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1.
Homeopathy ; 2022 Apr 27.
Article in English | MEDLINE | ID: mdl-35477183

ABSTRACT

OBJECTIVE: The present study aimed to identify possible phenotypic changes in 4T1 (murine mammary adenocarcinoma) cells in vitro, including viability, HER-2 (human epidermal growth factor receptor-type 2) expression, and metastatic potential, after treatment with Carcinosinum in different homeopathic dilutions (12cH, 30cH, 200cH) shaken mechanically in pure, sterile, water from a commercial stock dilution. METHOD: Treated cells were cultured in R10 medium, using 24-well plates, 105 cells per well, and treated with vehicle, Carcinosinum 12cH, 30cH or 200cH; untreated cells were used as the baseline control. After 24 hours of treatment, the percentage of apoptotic cells was analyzed by annexin V. Cell morphology was evaluated by microscopy after hematoxylin-eosin and Giemsa staining, whilst HER-2 expression was assessed using immunocytochemistry. The metastatic potential was determined by the expression and activity of the enzyme matrix metalloproteinase 9 (MMP-9) using zymography. The cytokine profile was established using the cytometric bead array method. RESULT: Treatment of 4T1 cells in vitro with Carcinosinum 30cH produced an increase in the number of annexin V-positive cells (apoptosis) and decreased expression of proactivated MMP-9. Cells treated with Carcinosinum 200cH presented hyper-expression of HER-2 on the plasma membrane, identified by immunocytochemistry. There were no differences in cytokine production among treatments. CONCLUSION: The data show promising results for Carcinosinum 30cH in vitro, but in vivo studies are also required to evaluate the role of tumor microenvironment in its effects.

2.
Homeopathy ; 110(4): 244-255, 2021 11.
Article in English | MEDLINE | ID: mdl-34474498

ABSTRACT

INTRODUCTION: Finding solutions to mitigate the impact of pollution on living systems is a matter of great interest. Homeopathic preparations of toxic substances have been described in the literature as attenuation factors for intoxication. Herein, an experimental study using Artemia salina and mercury chloride was developed as a model to identify aspects related to bioresilience. AIMS: The aim of the study was to describe the effects of homeopathic Mercurius corrosivus (MC) on Artemia salina cysts hatching and on mercury bioavailability. METHODS: Artemia salina cysts were exposed to 5.0 µg/mL of mercury chloride during the hatching phase. MC potencies (6cH, 30cH, and 200cH) were prepared in sterile purified water and poured into artificial sea water. Different controls were used (non-challenged cysts and challenged cysts treated with water, succussed water, and Ethilicum 1cH). Four series of nine experiments were performed to evaluate the percentage of cyst hatching. Soluble total mercury (THg) levels and precipitated mercury content were also evaluated. Solvatochromic dyes were used to check for eventual physicochemical markers of MC biological activity. RESULTS: Significant delay (p < 0.0001) in cyst hatching was observed only after treatment with MC 30cH, compared with controls. This result was associated with an increase of THg concentration in water (p = 0.0018) and of chlorine/oxygen ratio (p < 0.0001) in suspended micraggregates, suggesting changes in mercury bioavailability. A specific interaction of MC 30cH with the solvatochromic dye ET33 (p = 0.0017) was found. CONCLUSION: Changes in hatching rate and possible changes in Hg bioavailability are postulated as protective effects of MC 30cH on Artemia salina, by improving its natural bioresilience processes.


Subject(s)
Homeopathy , Mercury , Animals , Artemia , Chlorides , Mercuric Chloride
3.
Homeopathy ; 110(1): 52-61, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33348418

ABSTRACT

BACKGROUND: The homeopathic medicines Silicea terra (Sil) and Zincum metallicum (Zinc) modulate macrophage activity and were assessed in an experimental study in-vitro for their effects on macrophage-BCG (Bacillus Calmette-Guérin) interaction. METHODS: RAW 264.7 macrophages were infected with BCG, treated with different potencies of Sil and Zinc (6cH, 30cH and 200cH) or vehicle, and assessed 24 and 48 h later for bacilli internalization, hydrogen peroxide (H2O2) and cytokine production, and lysosomal activity. RESULTS: Treatment with vehicle was associated with non-specific inhibition of H2O2 production to the levels exhibited by uninfected macrophages. Sil 200cH induced significant reduction of H2O2 production (p < 0.001) compared with the vehicle and all other treatments, as well as higher lysosomal activity (p ≤ 0.001) and increased IL-10 production (p ≤ 0.05). Such effects were considered specific for this remedy and potency. The number of internalized bacilli was inversely proportional to Zinc potencies, with statistically significant interaction between dilution and treatment (p = 0.003). Such linear-like behavior was not observed for Sil dilutions: peak internalization occurred with the 30cH dilution, accompanied by cellular degeneration, and IL-6 and IL-10 increased (p ≤ 0.05) only in the cells treated with Sil 6cH. CONCLUSION: Sil and Zinc presented different patterns of potency-dependent effect on macrophage activity. Bacterial digestion and a balanced IL-6/IL-10 production were related to Sil 6cH, though reduced oxidative stress with increased lysosomal activity was related to Sil 200cH. Degenerative effects were exclusively related to Sil 30cH, and potency-dependent phagocytosis was related only to Zinc.


Subject(s)
Bacillus/drug effects , Macrophages/drug effects , Materia Medica/pharmacology , Zinc/pharmacology , Brazil , Humans , Mycobacterium bovis/drug effects
4.
Homeopathy ; 110(2): 76-85, 2021 May.
Article in English | MEDLINE | ID: mdl-33348419

ABSTRACT

BACKGROUND: Complementary and alternative medicine, including homeopathy, is widely used to improve well-being among cancer patients and reduce adverse effects of conventional treatment. In contrast, there are few studies on the use of homeopathic medicines to treat the disease itself. Yet, evidence of possible effectiveness of homeopathic high dilutions in experimental cancer models has been published during the past 20 years. AIM: The aim of the study was to perform a systematic review of fundamental research studies on homeopathic high dilutions in cancer. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, we conducted a literature search in the database PubMed for original publications, from 2000 to 2018 and in English, on in vitro and in vivo experimental cancer models testing homeopathic high dilutions. RESULTS: Twenty-three articles met the inclusion criteria-14 in vitro, eight in vivo, and one in vitro plus in vivo experimental models. Most studies were from India. Research prominently focused on cytotoxic effects involving apoptotic mechanisms. Intrinsic aspects of homeopathy should be considered in experimental designs to emphasize the specificity of such effects. CONCLUSION: Fundamental research of homeopathy in cancer is still at an early stage and has mainly been performed by a few groups of investigators. The results point to an interference of well-selected homeopathic medicines with cell cycle and apoptotic mechanisms in cancer cells. However, these findings still need independent reproduction.


Subject(s)
Materia Medica/therapeutic use , Models, Theoretical , Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Humans , India
5.
Homeopathy ; 109(3): 126-132, 2020 08.
Article in English | MEDLINE | ID: mdl-32052392

ABSTRACT

BACKGROUND: Highly diluted and succussed solutions interact with solvatochromic dyes, indicating that changes in solvent and solute polarity could be related to their mechanism of action. It is not known, however, how the activity associated with succussed high dilutions is transferred to untreated water and what the limits of this process are. AIMS: The aims of the present study were to ascertain whether a succussed high dilution of phosphorus (1.5 × 1-59 M; Phos 30cH) seeded into a natural water source that fed a fjord and two connected lakes could propagate itself through the lake system (total volume 2200 m3) and, moreover, whether the process could be tracked using solvatochromic dyes. METHODS: Samples of water were collected before and after seeding, at different times and places throughout the lake system. Controls comprised water taken from an untreated and adjacent, but independent, lake (1385 m3). RESULTS: Water samples taken up to 72 hours after the source treatment produced significant increases (p ≤ 0.03) in the absorbance of the solvatochromic dye methylene violet (MV), while samples from the control lake produced no changes. CONCLUSIONS: The study indicates that activity associated with Phos 30c can propagate itself through large volumes of water, causing changes throughout a whole connected lake system, and that these changes can be tracked using the solvatochromic dye MV. This in turn means the use of homeopathic medicines in large volumes of drinking water, in farming and ecological contexts, now has the potential to be assessed with physico-chemical monitoring.


Subject(s)
Coloring Agents/analysis , Dye Dilution Technique , Homeopathy , Phosphorus/analysis , Water , Humans
6.
Homeopathy ; 109(2): 79-86, 2020 05.
Article in English | MEDLINE | ID: mdl-31604351

ABSTRACT

BACKGROUND: The mechanism by which highly diluted and agitated solutions have their effect is still unknown, but the development in recent years of new methods identifying changes in water and solute dipole moments is providing insights into potential modes of action. OBJECTIVE: The objective of the current study was to compare the biological effects of Antimonium crudum (AC) previously obtained by our group and already described in the literature with now measurable physico-chemical effects on solvatochromic dyes. METHODS: Different dilutions of AC and succussed water have been characterized with respect to their effect on the visible spectra of the solvatochromic dyes methylene violet (MV), a pyridinium phenolate (ET33), and a dimethylamino naphthalenone (BDN) compared with in-vitro action against Leishmania amazonensis-infected macrophages. RESULTS: Dye responses varied according to the dye used and the level of AC dilution and results were found to corroborate previously published in-vivo and in-vitro effects of AC. In addition, a very significant enhancement in the absorbance increase of MV was seen using the supernatant from AC 200cH-treated cells (15%; p < 0.0001) over that seen with AC 200cH itself (4%; p = 0.034), suggesting the amplification of ultra-high dilution effects by biological systems. Furthermore, supernatants from AC-treated cells increased the range of dilutions of AC that were capable of producing effects on the spectra of MV. The effect of AC dilutions on dye ET33 was eliminated by a weak electric current passed through potency solutions. CONCLUSION: The data confirm a correspondence between the biological effects of dilutions of AC in-vitro and physico-chemical effects on solvatochromic dyes as measured by changes in their visible spectra. Results also indicate high dilutions of AC are sensitive to exposure to electric currents and biological systems.


Subject(s)
Antimony/chemistry , Antimony/pharmacology , Coloring Agents/chemistry , Homeopathy , Solvents/chemistry , Coloring Agents/pharmacology , Leishmania mexicana/drug effects , Macrophages , Solvents/pharmacology , Spectrophotometry, Ultraviolet
7.
Homeopathy ; 108(3): 188-200, 2019 08.
Article in English | MEDLINE | ID: mdl-30999383

ABSTRACT

INTRODUCTION: Encephalitozoon cuniculi (E. cuniculi), a fungus that acts as an intracellular pathogen, causes a marked neurological syndrome in many host species and is a zoonotic concern. Although no well-established treatment for this syndrome is known, previous successful clinical experience using homeopathic phosphorus has been described in which symptom remission with no mortality occurred in 40/42 animals by means of unknown immunological mechanisms. The latter observation was the main motivation for this study. OBJECTIVE: To verify, in an in-vitro model, if macrophages infected with E. cuniculi can change in function after treatment with different potencies of phosphorus. MATERIALS AND METHODS: RAW 264.7 macrophages were infected with E. cuniculi in-vitro and treated with various homeopathic potencies of phosphorus. The vehicle was used as a control solution (0.06% succussed ethanol). After 1 and 24 hours, the following parameters were analyzed: parasite internalization (by the Calcofluor staining method), lysosome activity (by the acridine orange method), cytokine/chemokine production (by the MAGPIX system), and cell ultrastructure. Automatic image analysis was used when applicable, and the experiments were performed in triplicate. RESULTS: Treatment with vehicle alone increased interleukin (IL)-6, tumor necrosis factor alpha and monocyte chemotactic protein -1 production (p ≤ 0.05) and reduced the number of internalized parasites (p ≤ 0.001). A progressive and time-dependent increase in RANTES (regulated on activation, normal T-cell expressed and secreted) and lysosome activity (p ≤ 0.002) was observed only after treatment with the highest potency of phosphorus (Phos 200cH), together with decreased apoptosis rate, intense parasite digestion, and the presence of non-internalized spores. CONCLUSIONS: Phos 200 cH has a modulatory action on the activity of infected macrophages, especially a specific increase in RANTES, a key element in the prognosis of E. cuniculi-infected and of immunosuppressed patients bearing infections.


Subject(s)
Encephalitozoon cuniculi/drug effects , Macrophages/drug effects , Phosphorus/therapeutic use , Animals , Encephalitozoon cuniculi/pathogenicity , Encephalitozoonosis/drug therapy , Homeopathy/methods , Homeopathy/standards , Macrophages/microbiology , Phosphates/therapeutic use , Rabbits
8.
Homeopathy ; 108(1): 12-23, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30290377

ABSTRACT

INTRODUCTION: According to the "silica hypothesis" formulated to explain homeopathy, the information of starting materials would be transferred to cells by silica nanoparticles detached from the glassware walls by serial dilution and agitation through epitaxy. We compared the biological activity, electrical current and silicon microparticle content (by means of scanning electron microscopy/energy-dispersive X-ray spectroscopy) of high dilutions (HDs) of arsenic prepared in plastic and glass vials to investigate the role of silica in their biological effects in vitro. MATERIALS AND METHODS: Co-cultures of macrophages and yeast (Saccharomyces cerevisiae) were treated with different HDs of arsenic prepared in plastic and glass vials. Macrophage morphology, phagocytosis index, nitric oxide (NO), and cytokine production were evaluated. RESULTS: Measurable amounts of silicon microparticles were detected only in the HDs prepared in glass vials, but ultra-centrifugation eliminated them. Specific and non-specific results were observed. Non-specific pro-inflammatory effects were seen in all dilutions prepared in plastic vials, including elevation of pro-inflammatory cytokines, NO and macrophage phagocytic index. Only the 200th centesimal dilution of arsenic produced specific decrease in interleukin-6 production in macrophages, and it was independent of the vial type or the presence of microparticles of silica in the medicine samples. The nature of the vials had an impact on the electric flow in the respective fluids. CONCLUSION: The non-specific, pro-inflammatory effects might be attributed to organic residuals detached from the vials' plastic walls during manipulation. Instead, specific silica-independent effects of the homeopathic medicine can be attributed to the decrease of interleukin-6 after treatment with the 200th centesimal dilution of arsenic.


Subject(s)
Arsenicals/isolation & purification , Electric Conductivity , Silicon/isolation & purification , Cytokines/isolation & purification , Homeopathy/methods , Humans , Microscopy, Electron, Scanning/methods
9.
Homeopathy ; 107(3): 172-180, 2018 08.
Article in English | MEDLINE | ID: mdl-29768636

ABSTRACT

INTRODUCTION: There are two critical pillars of homeopathy that contrast with the dominant scientific approach: the similitude principle and the potentization of serial dilutions. Three main hypotheses about the mechanisms of action are in discussion: nanobubbles-related hormesis; vehicle-related electric resonance; and quantum non-locality. OBJECTIVES: The aim of this paper is to review and discuss some key points of such properties: the imprint of supramolecular structures based on the nanoparticle-allostatic, cross-adaptation-sensitization (NPCAS) model; the theory of non-molecular electromagnetic transfer of information, based on the coherent water domains model, and relying (like the NPCAS model) on the idea of local interactions; and the hypothesis of quantum entanglement, based on the concept of non-locality. RESULTS AND DISCUSSION: The nanoparticles hypothesis has been considered since 2010, after the demonstration of suspended metal nanoparticles even in very highly diluted remedies: their actual action on biological structures is still under scrutiny. The second hypothesis considers the idea of electric resonance mechanisms between living systems (including intracellular water) and homeopathic medicines: recent findings about potency-related physical properties corroborate it. Finally, quantum theory of 'non-local' phenomena inspires the idea of an 'entanglement' process among patient, practitioner and the remedy: that quantic phenomena could occur in supra-atomic structures remains speculative however. CONCLUSION: Further studies are needed to ascertain whether and which of these hypotheses may be related to potential cellular effects of homeopathic preparations, such as organization of metabolic pathways or selective gene expression.


Subject(s)
Homeopathy/methods , Materia Medica/chemistry , Nanoparticles/chemistry , Plant Extracts/chemistry , Allostasis , Humans , Models, Theoretical , Quantum Theory
10.
Res Vet Sci ; 117: 178-186, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29288959

ABSTRACT

Ivermectin (IVM) is an antiparasitic agent widely used in agricultural, domestic animals and in human clinical practice. In the present study, the temporal effects of therapeutic doses of IVM in the morphometric and histological assessment of testis were studied to verify if IVM acute administration impaired the spermatogenesis and spermiogenesis of adult rats, if these effects are reversible. The testosterone levels and the plasmatic IVM levels were assessed. The results show: 1) IVM acute exposure, mainly in the higher dose, reduced the testicular volume, the tubular diameter and the germinal epithelium height; 2) no interferences on Leydig cells frequency; 3) histological studies show that tubular sections containing several histological changes indicative of spermatogenesis interruption, such as disorganization of germinal epithelium, vacuolar degeneration of the germ cells and sloughing of cells into the tubular lumen; 4) no differences in testosterone levels; 5) The IVM plasmatic levels were significantly reduced at 72h after the 0.2mg/kg. It was concluded that acute IVM impaired the spermatogenesis and spermiogenesis of rats. Probably these effects were not consequence of IVM at the Leydig cells because no effects were observed at this level. Finally, our results suggest that some testicular effects are reversible and correlated with the plasmatic levels of IVM.


Subject(s)
Ivermectin/pharmacology , Spermatogenesis/drug effects , Adult , Animals , Humans , Leydig Cells , Male , Rats , Testis , Testosterone
11.
Int. j. high dilution res ; 17(3/4): 20-41, 2018.
Article in English | LILACS, HomeoIndex Homeopathy | ID: biblio-1050007

ABSTRACT

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)


Subject(s)
Animals , Mice , Carcinoma, Ehrlich Tumor , High Potencies , Thymolum , Neoplasms
12.
Homeopathy ; 106(3): 160-170, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28844289

ABSTRACT

BACKGROUND: A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. METHODS: Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). RESULTS: AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800 nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68 J/g in comparison to non-dynamized lactose (LAC; p < 0.05). CONCLUSIONS: Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.


Subject(s)
Differential Thermal Analysis/methods , Homeopathy/methods , Lactose/analysis , Zinc/analysis , Humans , Microscopy, Electron, Transmission/methods , Spectrometry, X-Ray Emission/methods
13.
Cytokine ; 99: 80-90, 2017 11.
Article in English | MEDLINE | ID: mdl-28738234

ABSTRACT

Leishmaniasis is a term referring to a range of clinical conditions caused by protozoan parasites of the genus Leishmania, Trypanosomatidae family, Kinetoplastida order that is transmitted by the bite of certain species of mosquitoes Phlebotominae subfamily. These parasites infect hosts wild and domestic mammals, considered as natural reservoirs and can also infect humans. Leishmania are obligate intramacrophage protozoa that have exclusively intracellular life style. This suggests that the amastigotes possess mechanisms to avoid killing by host cells. Cutaneous leishmaniasis, the most common form of the disease, causes ulcers on exposed parts of the body, leading to disfigurement, permanent scars, and stigma and in some cases disability. Many studies concluded that the cytokines profile and immune system of host have fundamental role in humans and animals natural self-healing. Conventional treatments are far from ideals and the search for new therapeutic alternatives is considered a strategic priority line of research by the World Health Organization. A promising approach in the field of basic research in homeopathy is the treatment of experimental infections with homeopathic drugs prepared from natural substances associations highly diluted, which comprise a combination of several different compounds considered as useful for a symptom or disease. Therefore, this study aimed to evaluate the effect of M1, a complex homeopathic product, in macrophage-Leishmania interaction in vitro and in vivo. It was used RAW cells lineage and BALB/c mice as a host for the promastigotes of L. amazonensis (WHOM/BR/75/Josefa). Several biochemical and morphological parameters were determined. Together, the harmonic results obtained in this study indicate that, in general, the highly diluted products trigger rapid and effective responses by living organisms, cells and mice, against Leishmania, by altering cytokines profile, by NO increasing (p<0.05), by decreasing parasitic load (p<0.001), and modifying classical maturation and biogenesis of parasitophorous vacuoles (p<0.001). M1 complex decreased endocytic index (p<0.001), and the % of infected macrophages (p<0.05), preventing the development of lesions (p<0.05) caused by L. amazonensis by increasing Th1 response (p<0.05). Therefore the M1complex can be a good candidate for a complementary therapy to conventional treatments, since all the parameters observed in vitro and in vivo improved. It could be an interesting clinical tool in association to a classical anti-parasitic treatment, maybe resulting in better quality of life to the patients, with less toxicity.


Subject(s)
Homeopathy , Leishmania/physiology , Animals , Biological Assay , Cytokines/metabolism , Hydrogen Peroxide/metabolism , Leishmania/ultrastructure , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/pathology , Macrophages/parasitology , Macrophages/ultrastructure , Male , Mice , Mice, Inbred BALB C , Nitric Oxide/metabolism , Parasite Load , RAW 264.7 Cells
14.
Exp Ther Med ; 13(6): 2723-2740, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28596809

ABSTRACT

Mistletoe (Viscum album L.) has been used as complementary anticancer treatment for ~100 years. Although the clinical efficacy of mistletoe in cancer and associated survival benefits remain contested, several studies point to its effectiveness and others have reported antitumor and immunomodulatory properties. In the present review, a search was conducted for original articles reporting the outcomes of treatments for experimental animal tumors with mistletoe. The inclusion criteria were: Publication in English, from 1996 onwards and in peer-reviewed journals included in the database PubMed. The parameters analyzed were: Provenance and time of publication, rationale, methods (animal species used, mistletoe preparation, treatment protocol, tumor lineage, blinding, randomization, controls and concomitant treatments), outcomes and investigated mechanisms of action. A total of 37 studies met the inclusion criteria. The quality of the studies was adequate in the terms of sample size and use of controls, and the only animal species employed were mice and rats. However, few studies reported having performed random allocation and none reported blinding. There was wide variation in the type and preparation of mistletoe used, route of administration, regimen, tumor type and the mechanism of action assessed. A temporal trend was identified; earlier studies sought to establish the antitumor effect of mistletoe and its possible mechanisms, cytotoxicity and immunomodulation in particular, whereas the later ones tended to focus more on biologically active principles, genomics and oxidative stress. A total of 32/37 studies reported an antitumor effect, 3 of which had mixed results. A total of 2 studies did not detect any antitumor effect and a further 2 found stimulation of tumor growth in the treated groups. One study did not assess antitumor effects, investigating immunomodulation action instead. The quality of the studies was satisfactory and the majority reported positive outcomes. Nevertheless, there is a great deal of methodological heterogeneity among the studies, which precludes conclusive comparisons. Based on these results, the present authors strongly suggest developing guidelines for reporting in vivo mistletoe cancer treatment experiments.

15.
Arch Oral Biol ; 80: 164-174, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28433620

ABSTRACT

OBJECTIVE: The present study evaluated the nociceptive response induced by dentin hypersensitivity after dental erosion in rats that were exhibited to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior. DESIGN: Adult male rats were subjected to UCMS (depression [D] group) or not (no depression [ND] group) for 30days and received either acidic solution to induce dental erosion (E) or water (W), thus forming the WND, END, WD, and ED groups. After the end of treatment, depressive-like parameters (i.e., sucrose preference and immobility in the forced swim test) and dentin hypersensitivity were evaluated. Plasma tumor necrosis factor α (TNF-α) and corticosterone levels were measured, and astrocytic glial fibrillary acidic protein (GFAP) expression was evaluated in the prefrontal cortex, hippocampus, amygdala, and hypothalamus. RESULTS: Administration of the acidic solution potentiated dentin hypersensitivity and increased corticosterone levels in the ED group compared with the WD group. TNF-α levels only increased in the WD group. The ED group exhibited an increase in astrocytic GFAP expression in the hypothalamus and prefrontal cortex but decreases in the hippocampus. CONCLUSIONS: These results suggest that UCMS exacerbated the nociceptive response associated with dentin hypersensitivity, concomitant with an increase in plasma corticosterone levels. Hypothalamic and prefrontal cortex astrogliosis in the ED group may be attributable to the increase in corticosterone associated to UCMS procedure. The reduction of astrocytic GFAP expression in the hippocampus in the ED group supports the association between dentin hypersensitivity and depression.


Subject(s)
Dentin Sensitivity/etiology , Depression/complications , Stress, Physiological , Animals , Corticosterone/blood , Depression/metabolism , Disease Models, Animal , Glial Fibrillary Acidic Protein/metabolism , Immunoenzyme Techniques , Male , Microscopy, Electron, Scanning , Rats , Rats, Wistar , Surface Properties , Tumor Necrosis Factor-alpha/blood
16.
Cytokine ; 95: 97-101, 2017 07.
Article in English | MEDLINE | ID: mdl-28254560

ABSTRACT

The prevalence of Th1/Th2 response, spleen changes and megakaryocytes were investigated in BALB/c mice (n=138) infected with Leishmania infantum, and treated with Leishmania infantum 30× (10-30) biotherapy - BioLi30×. We performed controlled experiments using 8-to-12-week-old mice, infected with 5×107L. infantum promastigotes, divided into eight groups: G1 (healthy), G2 (infected with L. infantum), G3 (BioLi30× pre-treated), G4 (BioLi30× pre/post-treated), G5 (BioLi30× post-treated), G6 (Water 30× post-treated), G7 (Antimonium crudum 30× post-treated) and G8 (Glucantime® post-treated). G3-G7 groups were orally treated with their respective drugs diluted in filtered water (1:10), and G8 received Glucantime® (0.6mg/100µl of PBS), intraperitoneally. Spleen fragments were submitted to double blind histopathological evaluation and the number of megakaryocytes was counted. Besides, animals' serum was measured after 49days of infection, and cytokines (IFN-γ, IL-4, IL-10, IL-12), as well as the Th1/Th2 correlation (IFN-γ/IL-4 and IFN-γ/IL-10), were analyzed. Spleen histological parameters were classified as: healthy appearance (G1); discreet (G3-G7), moderate (G2) and moderate to severe (G8) white pulp hyperplasia; proliferation of megakaryocytes (G2-G8), and intense disruption (G2-G8). All groups, except for G7, showed higher percentages of megakaryocytes per field ranging from 87% to 15%, when compared to healthy animals (G1). Th1 predominance in IFN-γ/IL-4 ratio (comparing to G2) was detected in G4, G5, G6 and G7. Finally, pre/post (BioLi30x) and post-treatment (Antimonium crudum 30x) presented reduction of megakaryocytes/spleen changes due to immunomodulation animal process, controlling the infection process, probably by the Th1 cytokine predominance.


Subject(s)
Homeopathy , Leishmania infantum , Leishmaniasis, Visceral/therapy , Megakaryocytes/pathology , Spleen/pathology , Th1 Cells/immunology , Animals , Cytokines/blood , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/pathology , Mice, Inbred BALB C , Th1-Th2 Balance , Th2 Cells/immunology
17.
Cytokine ; 92: 103-109, 2017 04.
Article in English | MEDLINE | ID: mdl-28142108

ABSTRACT

OBJECTIVE: This is a random blinded placebo controlled murine experimental model to study the effects of Cantharis 6 CH, a homeopathic medicine, on E coli-induced cystitis. METHODS: 24 adult susceptible female BALB/c mice were inoculated with E coli - UPEC O4:K-:H5 by a transurethral catheter. Cantharis 6cH or vehicle (placebo) was offered to mice by free access into the drinking water (1:100), during 24 h after infection. Spleen, bladder and kidneys were processed for quantitative histopathology after immunohistochemistry, using anti-CD3, CD79, MIF, NK and VEGF antibodies; the cytokines present in the bladder washing fluid were measured using a LUMINEX-Magpix KIT. Mann-Whitney and Fisher exact test were used as statistical analysis. RESULTS: Cantharis 6 CH increased IL12p40, IFN-γ and decreased IL10 concentrations in the bladder fluid (p⩽0.05); in the bladder mucosa, it increased the ratio between B and T lymphocytes (31%) and between B lymphocytes and MIF+ macrophages (57%, p⩽0.05). In the pelvis, instead, it decreased the B/T cells ratio (41%, p⩽0.05) and increased the M1/M2 macrophage ratio (42%, p⩽0.05). No differences were seen in the kidney and spleen analysis. CONCLUSION: The inverted balance of inflammatory cells and cytokines in bladder and pelvis mucosa shows specific local immune modulation induced by Cantharis 6cH.


Subject(s)
Cystitis/drug therapy , Escherichia coli Infections/drug therapy , Materia Medica/pharmacology , Urinary Tract Infections/drug therapy , Uropathogenic Escherichia coli/immunology , Animals , Cystitis/immunology , Cystitis/microbiology , Cystitis/pathology , Cytokines/immunology , Escherichia coli Infections/immunology , Escherichia coli Infections/pathology , Female , Mice , Mice, Inbred BALB C , Urinary Tract Infections/immunology , Urinary Tract Infections/pathology
18.
Cytokine ; 92: 33-47, 2017 04.
Article in English | MEDLINE | ID: mdl-28092793

ABSTRACT

BACKGROUND: In previous results mice treated with high dilutions of antimony presented reduction of monocyte migration to the site of infection with increase in B lymphocytes population in the local lymph node. AIMS: To know the mechanisms involved, a series of in vitro studies was done, using co-cultures of macrophages (RAW 264.7) and Leishmania (L.) amazonensis treated with different dilutions of antimony (Antimonium crudum or AC), in different times. METHODOLOGY: Spreading, phagocytosis, the oxidative activity of macrophages, the viability of free promastigotes and the cytokines/chemokines concentration in the supernatant were evaluated. The assays were performed in quadruplicate. RESULTS: Cells treated with AC 30cH (10-58M) and AC 200cH (10-398M) presented a temporary reduction of the spreading after 02h of incubation, followed by increase after 48h, being the most significant increase observed after the AC 200cH treatment. However, the percentage of internalized parasites at 48, 96 and 120h of incubation was also higher in cells treated with AC 200cH. It is suggested that the AC 200cH improves the ability of phagocytes to internalize the parasites, but not to digest them. The cytokines-chemokines panel corroborated these results. Both dilutions potentiated the parasite-induced reduction of cytokines production, especially IL-6, IL 12 p40 and γ-IFN, after 48h of incubation. In addition, the production of MIP-1 beta (CCL4), a chemokine involved in chronic inflammation, was also reduced after 120h. A specific effect of AC 30cH was seen by the inhibition of two peaks of CCL2 (MCP-1) observed in infected macrophages, at 24 and 120h. Since this cytokine is an important chemokine for monocytes, it explains the results obtained formerly in vivo. The morphology of macrophages after acridine orange staining revealed that the treatment with AC 30cH reduced substantially the acid vacuoles in the cytoplasm, indicating a certain inability of these cells to digest the parasites. On the other hand, a large peak of VEGF-A, associated with increase of internalized parasites was observed after 120h of treatment with AC 200cH, which could be associated to the regulation of the chronic inflammation events by M1-M2 polarization. There was no statistical difference among groups regarding the production of TNF, NO and H2O2, showing that the drugs do not alter macrophage cytotoxic activity. A clear quantitative and qualitative variation of the modulatory effects of AC 30cH and 200cH was seen, in function of time. CONCLUSIONS: Both dilutions were able to potentiate the decrease of most of cytokines and chemokines induced by the parasite infection in vitro, which explains the clinical improvement seen previously in vivo, however, the mechanisms involved and the epidemiological significance of these findings are still under discussion.


Subject(s)
Antimony/pharmacology , Leishmania/immunology , Leishmaniasis/immunology , Macrophages/immunology , Monokines/immunology , Animals , Leishmaniasis/pathology , Macrophages/parasitology , Mice , RAW 264.7 Cells
19.
Rev. homeopatia (São Paulo) ; 80(1/2): 89-97, 2017. tab
Article in Portuguese | HomeoIndex Homeopathy | ID: hom-11971

ABSTRACT

A pesquisa básica em homeopatia evoluiu muito nos últimos 20 anos. Desde estudos exploratórios realizados em animais e plantas para a caracterização dos efeitos sistêmicos dos medicamentos homeopáticos até estudos realizados in vitro, com sistemas celulares isolados, para avaliar mudanças nos mecanismos de adaptação celulares e nos processos de sinalização intracelular frente a tratamentos homeopáticos diversos. O volume de artigos acumulados ao longo dos anos permitiu a elaboração de várias revisões sistemáticas sobre o tema. Recentemente, a demonstração de que medicamentos homeopáticos podem modificar as funções celulares por mecanismosepigenéticos (metilação e desmetilação do DNA) abriu espaço para uma nova frente de pesquisas. Em paralelo, a partir de 2010, a descoberta da existência de nanopartículas e de propriedades físicas da água específicas nas preparações homeopáticas também jogou luz num campo até então pouco conhecido, em que se acreditava não existir nada além de água. Os desafios para o futuro se concentram, então, na demonstração,ou não, de que ambos os processos se inter-relacionam. (AU)


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 published articles amassed over time allowed for several systematic reviews on this subject. Recently, the demonstration the homeopathic medicines might alter 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 in the homeopathic dilutions brought light into a field poorly known before, as it was believe that homeopathic dilutions consist in nothing but water. Thus being, the challenges forthe future concern the demonstration, or not, of the interrelationship between both phenomena. (AU)


Subject(s)
Homeopathy , Nanoparticles , Intervention Studies , Epigenetic Repression , Basic Research
20.
Rev. homeopatia (São Paulo) ; 80(3/4): 82-89, 2017. tab
Article in English | HomeoIndex Homeopathy | ID: hom-12034

ABSTRACT

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.(AU)


Subject(s)
Homeopathy , Nanoparticles , Intervention Studies , Homeopathy Foundation , Epigenetic Repression , Basic Research
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