Adjuvant ArtinM favored the host immunity against Cryptococcus gattii infection in C57BL/6 mice.

Aim: Cryptococcus gattii causes a severe fungal infection with high mortality rate among immunosuppressed and immunocompetent individuals. Due to limitation of current antifungal treatment, new immunotherapeutic approaches are explored. Methods: This study investigated an immunization strategy utilizing heat-inactivated C. gattii with ArtinM as an adjuvant. C57BL/6 mice were intranasally immunized with heat-killed C. gattii and ArtinM was administrated either before immunization or along with HK-C. gattii. Mice were infected with C. gattii and the efficacy of the immunization protocol was evaluated. Results: Mice that received ArtinM exhibited increased levels of IL-10 and relative expression of IL-23 in the lungs, reduced fungal burden and preserved tissue integrity post-infection. Conclusion: Adjuvant ArtinM improved immunization against C. gattii infection in C57BL/6 mice.

Cryptococcus gattii is a fungus that can make lungs sick. Right now, there are no good treatments for it, so scientists are trying to find new ways to fight it. In a recent study, they tested a type of immunotherapy called ArtinM to see if it could help. When they gave ArtinM to mice, the mice got healthier and had less fungus in their lungs. This means ArtinM might be able to help fight this fungus.

Correction: "Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

[This corrects the article DOI: 10.1371/journal.pone.0284248.].

"Acute kidney injury in critically ill patients with COVID-19: The AKICOV multicenter study in Catalonia".

This study describes the incidence, evolution and prognosis of acute kidney injury (AKI) in critical COVID-19 during the first pandemic wave. We performed a prospective, observational, multicenter study of confirmed COVID-19 patients admitted to 19 intensive care units (ICUs) in Catalonia (Spain). Data regarding demographics, comorbidities, drug and medical treatment, physiological and laboratory results, AKI development, need for renal replacement therapy (RRT) and clinical outcomes were collected. Descriptive statistics and logistic regression analysis for AKI development and mortality were used. A total of 1,642 patients were enrolled (mean age 63 (15.95) years, 67.5% male). Mechanical ventilation (MV) was required for 80.8% and 64.4% of these patients, who were in prone position, while 67.7% received vasopressors. AKI at ICU admission was 28.4% and increased to 40.1% during ICU stay. A total of 172 (10.9%) patients required RRT, which represents 27.8% of the patients who developed AKI. AKI was more frequent in severe acute respiratory distress syndrome (ARDS) ARDS patients (68% vs 53.6%, p<0.001) and in MV patients (91.9% vs 77.7%, p<0.001), who required the prone position more frequently (74.8 vs 61%, p<0.001) and developed more infections. ICU and hospital mortality were increased in AKI patients (48.2% vs 17.7% and 51.1% vs 19%, p <0.001) respectively). AKI was an independent factor associated with mortality (IC 1.587-3.190). Mortality was higher in AKI patients who required RRT (55.8% vs 48.2%, p <0.04). Conclusions There is a high incidence of AKI in critically ill patients with COVID-19 disease and it is associated with higher mortality, increased organ failure, nosocomial infections and prolonged ICU stay.

Adjuvant Pam3CSk4 does not improve the immunization against Cryptococcus gattii infection in C57BL/6 mice.

Background: Cryptococcosis is a relevant invasive fungal infection that affects immunocompromised and immunocompetent individuals when caused by Cryptococcus gattii. Host innate and adaptive immune responses can be subverted by C. gattii, that blocks the differentiation of T helper (Th) 1 and Th17 cells, which are involved in the protection against cryptococcosis. Moreover, the macrophage polarization is modulated by C. gattii infection that requires a balance in the macrophage subsets to control the C. gattii infection. Toll-like receptor (TLR) 2 agonists are important immunomodulators favoring a pro-inflammatory response with potential fungicidal activity, and TLR2 agonists have been used as adjuvants in vaccines against infections caused by bacteria or viruses. Therefore, this work aimed to evaluate the immunomodulatory effect of the tripalmitoyl lipopeptide S-glycerol cysteine (Pam3CSK4 or P3C4), a TLR2 agonist, as an adjuvant in the vaccination against C. gattii infection. Methods and Results: C57BL/6 mice were immunized with 2 × 107 inactivated yeasts of C. gattii via intranasal route on day 1, 14 and 28 (Immunized group). Immunization was associated with 1µg or 10µg of adjuvant P3C4 (Immunized+P3C4-1µg or Immunized+P3C4-10 µg), followed by C. gattii infection on day 42 after the immunization protocol. Immunized+P3C4-1 µg group had reduced levels of IgG1, IgG2a and IgA and no significant difference in the IgG and IgM anti-GXM antibody titer was detected, compared to the Immunized group. High levels of IL-17 and IL-1ß in lung tissue of mice from the Immunized+P3C4-1µg group did not promote a predominance of Th17 cells, in contrast, the frequency of TLR2+ cells was increased in immunized mice that received 1 µg of P3C4. The reduction in the relative expression of T-bet and high levels of Foxp3 detected in the lungs of the Immunized+P3C4-1µg group suggest a prevalence of regulatory T cells in the tissue, which did not contribute to the control of C. gattii infection. The immunization protocol associated with 10 µg of adjuvant P3C4 induced high levels of IL-17 in the lung tissue, whereas the levels of pro-inflammatory cytokines were downregulated. To evaluate the effect of adjuvant P3C4 in the control of C. gattii infection, quantification of the fungal burden in the lungs was performed by the CFU assay, and the groups with adjuvant P3C4 showed a pulmonary C. gattii burden that was not significantly altered when compared with the immunized group. The mice that received 1 µg of adjuvant P3C4 had a lower percentage of inflammatory infiltrate in the lungs. Conclusion: The immunomodulatory effect of P3C4, associated with the immunization protocol, plays an imbalance between pro- and anti-inflammatory response in the lungs that did not favor a protection against C. gattii infection, which is related to the immune response characterized by a suppressive/regulatory profile in the pulmonary microenvironment after C. gattii infection.

Molecular analysis of the prevalence of Acinetobacter baumannii in hospitals and the surrounding environments: a cross-sectional study

Acinetobacter baumannii is widely recognized in clinical environments due to its infectious capacity, antimicrobial adaptability, and lethality. Analyzing the prevalence of this agent in intra- and extra-hospital environments may reveal target indicators for appropriate management interventions. In this observational cross-sectional study, we evaluated the prevalence of A. baumannii within hospitals with intensive care units and in their external surroundings in a macro-health region of Brazil. Samples of Columba livia (pigeon) droppings from the external environment of four hospitals (n = 40), from floor surfaces (n = 20), and door handles (n = 20) of different hospital wards were collected based on random sampling, all of which were evaluated for the presence of A. baumannii using polymerase chain reactions (PCR). The sensitivity and specificity of the technique was verified after the collected samples were contaminated with clinical samples positive for A. baumannii. We detected a significantly higher A. baumannii prevalence (87.50%, CI = 71.29­100.00) in samples collected within the hospital environment compared with those obtained from the external environment (12.50%, CI = 0.00­28. 71) (p = 0.003). In addition, samples collected from floor surfaces contained bacterial densities (181.3 ± 11.58) that exceeded those in environmental (93.32 ± 1.56) and door handle (142.70 ± 17.14) samples by 94% and 78.71%, respectively. The findings of this study will enhance our understanding of the spatial distribution of A. baumannii and additionally, validate the efficiency of PCR for diagnosis of this infectious agent.

In vitro antifungal activity of Morinda citrifolia (noni) extract against Candida albicans.

INTRODUCTION: Candida albicans is the main agent of the most common fungal infection, Candidiasis. It is an opportunistic and dangerous pathogen, especially in immunosuppressed patients. The biological properties of Morinda citrifolia (noni) make it a potent antifungal. In this study, antifungal effect of M. citrifolia was evaluated to verify its effect on human cells. METHODOLOGY: Extract of M. citrifolia was used against strains of C. albicans (cEC 1291). Glucose consumption in C. albicans biofilm was determined at different concentrations of M. citrifolia, and germ tube formation was evaluated in the presence and absence of M. citrifolia. Fungicidal activity was determined by the kinetics of fungal cell death. THP-1 and HeLa cells were used for cell viability and apoptosis, and cell proliferation assays, respectively. RESULTS: Cells treated with M. citrifolia maintained higher concentration of glucose than the control group (p < 0.05). Germ tube formation was inhibited in cells treated with M. citrifolia (p < 0.05). M. citrifolia exerted a cytotoxic effect on C. albicans cells with 99.99% lethality after 6.82 h (1:1 and 1:2), and reduced the viability of THP-1 cells by 25% and 67% after 12 and 36 h, respectively. Annexin V expression in THP-1 increased in groups that received higher concentrations of M. citrifolia (p < 0.05), reducing the proliferation of THP-1 and HeLa cells (2.8-fold). A greater cytotoxic effect was observed in fungal cells. CONCLUSIONS: These results indicate that M. citrifolia exerts biological activity against C. albicans and reduces the viability and proliferation of human cells.

Predicting Blood Parasite Load and Influence of Expression of iNOS on the Effect Size of Clinical Laboratory Parameters in Acute Trypanosoma cruzi Infection With Different Inoculum Concentrations in C57BL/6 Mice.

In Chagas disease, the initial responses of phagocyte-mediated innate immunity are strongly associated with the control of Trypanosoma cruzi and are mediated by various signaling pathways, including the inducible nitric oxide synthetase (iNOS) pathway. The clinical and laboratory manifestations of Chagas disease depend on the parasite-host relationship, i.e., the responsive capacity of the host immune system and the immunogenicity of the parasite. Here, we evaluated effect sizes in clinical and laboratory parameters mediated by acute infection with different concentrations of T. cruzi inoculum in mice immunosuppressed via iNOS pathway inactivation. Infection was induced in C57BL/6 wild-type and iNOS-/- mice with the "Y" strain of T. cruzi at three inoculum concentrations (3 × 102, 3 × 103, and 3 × 104). Parasitemia and mortality in both mouse strains were monitored. Immunohistochemistry was performed to quantify amastigotes in cardiac tissues and cardiac musculature cells. Biochemical parameters, such as blood urea nitrogen, sodium, albumin, and globulin concentrations, among others, were measured, and cytokine concentrations were also measured. Effect sizes were determined by the eta squared formula. Compared with that in wild-type animals, mice with an absence of iNOS expression demonstrated a greater parasite load, with earlier infection and a delayed parasitemia peak. Inoculum concentration was positively related to death in the immunosuppressed subgroup. Nineteen parameters (hematological, biochemical, cytokine-related, and histopathological) in the immunocompetent subgroup and four in the immunosuppressed subgroup were associated with parasitemia. Parasitemia, biochemical parameters, and hematological parameters were found to be predictors in the knockout group. The impact of effect sizes on the markers evaluated based on T. cruzi inoculum concentration was notably high in the immunocompetent group (Cohen's d = 88.50%; p <.001). These findings contribute to the understanding of physiopathogenic mechanisms underlying T. cruzi infection and also indicate the influence of the concentration of T. cruzi during infection and the immunosuppression through the iNOS pathway in clinical laboratory heterogeneity reported in acute Chagas disease.

Adjuvant Curdlan Contributes to Immunization against Cryptococcus gattii Infection in a Mouse Strain-Specific Manner.

The low efficacy and side effects associated with antifungal agents have highlighted the importance of developing immunotherapeutic approaches to treat Cryptococcus gattii infection. We developed an immunization strategy that uses selective Dectin-1 agonist as an adjuvant. BALB/c or C57BL/6 mice received curdlan or ß-glucan peptide (BGP) before immunization with heat-killed C. gattii, and the mice were infected with viable C. gattii on day 14 post immunization and euthanized 14 days after infection. Adjuvant curdlan restored pulmonary tumor necrosis factor- α (TNF-α) levels, as induced by immunization with heat-killed C. gattii. The average area and relative frequency of C. gattii titan cells in the lungs of curdlan-treated BALB/c mice were reduced. However, this did not reduce the pulmonary fungal burden or decrease the i0,nflammatory infiltrate in the pulmonary parenchyma of BALB/c mice. Conversely, adjuvant curdlan induced high levels of interferon-γ (IFN-γ) and interleukin (IL)-10 and decreased the C. gattii burden in the lungs of C57BL/6 mice, which was not replicated in ß-glucan peptide-treated mice. The adjuvant curdlan favors the control of C. gattii infection depending on the immune response profile of the mouse strain. This study will have implications for developing new immunotherapeutic approaches to treat C. gattii infection.

Metabolomic Evaluation of Chronic Periodontal Disease in Older Adults.

Periodontal disease is an infectious inflammatory disease related to the destruction of supporting tissues of the teeth, leading to a functional loss of the teeth. Inflammatory molecules present in the exudate are catalyzed and form different metabolites that can be identified and quantified. Thus, we evaluated the inflammatory exudate present in crevicular fluid to identify metabolic biological markers for diagnosing chronic periodontal disease in older adults. Research participants were selected from long-term institutions in Brazil. Participants were individuals aged 65 years or older, healthy, or with chronic periodontal disease. Gas chromatography/mass spectrometry was used to evaluate potential biomarkers in 120 crevicular fluid samples. We identified 969 metabolites in the individuals. Of these, 15 metabolites showed a variable importance with projection score > 1 and were associated with periodontal disease. Further analysis showed that among the 15 metabolites, two (5-aminovaleric acid and serine, 3TMS derivative) were found at higher concentrations in the crevicular fluid, indicating their potential diagnostic power for periodontal disease in older adults. Our findings indicated that some metabolites are present at high concentrations in the crevicular fluid in older adults with periodontal disease and can be used as biomarkers of periodontal disease.

Peroxisome Proliferator-Activated Receptor Alpha Mediates the Beneficial Effects of Atorvastatin in Experimental Colitis.

The current therapeutic options for Inflammatory Bowel Diseases (IBD) are limited. Even using common anti-inflammatory, immunosuppressive or biological therapies, many patients become unresponsive to the treatments, immunosuppressed or unable to restrain secondary infections. Statins are cholesterol-lowering drugs with non-canonical anti-inflammatory properties, whose underlying mechanisms of action still remain poorly understood. Here, we described that in vitro atorvastatin (ATO) treatment was not toxic to splenocytes, constrained cell proliferation and modulated IL-6 and IL-10 production in a dose-dependent manner. Mice exposed to dextran sulfate sodium (DSS) for colitis induction and treated with ATO shifted their immune response from Th17 towards Th2, improved the clinical and histological aspects of intestinal inflammation and reduced the number of circulating leukocytes. Both experimental and in silico analyses revealed that PPAR-α expression is reduced in experimental colitis, which was reversed by ATO treatment. While IBD patients also downregulate PPAR-α expression, the responsiveness to biological therapy relied on the restoration of PPAR-α levels. Indeed, the in vitro and in vivo effects induced by ATO treatment were abrogated in Ppara-/- mice or leukocytes. In conclusion, the beneficial effects of ATO in colitis are dependent on PPAR-α, which could also be a potential predictive biomarker of therapy responsiveness in IBD.

Corrigendum to "scFv against HSP60 of Strongyloides sp. and Its Application in the Evaluation of Parasite Frequency in the Elderly".

[This corrects the article DOI: 10.1155/2020/4086929.].

Administration of artinm lectin reduces the severity of the acute phase infection with Trypanosoma cruzi.

The acute phase of experimental Trypanosoma cruzi infection is associated with a strong inflammatory reaction, physiological changes, amastigote nests in tissues, and hematological alterations. ArtinM, a lectin extracted from Artocarpus heterophyllus seeds, is a homotetramer exhibiting immunomodulatory properties that promotes Th1 immune responses against intracellular pathogens, including the induction of neutrophil migration and increase in IL-12 production. This study aimed to evaluate the effects of ArtinM on experimental Chagas disease in mice. We evaluated mouse survival curves, parasitemia, hematological parameters including quantification of inflammatory infiltrates, and amastigote nests in cardiac tissue during infection. The results showed a reduced number of parasites in the blood, an increase in animal survival, improvements in hematological parameters, and decrease in inflammatory infiltrates and amastigote nests in the group treated with ArtinM. Collectively, these data suggest that the administration of ArtinM can lower the number of parasites in peak parasitemia caused by the Colombian strain of T. cruzi and can increase survival of infected mice. The observed reduction in cardiac tissue injury may be due to fewer T. cruzi amastigote nests and lower levels of inflammatory infiltrates. This study highlights the need for further investigation into the use of ArtinM as a potential alternative therapeutic for treating Chagas disease.

Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.

scFv against HSP60 of Strongyloides sp. and Its Application in the Evaluation of Parasite Frequency in the Elderly.

The present study is aimed at evaluating serological method using scFv anti-Strongyloides sp. and reporting the frequencies of the results with conventional parasitological technique (faeces) in elderly individuals. Among 112 elderly individuals (≥60 years of age), 14.28% were positive for at least one enteroparasite, with one individual positive for S. stercoralis. Sera were evaluated for the presence of anti-Strongyloides sp. antibodies using total or detergent fraction extracts of Strongyloides venezuelensis, which presented positivity rates of 19.64% and 10.71%, respectively. An anti-HSP60 single-chain variable fragment from Strongyloides sp. was used to detect parasite antigens, with 5.36% (6 individuals) of ELISA-positive individuals returning a positive result. While the serological test indicates previous or recent infection and may be limited by antigen purification, the anti-HSP60 method reflects the presence of Strongyloides sp. immune complexes and exhibits greater sensitivity and specificity. Our results demonstrate the variable occurrence of enteroparasites in elderly individuals residing in long-term nursing homes and validate a novel epidemiological tool to describe infection cases by Strongyloides sp.

Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection" [Cytokine: X 2 (2020) 100034].

[This corrects the article DOI: 10.1016/j.cytox.2020.100034.].

Interleukin-6, tumor necrosis factor-α, C-reactive protein, and hematological parameters in experimental periodontal disease after ß-adrenergic blockade.

BACKGROUND: Changes in the levels of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) observed during periodontal disease were linked with vascular manifestations. Recent studies showed that the beta-blocker propranolol reduces the pathological parameters associated with certain molecules at sites of bone injury. Hence, in this study, we evaluated the activity of propranolol on hematological parameters and systemic concentrations of inflammatory proteins in a model of experimental periodontitis. MATERIALS AND METHODS: Periodontal disease was induced in rats. After euthanasia, the number of inflammatory cells in each rat was quantified using histopathological assays. In addition, hematological parameters were quantitated using automated analysers, cytokine levels were determined using an enzyme-linked immunosorbent assay, and CRP levels were determined using a high-sensitivity immunoturbidimetric assay. RESULTS: Low doses of propranolol suppressed the systemic production of CRP, TNF-α, and IL-6; however, the hematological parameters were not affected. CONCLUSIONS: ß-adrenergic activation indirectly contributes to the pattern of systemic inflammatory molecules observed in periodontal disease. These molecules may initiate cardiovascular diseases as a consequence of periodontitis.

Absence of NOD2 receptor predisposes to intestinal inflammation by a deregulation in the immune response in hosts that are unable to control gut dysbiosis.

Mutations in NOD2 predisposes to Inflammatory Bowel Diseases. Therefore, we evaluated the role of this innate receptor in the modulation of immunity in face of host microbiota changes. NOD2-/- mice presented higher susceptibility to experimental colitis than WT, with increased CD4 and CD8 T lymphocytes in the spleen. NOD2 deficiency also led to reduced Th17-related cytokines in the colon, with overall augmented IFN-γ in the gut and spleen. Nonetheless, there was increased frequency of CD4+IL-4+ cells in the mesenteric lymph nodes besides elevated CTLA-4 and FoxP3 regulatory markers in the spleen of NOD2-/- mice, although it did not result in more efficient control of gut inflammation. Indeed, these animals also had augmented IL-1ß and IL-5 in the peritoneum, indicating that this receptor may be important to control bacteria translocation too. Microbiota exchanging between cohoused WT and NOD2-/- mice led to colitis worsening in the absence of the receptor, while antibiotic therapy in WT mice abrogated this effect. Then, not only the genetic mutation confers increased susceptibility to inflammation, but it is also influenced by the microbiota harbored by the host. Finally, NOD2-/- mice are more prone to intestinal inflammation due to deregulated immune response and increased susceptibility to colitogenic bacteria.

Macrophage Migration Inhibitory Factor (MIF) Prevents Maternal Death, but Contributes to Poor Fetal Outcome During Congenital Toxoplasmosis.

Migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important roles in physiology, pathology, immunology and parasitology, including the control of infection by protozoa parasites such as Toxoplasma gondii. As the MIF function in congenital toxoplasmosis is not fully elucidated yet, the present study brings new insights for T. gondii infection in the absence of MIF based on pregnant C57BL/6MIF-/- mouse models. Pregnant C57BL/6MIF-/- and C57BL/6WT mice were infected with 05 cysts of T. gondii (ME49 strain) on the first day of pregnancy (dop) and were euthanized at 8 dop. Non-pregnant and non-infected females were used as control. Our results demonstrated that MIF-/- mice have more accentuated change in body weight and succumbed to infection first than their WT counterparts. Otherwise, pregnancy outcome was less destructive in MIF-/- mice compared to WT ones, and the former had an increase in the mast cell recruitment and IDO expression and consequently presented less inflammatory cytokine production. Also, MIF receptor (CD74) was upregulated in MIF-/- mice, indicating that a compensatory mechanism may be required in this model of study. The global absence of MIF was associated with attenuation of pathology in congenital toxoplasmosis, but resulted in female death probably because of uncontrolled infection. Altogether, ours results demonstrated that part of the immune response that protects a pregnant female from T. gondii infection, favors fetal damage.

Rheumatoid arthritis-increased gene expressions in muscle atrophy are restored back to control as a response to acute resistance exercise / Estímulo agudo de musculação promove regulação de genes alterados pela atrofi a muscular

This study had as objective to analyze the acute eff ects of resistance exercise (RE) on the mRNA levels of the following genes (MyoD, myogenin, IGF-1, atrogin-1, MuRF-1, and myostatin) in rheumatoid arthritis (experimental arthritis). Therefore, 26 females rats were randomly allocated into four groups, control (CT, n=7), exercise (Ex, n=6), rheumatoid arthritis (RA, n=6) and RA with exercise (RAEx, n=7). Met-BSA was injected into the tibiotarsal joint in the RA and RAEx groups. After 15 days from injection, the animals were submitted to an acute bout of RE and six hours post protocol the animals were euthanized. We evaluated the joint thickness, infl ammation score, cross-sectional area (CSA) of gastrocnemius muscle fi bers and mRNA expression of the IGF-1, MyoD, myogenin, myostatin, MuRF-1, atrogin-1 and GAPDH. It was observed that the joint thickness and score strongly increased in arthritic rats (p <0.001) while the CSA decreased (p ≤ 0.05). Increased mRNA levels of IGF-1 (2.0 fold), myostatin (4.5 fold), atrogin-1 (2.5 fold), MyoD (3.7-fold) and myogenin (5 fold) were observed in muscle of arthritic rats. The mRNA expression of myostatin, atrogin-1, MyoD and myogenin decreased in the RAEx group. In this way, we can conclude that experimental arthritis-increased gene expressions in muscle atrophy myostatin, atrogin-1, MyoD and myogenin) are restored back to control as a response to acute RE....(AU)

O presente estudo teve como objetivo analisar o efeito agudo do Exercício com pesos sobre os níves de mRNA de genes envolvidos no anabolismo ou catabolismo muscular em um modelo experimental de Artrite Reumatóide. Para tanto, 26 ratas fêmeas foram randomicamente alocadas em quatro grupos, controle (CT, n=7), Exercício (Ex, n=6), Artrite Reumatóide (AR, n=6) e Artrite Reumatóide com exercício (AREx, n=7). Uma substância contendo Albumina bovina metilada foi injetada na articulação tíbio-tarsal nos grupos AR e AREx para indução da Artrite Reumatóide. Após 15 dias da injeção, os animais foram submetidos a um estímulo agudo de treinamento com pesos e 6 horas após o exercício os animais foram eutanasiados. Nós avaliamos a espessura da articulação, escore de infl amação, a área de secção transversa (AST) das fi bras do músculo Gastrocnêmio e a mRNA de IGF-1, MyoD, Myogenina (genes envolvidos no anabolismo muscular), e MuRF-1, atrogina-1 (genes envolvidos no catabolismo muscular), além do gene controle , GAPDH. Foi observado que a espessura articular e o escore de infl amação aumentaram fortemente nas ratas induzidas a Artrite Reumatóide (p <0,001), enquanto a AST reduziu (p ≤ 0,05). Um aumento nos níveis de mRNA de IGF-1 (2,0 vezes), miostatina (4,5 vezes), atrogina-1 (2,5 vezes), MyoD (3,7 vezes) e miogenina (5 vezes) foi observado no músculo das ratas induzidas a Artrite Reumatóide. mRNA de miostatina, atrogina-1, MyoD e miogenina reduziu no grupo RAEx. Desta forma, podemos concluir, que o modelo experimental de Artrite Reumatóide induziu um aumento da expressão de genes durante a atrofi a muscular (myostatin, atrogin-1, MyoD and myogenin) e que estas alterações foram reguladas pelo Exercício com peso....(AU)