La solidez de la investigación homeopática fundamental / The strength of fundamental homeopathic research

La investigación fundamental en homeopatía ha avanzado considerablemente en los últimos 20 años: desde estudios exploratorios con animales y plantas hasta la caracterización de los efectos sistémicos de los medicamentos homeopáticos y estudios in vitro con sistemas celulares aislados para evaluar los cambios en los mecanismos de adaptación celular y señalización intracelular frente a tratamientos homeopáticos variables. El número de artículos publicados a lo largo del tiempo ha permitido realizar varias revisiones sistemáticas. Recientemente, la demostración de que los medicamentos homeopáticos podrían modificar las funciones celulares a través de mecanismos epigenéticos (metilación y desmetilación de ADN) preparó el camino para un campo de investigación completamente nuevo. En paralelo, el descubrimiento de las nanopartículas y propiedades físicas específicas de las diluciones homeopáticas ha arrojado luz hacia un campo antes poco conocido, dado que se consideraba que las diluciones homeopáticas no consistían más que de agua. Así las cosas, los retos para el futuro conciernen a la demostración, o no, de la interrelación entre ambos fenómenos.

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Macrophage activity regulation by high dilution of aspirin and its possible mechanism

Under LPS-stimulus, platelets can activate macrophagesby a cell-to-cell contact or through cytokine degranulation. Rebound effects of anti-thrombotic agents, such as prostanoids and COX inhibitors can lead to thrombosis, infarct, and stroke. Aspirin has been prescribed for decades due to its powerful antiplatelet action, but it is also related to paradoxical effects such as withdrawal syndrome peaks, resistance, and thrombogenesis. Ultra-diluted aspirin can also produce the same effect in one hour, regardless of Cox-2, by still unknown pathways. Antithrombotic effects of aspirin are also reversed by its high dilutions.Aims: This study aims to characterize the effects of aspirin 15cH on macrophages challenged with LPS, a Cox-2 activator.Methodology: RAW 264.7 macrophages were sown in 24 wells plates using R10medium, boosted with 1µg/ml LPS,and treated with aspirin 15 cH and controls. The activity was evaluated after 24 hours. Supernatants were evaluated for cytokines, nitric oxide, and dielectric oscillations, through solvatochromic dyes (Cartwright's method).Results and discussion: macrophage spreading was increased by aspirin 15 cH, anLPS-like effect. Paradoxically, a significant reduction of this effect was noted when both, LPS and aspirin 15 cH, were added. Succussed water reversed the effect of LPS, leading to TNF (p<0.05) production close to baseline levels. Also, the single treatment with succussed water inhibited IL-10 production (p<0.05), but aspirin 200 µg/mL (positive control) highly increased it (p<0.0001), showing the validity of the model. Nitric oxide production was strengthened by LPS presence (p<0.0001), as expected, but partially downregulated after treatment with aspirin 200 µg/mL, water and succussed water. A pilot study with solvatochromic dyes showed no significant difference among treatments.Conclusion: The main data suggest that aspirin 15 cH increases macrophage activity but presents a paradoxal effect when mixed with LPS. On the other hand, succussed water itself has modulatory effects on macrophages.

In vitro evaluation of the effects of Viscum album homeopathic preparations on murine melanoma cells

Viscum album extract (VA) is a complementary treatment in cancer, with in vitro and in vivo cytotoxic effects on several tumor types when applied in phytochemical doses. However, highly diluted ethanolic homeopathic preparations' effects and mechanisms need further study. Aims:To assess the in vitro effects of highly diluted VA from the subspecies V. album abietis and V. album album at different potency levels in different dilution ratios on murine melanoma cells. Methodology:The VA mother tinctures (MT)from Abies alba (MTA) and Quercus robur (MTQ) were prepared with summer and winter samples, harvested in Switzerland. They were submitted to homeopathic ethanolic maceration and a subsequent dynamization process. MTA, MTQ and the following respective potencies were tested in B16F10 murine cells: 3x, 12x, 30x, 6cH, 12cH, 200cH, 2LM, 3LM, and 5LM. Dynamized water, dynamized and non-dynamized ethanol, and carboplatin were used as control groups. The mitochondrial activity and cell viability analysis were performed at 1, 24, 48, and 72 hours by in vitro incubation. MTA and MTQ harvested in summer, as well as 12x, 200cH and 5LM potencies were also tested to cell apoptosis and necrosis markers, reactive oxygens species (ROS) production, inflammatory cytokines profile, cell morphology, and migratory capacity. Results and discussion: MTA and MTQ induced a decrease in cell metabolism and higher cytotoxicity within 1 hour, with significant morphological changes and increased production of ROS and inflammatory cytokines. Both homeopathic dilutions 12x and 5LM showed an influence on cell metabolism, cell replication, and oxidative stress modulation with inflammatory cytokines, mitosis, and migration pattern changes. On the other hand, Quercus robur and Abies alba 200cH showed increased on cytotoxicity and ROS levels, respectively. Conclusion:The in vitro effects of Viscum album homeopathic solutions in melanoma cells highlight the promising antitumoral potential and reinforce the need for further research to better understanding their mechanisms of action.

Exposure of Artemia salinato glyphosate and bioremediation by isotherapy

Artemia salina, an ecotoxicity bioindicator, isa microcrustacean belonging to the order Anostraca. Glyphosate is an herbicide widely used to control weeds. However, its intoxication can cause serious damage to human health and the balance of the environment, given its effects as an endocrine disruptor.Objective:verify the possible protection of the artemia exposed to glyphosate by the addition of its isotherapic into water, by means of the evaluation of the behavioral and morphological features of nauplii and of the physical properties of remedies andtreated water, to elucidate the involved mechanisms. Methods:Artemia salinacysts were kept in culture bottles containing artificial seawatercontaining glyphosate at LC 10 (lethal concentration 10%), to promote hatching within 48 hours. The isotherapic preparations were inserted in each bottle in a 10% of the total water volume. Part of the nauplii was distributed in transparent tubes, being 10 nauplii per tube and 6 tubes per group, for behavioral analysis, and part were collected for a detailed morphological analysis, under an optical microscope. About 80 to 270 nauplii were analyzed per group. The reserved water was divided into aliquots for physicochemical analysis, that is, evaluation of the water dipole behavior by Cartwright ́s method.Results:Gly 6cH presented selective effects on nauplii hatching (p=0.02) and on defected/healthy ratio (p=0.001), representing some protective action. This result was dependent of the salinity of water and presented correspondence with the effects on solvatochromic dyes, indicating that charges and ions can be critical factors involved in the mechanism of action. We concluded that the use of isotherapics could be a plausible tool to reduce the environmental impact of the indiscriminate use of glyphosate, since these results can be reproduced in further studies.

Environmental parameters modulate lead chloride toxicity on Artemia salina

Different environmental conditions can influence the effects of toxic agents on living beings. Recently, a series of experiments performed in Artemia salina submitted to different kinds of intoxication have shown that both, isotherapic and succussed watercan change Artemia salina ́s bio resilience at different levels. Moreover, it seems to vary according to the circalunar cycle. Objective:To verify if circalunar phases and water agitation can modify the toxicity of lead chloride on Artemia salina in vitro. Methodology:Artemia salina cysts were exposed to seawater containing 0.04% of lead chloride (equal to EC10 or 10% effective concentration, previously determined in a pilot study) in 96-well culture plates. Thirty-six experimental repetitions were performed in four series to observe the possible effects of adding stirred water, the so-called succussed water, and the moon phases. The hatched cysts were recorded after 48 hours using a digital microscope (1000x magnification) to identify the hatching percentage and the viability and mobility of the born nauplii. Results:The exposition of cysts to PbCl2 led to an increase in the hatching rate, and it was more evident during the full moon (p = 0.00014) The addition of succussed water into the seawater medium reduced this effect to the baseline levels. An increase in mobility was seen in nauplii born from exposed cysts during the full moon (p = 0.00077), but this effect was not affected by the treatment with succussed water. Discussion:Although the effects of lead chloride EC10 on the increase of nauplii hatching were expected, two environmental variables changed the sensitivity of cysts to this harmful stimulus. The circalunar cycle varied the hatching rate according to the moon phase, even in laboratory conditions, and the addition of succussed water into the medium reduced the hatching rate, even with different intensities according to the moon phase. The organization of nano and microbubbles generated after the succussion of water could be related to this protective effect and can explain, at least partially the effects of high diluted preparations on this biological context. Conclusion:Environmental factors, such as the circalunar cycle and products of water agitation, can modulate the adaptative control of hatching in Artemia salina exposed to lead chloride at EC10.

Characterization of physicochemical markers for homeopathic medicines and biological supernatant samples

Solvatochromic dyes are probes to detect variations on the dipole moment of solvents after the insertion of homeopathic potencies. Recent studies have shown they can be useful tools in laboratory and field studies to detect the activity of homeopathic remedies.Objective: Determine whether solvatochromic dyes can be a diagnostic tool for cells infected by different agents and/or markers to identify the activity of homeopathic medicines. Methods: Ethilicum1cH, Siliceaterra6, 30, 200cH; Zincummetallicum6, 30, 200cH and Phosphorus6, 30 and 200cH were analyzed by pouring the samples (in a 1:60 rate) into a series of seven dyes (rhodamine, ET 33, ET 30, coumarin 7, NN DMIA, Nile red, methylene violet) diluted in absolute ethanol using pre-established working concentrations. Oscillations of dye absorbance were observed at visible light spectrophotometry according to the remedy and potency. Water and succussed water were used as controls. In a second moment, the absorbance profile of the remedies will be compared with those of biological samples (supernatants) and checked with the biological effect previously obtained from each treatment.Supernatants of RAW 264.7 macrophages stimulated by Calmette-Guérin bacilli (BCG) or infected with Encephalitozoon cuniculiwill be analyzed. Results: Preliminary results have shown that Siliceaterra6cH, Phosphorus30 and 200cH and Zincummetallicum6, 30 and 200cH reduced the absorbance of methylene violet (p=0.01). Repetitions and analysis of supernatants are expected to be performed in the next steps of the study. Future perspectives: Establish a pattern of reactivity of the studied medicines with different dyes and the putative relation with the corresponding supernatants, as an attempt to obtain a "physicochemical signature" for each kind of infection and/or treatment.

Carcinosinumproduces phenotypic changes of 4T1 tumor cells in vitro

Considering that there are few published studies that specifically address the exclusive use of Carcinosinumin different potencies and, most of them focused on genotypic and clinical effects, the present study was proposed to identify possible phenotypic changes, including viability, expression of HER-2 and metastatic abilities, using 4T1 cells in vitroas a model. Carcinosinum was tested in different homeopathic potencies (12cH; 30cH; 200cH) mechanically prepared using sterile pure water. The time space between preparing the potencies and using them was 24 hours.The final dilutions were inserted into the culture medium in a volume equal to 10%, at the time of cell seeding. The same succussed vehicle used to prepare the drugs (70% ethanol) diluted 1:100 in sterile pure water was used as control. All treated cells were cultured in 25 mL flasks, with cell density of 5 x 105cells/mL. After 24 hours of treatment, cells were analyzed for apoptosis index using Annexin V kit and the Countess® system. The morphology of 4T1 cells was monitored by staining cell smears with hematoxylin-eosin and Giemsa methods. HER-2 expression was assessed by immunocytochemistry and metalloproteinase activity was assessed by zymography. The determination of the cytokine profile was performed using Cytometric Bead Array (CBA). The samples were evaluated in quadruplicate and the data were analyzed by one-way ANOVA. Carcinosinum30cH presented the highest apoptotic index and reduction of MMP-9-Pro expression; Carcinosinum200cH produced the highest positivity for HER-2 and no specific effect was seen after the treatment with Carcinosinum12cH. No change in cytokine expression was seen among treatments. We conclude that Carcinosinum30cH and 200cH can change phenotypic features important totumor development in vitro. The clinical meaning of these data deserves further investigation.

Effects of homeopathic preparations on raphidiopsis raciborskii (Cyanobacteria) toxicity in artemia salina mode

Cyanobacteria are microorganisms found in different parts of the world. Some genera are cyanotoxins producers a sodium channel blockingneurotoxin (saxitoxins). Some homeopathic preparations have been identified as remedial action on toxicity models in Artemia salina. This study aimed to observe whether homeopathic products influence the toxicity ofR.raciborskiiextract onA.salinaby inducing cyst hatching arrest, anembryo bioresiliencemodel previously developed in our laboratory (Pinto et al., 2021; Mohammad et al., 2022). Thus, previous toxicity testswere carried out on cysts in 96-well plates, using different concentrations of the extract obtained from regular cultivation of R. raciborskii in HCl 0.05M, whose strain, named T3, is kept in the laboratory of Cyanobacteria at FURGS, Brazil.The standardization of toxin concentration was based on an established scale developed at FURGS, in which the number of T3 filaments is associated withspecific saxitoxin concentrationsdefined by chromatography. The concentration of 2.6 µg/L was chosen since it reducedthe cysthatching rate by 30%, the ideal level to observe embryo bioresilience. Then, a screeningstudy with 22 homeopathic preparations was tested blind in three experimental series, in duplicate,against threecontrols (unchallenged, water,and succussed water)for possible toxicity attenuationon Artemia salinacysts hatching rate. Homeopathic medicines were prepared in pure,sterile water from a stock homeopathic solution, one potency below the working potency. After the 1:100 dilution, 100 succussions were made using a robotic arm (Denise, Autic). The medicines were inserted into the seawater on a 10% basis. Due to the high sensitivity of A. salinato the circalunar variations, all experiments were performed during the first quarter moon. Statistical analysis was performed by two-way ANOVA followed by Tukey, with α=0.05. The most significant results indicative of bioresilience improvement were seen after the treatment with Nitric acidum6 cH, Plumbum metallicum6 cH, isotherapic 200 cH, and hydrochloric acid 1 cH being the last one used as a vehicle of the extracts. Thus, these preparations were chosen to be used in further experiments. In conclusion, the Artemia salinamodel has also beenuseful to study bioresilienceimprovement by homeopathic medicines after intoxication with saxitoxin.

Homeopathy treatment of Malassezia Pachydermatis in vitro

A common clinical occurrence in dogs is otitis externa caused by excessive growth of yeasts Malassezia pachydermatis, which can become chronic after wrong treatments, in which microbial resistance can occur. Homeopathic remedies can be considered a successful alternative, selecting the medicine through the similitude principle. Herein, 50 µL of a 1:1000 dilution of Malassezia pachydermatis suspension at 0.5 McFarland scale was used to seed the yeast into Sabouraud dextrose agar plates using a Drigalski spreader to proceed with colony unit counting. Before being seeded, the yeast suspensions were treated with 1% of different homeopathic treatments previously selected from a pilot study, which means Sulphur 6cH, Dolichos pruriens 6cH, and Kali carbonicum 6cH, being water, and succussed water used as controls. For comparison, a set of Sabouraud dextrose agar plates containing 1% Tween 80 was seeded in parallel. The treatments were made blind and evaluated in triplicate. Contaminated cultures were withdrawn. The number of colonies per plate was assessed, and smears were made from the cultures to classify yeast growth according to cytomorphology on ImageJ®software. The preliminary results show no significant effect of all tested medicines compared to the controls. High data variability was also observed, mainly in those cultures whose medium was prepared with Twin 80. In conclusion, at this point of the study, no evidence of the effects of the studied medicines on Malassezia pachydermatis growth in vitro could be identified. The analysis of cytomorphology is still in course.

Homeopathy and high dilutions in the context of water structure research: the experience in the 9thWorld Water Forum ­2022

Water plays a vital role in adapting natural and human systems in a climate change scenario. Understandinghow this fundamental element of life is organized and functioning is essentialtogather, disseminate, and advanceknowledge about water at the micro and nanostructure level. With developments in the different research areas, the International Panel on Water Structure­IPWS was created during the 8thWorld Water Forum(WWF)inBrasília,2018,to connect researchersspecialized inwater structure under aninterdisciplinary perspective.In 2020 a partnership between CIRAT ­International Center on Water and Transdisciplinarityand WATER­a Multidisciplinary Research Journalhasbegun, intendedto organize a special edition on Water and Transdisciplinarityto be launched during the 9thWWF, in Dakar, on March 24th, 2022, in response to the challenges of our century, with the aim to disclose advanced knowledge about water at different structural levels, leading to a new understanding of it.The whole project was organized by Prof. Leoni Bonamin, from UniversityPaulista, with the support of the Editor-in-Chief Prof. Gerald Pollack, from Washington University at Seattle. The focus was on the cross-over of information with technical quality and bold thinking, as shown in Figure 1 below.Homeopathy wasincludedamong the themes.Aftera multi-step process, in which manuscripts were received (after personal invitationssent to more than 200 researchers in the field)andevaluated in a two-step peer review processto ensure maximum scientific understanding, the result showed a set of innovative contributions in which authors were allowed to be bold in their projects while careful with the methodology. Theentire process was carried out voluntarily by all the actors involved.Thus, the whole editorial process was philanthropic, there were no costs for the authors, and all articles were published as open access. Authors from five countries participated in this project: Brazil, India, Italy, Russia, and the United States. Different sessions were organized according to the topics: "Opinion Article," "Hypotheses," "Water Structure," "High Dilutions," "Water and Environment," and "New Devices."Fiveof twelve articles reported results on high dilutions, including its physicochemical propertiesandthe implications on biological systems, such as plants and aquatic animals [1-4]. This initiative inspired all to envision the possibility of offering practical solutions to old problems involving different ways of water management, which couldreduce social gaps and improve the quality of life fairly and universally.

Mercury chloride toxicity attenuation of the Brine Shrimp Artemia Salinaafter treatment with Mercurius corrosivusas isotherapic

Isotherapics preparedfromtoxic substances have been described as attenuation factors for heavy metal intoxicationin aquatic animals. Herein, Artemia salinaand mercury chloride were usedas a model to identify treatment-related bioresilience. The aim was to describe the effects of Mercurius corrosivus(MC) in different potencies on Artemia salinacyst hatching and on mercury bioavailability. Artemia salinacysts were exposed to 5.0 µg/mL of mercury chloride during the hatching phase. MC6cH, 30cH, and 200cHwere prepared and poured into artificial seawater. Different controls were used (nonchallenged cysts and challenged cysts treated with water, succussed water, and Ethilicum 1cH). Four series of nine experiments were performed for4 weeks to evaluate the percentage of cyst hatchingconsidering all moon phases. Soluble total mercury (THg) levels and precipitated mercury content were also evaluated. Solvatochromic dyes were used to check for eventual physicochemical markers of MCbiological activity. Two-way analysis of variance (ANOVA) with mixed modelswas used for evaluating the effect of different treatments andthe simultaneous influence of the moon phases on the cystshatching rate, at both observation times (24 and 48 hours).When necessary, outliers were removed, using the Tukeycriterion.Thelevel of significance αwas set at 5%. Significant delay (p<0.0001) in cyst hatching was observed after treatment with MC30cH, compared with the controls. An increase inTHg concentration in seawater (p<0.0018) and of chlorine/oxygen ratio (p<0.0001) in suspended micro-aggregateswas also seen, with possiblerelation with mercury bioavailability. Specific interaction of MC30cH with the solvatochromic dye ET33 (p<0.0017) was found. The other observed potencies of Mercurius corrosivus6 and 200 cH were not significant in relation to the observed groups.The results werepostulated as being protective effects of MC30cH on Artemia salina, by improving its bioresilience.

Avaliação da atividade biológica de preparações homeopáticas de antiadiponectina em camundongos submetidos a dieta hipercalórica / Biological activity of homeopathic preparations of adiponectin in mice subjected to a hypercaloric diet

A adiponectina foi originalmente identificada como uma proteína expressa e produzida por adipócitos do tecido gorduroso abdominal de várias espécies animais, cuja função é manter a homeostase do tecido adiposo em relação às demandas energéticas do corpo. Preparações homeopáticas de substâncias endógenas são capazes de modular diferentes funções celulares. Neste projeto, buscou-se conhecer os possíveis efeitos de uma preparação homeopática de anticorpos antiadiponectina no controle do depósito adiposo subcutâneo abdominal, utilizandose modelo experimental. Quarenta camundongos Swiss machos adultos oram divididos em um grupo experimental e 3 controles. Os animais foram alimentados durante 1 mês e 7 dias com suplemento dietético comercial e tratados simultaneamente, por via oral, com antiadiponectina 6cH. Foi avaliado o ganho de peso corporal, bem como características macro e microscópicas do tecido adiposo subcutâneo e do fígado. Os resultados mostraram discreta redução no ganho de peso e redução estatisticamente significativa no diâmetro dos adipócitos no grupo experimental. Não foram observadas alterações inflamatórias ou degenerativas significativas no fígado. Os mecanismos envolvidos nestas alterações metabólicas precisam ser pesquisados em estudos futuros. (AU)

Adiponectin was originally identified as a protein expressed and produced by the abdominal fat adipocytes of several animal species which function is to maintain the homeostasis of the adipose tissue vis-à-vis the body energy demands. Homeopathic preparations of endogenous substances are able to modulate several cell functions. In the present study we investigated possible effects of a homeopathic preparation of anti-adiponectin antibodies on the control of the abdominal fat by means of an experimental model. Forty Swiss male adult mice were fed a commercial dietary supplement for 1 month and 7 days and treated with anti-adiponectin 6cH per oral route. Parameters assessed were weight gain and macro- and microscopic characteristics of the subcutaneous adipose tissue and liver. The experimental group exhibited slightly less weight gain and statistically significant reduction of the adipocyte diameter. We did not detect significant inflammatory or degenerative changes in the liver. The mechanisms involved in the detected changes need to be investigated in future studies. (AU)

High-diluted thymulin on Ehrlich tumor growth in mice and the importance of tumor microenvironment

Introduction: The aim of the present study was to describe different biological aspects of Ehrlich tumor in mice, such as body weight evolution, tumor growth rate, histological organization and systemic immune response after treatment with high-diluted thymulin (10-9 M, named 5CH). Methods: Tumor assessment was focused on macro- and microscopic aspects; parameters included occurrence of necrosis, embolism and tumor development, in addition to quantitative analysis of apoptosis (caspase-3), cell proliferation (Ki-67) and angiogenesis (vascular endothelial growth factor - VEGF) by means of specific immunohistochemistry markers. Spleen cell populations were evaluated by flow cytometry analysis. Results: Mice treated with thymulin 5CH exhibited changes in the tumor microenvironment, such as reduced micro-embolism incidence and cytokeratin expression, with increased caspase-3 expression in the tumor cells. These findings indicate some apoptotic activity by the tumor cells induced by the treatment, even though no reduction of the macroscopic tumor mass occurred. No changes in the systemic immune response were detected, as the balance among spleen cell populations remained unchanged. Conclusions: The results indicate that treatment of mice bearing Ehrlich tumor with thymulin 5CH induces some specific changes in the tumor environment. However, it did not influence systemic immunity parameters. Adjuvant use of thymulin 5CH in oncological clinical practice is still a matter of discussion. (AU)

The soundness of homeopathic fundamental research

Fundamental research in homeopathy has much advanced in the past 20 years. From exploratory studies with animals and plants to the characterization of the systemic effects of homeopathic medicines and in vitro studies with isolated cell systems to assess changes in the mechanisms of cell adaptation and intracellular signaling facing variable homeopathic treatments. The amount of articles published over time enabled several systematic reviews. Recently, demonstration that homeopathic medicines might modify cell functions through epigenetic mechanisms (DNA methylation and demethylation) paved the road for a fully new field of research. In parallel, the discovery of nanoparticles and specific physical properties of homeopathic dilutions brought light to a previously poorly known field, as it was believed that homeopathic dilutions consist in nothing but water. Thus being, challenges for the future concern the demonstration, or not, of the interrelationship between both phenomena.

Homeopathy in parasitic diseases

Background: The use of homeopathic medicines has increased, partly because conventional drugs do not always elicit the desired effects, and partly because their side effects might compromise the patient’s’ adherence to treatment. Several studies showed benefits in the use of highly diluted medicines for the treatment of infectious diseases. Aim: The aim of the present review was to perform a critical discussion about aspects of homeopathy and the current status of veterinary experimentation, as well as of the use of highly diluted drugs in infectious and parasitic diseases. The main aspects of effects, therapeutic regimens and / or dynamizations used in various models are discussed. Methods: Articles published since 2000 in journals included in databases PubMed and SciELO and specialized journals sought for and reviewed using keywords “parasitic diseases/homeopathy” and “parasitic diseases/ ultra-dilutions”. Results: Several recent experimental studies demonstrated the biological effect of highly diluted medications on parasitic infections, with reduction of the number of parasites and improvement of the clinical condition of the affected animals. Several articles exhibit problems in the description of methods, which threaten the reproducibility of experiments. Conclusion: The acknowledgment of homeopathy depends on the credibility of investigators. Although research on homeopathy has clearly increased in recent years, relative to both implementation of more consistent methods and description of data and methods, improvement is still required. Precise and detailed descriptions will contribute to advance the use of homeopathy, so that society at large might benefit in actual practice.

Introdução: O uso de homeopáticos tem crescido devido o fato de que medicamentos convencionais algumas vezes não produzem o efeito esperado e também devido os seus efeitos indesejados que comprometem a adesão ao tratamento. Alguns trabalhos mostram os benefícios da utilização de medicamentos ultradiluídos no tratamento de doenças infecciosas. Objetivo: Esta revisão é uma discussão crítica sobre os aspectos da homeopatia, o estado atual da experimentação veterinária e o uso de medicamentos ultradiluídos nas infecções e doenças parasitárias. Os principais aspectos dos efeitos, esquemas de tratamento e/ou dinamizações utilizadas nos diferentes modelos são discutidos. Metodologia: Uma revisão de artigos publicados desde 2000 em revistas indexadas nos bancos de dados PubMed e Scielo e revistas especializadas foi utilizada para pesquisa das palavras-chave: parasitoses/ homeopatia e parasitoses/ ultradiluídos. Resultados: Experimentos recentes demonstraram o efeito biológico dos medicamentos ultradiluídos nas infecções parasitárias, com redução no número de parasitos e melhora da condição clínica nos animais tratados. Alguns artigos apresentaram problemas na descrição da metodologia o que pode comprometer a reprodutibilidade dos experimentos. Conclusão: O conhecimento da homeopatia depende da credibilidade dos grupos de pesquisa. Embora nos últimos anos a pesquisa em homeopatia tenha apresentado um claro desenvolvimento, tanto na implantação de metodologias mais consistentes quanto na descrição dos dados e métodos publicados, muito ainda deve ser melhorado neste campo. Descrições precisas e detalhadas poderiam contribuir para o avanço do uso da homeopatia, o que poderia beneficiar a comunidade em geral , na prática, a partir destes resultados.

A medicina dos druidas e o Viscum album / The medicine of the druids and the Viscum album

Os autores apresentam uma revisão histórica sobre o Viscum album, planta utilizada na Farmacopeia homeopática e sua relação com a cultura Druida.

Biosemiotics and Body Signifier Theory: a way to understand High Dilutions / Biosemiotics and Body Signifier Theory: a way to understand High Dilutions

Since the 80´s Madeleine Bastide and Agnès Lagache have worked on the idea of the Body Signifier Theory, in which the living systems could be defined as ?sensible? systems not only able to self-organize, but also to receive and process non-molecular information according to the Pierce semiotic triad: matrix, receiver and carrier. These ideas were built along 20 years of experimental observations, whose results presented some kind of stereotyped pattern that emerged from cells or animals exposed to high dilutions, according to the similia principle. Curiously, at the same time, classical scientific communities have developed the concept of biosemiotics after the observation that living systems are semiotics entities able to deal with codes and meanings, even in molecule-driven processes. Not only the genetic code, but all regulatory functions in living systems represent coding processes. The development of methodologies to identify and understand these codes and its outputs is the aim of biosemiotic science. Putting both concepts together (body signifiers and biosemiotics), it is possible to recognize strong similarities between their approaches and methodology, allowing logical connections between non-molecular signals and changes in cell interactions patterns. Thus, the general concept of biosemiotic could be a theoretical platform on which the construction of a solid phenomenological description of high dilutions effects could be done.

Inflammation in rats born to mothers treated with dexamethasone 15cH during pregnancy: an immunohistochemical study / Inflammation in rats born to mothers treated with dexamethasone 15cH during pregnancy: an immunohistochemical study

In previous studies, we observed that rats born to mothers treated with dexamethasone 15CH (10-33M) had a higher level of mast cell degranulation and greater arteriolar dilation after the exposure of an inflammatory stimulus, suggesting the possibility of vertical transmission of the effects of ultra-diluted substances between mother and offspring. In this study, a more detailed assessment of the cellular events in acute inflammation was made using techniques of immunohistochemistry. The identification of adhesion molecules expression was made by the markers: anti-CD54 (ICAM-1) and anti-CD18 (?2-Integrin). The identification of inflammatory cells was performed by the markers anti-MAC387 (mononuclear cells) and anti-CD163 (active macrophages). Polymorphonuclear cells were identified by hematoxylin-eosin staining. The number of labeled cells per was recorded, except for the anti-CD54 marker, whose intensity of staining on the endothelial cells was defined by scores assigned by two independent observers. The results point toward to an up regulation of the whole inflammatory process in rats born to mothers treated with dexamethasone 15CH during pregnancy. This conclusion is justified by the following statistically significant (p?0.05) findings: a) bigger mast cell degranulation and increased of arteriolar diameter; b) increased migration of polymorphonuclear cells in relation to the mononuclear cells; c) earlier expression of CD163 in monocytes, d) higher level of adhesion molecules expression.

Triiodothyronine, diluted according homeopathic techniques, modifies the programmed cell death of tadpole tail?s explants / Triiodothyronine, diluted according homeopathic techniques, modifies the programmed cell death of tadpole tail?s explants

High Dilution is a solution beyond the Avogadro limits that, in the dependence of the applied succussion elicits a suppressive or a stimulant effect on a living cell, with a consequent generation of an oscillatory doseeffect curve. According to Bonamin et al. [1], ?Perhaps, the most enigmatic feature regarding the properties of high dilutions is the non-linearity of their effects. In several studies employing in vivo and ex vivo models, especially involving iso-endopathy, an oscillatory potency-effect curve has appeared. The first observations were initially considered as artifacts, but the repetition of this pattern in different studies involving completely different experimental models, in times and places equally different, points out to the existence of a property intrinsic to dynamized systems.? The entire process of anuran amphibian metamorphosis is under thyroid hormones control, included the complete resorption of the tadpole tail. In the present study, we had successfully established a protocol model to culture Rana catesbeiana tadpoles? tail tips in vitro. A random and blind study was performed, with the intent to prove that T3 5.10-24 M (10 cH) modifies the apoptosis induction of T3 100 nM in explants of Rana catesbeiana tadpoles? tail. 60 explants were distributed in three ways: Group A: without T3 action, at pharmacological and HD dose; Group B (test): under the action of T3 100 nM and treated with T3 10 cH (HD); Group C (control): under the action of T3 100 nM and treated with ethanol 70% unsuccussed. After 96 hours of tissue culture, the mean of initial and final area (1.05 vs. 0.98 cm2) and apoptotic index of the explants from Group A were with minimal difference range and for this reason it wasn?t included in the statistical study. In order to identify significant differences in the area and in the apoptotic index of the remainder explants of the 2 groups, B (test) and C (control), we used a student t-test. However, the mean initial and final explants? area from test and control groups were respectively 1.09 vs. 0.22 cm and 1.00 cm vs.0.24 cm, with a mean reduction of 0.87 cm2 and 0.76 cm2, but this difference didn?t achieve statistical significance (p>0.05). In contrast, apoptosis index was significantly higher in test than in control group 11.7 vs. 7.9 (p<0.05), with is confirmed at the table 1.