NMR analysis: potential and challenges as a homeopathic basic research tool

Homeopathic ultra-diluted solutions surpass the threshold of matter dispersion and, consequently, their chemical constitution is similar to inert solvent. Nevertheless, randomized clinical trials have shown that the clinical effects of these homeopathic medicines are superior to placebo1. Nuclear magnetic resonance (NMR) is one of the most promising techniques to detect physicochemical alterations induced by homeopathic procedures2,3. Aims: To investigate T2 NMR relaxation times of Zincum metallicumand lactose dynamized samples. Methodology: Zincum metallicumsamples were ground until 6dH using lactose as an excipient. Subsequently, these samples were dynamized with ultrapure water to produce 8dH, 9dH, 10dH,and 11dH. Lactose dynamized samples (6dH-11dH) were used as control. Aliquots of 540µl of each sample were diluted with 60µl of deuterated water (D2O) in 5mm tubes. The analyses were carried out in Bruker Ascend TM 500MHZ spectrometer at 288 K. Results and discussion: The Zincum metallicumand lactose T2 relaxation times were very similar, except for Zincum metallicum8dH, which presented a value of 1.226 in comparison to 1.036 of lactose 8dH. The following T2 values were registered: 1.287 -9dH; 1.413 -10dH; 1.467 -11dH, and 1.303 -9dH; 1.400 ­10dH; 1.350 -11dH, for Zincum metallicumand lactose, respectively. The differences detected in 8dH samples are probably due to the presence of lactose in the first dilution step, in which 1 part of the 6dH triturated mixture was diluted in 9 parts of water, to prepare 7dH. Following this homeopathic procedure, 8dH solutions remain around 1% of lactose which could be influenced by the T2 values registered.Conclusion: These preliminary results showed the possibility to apply the NMR technique to evaluate the influence of dynamization in the relaxation parameters. Further studies should be carried out with other potencies and/or other homeopathic substances, in addition to the evaluation of T1 and the T1/T2 parameters, as previously described by other groups.

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.

High Dilutions of Drugs show Distinct Variation from each other in their Electronic Spectra

Drugs at high dilution (HD) produce therapeutic effect on man, animals and plants. Experimental evidence shows that free water molecules and hydrogen bond strength of OH groups constitute the physical basis of HDs which are otherwise devoid of original drug molecules. HDs are produced in aqueous EtOH by serial dilution of a substance with mechanical agitation or succussion in each step, and are called potencies. Three potencies 6 cH, 12 cH and 30 cH of two drugs Anacardium orientale and Natrum muriaticum(NaCl) and their mother tincture (MT) are used in this study. Electronic spectra of these MTs and potencies, all in 90% EtOH, were taken in the wavelength region of 190 nm ­350 nm. The objective is to find out any additional physical-chemical entities in potencies besides the aforesaid two factors. It was reported earlier that charge transfer (CT) interaction accompanies potentization of drugs. This study focused on the CT interaction. The results indicate that spectral pattern and absorbance intensities of the test samples vary from each other. Natm 6cH (absorbance 0.30 at 196.53nm), 12cH (abs. 0.06 at 196.53nm) and 30cH (abs. 1.32 at 196.5nm). Anac 6cH (abs. 0.33 at 203nm), 12cH (abs. 0.61 at 208nm) and 30cH (abs. 0.09 at 200.67nm). The spectrum of each potency shows two peaks. The 2nd peak at higher wave length belongs to CT interaction. Anac 6cH suc, 7cH unsuc. Insersections at 197.14nm with abs. 0.05, and 290nm with abs. 0.01. Anac 12cH suc, 13cH unsuc. Intersections at 196.93nm with abs. 0.06, and 273nm with abs. 0.00. Anac 30cH suc, 31cH unsuc. Intersections at 194.42nm with abs. -0.05, 238.03nm with abs. -0.01, 252.15nm with abs. -0.002, and 261nm with abs. 0.004. Natm 6cH suc, 7cH unsuc. Intersection at 199.44nm with Abs -0.11. Natm 12cH suc, 13cH unsuc. Instersection at 200.48nm with abs. -0.11. Natm 30cH suc, 31cH unsuc. Intersection at 204.24nm with abs. -0.08. Potentization involves CT interaction in consecutive potencies. Water and EtOH do not form a homogeneous mixture and have aggregates of EtOHand water molecules. CT interactions occur in these individual aggregates and are mostly inter molecular within EtOH or water. These aggregates vary from each other in the test samples. The spectra of test samples were analysed for margin of error (MOE). The MOE is very small (0.001-0.002%), and for this reason the difference between the spectra is significant. Besides that the intersection between consecutive spectra vary in number and position. It is concluded that water and EtOH aggregates and their relative distribution constitute additional physical-chemical basis of potencies.

Study of germination efficiency and temperature/drowning resistance in some ornamental plants treated with ultra high dilute compounds

The ultra-high dilutions (UHDs) can be used for decreasing stress conditions causing by climate variations. The present research investigated the effects of ultra-highdilutions (UHDs) on some ornamental plants, germination, and hormonal variations.Methods: In order to study the effect of UHDs (Calendula officinalisCalen. andArnica montanaArn.) on the physiological, primary metabolite, and hormonal variations of theOryza 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 plant 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 inS. officinalisincreased under UHDs treatment while decreasing 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 increases the tolerance of seeds under higher/lower temperatures and draught/drowning. The results of this study open up a window to reduce germination survival and increase their resistance to sudden climate change.

La escala cincuentamilesimal (LM) / The cincuentamilesimal scale (LM)

Después de 12 años de práctica exclusiva y literal con la técnica de la escala cincuentamilesimal (LM o Q) de potencias, descrita en la 6a edición del Organon, elautor analiza sus diferencias básicas con las directrices de la 5a edición de dicha obra. Describe la manera de administrar el medicamento, sus ventajas y desventajas, y enumera todas las conductas posibles durante el uso de esta técnica, la cual, concluye, es la que mejor se encamina para lograr una curación rápida y suave, ideal máximo de Samuel Hahnemann. (AU)

After 12 years of literal and exclusive practice with the 50 millesimal scale according to the 6th edition of the Organon, the autor analyses its basic differences with the guidelines of the 5th edition. He describes the posible procedures during the usage of this kind of medication; it´s advantages, disvantages and enumerates all the possible conducts of this technique, therefore concluding that this is the one that leads to a rapid and mild cure. Samuel Hahnemann´s maximum ideal (AU)

Revisión bibliográfica no sistemática sobre la escala cincuentamilesimal / Non-systematic bibliographic review on the fifty-thousand-scale scale

En cuanto a la preparación y la dosis del remedio homeopático Hahnemann hizo modificaciones en busca de una curación suave, pronta y duradera culminando con la propuesta de la escala cincuentamilesimal (LM), expuesta por primera vez en la VI edición del Órganon de la medicina; tuvo la oportunidad de experimentar y comprobar mucho más tiempo con la escala centesimal (C) y se calcula que manejó la escala LM en sus últimos cinco años de práctica médica, experiencia que quedó consignada en sus libros de Casos de París. Este fue uno de los últimos aportes de Hahnemann en la Homeopatía, con la intención que el medicamento fuera administrado según la individualidad del enfermo, buscando disminuir el tiempo de tratamiento y minimizar la agravación homeopática, alcanzando con esta técnica su método "casi ideal", volviéndose referencia puntual para que los médicos homeópatas pudieran usarla en forma más continua. Se realizó una revisión no sistemática de la literatura para la recolección de la información que existe actualmente relacionada con el tema de la escala LM con el fin de aportar a los estudiantes de homeopatía, así como a los médicos homeópatas ya formados, que sirva de base para proponer temas de estudio y futuras investigaciones a partir de la misma.

Semiotic processes implied in the High Dilution phenomena / Semiotic processes implied in the High Dilution phenomena

Semiotic processes ( or semiosis) refer to those process which are carriers of meaning and are performed through signs. A sign is something that stands for something else, and is the main mediating factor between an object and an interpreter, able to connect them and give rise to significations. The semiotic perspective, according to Charles Sanders Peirce, is basically triadic: all aspects of reality are triadic, comprising the categories of Firstness, Secondness, and Thirdness in a continue and virtually infinite process of semiosis, i.e of various forms of giving rise to meanings that accordingly will generate reactions, actions and transformations. The aim of the present paper is to examine the possible levels of semiosis implied in the high dilution phenomenon, beginning with the process of so called ?potency? of substrata (where every potency may be considered a sign for the next one) and arriving to the complex responses of the living bodies to infinitesimal signs

Desenvolvimento, validação e comparação de métodos analíticos para determinação de bloqueadores neuromusculares derivados de esteróides / Development, validation and comparison of analytical methods for determination of neuromuscular blocking derivatives of steroids

Os relaxantes neuromusculares não despolarizantes são fármacos indispensáveis nos procedimentos cirúrgicos que requerem entubação endotraqueal, visto que diminuem o tônus muscular. Quimicamente são divididos em derivados isoquinolinicos e derivados de esteróides, esses últimos com maior aplicação clinica e comercialização no Brasil. Assim sendo, é importante a validação de métodos analíticos para o controle de qualidade com alternativas confiáveis que garantam sua eficácia e segurança. Os brometos de vecurônio, de pancurônio e de rocurônio são fármacos relaxantes neuromusculares não despolarizantes derivados de esteróides. As propriedades farmacológicas destes fármacos são significativamente diferentes entre si, porém, as propriedades químicas são bastante similares. Na presente pesquisa foram desenvolvidos e validados métodos analíticos de separação (cromatografia líquida de alta eficiência e eletroforese capilar) para cada fármaco. Estes métodos foram aplicados a medicamentos comercializados no Brasil. Para todos os métodos cromatográficos foi utilizada uma coluna amino devido a seu caráter polar. Em função da baixa absorção dos três fármacos na região ultravioleta, os métodos eletroforéticos foram aplicados com detecções indiretas utilizando substâncias cromóforas. Comparando-se as técnicas utilizadas para determinação dos fármacos nos medicamentos isoladamente, não houve diferença significativa com nível de confiança de 95,0%. Nos testes de hipótese aplicados (F-Snedecor e t-Student), não foram observadas diferenças na precisão (variâncias) e no valor encontrado dos fármacos contidos nas amostras estudadas (comparação de duas médias).

The non-depolarizing neuromuscular relaxant drugs are essential in surgical procedures requiring endotracheal intubation, as they decrease muscle tonics. These drugs are chemically divided in isoquinolines derivatives and steroid derivatives, this latter group, with greater clinical application and commercialization in Brazil. Therefore, the study and validation of analytical methods are important for quality control with reliable alternatives to ensure their effectiveness and safety. The vecuronium, pancuronium and rocuronium bromides are steroid derivatives presenting non-depolarizing neuromuscular relaxant action. Pharmacological properties of these drugs differ significantly, however, its chemical properties are quite similar. In this research, analytical separation methods (high performance liquid chromatography and capillary electrophoresis), for each drug, were developed and fully validated. The methods were applied to pharmaceutical formulations commercialized in Brazil. For all chromatographic methods, an amino column was used, due to its polar characteristics. Due to the low absorption of the three drugs in the ultraviolet region, electrophoretic methods has been applied with indirect detection using chromophoric substances. When comparing both techniques used for quantitative determination of these drugs in pharmaceutical products, no significant difference was observed using a confidence level of 95.0%. By applying hypothesis tests (F-Snedecor and t-Student), it was not observed difference in precision (variance) and in the found amount of drugs contained in the selected samples (comparison of two means).

Estudio de la disolución del calcio a partir de una nueva formulación de comprimidos bucodispersables y su comparación con formulaciones masticables convencionales / Study of the dissolution of calcium contained in a novel orodispersible tablet formulation and its comparison with conventional chewable formulations

Los suplementos de calcio con vitamina D constituyen un componente habitual de los tratamientos de la osteoporosis. La absorción del calcio suministrado requiere su disolución previa. Sin embargo, las sales de calcio habitualmente utilizadas son muy poco solubles y dependen del ácido gástrico para liberar el calcio en forma biodisponible. Se ha desarrollado una nueva formulación bucodispersable de calcio y vitamina D (Natecal D Flas). Esta formulación no sólo facilita el cumplimiento terapéutico del tratamiento, sino también la disolución del calcio y, por tanto, su biodisponibilidad. En este estudio se ha comparado la disolución del calcio de comprimidos masticables convencionales con la nueva formulación bucodispersable, tanto en medio gástrico artificial (pH ácido) como en agua (ausencia de ácido). Los resultados indican que en medio gástrico artificial, simulando condiciones fisiológicamente normales, los comprimidos bucodispersables producen una disolución significativamente más rápida del calcio que los comprimidos masticables. En el caso del agua, simulando una condición de aclorhidria absoluta, no se produce disolución del calcio en el caso de los comprimidos masticables mientras que existe una disolución parcial, pero significativa, en el caso de los comprimidos bucodispersables. Estos resultados indican que la nueva formulación bucodispersables de carbonato cálcico y vitamina D (Natecal D Flas) contribuye a una mejor absorción del calcio en aquellos pacientes en la que ésta puede estar disminuida por circunstancias fisiológicas (AU)

Calcium supplements with vitamin D are standard components of treatments for osteoporosis. The absorption of the calcium provided requires its prior dissolution. However, the solubility of the calcium salts usually employed is limited and the release of the calcium in a bioavailable form depends on gastric acid. A novel orodispensible formulation of calcium and vitamin D (Natecal D Flas) has been developed. This formulation not only facilitates treatment compliance, but the dissolution of the calcium as well, thus enhancing its bioavailability. In this study, the authors have compared the dissolution of the calcium contained in conventional chewable tablets with that of the new orodispersible formulation, both in artificial gastric juice (acidic pH) and in water (absence of acid). The results indicate that, in artificial gastric juice, simulating normal physiological conditions, the orodispersible tablets produce a significantly more rapid dissolution of calcium than the chewable tablets. In the case of water, simulating conditions of absolute achlorhydria, there is no dissolution of the calcium contained in the chewable tablets, whereas partial, but significant, dissolution is observed with the orodispersible tablets. These findings indicate that the novel orodispersible formulation of calcium carbonate and vitamin D (Natecal D Flas) contributes to better absorption of calcium in those patients in whom this process may be compromised by physiological circumstances (AU)

O legado de Hahnemann padrões de qualidade para medicamentos homeopáticos / The Hahnemann inportance quality standard for homeopathic drugs

Com base em mais de 50 anos de pesquisa, Hahnemann introduziu melhorias no preparo de medicamentos homeopáticos, para aumentar os padrões de qualidade. No caso das potências cinqüenta-milesimais (potências Q ou LM), tais melhorias relacionaram-se ao frescor das matérias primas; ao princípio de triturar todas as substâncias até a C3; à manutençäo de um tamanho de lote regular; ao número de sucussões e ao método de impregnaçäo. Posteriormente, os fabricantes ignoraram essas práticas ou abandonaram-nas, sem fornecer razões válidas. Uma qualidade consistente e de alto nível só pode ser atingida pelo cumprimento dos métodos rigorosos estabelecidos, por exemplo, para potências Q de qualidade "Pe".(AU)

A arte de fazer medicamentos / The Art of Making Medication

O interesse do homem pela descoberta e preparação de medicamentos antecede a era cristã. Ao longo dos tempos, a elaboração do produto farmacêutico aprimorou-se no que diz respeito às suas fontes de obtenção e aos procedimentos de avaliação de sua eficácia e segurança. A inserção do novo produto farmacêutico na sociedade ocorre somente após a realização de investigações detalhadas presentes nos estudos pré-clínicos e clínicos

Avaliaçäo controlada de dois bioteráicos preparados a partir de Neisseria meningitidis em ratos balb/cj. Resultados preliminares / Controlled evaluation of two Biotherapics prepared from Neisseria meningitidis in mice

O presente experimento mostra resultados interessantes a favor da terapêutica homeopática quando comparada ao resultado do grupo-controle. Técnicas diferentes de preparo do bioterápico säo comparadas näo mostrando diferença significativa entre si.

Avaliaçäo controlada de um bioterápico preparado a partir do proteoliposoma constituinte de VA-MENGOC-BC em ratos balb/cj. Resultados preliminares / Controlled evaluation of Biotherapic prepared from the constituent Proteolipossoma of VA-MENGOC-BC in balb mice/cj - results preliminaries

O presente experimento demonstrou em ratos que o protoliposoma diluído homeopaticamente pode desencadear uma açäo bactericida. Comparaçöes säo feitas.

Padronizaçäo de tinturas-mäe (TM) de stramonium / Standartization of stramonium mother - tinctures

No presente trabalho foram produzidas em laboratório TM de Stramonium por diferentes processos. Estas tinturas foram submetidas a análises químicas e físicas juntamente com três TM comerciais. As TM produzidas no laboratório foram usadas como padräo de comparaçäo para o controle de qualidade das demais tinturas

Consideraçöes sobre os métodos de preparo empregados na obtençäo do medicamento Pyrogenium / Considerations for preparation methods utilized to obtain Pyrogenium

A autora faz um trabalho de revisäo mostrando historicamente as diversas técnicas de preparo do medicamento homeopático Pyrogenium e uma interpretaçäo atual, de acordo com a evoluçäo do conhecimento químico e biológico