Different treatment schemes and dynamizations of Trypanosoma cruzi biotherapies: what information do they transfer to the organism in infected mice?

BACKGROUND: The use of biotherapies in Trypanosoma cruzi infection can provide an understanding about effects of these highly diluted medications. OBJECTIVES: To evaluate different treatment schemes and dynamizations of biotherapies prepared from blood trypomastigotes (buffy coat) in mice infected with T. cruzi. METHODS: Swiss mice infected with Y strain of T. cruzi were divided into two experiments. Experiment 1, all treated groups received biotherapy 7dH (10 µL/mL ad libitum) in different treatment schemes: TB7dH - treated 3 days before infection; TBA7dH - treated 3 days before and after infection; TBAe.d.7dH - treated 3 days before infection and every day after infection and IC - infection control. Experiment 2, all treated groups received medication in different dynamizations 3 days before and after infection (10 µL/mL ad libitum): TBA15dH - treated with biotherapy 15dH; TBA16dH - treated with biotherapy 16dH; TBA17dH - treated with biotherapy 17dH; TBAp.chords - treated with biotherapy 'potency chords' and IC - infection control. We evaluated parasitological and clinical parameters. RESULTS: Experiment 1 showed that different treatment schemes with biotherapy 7dH produced different effects on infection evolution. TBA7dH group had the best outcome, with lower parasitemia, higher survival, and better clinical evolution compared to IC. Experiment 2 showed that biotherapy 'potency chords' had effects different from the individual dynamizations that it contained (15dH, 16dH, and 17dH). Animals that had patent parasitemia had delayed emergence of parasites in blood and subsequent increase in parasitemia, but had better clinical evolution compared to IC. CONCLUSIONS: The effects of T. cruzi biotherapies depend on frequency at which they are administered, dynamization, and host-parasite relationship/individual susceptibility of treated organism. Biotherapy appeared to transfer to infected organism 'antigenic information' related to parasite and 'disease information' related to molecules produced by host's immune response and contained in the buffy coat used to prepare the medication.

Trypanosoma cruzi: biotherapy made from trypomastigote modulates the inflammatory response.

UNLABELLED: This study evaluates the effect of Trypanosoma cruzi biotherapy 17dH (BIOT) on mice of different ages, infected with the protozoa concerned. METHOD: Performing a blind, controlled, randomized by drawing experiment, 110 animals four or eight-week-old, Swiss, male mice were divided into infected control treated hydroalcoholic 7% (CI-4 = 34 or CI-8 = 21 animals) and infected control treated with biotherapy 17dH-0.2 mL/animal/20 consecutive days/oral regimen (BIOT-4 = 33 or BIOT-8 = 21 animals). Animals were inoculated intraperitoneally with 1400 trypomastigote, T. cruzi Y-strain. Parasitological, immunological and histopathologic parameters were evaluated statistically, using Statistica-8.0 and R 3.0.2 program to analysis of survival. The study was approved by the Ethics Committee for Animal Experimentation/UEM. RESULTS: Four-week-old mice showed no statistical difference in parasitemia (P = 0.5718) between the treated and control group. Eight-week-old mice from the treated group had a higher parasite peak (P = 0.0424) and higher parasitemia (P < 0.005) than the control. To both groups of 4 and 8 weeks of age, treated or untreated, survival of mice was higher in the treated group than in the control, although it was not statistically significant (p-value = 0.32, 0.55 respectively). Four-week-old mice displayed a spleen section with a number of amastigote nests significantly higher in BIOT-4 than CI-4 (P = 0.01). In eight-week-old mice the number of amastigote nests (P < 0.001) and inflammatory foci (P < 0.06-10% significance) in the liver section were smaller in BIOT-8 than CI-8. Spleen giant cells were significantly higher in CI-8 than in BIOT-8 (P < 0.01). Eight-week-old animals treated with biotherapy showed higher parasitemia and lower tissue parasitism. Opposite pattern was observed in four-week-old animals. CONCLUSION: There is a difference of high diluted medication effect in four and eight-week-old mice. In the group of animals 8 weeks the immunomodulatory effect seems to have been higher. Hence, treatment with the medicine produced from T. cruzi modulates the inflammatory response with increased apoptosis and decreased serum levels of TGF-ß.

H3N2 homeopathic influenza virus solution modifies cellular and biochemical aspects of MDCK and J774G8 cell lines.

BACKGROUND: Influenza viruses cause highly contagious acute respiratory illnesses with significant mortality, especially among young children, elderly people, and individuals with serious medical conditions. This encourages the development of new treatments for human flu. Biotherapies are diluted solutions prepared from biological products compounded following homeopathic procedures. OBJECTIVES: To develop a biotherapy prepared from the infectious influenza A virus (A/Aichi/2/68 H3N2) and to verify its in vitro response. METHODS: The ultradiluted influenza virus solution was prepared in the homeopathic dilution 30dH, it was termed Influenzinum RC. The cellular alterations induced by this preparation were analyzed by optical and electron microscopy, MTT and neutral red assays. Glycolytic metabolism (PFK-1) was studied by spectrophotometric assay. Additionally, the production of tumor necrosis factor-α (TNF-α) by J774.G8 macrophage cells was quantified by ELISA before and after infection with H3N2 influenza virus and treatment. RESULTS: Influenzinum RC did not cause cytotoxic effects but induced morphological alterations in Madin-Darby canine kidney (MDCK) cells. After 30 days, a significant increase (p < 0.05) in mitosis rate was detected compared to control. MDCK mitochondrial activity was changed after treatment for 10 and 30 days. Treatment significantly diminished (p < 0.05) PFK-1 activity. TNF-α in biotherapy-stimulated J774.G8 macrophages indicated a significant (p < 0.05) increase in this cytokine when the cell supernatant was analyzed. CONCLUSION: Influenzinum RC altered cellular and biochemical features of MDCK and J774G8 cells.

Effects of Highly Diluted Drugs on Experimental Infection with Trypanosoma cruzi In Vivo: Systematic Review.

Objective: To investigate, through a systematic review, the effects of the use of highly diluted drugs in the treatment of experimental infection with Trypanosoma cruzi. Design: The authors searched for scientific publications in the databases PubMed, Web of Science, SCOPUS, LILACS, and the Google Scholar search system, from 2000 to 2018, following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. According to the criteria established, a total of 22 studies were included. Settings/Location: The study took place at the State University of Maringá, Maringá, PR, Brazil. Subjects: Male mice (Mus musculus) or rats (Rattus norvegicus). Interventions: Highly diluted drugs. Outcome measures: The parameters evaluated in the studies were parasitological, clinical, immunological, histopathological and hematological. Results: The studies demonstrated that the effects of highly diluted drugs are related to their dynamizations, treatment regimen, and host susceptibility to T. cruzi infection, and depend on the initial information transmitted to the treated organism, making this information the "model" of how the treated organism will react. Regardless of the mechanism of action, these drugs provide a decrease in inflammation, which is one of the central phenomena of the pathogenesis of T. cruzi infection. Conclusions: This systematic review brings out the importance of the T. cruzi infection model as a reliable and valid model for studying different effects produced by highly diluted drugs. Considering the findings and in a broader perspective, this study contributes to considering these drugs as a possible way of dealing with "treatment" in general, presents the need to reexamine the biochemical model and develop a model for the effect of high dilutions in general, as well as for the treatment of parasitic infections.

Hyperadrenocorticism treatment of a dog with high dilution: case report

Hyperadrenocorticism is a common endocrinopathy in dogs, associated to an excessive production or administration of cortisol.Aims:Report the evolution of homeopathic treatment in spontaneous hyperadrenocorticism analyzing with basal and post-acth stimulation cortisol values of a yorkshire male dog with 10 years old, diagnosed from the suppression test with low dose of dexamethasone and stimulation with ACTH, as well as complementary tests.Methodology: Homeopathic treatment was chosen, based on the principle of similitude usingIgnatia amarabecause the patient presents repertorized mental symptoms such as separation anxiety syndrome, docility, annoyances and jealousy and also because it is efficient and less harmful. It was associated to cortisol biotherapy to inhibit cortisol production and adrenal biotherapy to control the response of excess of the cortisol producted by the gland. The exposed information is consented by the tutor.Results:The dog was in convencional treatment with trilostane but didn't response to the therapy, showing 5,41 µg/dL of basal result and 11,8 µg/dL of post-acth result and the symptoms were worst on 12/12/2021, presenting lethargic, panting, more evident alopecia and severe muscle weakness which the patient unable to stand. Therefore, the protocol was recommended for 3 months, included 3 globules ofIgnatia amara30cH orally, every 12 hours, 3 globules of cortisol biotherapy 30 cH and also of adrenal biotherapy 6 cH every 24 hours. On 03/28/2022 the basal and post-acth stimulation results was 3,71 µg/dL e 5,79 µg/dL respectively and the patient was more active, the skin was better and even with difficulty it was movingand having more independence.Conclusion: Homeopathic treatment with high dilution was effective, keeping the indices with the recommended range of post acth between 2.0 and 5.0, confirming an adequate therapeutic monitoring and symptomatic improvement.

Highly diluted medication reduces parasitemia and improves experimental infection evolution by Trypanosoma cruzi.

BACKGROUND: There is no published information about the use of different protocols to administer a highly diluted medication.Evaluate the effect of different protocols for treatment with biotherapic T. cruzi 17 dH (BIOT(Tc17dH)) on clinical/parasitological evolution of mice infected with T. cruzi-Y strain. METHODS: A blind, randomized controlled trial was performed twice, using 60 28-day-old male Swiss mice infected with T. cruzi-Y strain, in five treatment groups: CI - treated with a 7% ethanol-water solution, diluted in water (10 µL/mL) ad libitum; BIOT(PI) - treated with BIOT(Tc17dH) in water (10 µL/mL) ad libitum during a period that started on the day of infection; BIOT(4DI) - treated with BIOT(Tc17dH) in water (10 µL/mL) ad libitum beginning on the 4th day of infection; BIOT(4-5-6) - treated with BIOT(Tc17dH) by gavage (0.2 mL/ animal/day) on the 4th, 5th and 6th days after infection; BIOT(7-8-9) - treated with BIOT(Tc17dH) by gavage (0.2 mL/ animal/day) on the 7th, 8th and 9th days after infection. We evaluated: parasitemia; total parasitemia (P(total)); maximum peak of parasites; prepatent period (PPP) - time from infection to detection of the parasite in blood; patent period (PP) - period when the parasitemia can be detected in blood; clinical aspects; and mortality. RESULTS: Parasitological parameters in the BIOT(PI) and mainly in the BIOT(4PI) group showed better evolution of the infection compared to the control group (CI), with lower P(total), lower maximum peak of parasites, higher PPP, lower PP and longer survival times. These animals showed stable body temperature and higher weight gain and water consumption, with more animals having normal-appearing fur for longer periods. In contrast, groups BIOT(4-5-6) and BIOT(7-8-9) showed worse evolution of the infection compared to the control group, considering both parasitological and clinical parameters. The correlation analysis combined with the other data from this study indicated that the prepatent period is the best parameter to evaluate the effect of a medication in this model. CONCLUSIONS: The BIOT(4DI) group showed the best clinical and parasitological evolution, with lower parasitemia and a trend toward lower mortality and a longer survival period. The prepatent period was the best parameter to evaluate the effect of a medication in this model.