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Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti-inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding.

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Besides being scarce, the drugs available for treating cutaneous leishmaniasis have many adverse effects. Ozone is an option to enhance the standard treatment due to the wound-healing activity reported in the literature. In this study, we evaluated the efficiency of ozonated sunflower oil as an adjuvant in treating cutaneous lesions caused by Leishmania amazonensis. BALB/c mice were infected with L. amazonensis, and after the lesions appeared, they were treated in four different schedules using the drug treatment with meglumine antimoniate (Glucantime®), with or without ozonated oil. After thirty days of treatment, the lesions' thickness and their parasitic burden, blood leukocytes, production of NO and cytokines from peritoneal macrophages and lymph node cells were analyzed. The group treated with ozonated oil plus meglumine antimoniate showed the best performance, improving the lesion significantly. The parasitic burden showed that ozonated oil enhanced the leishmanicidal activity of the treatment, eliminating the parasites in the lesion. Besides, a decrease in the TNF levels from peritoneal macrophages and blood leukocytes demonstrated an immunomodulatory action of ozone in the ozonated oil-treated animals compared to the untreated group. Thus, ozonated sunflower oil therapy has been shown as an adjuvant in treating Leishmania lesions since this treatment enhanced the leishmanicidal and wound healing effects of meglumine antimoniate.

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C. brachyspora, a widespread dematiaceous fungus, was evaluated in this study to optimize the production of exopolysaccharides (CB-EPS). Optimization was performed using response surface methodology, and the best production yielded 75.05% of total sugar at pH 7.4, with 0.1% urea, after 197 h. The obtained CB-EPS showed typical signals of polysaccharides, which was confirmed by FT-IR and NMR. The HPSEC analysis indicated a polydisperse polymer, showing a non-uniform peak, with an average molar mass (Mw) of 24,470 g/mol. The major monosaccharide was glucose (63.9 Mol%), followed by mannose (19.7 Mol%), and galactose (16.4 Mol%). Methylation analysis encountered derivatives that indicated the presence of a ß-d-glucan and a highly branched glucogalactomannan. CB-EPS was tested on murine macrophages to verify its immunoactivity, and the treated cells were able to produce TNF-α, IL-6, and IL-10. However, the cells did not produce superoxide anions or nitric oxide nor stimulated phagocytosis. The results demonstrated an indirect antimicrobial activity of macrophages by stimulating cytokines, showing another biotech applicability for the exopolysaccharides produced by C. brachyspora.

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OBJECTIVE: This study aimed to evaluate whether ligature-induced periodontitis and rheumatoid arthritis (RA) potentiate the deleterious effects on functional capacity, periodontal and synovial tissues, leukocyte migration, and interleukin 17 (IL-17) levels, and to investigate the repercussions of single Freund's Complete Adjuvant (FCA) injection associated with periodontitis. MATERIALS AND METHODS: Fifty-one male Wistar rats were randomised into six groups: control (CG, n = 8), RA (RAG, n = 9), periodontitis (PG, n = 9), periodontitis and RA (PRAG, n = 9), periodontitis and intradermal injection (PIDG, n = 9), and periodontitis and intra-articular injection (PIAG, n = 7). The animals underwent ligature placement and one or two injections with FCA to induce RA. Motor disability, nociceptive threshold, joint edema, and muscle strength were assessed, and the animals were euthanized on day 30. Synovial fluid, hemimandibles, and knee joints were collected. RESULTS: PRAG showed no reduction of edema or improvement of muscle strength, whereas it showed most significant changes in leukocyte migration, morphological analyses of the synovial membrane (SM), and radiographic and histometric analyses of the jaw. The PIAG showed some alterations, though not permanent. CONCLUSION: Ligature-induced periodontitis and RA induced by two FCA injections accentuated the deleterious effects on functional capacity, leukocyte migration, synovial and periodontal tissues.

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Mycocins are substances that have the potential to affect other sensitive yeasts or microorganisms. Wickerhamomyces anomalus is a yeast that produces mycocins that have great biotechnological potential, being highly competitive in many habitats, as it is adaptable to a wide range of environmental conditions. Thus, they are targets for studies in different areas, including the environment, industry, and medical sciences. Yeasts of the genus Candida are of great importance due to the high frequency with which they colonize and infect the human host. Yeast infections are often difficult to treat due to the acquisition of resistance against antifungals, leading to studies focusing in new treatment alternatives. This work aims to verify the inhibition of Candida albicans isolated from vaginal secretion by mycocins produced by Wickerhamomyces anomalus. Tests were carried out in solid medium and microdilution tests, where mycocins proved to be efficient in inhibiting the growth of C. albicans, hemolysis, and irritation in an organotypic model, which showed that the mycocins produced by W. anomalus are safe and non-irritating. Thus, the results of this work can provide scientific evidence for the application of mycocins in the production of new antifungal alternatives.

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Gout arthritis commonly affects joint regions by deposition of crystals, promoting functional damage mainly during periods of exacerbation. Cryotherapy is a commonly used resource to contain inflammatory processes, however, its use during a gout crisis is not yet well understood. Therefore, the objective was to evaluate the parameters of Wistar rats submitted to an experimental gout model and treated with dual cryotherapy protocol. Twenty-one male Wistar rats were used, separated into three groups: control group (CG), lesion group (LG), and lesion + cryotherapy group (LCG). Gout model induction was through intra-articular injection, with urate crystal solution, in the right knee and cryoimmersion treatment was performed for 20 minutes at a temperature of 5° ± 2°C. Seven evaluations and two treatment moments were performed, and the following parameters were analyzed: joint edema, grip strength, joint disability, motor function, and leukocyte migration through synovial lavage. In the statistical analysis we used SPSS 20.0 with Generalized Linear Models, with least significant difference posttest, always with 5% significance level. The treatment reduced edema, promoted strength recovery, and was effective in reducing total leukocytes in the synovial fluid. No difference was observed between the injured groups for joint disability and motor function. Cryotherapy promoted edema reduction and increased pelvic limb grip strength in Wistar rats during the acute period.

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OBJECTIVES: This study aimed to evaluate the in vitro anti-Leishmania activity of chalcone-rich three extracts (LDR, LHR and LMR) from Lonchocarpus cultratus (Vell.) A.M.G. Azevedo & H.C. Lima against L. amazonensis. Also, the immunomodulatory and antioxidant capacity was assessed. METHODS: Successive extraction with hexane, dichloromethane and methanol were performed to obtain LHR, LDR and LMR extracts from L. cultratus roots, which were characterized by 1H NMR. Promastigotes, amastigotes and peritoneal macrophages were exposed to crescent concentrations of the three extracts, and after incubation, the inhibition rates were determined to both types of cells, and morphological analyses were performed on the parasite. The immunomodulatory activity was determined against stimulated macrophages. KEY FINDINGS: LDR, LHR and LMR inhibited promastigote cell growth (IC50 0.62 ± 0.3, 0.94 ± 0.5 and 1.28 ± 0.73 µg/ml, respectively) and reduced the number of amastigotes inside macrophages (IC50 1.36 ± 0.14, 1.54 ± 0.26 and 4.09 ± 0.88 µg/ml, respectively). The cytotoxicity against murine macrophages resulted in a CC50 of 13.12 ± 1.92, 92.93 ± 9.1 and >300 µg/ml, resulting in high selectivity index to promastigotes and amastigotes. The extracts also inhibited the nitric oxide secretion in RAW 264.7 macrophages. The antioxidant capacity resulted in a higher scavenger LMR ability. CONCLUSIONS: These results suggest that L. cultratus extracts have anti-Leishmania potential, are non-toxic, and immunosuppress macrophages in vitro.

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Trypanosoma cruzi is the agent of Chagas disease, an infection that affects around 8 million people worldwide. The search for new anti-T. cruzi drugs are relevant, mainly because the treatment of this disease is limited to two drugs. The objective of this study was to investigate the trypanocidal and cytotoxic activity and elucidate the chemical profile of extracts from the roots of the Lonchocarpus cultratus. Roots from L. cultratus were submitted to successive extractions with hexane, dichloromethane, and methanol, resulting in LCH, LCD, and LCM extracts, respectively. Characterization of extracts was done using 1H-RMN, 13C-RMN, CC and TLC. Treatment of T. cruzi forms (epimastigotes, trypomastigotes, and amastigotes) with crescent concentrations of LCH, LCD, and LCM was done for 72, 48, and 48 h, respectively. After this, the percentage of inhibition and IC50/LC50 were calculated. Benznidazole was used as a positive control. Murine macrophages were treated with different concentrations of both extracts for 48 h, and after, the cellular viability was determined by the MTT method and CC50 was calculated. The chalcones derricin and lonchocarpine were identified in the hexane extract, and for the first time in the genus Lonchocarpus, the presence of a dihydrolonchocarpine derivative was observed. Other chalcones such as isocordoin and erioschalcone B were detected in the dichloromethane extract. The dichloromethane extract showed higher activity against all tested forms of T. cruzi than the other two extracts, with IC50 values of 10.98, 2.42, and 0.83 µg/mL, respectively; these values are very close to those of benznidazole. Although the dichloromethane extract presented a cytotoxic effect against mammalian cells, it showed selectivity against amastigotes. The methanolic extract showed the lowest anti-T. cruzi activity but was non-toxic to peritoneal murine macrophages. Thus, the genus Lonchocarpus had demonstrated in the past action against epimastigotes forms of T. cruzi but is the first time that the activity against infective forms is showed, which leading to further studies with in vivo tests.

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The current treatment of leishmaniasis presents some problems, such as cell toxicity, parenteral route, and time of treatment. Ozone emerges as an option to accelerate the standard treatment due to the immunomodulatory, antioxidant, and wound healing activity reported in the literature. This work aimed to evaluate the efficacy of aqueous ozone as an adjuvant to the standard treatment of cutaneous lesions caused by Leishmania amazonensis in an experimental model. For in vivo experiments, mice were randomly distributed in 6 groups, which were infected with L. amazonensis and treated in five different schedules using the standard treatment with Glucantime® with or without aqueous ozone. After the last day of treatment, the animals were euthanized and were analyzed: the thickness of lesions; collagen deposition, the parasitic burden of the lesions; blood leukocyte number; NO; and cytokine dosages and arginase activity from peritoneal macrophages. All treated groups showed a decrease in the lesion, but with a significative deposition of collagen in lesions with local ozone treatment. The parasite burden showed that ozone enhanced the leishmanicidal activity of the reference drug. The reduction of NO production and blood leukocyte count and increases in the arginase activity showed an immunomodulatory activity of ozone in the treated animals. Thus, ozone therapy has been shown to work as an adjuvant in the treatment of Leishmania lesions, enhancing leishmanicidal and wound healing activity of standard treatment.

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Rheumatoid arthritis denotes hyperplasia and intense inflammatory process. Treatment involves exercise protocols and use of resources such as low-level laser therapy (LLLT) to modulate the inflammatory process and maintain physical capacity. The objective was to investigate whether treatment with LLLT and exercise modulates the inflammatory process and peripheral functionality. Sample is composed of 128 male rats, separated into three groups, control, treated and untreated, in the acute and chronic period of the disease with 64 animals in each group, divided into 8 subgroups with n = 8. The animals were immunized with injection at the base of the tail and 7 days after intra-articular injection with complete Freund adjuvant (CFA) for lesion groups, and saline solution for the controls. Joint disability was evaluated by PET (paw elevation time) and joint edema and treated with LLLT and/or resisted stair climbing exercise. Normality Shapiro-Wilk test, ANOVA mixed for the functional analyses, and ANOVA one-way for the variables of cellular differentiation, with Bonferroni post hoc, p = 5% were used. For the evaluations of joint disability and nociception, there was a significant difference between the evaluations, the groups, and the interaction groups-evaluations. The treated groups showed recovery of functionality; it is still verified that laser therapy increased the nociceptive threshold of the chronic inflammatory period, and the exercise reflected in significant functional improvement and modulation of the inflammatory process both in the acute and chronic periods. LLLT, resistance exercise, or a combination of treatments had a positive effect on the modulation of the inflammatory process, reducing the migration of leukocytes, in addition to helping the return of peripheral functionality by reducing joint disability in a model of rheumatoid arthritis induced by CFA in rats.

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