Ultra-high Dilutions Research Articles

Discussion on a null hypothesis for a bibliometric study

In a bibliometric study [1] we located around 100 high-potency studies, each of which scrutinized an earlier study. An expert round was set to discuss whether it was justified to use the null hypothesis that no difference would be found between the respective test and control groups.
 
 The following two viewpoints were juxtaposed: 
 
 1) The classical null hypothesis states that the results from a test group and its respective control will not differ. If difference is found, the null hypothesis must be rejected. In this case, whether the values found in the test group were higher or lower than the ones of the control group is irrelevant. However, in some instances lack of difference between the test and the control groups is not helpful to make an informed decision. In the case of the analyzed bibliometric study, the research question is as follows: is the number of replication studies which produced a result of the same kind as the original study greater than the number of replication studies which produced a result of the opposite kind?
 
 2) Often there is a pragmatic interest in a one-sided difference or in a deviation in one specific direction. A null hypothesis to this end will state, for example, that the result of the test group will not be better than that of the control group. If difference in favor of the test group is found, the null hypothesis must then be rejected. If, conversely, no difference is found or the result of the control group is better, the null hypothesis can be maintained. For the analyzed bibliometric study the question is: is the number of replication studies which yielded a result of the same kind as the original study greater than the number of all other replication studies?
 
 From viewpoint (1) the outcome was that 70% of replication studies yielded the same result as the original study, 10% per cent the opposite result, and in 20% no difference was found between test and control. From this view point the standing is 70 positive, 10 negative and 20 undecided results. Broken down further, the outcome for laboratory-internal replication was 83 and 5 (12 undecided results) while the outcome for multicenter replication was 75 and 11 (14) and that for external replication was 48 and 14 (38).
 
 From viewpoint (2) the outcome was that 70% of replication studies yielded the same result as the original study, and that 30% (= 10% + 20%) either resulted in no difference between the test and the control group or a result opposite to the one of the original study. From this viewpoint the standing is 70 ‘for reproducibility’ versus 30 ‘not for reproducibility.’ Broken down further, the outcome for laboratory-internal replication was 83 and 17 (= 5 + 12), while that for multicenter replication 75 and 25 (= 11 + 14) and the one for external replication 48 and 52 (= 14 + 38).
 
 We conclude that the 2 two viewpoints should be treated as equally valid when discussing the outcome of the analyzed bibliometric study
 
 Keywords: high dilution, experiment repetition, null hypothesis 
 
 
 References 
 [1] Endler PC, Bellavite P, Bonamin L, Jäger T. Mazon S. Replications of fundamental research models in ultra high dilutions, 1994 and 2015: an update on a bibliometric study. Homeopathy 2015;104:235-245

"˜Regression toward the mean" in replications of fundamental research studies on homeopathic high potencies?

Around 100 high-potency studies, each one replicating earlier studies, were located in a bibliometric study on fundamental research [1]. 70% of the replication studies yielded the same result as the original study, 10% the opposite result, and 20% found no difference between the test and control groups. This is to say, the final standing was 70 positive, 10 negative and 20 undecided results. Among the replication studies performed by the original laboratory, the outcomes were 83 positive and 5 negative (12 undecided); in the ones performed in laboratories of independent researchers invited to participate in a multicentric study the corresponding outcomes were 75 and 11 (14), and the ones of studies performed by external researchers 48 and 14 (38). Had the experiments been performed on purely random phenomena the most probable outcomes would have been 33 : 33 : 33.
 
 In a follow-up study we sought to establish whether the outcomes of the replication studies might be attributed to regression toward the means. As is known, this term describes the situation in which a random experiment yields an extreme result, while subsequent replications give average results quite independent from the initial one. By contrast, when the experiment is not entirely based entirely on chance, subsequent replications tend to yield results that deviate from the average in the same direction as the initial one. 
 
 We thus grouped the studies into 3 clusters of at least 7 articles according to their date of publication. The relative frequencies of positive, undecided and negative results were graphically represented through by curves to allow for visual comparison of the initial result versus the results of the replication studies for each of the 3 clusters.
 
 Regression towards the mean was neither observed in the results of the replication studies taken together nor in the group of laboratory-internal replication studies. By contrast, the group of multicentric replication studies exhibited increase of the relative frequency of undecided results and decrease of the one of positive results. In the group of external replication studies the relative frequency of undecided results increased and the one of positive and of negative results decreased.
 
 The statistical probability of drawing a ‘positive result’ from a total of 3 equally probable options (positive, undecided, negative) is 33.3%. By contrast, within the entirety of replication studies the frequency of positive results was 77% on the first replication, 66.7% on the second and 66.7% on the third. Unlike the results from the group of laboratory-internal studies, the ones of multicentric and external replications are suggestive of regression towards the mean. However the magnitude of this effect is far weaker than would be expected from a purely random distribution of results. One question that remains is why there appears to have been practically no regression in the laboratory-internal replications. This should not be cheaply attributed to publication bias. Especially in experiments on homoeopathic high potencies, it could well be that numerous, in some part hidden factors of influence are involved, which internal laboratories – possibly unwittingly through unreflected working habits– are better at controlling than external laboratories, regardless of the effort invested to this end. 
 
 Keywords: high dilution, replication experiments, regression to the mean
 
 
 References 
 [1] Endler PC, Bellavite P, Bonamin L, Jäger T. Mazon S. Replications of fundamental research models in ultra high dilutions, 1994 and 2015: an update on a bibliometric study. Homeopathy 2015;104:235-245

The phenomenon of interdependent states of animals and humans: tactics and treatment strategy using ultra-high dilutions of substances, 20-year research

Before the start of our research, there already was empirically developed experience on the appearance of similar conditions in animals and humans in close contact. However, there was no scientific explanation for this phenomenon, or scientifically grounded recommendations for its application in medical practice. Since 1995 we have been systematically studied cases of humans and animals in close contact exhibited a same pathological condition. The aim of the present study was to establish the features of these interdependent states and the factors that influence them.
 The experimental and clinical studies described here were performed based on spontaneous procurement by the animals’ owners at Department of Pharmacology and Toxicology, St. Petersburg State Academy of Veterinary Medicine and at Research Center of “POLEVET” Veterinary Clinic.
 
 Clinical, hematological, biochemical and immunologic parameters describing the condition of the animals during homeopathic treatment preparations were recorded. To assess the reliability of differences at 0.05 significance level was used.
 
 Statistical analysis was made of 8,061 episodes of addresses of animals and their owners. Based on these materials and using modern achievements in biology, genetics, physiology and neurophysiology, the main theses providing theoretical substantiation for this phenomenon were formulated, and the mechanisms of development of one and the same disease in both humans and animals according to modern scientific conceptions were revealed. Also a tactic and strategy for treatment of sick animals and humans in close contact are suggested. To correct interdependent conditions, a method of application of the effects of ultra-high dilutions of drugs was developed and proposed for practical use, which might enable veterinary specialists - based on the knowledge of the phenomenon of interdependent conditions - to significantly improve the recovery of their patients. The effectiveness of this approach was confirmed in practice by many specialists who made use of our results.
 
 The work performed and the attention paid by specialists to these studies, as well as the possibility to correct the phenomenon of interdependent conditions of animals and humans using ultra-high dilutions of substances, demonstrate the potential for further scientific developments in this field of medical practice.

Comparison of aluminum toxicology and homeopathic Alumina: a mixed methods study

Toxicology forms part of homeopathy. The founder of homeopathy, Samuel Hahnemann, incorporated many toxicological symptoms in his Materia Medica. These symptoms are part of the information homeopathic practitioners relay on to choose the appropriate medication for their patients. This medication is administered in form of ultra-high dilutions. Hahnemann also developed Materia Medica on the base of provings done with high diluted substances only – simply because these substances did not have a known toxicology at his time. Alumina is one of these substances. Today we possess a reliable toxicology of aluminum and its compounds. The objective of this study was to determine the grade of concordance between homeopathic (highly diluted) Alumina and aluminum toxicology. A striking concordance will add to evidence of homeopathically potentized substances. 
 
 The present was a literature-based investigation conducted from a phenomenologist stance. The design is a novel one. Symptoms of aluminum intoxication were obtained from case reports published in scholarly journals. 70 original research articles containing case-reports of 5 aluminum-induced diseases served for the extraction of over 300 symptoms. These symptoms were compared to Hahnemann´s Alumina proving symptoms. 
 
 A review of modern investigations of the toxic effects of aluminum showed that the conventional medical paradigm and basic science are just starting to explore the huge number of noxious effects the metal has on human, animal and plant health. Qualitative explorations of the relevant homeopathic literature (toxicology in homeopathy and Alumina in randomized controlled trials) resulted in the finding that toxicology plays a minor role in modern homeopathy and that Alumina has been poorly investigated. 
 
 The result of the quantitative part of this study – the comparison of proving and toxicology obtained from clinical cases – shows an uneven picture. It leads to only partly significant concordances between symptoms from both sources which are strong in core areas of Alumina´s remedy action while the overall comparison shows a coincidence of 50.76% (39.76% for symptoms probably produced by UHDs). 
 
 This study has to be seen as a pilot for a literature-based proof of the evidence of homeopathic potencies. There remains much to be done, especially in the realm of homeopathic proving and its design. Hahnemann´s procedure – to rely on sensible provers – should be reconsidered. The reproving of Alumina should be envisaged.
 
 Keywords: Homeopathy, proving, toxicology, homeopathic pathogenetic trial (HPT), Alumina, aluminum

Prevention and treatment of the side effects of poly-ADP-ribose polymerase-1 inhibitors (iPARP) in breast and ovarian cancer

Poly-ADP-ribose polymerase inhibitors (iPARP) are a new class of targeted therapy which block the DNA repair mechanisms of cancer cells causing their apoptosis. They are mainly used in ovarian cancers to prevent a recurrence. The most common side effects are nausea and fatigue; the most serious are blood toxicities. Prescribed over several months, supportive care is essential to improve quality of life and consequently compliance with iPARPs. In our experience, the use of homeopathy and of ultra-high dilutions of iPARP, reduces side effects and is a great help to patients. The lack of drug interactions makes it possible for them to be used safely. The low cost and very good tolerance of this supportive treatment make it very acceptable to patients. Preliminary clinical studies should be carried out to confirm our favourable clinical impression.

Nonclinical study of the new immunotropic drug effectiveness in salmonella infection treatment

The aim of the study was to evaluate the immunoregulatory activity of an experimental drug based on ultra-high dilutions of antibodies to MHC I and MHC II molecules against Salmonella enteritidis rif92 . Materials and methods. The drug tested: a sample of ultra-high water-alcohol dilutions of antibodies to MHC I and MHC II molecules applied to lactose powder (the theoretical level of the initial antibody concentration reduction is at least 10 24 times). A model of non-lethal Salmonella infection in chickens was induced by administering a virulent strain of Salmonella enteritidis rif92 with a concentration of 2.5 × 10 9 CFU/g in the volume of 0.5 ml/bird. The following groups were formed ( n = 15 in each group): 1 – drug; 2 – drug + antibiotic at the median effective dose (ED 50); 3 – placebo; 4 – placebo + antibiotic at ED50; 5 – intact control. The duration of the experiment was 12 days. The studied parameters included the survival rate during the observation period; daily body weight; feed consumption for the entire period; pathogen concentration in the litter on day 3, 6, and 9; the presence and concentration of the pathogen in the liver and cecum on day 12; and the index of antimicrobial activity on day 12. Results . In the groups receiving the experimental drug, the infectious process proceeded in a milder form and the bacterial load in chickens was lower. The bacterial count in the litter was reduced by two orders compared to the respective control when the drug was added both alone and in combination with the antibiotic. A protective effect of the experimental drug on the liver of the infected chickens was detected. Conclusion. A pronounced immunoregulatory activity of the studied drug against Salmonella enteritidis rif92 in chickens was demonstrated for the first time. The results obtained allow to consider the drug as a promising agent for the treatment of Salmonella infection.

Use of methods of the biocrystallomics in personification of the treatment with high diluted drugs

Background: One of most important trends in modern medicine is its transformation to personalized diagnostics and treatment. This tendency fully applies to homeopathy, especially considering that this discipline is based on the principles of individual approach to the patient. At the same time, the methods of individualization of treatment in homeopathy are relatively few. 
 Aims: Develop of methodology and methods of application biocrystalloscopic tests to personalize the homeopathic treatment. The proposed technology became previously proposed for ozone therapy practice as biocrystallomics pre-test. It includes study of the result of co-crystallization of a biological liquid of a patient with the intended dose of the drug. At the same time, the character of co-crystallization of biological liquid with several doses of tested drug or different parameters of the action of the studied factor is comparatively estimated for the purpose of individualization. Most appropriate for a particular patient believe the dose that causes optimal structuring in the dried microscopic slides obtained from a mixture of biological fluid and a solution containing a given dose of the drug. The comparison is made with a control sample of biological fluid, which has not been exposed to any effects. The optimal result is a sample that matches the control sample as much as possible. It is most preferably for biocrystallomics pre-test to use blood serum or plasma as an analyzed biological fluid.
 Methodology: To study the characteristics of the structuring of the semicroscopic slides we use the previously created system of semi-quantitative parameters. They are calculated on a straight four-point scale and include: crystallizability (semi-quantitative indicator of crystallization activity), structure index (complexity criterion for constructing crystal elements of facias), facia destruction degree (indicator of “correctness” of crystal formation) and clearity of facia marginal zone (parameter indicating the amount of native protein in the sample of biological fluid). These indicators comprehensively characterize all the main features of the process of dehydration structurization of biological substrate.
 Conclusion: It should be noted that the technique described above is universal and can be applied to any liquid or soluble compounds with potential therapeutic activity, including their ultra-high dilutions. The data obtained by us indicate the possibility of using this technology in homeopathy.

Sedative antistress activity of ultra high dilutions of fish skin containing alarm pheromone on hydrobionts in comparison with warm blooded animals.

The obtained results can be interpreted as the sedative and antistress anxyolitic effects of Pyscin used in high dilutions. This effect is universal for various species.

Study of Germination Efficiency and Temperature/Drowning Resistance in some Ornamental Plants treated with Ultra High Dilute Compounds

Background: The ultra-high dilutions (UHDs) can used for decreasing stress conditions causing by climate variations. Present research, it was investigated the effects of the ultra-high dilutions (UHDs) on some ornamental plants, germination, and hormonal variations.
 Methods: In order to study the effect of UHDs (Calendula officinalis Calen. and Arnica montana Arn.) on the physiological, primary metabolite and hormonal variations of the Oryza sativa L. (rice), 104 experiments were designed and statistically analyzed using the Design Expert 7.0.1 software over the general factorial design methodology. Two qualitative factors including the UHDs/placebo usage and the type of plant usage and two quantitative factors including temperature and irrigation were studied. The validated analysis was subjected to more extended studies on the variations in physiological growth, carbohydrate, protein content and levels of plants hormones including gibberellic acids, indole acetic acid, abscisic acid and salicylic acid.
 Results: The statistical analysis resulted in a prediction model which was more than 75% correlates with experimental results. The results showed that the UHDs increased the carbohydrate and protein content of seedlings. Also compared to placebo, the levels of hormones GA3 and IAA in all samples increase and the amount of GA4 decreases. The amount of ABA and SA hormones in S. officinalis increased under UHDs treatment while they decreased in the other two samples.
 Conclusion: The use of UHDs leads to an increase in the production of carbohydrate and protein content. Moreover, it causes significant variations in the growth inducing hormone and increase the tolerance of seeds under higher/lower temperature and draught/drowning. The results of this study open up a window to reduce the germination survival and increase their resistance to sudden climate change.

Systemic Agro-Homeopathy: A New Approach to Agriculture

Modern agriculture must meet the changing needs of society both in terms of food quality and with regards to the environmental issues related to primary production (e.g., biodiversity, habitats, the quality of water and air, and climate change). In this context, win-win solutions at the farm level are required, with more sustainable food production, as well as, a reduction in air, water, and soil pollution, and loss of biodiversity and natural resources. To address these issues, a new emerging discipline called “systemic agro-homeopathy” is currently being developed. This approach considers plants and their interactions with the environment as a unified agroecosystem, called the “holon” and it is based on the use of substances at ultrahigh dilutions that are safe for farmers and have no ecological side effects. This report describes the principles and the application of this approach.

The Influence of Ultra-High Diluted Compounds on the Growth and the Metabolites of Oriza sativa L.

Background: In the present research, we investigated the effects of the ultra-high dilutions (UHDs) on Oryza sativa L. (rice), physiological and biochemical variations.
 Methods: In order to study the effect of UHDs (Calendula officinalis in the dilution of 3×103X and Arnica montana in the dilution of 2 ×104 X), 28 experiments were designed and statistically analyzed via the Design Expert 7.0.1 software over the general factorial design methodology. Three qualitative factors were studied including the UHDs/placebo usage (A), sterile/non-sterile experimental condition (B) and the type and timing of the UHDs usage (C). The validated analysis was subjected into more studies on the variations in physiological growth, carbohydrate, protein content, pigment production, and amino acid patterns.
 Results: To evaluate the effects of UHDs on rice, we formed a desirable response percentage from a number of healthy seedling production, and studied the height percentage of the aerial parts and main roots. The statistical analysis resulted in the prediction model which was more than 97% correlates with experimental results. The results showed that the UHDs increased the pH variations, carbohydrate, protein and pigment levels by ~2.5, ~1.5, ~1.4, and ~1.4 fold, respectively. Also compared to placebo, the amount and proportion of amino acids has significantly varied. .
 Conclusion: Compared to placebo, the UHDs have statistically validated affected the rice germination and seedling growth. Also, they can affect the stress conditions caused by the sterilization process, seedlings entrance into the light and their transition into hydroponic culture medium. The use of UHDs leads to an increase in the production of chlorophyll, as well as carbohydrate and protein content. Moreover, they cause significant variations in the amino acid profile and the production of amino acids along with the photosynthesis, germination, and metabolism processes.

Exploring Possible Mechanisms of Hormesis and Homeopathy in the Light of Nanopharmacology and Ultra-High Dilutions.

Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond Avogadro’s limit defying conventional wisdom. They can show hormesis, and homeopathy uses them as medicines. Many studies confirm that they can have an impact on gene expression different than controls. Water in the exclusion zone phase can have memory but for a short period. However, the nanoparticle as the physical substrate can hold information. Nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. The Nanoparticle-Exclusion Zone Shell Model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. This model may also provide insight into the workings of hormesis. Hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. Hahnemann exploited it to establish homeopathy. The nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. They can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. It suggests homeopathy is a type of nanopharmacology.

Biophototic in azuki bean seeds treated with ultrahigh dilutions

Seed analysis is usually performed by destructive samples with time-consuming methods. Treatments that improve seed vigor are suggested based on bioassays and protocols for most plants. This includes the use of images to assess quality and pro- vide information that supports decisions. However, instrumental cost has not made these technologies widely used. The objective of this research was to study biophotonic images generated by low cost technologies - cold plasma scanner or gas discharge visualization (GDV) and speckle laser (BSL) - to evaluate the germination of adzuki beans seeds treated with ultrahigh dilutions (UHD). The research was carried out at the EPAGRI Homeopathy and Plant Health Laboratory, with a post-graduate support at the State University of Santa Catarina (UDESC). The images of the seeds were diagnosed mathematically, before and after germination, using “Local Connected Fractal Dimension Analysis” (LCFD) and “Time History Speckle Pattern” (THSP). The results show that the images identify the effects of high dilution - Bryonia alba and Silicea terra, at 6, 12 and 30 CH (centesimal hahnemannian dilution order) - on the seeds of azuki beans. There were statistically differences (p < 1% and p < 5%) of the treatments in relation to the control: water. Only Silicea terra 30CH inhibited seed germination. The signals found in the BSL images of the seeds were superior to the GDV signals, showing an average of 89% correct responses (BSL) against 87% (GDV).

High dilutions of two drugs induce changes in crystal water structure of lactose as revealed by thermogravimetry and differential scanning calorimetry

Ultra-high dilutions (UHD) of drugs used in homeopathy are preserved in sugars. How do solid sugars assimilate characteristics of UHDs? This study attempts to answer this question. The three UHDs of Acid fluoric, Acid nitric, and ethanol were mixed with lactose at 1 µL/g and analyzed by thermogravimetry (TG) and differential scanning calorimetry (DSC) to see any change in their crystal water. TG results show a mass loss of 4.9% at 146.8C for Acid fluoric 30 cH, of 7.1% at 146.6C for Acid nitric 30 cH, and5.1% at 146.5C for ethanol. DSC results show that the change in enthalpy for Acid fluoric 30 cH is 157.3 J/g at 153.8C, that for Acid nit 30 cH is 122.8 J/g at 148.3C, and that for ethanol is 154.9 J/g at 156.3C. Bound water in lactose crystals and corresponding enthalpies vary markedly in the three drugs tested. This indicates that the number of hydrogen bonds and their bond strength vary inbound water of medicated lactose crystals.

Evaluation of antipyretic activity of Belladonna and Pyrogenium ultrahigh dilutions in induced fever model.

Background Belladonna and Pyrogenium are commonly used to treat fever in homeopathy. But in vivo antipyretic activity of these medicines is not reported yet. The study was conducted to evaluate the effectiveness of ultrahigh dilutions of Belladonna (Bell) and Pyrogenium (Pyro) in fever model of rabbits induced by Baker's yeast. Methods Healthy, local strain rabbits (♂ and ♀) were divided into seven groups (n=42): Normal control, negative control, standard control, pyro 1000c, pyro 200c, Bell 1000c and Bell 200c. Fever was induced by intra peritoneal injection of 135 mg/kg Baker's yeast suspension. Rectal temperature was measured hourly. All the medicines were administered once a day. The results were expressed as mean ± SEM. ANOVA and least significant difference post hoc test were applied for checking the level of significance, p-value of ≤0.05 was considered significant statistically. Results Pyro in both potencies significantly reduced fever in rabbits compared to negative control group, while both potencies of Bell were ineffective. Paracetamol and Pyro 1000c reduced by 1.2 °C (39.7 ± 0.1 to 38.5 ± 0.1), while Pyro 200c reduced by 1 °C temperature (39.7 ± 0.5 to 38.7 ± 0.2). Conclusions Pyro possesses marked antipyretic activity in rabbit's Baker's yeast fever model. It would embolden its clinical use in fever with more guarantee of its efficacy. However, caveat of small sample size necessitates replication of experiment in large sample size.

MODERN ASPECTS OF HOMEOPATHIC MEDICINES STANDARDISATION

The article describes the status of homeopathic medicines standardisation in the leading world pharmacopoeias. It reviews main requirements for raw materials of plant, animal, and mineral origin, which are used in the production of homeopathic medicines. It also considers requirements for homeopathic pharmaceutical substances, including technologies of obtaining homeopathic mother tinctures, homeopathic dilutions, triturations, etc., mono- and multi-component homeopathic medicines, as well as quality control of homeopathic substances and homeopathic medicines. The article analyses the nomenclature of homeopathic raw materials and homeopathic substances used by the leading world pharmacopoeias. It dwells upon the results of work devoted to the development of requirements for the following homeopathic dosage forms: homeopathic granules, homeopathic eye drops, homeopathic ointments, homeopathic infusions and decoctions, homeopathic mother tinctures, homeopathic solutions for injection, homeopathic solutions and liquid dilutions, homeopathic syrups, homeopathic mixtures, homeopathic suppositories, homeopathic tablets, homeopathic triturations. The article illustrates significant potential of using vibrational spectroscopy and Raman spectroscopy for the detection of distinctive features of homeopathic medicines at ultra-high dilutions. The article presents methodology for structuring pharmacopoeial standards for raw materials used in the production of pharmaceutical substances, for pharmaceutical substances that are used in homeopathic medicines, and for dosage forms, including specific aspects of production and standardisation of homeopathic medicines, which was implemented during preparation of draft monographs for the State Pharmacopoeia of the Russian Federation.

Ultra-High Dilutions and Homeopathy: Can They Be Explained without Non-Local Theory?

We discuss questions related to the 'Benveniste Affair', its consequences and broader issues in an attempt to understand homeopathy. Specifically, we address the following points: 1.: The relationship between the experiments conducted by Benveniste, Montagnier, their collaborators and groups that independently tested their results, and 'traditional' homeopathy. 2.: Possible non-local components such as 'generalised entanglement' as the basis of the homeopathic phenomenon and experimental evidence for them. 3.: The capability of highly diluted homeopathic remedies to provoke tangible biological changes in whole organisms and cellular experimental systems. 4.: Aspects of the similia principle related to the above. 5.: Suggestions that can lead to experimental verifications of the non-local hypothesis in homeopathy.

Evidence that Extreme Dilutions of Paclitaxel and Docetaxel Alter Gene Expression of In Vitro Breast Cancer Cells.

Gene expression analysis of cells treated with extreme dilutions or micro amounts of drugs has been used to provide useful suggestions about biological responses. However, most of the previous studies were performed on medicines being prepared from a variety of herbal and metal sources. This study investigated the effects of ultramolecular dilution of the taxane anti-cancer drugs, which are not commonly used in homeopathic medicines, on mRNA expression profiles of five key genes (p53, p21, COX-2, TUBB2A and TUBB3) in the breast cancer cell line MCF-7. MCF-7 cells were exposed to paclitaxel (Taxol) or docetaxel (Taxotere) preparations (6X, 5C and 15C dilutions prepared from pharmacological concentration of 25 nmol/L) for 72 hours. The cell culture groups were evaluated with the trypan blue dye exclusion method for the proliferation/cytotoxicity rates, immuno-staining β-tubulin for microtubule organization, and reverse transcription polymerase chain reaction for gene expression levels.Fold-change in gene expression was determined by the ΔΔCt method. The administration of diluted preparations had little or no cytotoxic effect on MCF-7 cells, but altered the expression of genes analyzed with a complex effect. According to the ΔΔCt method with a five-fold expression difference (p < 0.05) as a cut-off level, ultra-high dilutions of paclitaxel and docetaxel showed differential effects on the studied genes with a concentration-independent activity. Furthermore, the dilutions disrupted the microtubule structure of MCF-7 cells, suggesting that they retain their biological activity. Despite some limitations, our findings demonstrate that gene expression alterations also occur with ultra-high dilutions of taxane drugs.

The Effect of Ultra-high Dilutions of Thyroxine on the Morphogenesis of Xenopus laevis Tadpoles

Background: The morphogenesis of Xenopus laevis is dependent on the thyroid system and the production of thyroxine. Numerous studies using the amphibian model have shown tadpoles to be responsive to ultra-high dilutions of Thyoxine. Ultra-high dilutions used in Homeopathy are not suitable to pharmacokinetic investigation due to their lack of detectable active ingredient and the lack of analytical methods with sufficient sensitivity; however, laboratory and clinical studies are providing experimental evidence contributing to the pharmacodynamics of high dilution remedies. Method: The experiment consisted of four groups, labelled according to the dilution each group was administered, Control (no treatment), Thyroxine 6C, Thyroxine 30C and Thyroxine 200C. Each group consisted of 90 tadpoles divided into three tanks of 30 tadpoles each. The respective dilutions were administered to the water the tadpoles were housed in every eight hours from Day 32 until Day 58 of the experiment. Tail length was measured every three days from Day 32 to Day 48 and every day from Day 48 to Day 58. Results: Thyroxine 6C was shown to have had a stimulatory effect while Thyroxine 30C had an inhibitory effect on the growth phase of the Xenopus laevis tadpole tail. Thyroxine 6C, 30C and 200C were shown to have had an inhibitory effect on the reduction phase of the Xenopus laevis tadpole tail. Conclusion: Where the results were shown to have had a stimulatory effect on the growth phase of the Xenopus laevis tadpole tail, it was likely due to a physiological effect, mimicking the action of the naturally circulating thyroxine. The results that were shown to have had an inhibitory effect are in line with the “Law of Similars” and the fact that a homeopathic preparation of Thyroxine would have an opposing effect to that of naturally circulating thyroxine.

Erratum: phytochemical analysis and evaluation of antioxidant potential of ethanolic extract of allium cepa and ultra-high homoeopathic dilutions available in the market: A comparative study

Erratum: phytochemical analysis and evaluation of antioxidant potential of ethanolic extract of allium cepa and ultra-high homoeopathic dilutions available in the market: A comparative study