cham), by succesive water dilution at a 1 : 100 rate and dynamisation (D), according to Hahnemann technique. The treatment was made per os. The effects of C dilutions, on central nervous systems (CNS), were studied. The blind screening methodology, used in experimental pharmacology, for CNS action investigation, on mice, was utilised. The effects on both “normal” and “sensitive” healthy individuals were investigated. In order to select the “sensitive” to Cham drug-type, an original procedure was used. The actometric test, which has lead to divide the animal collectivity, according to Gauss bell-shaped distribution curve, in individuals with medium spontaneous motor activity (“normals”) and in individuals with hypo- or hypermotility (“sensitive”), was chosen. The effects noticed in these researches have had, without exception, a highly statistical significance (p < 0.01) in “sensitive” extreme individuals and have been statistically insignificant (p > 0.05) in “resistant” extreme individuals. In the author's opion, the extreme individuals, within a population with normal Gauss-like biological variability, represent psycho-neuro-endocrine typologies with opposite dominants, which should make the object of future biological and pharmacological studies.

The effect of diluted thyroxine was tested on the transition from the 2-legged to the 4- legged stage in the grassfrog rana temporaria. (A) Throxine dilutions log 4 and log 5 prepared with a minimum of agitaiion (final concentration in the basin water log 9-10) exerted a stimulatory effect; the dilutions log 6 and log 8 prepared in a process of stepwise dilution by pipetting (final concentration log 11-13) clearly inhibited metamorphosis. This is discussed as a hormetic effect. (B) When the latter dilutions were prepared in a process of stepwise dilution and vigorous agitation, this inhibitory effect became even more marked; it was even found at log 5. This is discussed with regard to the ‘potency rule’ of homeopathy (C) The stimulatory effect of the thyroxine dilution log 5 was seen to decrease when an agitated dilution log 8 was applied simultaneously. This is discussed with regard to the ‘similarity rule’ of homoeopathy.

The aim of the present experiments is to study the specificity of the similia-principle. Previously it has been shown that the recovery of cells that were damaged by a specific stressor, is stimulated by the application of a low dose of the same stressor. The process of recovery is evaluated in terms of enhanced synthesis of heat shock proteins, which are involved in repair-processes, and the development of tolerance. With respect to the specificity of the similia-principle, our working hypothesis is that the most effective low-dose stimulation of heat shock protein induction in damaged cells is obtained with the same stressor or a stressor which has an identical pattern of induction of the different stress proteins. With less similarity between the damaged condition and the low-dose stimulating condition, the low-dose stimulation will be less or even absent. The present paper deals with the relationship between degree of similarity and efficiency of low dose stimulation. To this end, arsenite, heat shock and cadmium are used as damaging conditions. The same three conditions, at a low dose, are applied afterwards. The results confirm the aspect of specificity of the similia principle, which can be verified further by extending the number of damaging conditions.

The remarkably high variability of olfactory psychophysical thresholds could be interpreted as a transitory ability to detect, under certain, still undefined conditions, highly diluted odorants. One of the factors contributing to this phenomenon might be represented by Central modulation of detection thresholds. The present experiments deal with a particular case of tuning the threshold toward low concentrations of an odorant (amyl acetate, resembling banana smell). It is characterized by a decrease by about one or two orders of magnitude of ascending limit thresholds (estimated by gradually increasing stimulus concentrations from subthreshold values in a sequence of trials) in comparison with descending trials (estimated in the opposite way). Two factors seem to be relevanti:unidirectional stimulus ordering from sub-threshold toward supra-threshold values, probably activating physiological processes underlying stimulus expectation;and the lack of additional references a concerning stimulus intensity (other than the ordered sequence of preceding ascending concentrations).

The following sections are included:

• Introduction

• The state of enhanced sensitivity; its occurrence

• The state of enhanced sensitivity; its origin

• The state of enhanced sensitivity; its duration

• Is the degree of sensitization related to the level of tolerance developed later on?

• Stimulation of self-recovery is related to the occurrence of enhanced sensitivity

• References

The novel concept of immunomodulation proposed herein does not involve a new molecule or extract but rather a new approach to the use of conventional substances to modulate the immune response. The families of molecules we studied have different kinds of activity: thymic hormones which induce T lymphocyte maturation, bursin which participates in B lymphocyte maturation and cytokines which take part in cellular interaction. Our investigations were carried out with thymulin and natural mouse ap interferon or bursin, we sometimes tested other thymic hormones or interleukin 2. To transmit this information, we studied the effect of a series of highly diluted test substances according to the homeopathic procedure. Our results indicate that serial dilutions present immunomodulatory activity. Furthermore, the activity is specific and the higher the dilution, the greater the capacity of the test substance to transmit its information to the target cell or organism as shown in bursectomized chickens receiving highly diluted bursin. We suggest that the regulation of biological systems involves the notion of “information” rather than the quantity of molecules it receives. Therefore, it is possible that besides the regulatory mechanisms in living organisms reacting in response to hormones or cytokines and obeying the laws of classical pharmacokinetics, other mechanisms reacting in response to “information” might exist. These regulatory effects could be expressed at another level than those of the classical effector mechanisms of the cells.

The therapeutic effect of homeopathic dilutions of silica was investigated for two years in an experimental murine model of chronic wound induction. In conventional science, silica is used in pharmacological concentrations as a substance that is both inhibitory and cytotoxic to macrophages. In homeopathy, silica is used, among other things, as an anti-inflammatory remedy, especially for treating chronic wounds, ulcers, abscesses, etc. Silica is also regarded as an agent that causes rejection of foreign bodies from living organisms. In this study, each experiment consisted of three to four groups of ten mice. Holes were made in the ears of mice by perforation with a dental wire, which was then left hanging in the ear so that the constant friction would cause a persistent mechanical irritation. For 4 to 20 days, the following homeopathic dilutions of silica: 10⁻¹⁰ (C-5), 10⁻⁶⁰ (C-30), 10⁻⁴⁰⁰ (C-200) of the mother tincture and of saline , “10⁻¹⁰” (“C-5”), were added to the drinking water of the mice and the size of the hole was measured daily. In the first and second experiments, the size was graded from 0 to 4, and then we used an image analysis system. In 7 of 13 experiments, the size of the holes of the silica-treated animals was significantly smaller (P<0.05-0.001) and healed fester than those of the saline-treated control animals. Moreover, the therapeutic effect increased as the concentration of the silica decreased. The results of this study demonstrate that homeopathic dilutions of silica (even beyond Avogadro's number) have a therapeutic effect on chronic wounds. The results cannot be attributed to a placebo effect because experiments 3-6 were conducted as a double-blind study in which an objective measurement method was used. The mechanism of action is not clear. Although the effect of the low dilutions is probably due to the action of silica in conventional systems, the effect of the high dilutions remains an enigma because the C-30 and C-200 dilutions do not contain even one molecule. One explanation of this result could be an “imprint” of the “information” of the silica on the diluent. The successive augmentation of the therapeutic action of silica from low through medium to high dilutions suggests that the mode of action of all dilutions have the same foundation.

The clinical effects of coherence relate particularly to electrically hypersensitive patients. These are persons who usually have some chemical damage, and in whom one or more regulatory systems are on the verge of instability. Very weak EM fields or water ‘imprinted’ with their appropriate frequency can take them from stability to instability or vice versa. Water “memory” can be imprinted with an alternating magnetic field, an alternating magnetic vector potential or, by a person holding and/or succussing a glass tube of water. The latter forms the basis of a technique for determining the stabilising and de-stabilising frequencies for patients too sensitive to be exposed to any coherent frequency.

The ethanolic extract of a fungus Agaricus muscarius L at a dilution of 10⁻⁶⁰ induces in albino mice a very mild catalepsy which is highly potentiated when the drug is followed by the mixed dopamine agonist apomorphine and selective D2 agonist bromocriptine. The high dilutin of Agaricus is produced in 30 steps and in each step the dilution (1:100) is mechanically agitated or sonicated. The drug thus prepared is called potentized. Pretreatment of Agaricus markedly reduces haloperidol-induced catalepsy in mice. The potentized drug is effective only through the oral route and not through the intraperitoneal route. Agaricus also interferes with the locomotor activity of mice modified by the neurotransmitter drugs. It is suggested that potentized Agaricus acts on receptors in lingual epithelium and the impulse goes through afferent nerves to specific brain areas where specific G-proteins are expressed. These G-proteins associate with D2, D3 and D4 receptors and serve as their agonists resulting in the modulation of catalepsy in mice.

The Belladonna (B) tincture (containing 0.03 g% total alkaloids, expressed in atropine) was progressively diluted with water, at a geometrical ratio of 1: 100. Thus, a scale of centesimal dilutions (C) between the 1^st dilution 10⁻¹ (1C) and the 200^th dilutions 10⁻⁴⁰⁰ (200 C), with a content of 6.023 × 10¹⁷ and respectively 6.023 × 10^”381 atropine molecules/100 ml, was obtained. The dilutions were prepared in two ways: a) by simple homogenization (N dilutions) and b) by “dynamization” with manual succussion according to Hahnemann's homeopathic technique (D dilutions). The in vitro classical pharmacodynamic technique, on the isolated rat duodenum, mounted in the isolated organ bath, with special precautions was used. The isotonic contraction was recorded. The effects on the spasm induced by acetylcholine (ACH), at the standard dose of 10⁻⁶ g/ml bath, in the aqueous N solution, with a content of 33.55 − 10¹⁸ ACH molecules/100 ml was studied. On the scale of D dilutions 1C - 200C of B, the effect had a sinusoidal course (bidirectional multiphase effect). In the light of the author's informational theory of dosages, this double way (stimulator - inhibitor) effect is possible at different value scales of concentrations. In accordance with this theory, the information of biological and drug signals come out, may change and diversify, not only from the nature of substance and energy and also from their order and organisation in space and time, but also with their quantity, within certain limits. The defmite organisation of a solvent as the specific informational substrate of very high D dilutions of B was investigated, by a calorimetric methodology.

In 1983, staff members of our institute and colleagues at the Institute of Psychology studied the effect of antioxidants on the electrical activity of an isolated neuron of an edible snail (Helix pomatia) and obtained an unexpected result. The initial dose of the substance (10⁻³M), was, for the neuron, not only active, but quite toxic, which made it necessary to use a weaker solution. To our surprise, a dose that was 10⁴ lower than the initial dose proved not only less toxic, but more effective. Its further reduction heightened the effect, which reached a maximum (at 10⁻¹⁵M) and then declined until the results (at 10⁻¹⁷M) virtually coincided with the pilot results [1]. The same effects were later recorded in experiments involving animals when an antioxidant was administered, and the sensitivity of a choline mimetic arecoline was studied.

We examined these effects on animal and plant cells, at the organism level, the biomacromolecule level, etc. The action of antitumor and antimetastatic substances, radiation protection preparations, plant growth inhibitors and promoters, various classes of neurotropic preparations, hormones, adaptogens, immunomodulators, detoxifying agents, antioxidants, and physical factors (such as ionizing radiation) were subjected to analysis. Ten years of work (1983–1993) led us to believe that this is not a specific action of one individual preparation or a specific response of an individual biological agent, but a new law of interaction between a biological object and ultra-low doses of biologically active substances (BAS). Each of this substances can have a target, an enhancement mechanism and metabolic features of its own, but, when used in ultra-low doses they display a number of common properties. It was later discovered that low-intensity physical factors display analogous characteristic.

The levels of biological organization at which the effect of ultra-low doses of BAS was discovered also vary from cells, macromolecules, organs, and tissues to animal and plant organisms and even populations. This does not mean that the effect was observed, when ultra-low doses of any BAS were used on any biological object. I only wish to strss that the effect of the action of BAS concentrations of 10⁻¹³-10⁻¹⁷M and lower cannot be linked to any definite substance structure or biological organization level.

Rats, which are quickly exhausted and remain passive when subjected to inescapable swimming in a tub of water, are potential alcoholics. These rats were given 20% alcohol for 10 days and then both 20% alcohol and water in a two-choice bottle test. They were treated by oral route with the potentized extract Strychnos nuxvomica L such as Nux vom 1000 and 30s. The latter potency was prepared by sonication instead of succussion. Both potencies of Nux vom significatly reduced alcohol consumption and Nux 30s was more effective than Nux vom 1000 in this regard. Nux vom 30s given intraperitoneally to another batch of rats produced no effect on alcohol consumption. Nux vom 200 and 1000, applied on the tongue of anaesthetised alcoholic rats, increased the neuronal activity of the LHA while 20% alcohol, distilled water and Nux vom mother tincture decreased it. The inhibitory effect of the latter might be due to alcohol in the mother tincture rather than to the crude drug. The antialcoholic effect of potentized Nux vom appears to be mediated through tongue receptors and hypothalamic neurons. In another experiment rats were kept on 20% alcohol and normal food for 2 months. Then they were treated with Nux vom 30s, one dose every 15th day for 4 months, and kept on a two-choice bottle. Noradrenergic nerve terminals in atrioventricular valves degenerated considerably in untreated alcoholic rats. Treatment with Nux vom 30s not only reduced alcohol consumption in rats but also helped in regeneration of most of the nerve terminals.

Silver nitrate is well-known to be generally biostatic. However, it is also discussed as a biologically vital trace substance. This substance has been prepared in a standardized process of stepwise dilution and agitation. Its influence on the development of wheat seedlings has been studied. When seedlings are exposed to silver nitrate at high molecular concentration, growth is normally inhibited. Interestingly, growth was stimulated by a dilution log 24 of this probe. In our experiments, addition of one more standardized step of dilution and agitation, or agitation alone, to the dilution log 24, significantly diminished the effect of the test dilution, whereas addition of two steps again enhanced the stimulatory effect (“double switch” kinetics). This was found by different independent researchers. Furthermore, optimized conditions for performance of the experiment are discussed.

Agaricus muscarius 30s, a potentized drug prepared by successive dilution with 90% alcohol followed by sonication, when given through oral route, suppressed haloperidol-induced catalepsy in Swiss albino mice significantly. This anticataleptic effect was dose dependent being maximum with the undiluted Agaricus 30s and minimum with its dilution 1:20,000. Higher dilutions like 1:40,000 and 1:50,000 did not produce any anticataleptic effect. The effect reappeared when the dilution 1:50,000 was sonicated. An amount of 0.05 ml of the dilution 2X10⁻⁴ of Agaricus 30s is quantitatively equivalent to 0.075 ml of the dilution 3X10⁻⁴ and to 0.16ml of the dilution 4x10⁻⁴. Three groups of mice were pretreated with the three dilutions of Agaricus 30s in such a way that each group received an equivalent volume dose of the drug. Of the three dilutions, only the lowest one 2x10⁻⁴ was effective in reducing haloperidol has an active physical entity which can be attenuated by dilution and multiplied by mechanical agitation or sonication. It is also suggested that potentized Agaricus acts through tongue receptors.

Various substances, among which some purine derivatives, notably caffeine and adenine, exert teratogenic effect on mice. If administered during pregnancy, the litters present anatomical, biochemical and behavioural consequences; at higher doses, the death and resorption of foetuses occur. We investigated the possibility to prevent and/or abolish the teratogenic effect of caffeine and adenine in mice by means of high dilutions of substances chosen according to the isopathic or homeopathic criterion (either the same teratogenic agent, or other substances): the effect has been either prevented, or counteracted by highly diluted substances administered either before or after the intoxication by the teratogenic agent. The amount of the effect depends on the type of substance used and on the degree of its dilution.

The aim of this study was to investigate the anti-inflammatory activity of two homeopathic diluted drugs : Urtica urens and Apis mellifica, by a non invasive and non subjective cutaneous technique. This method consisted to induce a skin inflammation, provided by an application of an aqueous methyl nicotinate solution (0.5%). The vasodilation induced was quantified in terms of cutaneous blood flow by a Laser Dopler Velocimeter (L.D.V.). This vasodilation could be inhibited, in part, by a skin pretreatment with homeopathic dilutions. The efficacy of these dilutions was expreessed by the value of the inhibition percentage, which was calculated by comparing responses supplied by the L.D.V., for the methyl nicotinate score, to the homeopathic dilutions scoresTen adult volonteers of either sex, aged from 20 - 50 years, took part.Under this protocol, homeopathic dilutions, placebo and positive control were assessed. The different dilutions gave significant results but with a different amplitude in the response : Urtica urens 4 CH exhibited the strongest anti-inflammatory effect reaching an inhibition of 37 % ; Urtica 7 CH reduced blood flow by up to 30,8% and Apis 4 CH to 21,2%. No significant difference was noted for Apis 7 CH and between the dilutions.

The following sections are included:

• Introduction

• Materials and Methods

• Results

• Discussion

• Bibliography

We determined if high dilutions of antiGABAergic drugs modulate the visuo-vestibular reflexes responsible for gaze stabilization, and examined a possible target for their biological activity. The horizontal optokinetic and vestibulo-ocular reflexes were first depressed by concentrated antiGABAergic drugs (10⁻³ M purified picrotoxin in 15/15 rats or 10⁻⁶ M picrotoxin in unpurified mother tincture of Cocculus in 44/59 animals). The reflexes returned normal to compensate visual and vestibular stimulations after a subsequent injection (1ml) of Cocculus 4CH (10⁻¹³M picrotoxin) in 11/12 rats, but not of the solvent alone (5/7 rats). An amelioration was also observed after an injection of higher dilutions (6/6 rats). These results demonstrate a high sensitivity of the oculomotor system to antiGABAergic drugs with a dose related effect, and a modulation of the toxic effect by diluted agonists. The deficits of the reflexes were correlated with the low level of GABA which was , found at the intoxicated state, but the amelioration was not correlated with any change of GABA level. The target of action of high dilutions appears different from that of concentrated drugs. Therefore it appears paradoxal. A possible explanation for physical mechanisms of action of high dilutions could result from biophysical modifications of the solvent as observed in NMR (nuclear magnetic resonnance).

An 1% solution of sodium chloride was prepared in 90% ethanol. This solution was agitated manually by ten downward strokes. This solution was serially diluted and agitated in a similar way in thirty steps to produce a dilution 10⁻⁶⁰ of sodium chloride. Phosphorus was also similarly prepared to produce a dilution 10⁻⁴⁰⁰ . Sodium chloride at a dilution of 10⁻⁶⁰ , applied on the tongue of albino rats kept on 4% salty food and 6% salt solution as drinks for 7 days, inhibited the spontaneous neuronal activity in lateral hypothalamic area(LHA) of those rats. The rats were on normal food and drink for one day before the test. Distilled water dropped on the tongue increased the rate of discharge of the LHA and this increase was more pronounced in rats which were on 8% salty diet continuously without a break before treatment. Sodium chloride at the dilution 10⁻⁶⁰ and phosphorus at the dilution 10⁻⁴⁰⁰ reduced firing rate of single neurons of the LHA of the rats which were given the same dilution of sodium chloride, one dose daily for 18 days. The rats were under anaesthesia during the recording of the neuronal activity. The results indicate that high dilution of sodium chloride, prepared with agitation could elicit very consistent and often prolonged response from the hypothalamic neurons of albino rats either on salty diet or on the same dilution of sodium chloride. Thus diet with excessive salt and sodium chloride at the dilution 10⁻⁶⁰ caused central and peripheral reorganization in the taste sensor system of the rats which became responsive to the high dilution of sodium chloride.

The following sections are included:

• Introduction

• Materials, methods and subjects

• Results

• Discussion

• Acknowledgements

• References

Several reports on animals, plants and cells suggest significant biological responses following exposure to agonists so highly diluted that very few molecules of the original substance, if any, could have remained. However, there is a large gap in our kwowledge on the information transfer mechanism, although a few theoretical studies have explained the effect in terms of a biophysical model. In our studies, we proposed that the effect of ultra-high dilutions, if any, is not dependent on molecular interaction, e.g., mixing, with the organism. We focussed our attention on a human test model. Using the control of subtle muscular movements as a parameter we studied human interactions and the effect of the proximity of specific ultra-high dilutions in sealed glass vials on this interaction.

The following sections are included:

• Introduction

• Basis of Nonlinearity at Low-Level Intensities

• Cell Growth as a Result of Nonlinearity at Low Intensities

• Coherence and Communication

• References

A wide range of biological cells show general oscillatory phenomena and a wide range of biomolecular systems are sensitive to weak environmental electromagnetic fields particularly in the low frequency region or to radiofrequency fields modulated by low frequencies. Human circadian rhythms and temporal morphology imply a high degree of coherence. Frequency information can be ‘imprinted’ into water and metals and on to a light beam but, deuterium oxide would not ‘imprint’. This implies that both the protons and electrons in water must be co-operatively coherent. The frequency information in ‘imprinted’ water can propagate through aqueous and metallic systems which thus become channels for bio-communication.

For the interpretation of high dilutions in water, the clathrate model is presented according to which round each molecule of the mother substance a clathrate is formed, made of water molecules interacting by hydrogen bonds. If forceful mechanical impulses are applied on the solution, the model assumes that a separation of the initial molecule from its clathrate is possible, a fact which leads to the formation of new clathrates round each of these two separated components. This effect is repeated again and again as we proceed in the preparation of a high dilution. Thus, eventually this dilution contains free molecules of the solvent (here water) and bound molecules of the solvent in the form of clathrates which are characteristic of the initial mother substance.

The following sections are included:

• Introduction

• Calculations and experiments

• Structured water in proteins

• The role of water clusters in protein function

• The role of water in active sites

• References

For a verification of the clathrate model, introduced in the previous paper, the dielectric and the differential scanning calorimetric methods are applied. The first method is capable of verifying that a high dilution contains free and bound (e.g., in the form of clathrates) molecules and the second that a change of phase occurs when the clathrates are destroyed (freeing their bound molecules) at a certain temperature. This temperature depends on the specific clathrate involved which is characteristic of the specific mother substance. Thus, while many more methods should be applied before a final conclusion is drawn, it is encouraging that the results of both methods applied here support the predictions of the clathrate model.

We can present the paradigm of signifiers as following: living beings communicate with their world in a non verbal way, whether on a somatic or psychological level. This paradigm takes place within the framework of the logic of analogy. The signifier is the semantic object which materially designates information to be transmitted and dealt with: the homeopathic remedy is the mimetic representation of the disease. Different levels of information organize the spread of signifiers; each level is the regulation and integration of the previous one. The living self is the never-ending process whereby levels of information are synthetized, in the face of the informing environment. Such structures meet each other in the communication between the patient and the physician-remedy system. The medical device has to reinform the patient and makes his symptoms move on towards a higher level of integration. The dilution of the remedy permits us to read it as information about disease. Symptoms can be recognized as an erroneous adaptation and the organism is engaged in a process of paradoxical negation. The action of the remedies consists of a dynamic analogy between pieces of information. The paradigm of signifiers gives therefore a new possibility in the exploration of informative therapeutics.

The following sections are included:

• Introduction

• Materials and Methods

• Clinical experiences

• Laboratory experiments

• Discussion

• References

The following sections are included:

• Introduction

• Materials and Methods

• Results

• Discussion

• References

The following sections are included:

• Introduction

• Materials and Methods
  • TFF on an animal model
  • TFF on a vegetal model

• Results
  • On an animal model
  • On a vegetal model

• Discussion

• References

Facts of nature can only be explained within a scientific structure. The structure of modem science has two characteristics, a mathematical and an analytical one. In ancient philosophy we find these characteristics in Plato's Timaeus. However, Hippocrates warns us for the analytical approach and tells us to start our medical examination from the individual Aristotle adopted this advice in his ontology. With the aid of Aristotle's hylomorphism we can explain the action of highly diluted substances on living cells.

In the history of medicine an important role is played by those medical practices which are usually known as non-conventional medicines. Non conventional medicines (also called “alternative medicines” or “traditional medicines”) make up a crowded group of different medical and therapeutic practices particularly distinct from so-called official or conventional medical science.

The single contributions to the general discussion are here summarized.

Karl W. KRAKTY comes back to the different models that have been presented, describing them in details, and points out that one has to see how they fit together, or whereas there are some problems or inconsistencies. The main problem is how it is possible to obtain High Dilutions without any molecules and which is the process of “imprinting” that allows the information transfer. Later, at the end of each intervention to the discussion, he puts critically in evidence the main points that have been treated…

The following sections are included:

• Members of the Scientific Committee, Lecturers and Members of Organizing Committee are indicated respectively by three, two and one asterisks