RESUMEN
INTRODUCTION: Chagas disease is caused by the protozoan Trypanosoma cruzi and is clinically divided into acute and chronic phases. Chronic Chagas cardiomyopathy is the most studied manifestation of the disease. Vitamin D deficiency has been suggested as a risk factor for cardiovascular disease. No studies demonstrate the action of this hormone in the cells of patients with chronic Chagas heart disease. OBJECTIVE: To evaluate the in vitro immunomodulatory effect of vitamin D on peripheral blood mononuclear cells of patients with the different chronic clinical forms of Chagas disease. Evaluating vitamin D's in vitro effect on blood cells by producing cytokines. METHODS: Thirteen patients of the undetermined form (IND), 13 of the mild cardiac form (CARD1) and 14 of the severe cardiac form (CARD2) of Chagas disease, and 12 with idiopathic heart disease (CARDid) were included. The cells obtained from peripheral blood were treated in vitro with vitamin D (1 × 10-7 M) for 24 h and cytokines were dosed in the culture supernatant. RESULTS: Although it was not possible to demonstrate statistically significant differences between the groups studied, our data showed that the cells treated with vitamin D modify (p < .05) the production of interferon-γ (IFN-γ) (decrease in IND), tumor necrosis factor-α (TNF-α) (decreased in CARD1 and CARDid), interleukin (IL)-6 (increased in all groups), and IL-10 (decreased in CARD1, CARD2, and CARDid) when compared to untreated cells. CONCLUSION: In vitro treatment with vitamin D distinctly modulated the production of cytokines by mononuclear cells of peripheral blood among patients with chronic and indeterminate cardiac clinical forms of Chagas disease.
Asunto(s)
Citocinas , Leucocitos Mononucleares , Vitamina D , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Vitamina D/farmacología , Masculino , Femenino , Persona de Mediana Edad , Citocinas/metabolismo , Adulto , Cardiomiopatía Chagásica/tratamiento farmacológico , Cardiomiopatía Chagásica/inmunología , Enfermedad Crónica , Trypanosoma cruzi/inmunología , Trypanosoma cruzi/efectos de los fármacos , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/parasitología , Anciano , Células CultivadasRESUMEN
BACKGROUND: Coronavirus disease 2019 originated in China and swiftly spread worldwide, posing a significant threat to public health. Caused by SARS-CoV-2, it manifests as a flu-like illness that can escalate to Acute Respiratory Distress Syndrome, potentially resulting in fatalities. In countries where HIV/Leishmania infantum is endemic, the occurrence of concurrent SARS-CoV-2/HIV/Leishmania infantum infections is a reality, prompting inquiries into appropriate clinical management. CASE PRESENTATION: We present the case of a 48-year-old woman who was hospitalized for 36 days across three different hospitals in the state of Pernambuco, Brazil. She was diagnosed with SARS-CoV-2/HIV/L. infantum coinfection. The patient exhibited severe COVID-19 symptoms, including fever, productive cough, and dyspnea. Throughout her hospitalization, she experienced oxygen saturation levels of ≤ 93%, along with fluctuations in blood pressure, respiratory rate, and heart rate. Her blood tests revealed lymphopenia, leukopenia, and neutropenia, while laboratory results indicated abnormal levels of d-dimer, AST, ALT, lactate dehydrogenase, ferritin, and C-reactive protein. A computed tomography scan revealed 75% involvement of the lung parenchyma with patchy ground-glass opacities. CONCLUSION: Against all odds, the patient was discharged. The leukopenia associated with HIV/L. infantum may have played a decisive role. Further studies are necessary to better understand diagnostic strategies and clinical management measures for HIV/L. infantum coinfected patients who are susceptible to SARS-CoV-2 infection.
Asunto(s)
COVID-19 , Coinfección , Infecciones por VIH , Leishmania infantum , SARS-CoV-2 , Humanos , Femenino , COVID-19/complicaciones , Persona de Mediana Edad , Coinfección/virología , Coinfección/parasitología , Infecciones por VIH/complicaciones , Leishmania infantum/aislamiento & purificación , Leishmaniasis Visceral/tratamiento farmacológico , Leishmaniasis Visceral/complicaciones , Leishmaniasis Visceral/diagnóstico , BrasilRESUMEN
Tadalafil, a potent phosphodiesterase inhibitor 5 (PDE-5), is commonly used for the management of erectile dysfunction. However, its therapeutic potential extends beyond this indication. This study aimed to investigate the impact of tadalafil on the recovery of testicular parenchyma in male Wistar rats exposed to testicular thermal stress. Fifty-four Wistar rats were subjected to testicular thermal stress and randomly assigned to receive either tadalafil treatment (TAD) or no treatment (control). TAD was administered intraperitoneally at a dose of either 0.9 mg/kg or 1.8 mg/kg. Biometric parameters, histopathological assessment of the testis, serum testosterone levels, oxidative stress, and interleukin levels were evaluated on days 7, 15, and 30 after thermal shock. The animals were euthanized at the end of each experimental period, and samples were collected. TAD treatment maintained testicular weight and reduced the testicular degenerative process up to day 7 post-injury. However, despite TAD therapy, serum testosterone levels were decreased in the treated groups at days 7 and 15 post-thermal stress. TAD also decreased TNF-α and NO levels at different doses but had no effect on IL-6. The treatment with TAD after heat shock demonstrated anti-inflammatory and antioxidant properties but did not prevent the aggravation of testicular lesions in subsequent periods, even with the systematic reduction in TNF-α and NO levels. Therefore, this selective PDE-5 inhibitor, at the dosages used, did not have a positive impact on testosterone levels during the post-thermal stress period, which could compromise the resumption of the spermatogenic process.
RESUMEN
Chagas disease (CD) is caused by the hemoflagellate protozoan Trypanosoma cruzi. The control of the infection depends of the innate and acquired immune response of host. Moreover, CD plays a significant role in the immune response, and, in this context, microalgae can be an interesting alternative due to its immunomodulatory and trypanocidal effects. This study aimed to evaluate, in vitro, immunomodulatory potentials of the aqueous extracts of Chlorella vulgaris and Tetradesmus obliquus. Both microalgae extracts (ME) were obtained by sonication, and the selectivity index (SI) was determined by assays of inhibitory concentration (IC50) in T. cruzi trypomastigotes cells; as well as the cytotoxic concentrations (CC50) in human peripheral mononuclear cells (PBMC). The immune response was evaluated in T. cruzi-infected PBMC using the IC50 value. ME led to inhibition of T. cruzi trypomastigotes after 24 h of treatment, in which the IC50 values were 112.1 µg/ml to C. vulgaris and 15.8 µg ml-1 to T. obliquus. On the other hand, C. vulgaris did not affect the viability of PBMCs in concentrations up to 1000 µg ml-1, while T. obliquus was non-toxic to PBMCs in concentrations up to 253.44 µg ml-1. In addition, T. obliquus displayed a higher SI against T. cruzi (SI = 16.8), when compared with C. vulgaris (SI = 8.9). C. vulgaris decreased the levels of IFN, indicating a reduction of the inflammatory process; while T. obliquus displayed an interesting immunomodulatory effect, since discretely increased the levels of TNF and stimulated the production of the anti-inflammatory cytokine IL-10. This study confirms that ME are effective against T. cruzi trypomastigotes, and may able to control the parasitemia and preventing the progress of CD while regulating the inflammatory process.
Asunto(s)
Enfermedad de Chagas , Leucocitos Mononucleares , Microalgas , Trypanosoma cruzi , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/inmunología , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Enfermedad de Chagas/inmunología , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Microalgas/química , Extractos Vegetales/farmacología , Citocinas/metabolismoRESUMEN
Trypanosoma cruzi is a parasite with a high capacity to adapt to the host. Animal models have already demonstrated that the tropism of this parasite occurs not only in cardiac/digestive tissues but also in adipose tissue (AT). That said, the consequences ofT. cruziinfection for AT and the implications of treatment with Benzonidazole in this tissue are under discussion. Here, we tested the hypothesis that T. cruzi infection in adipose tissue upon treatment with Benzonidazole (Bz) and the interaction of mononuclear immune cells (PBMC) influences the relative expression of ACAT1, FASN, and PNPLA2 genes. Thus, stem cells derived from adipose tissue (ADSC) after adipogenic differentiation were indirectly cultivated with PBMC after infection with the T. cruzi Y strain and treatment with Bz. We use the TcSAT-IAM system and RT-qPCR to evaluate the parasite load and the relative quantification (ΔCt) of the ACAT1, FASN, and PNPLA2 genes. Our results demonstrate that treatment with Bz did not reduce adipocyte infection in the presence (p-value: 0.5796) or absence (p-value: 0.1854) of cultivation with PBMC. In addition, even though there is no statistical difference when compared to the control group (AT), T. cruzi induces the FASN expression (Rq: 14.00). However, treatment with Bz in AT suggests the increases of PNPLA2 expression levels (Rq: 12.58), even in the absence of T. cruzi infection. During indirect cultivation with PBMC, T. cruzi smooths the expression of PNPLA2 (Rq: 0.824) and instigates the expression of ACAT1 (Rq: 1.632) and FASN (Rq: 1.394). Furthermore, the treatment with Bz during infection induces PNPLA2 expression (Rq: 1.871), maintaining FASN expression levels (Rq: 1.334). Given this, our results indicate that treatment with Benzonidazole did not decrease T. cruzi infection in adipose tissue. However, treating the adipocyte cells with Bz during the interaction with PBMC cells influences the lipid pathways scenario, inducing lipolytic metabolism through the expression of PNPLA2.
Asunto(s)
Aciltransferasas , Tejido Adiposo , Acido Graso Sintasa Tipo I , Leucocitos Mononucleares , Lipasa , Trypanosoma cruzi , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/parasitología , Tejido Adiposo/parasitología , Tejido Adiposo/metabolismo , Trypanosoma cruzi/efectos de los fármacos , Trypanosoma cruzi/genética , Lipasa/genética , Lipasa/metabolismo , Acido Graso Sintasa Tipo I/genética , Acido Graso Sintasa Tipo I/metabolismo , Acetil-CoA C-Acetiltransferasa/genética , Acetil-CoA C-Acetiltransferasa/metabolismo , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/genética , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Carga de Parásitos , Expresión Génica , Células CultivadasRESUMEN
Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.
Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Trypanosoma cruzi , Humanos , Interleucina-8 , Leucocitos Mononucleares , Factor D del Complemento , Interleucina-2/uso terapéutico , Tejido Adiposo , Adipocitos , Factor de Necrosis Tumoral alfa/uso terapéutico , Inmunidad , Insuficiencia del TratamientoRESUMEN
Tuberculosis (TB) is an infectious disease displaying a multifactorial pathology. The immunomodulatory role attributed to steroid hormones, such as vitamin D3 (VD3) and 17ß-estradiol (E2), highlighted the importance of these hormones against Mycobacterium tuberculosis (Mtb) infection. In order to understand their influence upon gene expression of immune and inflammatory responsive genes against Mtb we tested it in vitro using peripheral blood mononuclear cells (PBMCs). Cells were pretreated with VD3 (50 ng/mL) or E2 (100 nM/mL) and co-cultured with H37Rv Mtb or stimulated with lipopolysaccharide from Escherichia coli (LPS). After 24 h and 72 h of co-culture the Mtb viability in macrophages test was performed, as well the total RNA isolation for gene expression analysis by RT-qPCR of the following target genes: NLRP3, DC-SIGN, IL-1ß, and IL-10. We also measured IL-10, TNF, IFN-γ, IL-4, IL-6, and IL-2 supernatant levels. As the main results, we found that VD3 and E2 downregulated the expression of inflammatory genes NLRP3, IL-1ß, and IL-10 expression in Mtb co-cultured cells. Finally, VD3 treatment increased the release of the cytokine IFN-γ in Mtb-infected cells, while E2 treatment inhibited the release of IL-10, TNF, IFN-γ, and IL-6. Therefore, we report an immunogenetic influence of VD3 and E2 upon Mtb co-culture.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Interleucina-10/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Leucocitos Mononucleares/metabolismo , Interleucina-6/metabolismo , Tuberculosis/microbiología , Colecalciferol , Hormonas/metabolismoRESUMEN
Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.
Asunto(s)
Enfermedad de Chagas , Cardiopatías , Nitroimidazoles , Humanos , Enfermedad de Chagas/tratamiento farmacológico , Citocinas , Cardiopatías/tratamiento farmacológico , Cardiopatías/parasitología , Interferón gamma , Interleucina-2 , Interleucina-4 , Leucocitos Mononucleares , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: An assessment of the factors that interfere with serum levels and the persistence of anti-SARs-CoV-2 IgG antibodies is essential in order to estimate the risk of reinfection and to plan vaccination. We analyzed the impact of the severity of coronavirus disease 2019 (COVID-19) and the clinical and biological factors regarding the persistence of SARs-CoV-2 anti-spike protein (IgG-S) antibodies at 12 months. METHODS: This was an observational, longitudinal study with individuals who had recovered from COVID-19 between August 2020 and June 2021. Peripheral blood samples were collected from volunteers who were hospitalized (SERIOUS COVID-19) and those who required no hospitalization (COVID-19 LIGHT). Samples were grouped according to days after symptom onset: up to 90, between 91 and 180, ≥ 180 days after symptom onset. A semiquantitative test for IgG anti-spike protein S1(IgG-S1) was used. RESULTS: We analyzed 238 individuals who had recovered from COVID-19, of whom 87 had been hospitalized and 151 had not. They provided 148 and 220 samples, respectively. Among those hospitalized, males (65.5%), volunteers aged over 60 years (41.1%), comorbidities such as arterial hypertension (67.8%) and diabetes mellitus (37.9%) were most frequent. We observed higher median serum IgG-S1 titers among those who had recovered from COVID-19 and had been hospitalized, at all collection time intervals (p < 0.001). We observed a weak correlation of increasing age with humoral IgG-S1 response (Spearman correlation = 0.298). There was a greater probability of IgG-S1 antibody persistence over time among samples from hospitalized individuals compared to samples from non-hospitalized participants (p = 0.001). CONCLUSION: This study has revealed higher titers and a higher probability of the persistence of IgG-S1 in severe cases after SARs-CoV-2 primary infection in unvaccinated recovered patients. Thus, in this study, the severe clinical presentation of COVID-19 was the main factor influencing serum levels and the persistence of IgG-S1 antibodies in COVID-19.
Asunto(s)
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Persona de Mediana Edad , Anciano , Formación de Anticuerpos , Estudios Longitudinales , Inmunoglobulina G , Gravedad del Paciente , Anticuerpos AntiviralesRESUMEN
The therapeutic regimen for the treatment of American Tegumentary Leishmaniasis (ATL) is targeted at the death of the parasite; therefore, it is essential to develop a treatment that can act on the parasite, combined with the modulation of the inflammatory profile. Thus, the aim of this study was to make an in vitro evaluation of the therapeutic potential of Chlorella vulgaris extract (CV) and Imiquimod for ATL. Selectivity indices (SI) were determined by inhibitory concentration assays (IC50) in L. braziliensis cells and cytotoxic concentrations (CC50) were measured in human cells using the MTT method, based on the CV microalgae extract (IC50 concentrations of 15.63 to 500 µg/mL; CC50 concentrations of 62.5-1000 µg/mL) in comparison with the reference drugs and Imiquimod. The immune response was evaluated in healthy human cells by gene expression (RT-qPCR) and cytokine production (Flow Cytometry). The CV extract (SI = 6.89) indicated promising results by showing higher SI than meglumine antimoniate (SI = 3.44) (reference drug). In all analyses, CV presented a protective profile by stimulating the production of Th1 profile cytokines to a larger extent than the reference drugs. Imiquimod showed a high expression for Tbx21, GATA3, RORc and Foxp3 genes, with increased production only of the TNF cytokine. Therefore, the data highlight the natural extract and Imiquimod as strong therapeutic or adjuvant candidates against ATL, owing to modulation of immune response profiles, low toxicity in human cells and toxic action on the parasite.
Asunto(s)
Antiprotozoarios , Chlorella vulgaris , Leishmania braziliensis , Leishmaniasis Cutánea , Humanos , Imiquimod/uso terapéutico , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/parasitología , CitocinasRESUMEN
The present study aimed to inspect the serum levels of the soluble receptors, sTNFR1 and sTNFR2, in patients with COVID-19. The large production of inflammatory cytokines is an essential process in the pathogenesis of COVID-19. TNF is a multifaceted proinflammatory cytokine which has soluble and membrane receptors. Thus, knowing the role of these receptors will help better understand this disease's immunopathogenesis. We included 131 patients confirmed for SARS-CoV-2, separated into three groups: ward patients without O2 support, group A (n = 14); ward patients with O2 support, group B (n = 85), and patients in an intensive care unit (ICU), group C (n = 32), making up the receptors dosed by flow cytometry. The results showed that sTNFR1 and sTNFR2 are associated with disease severity, being higher in group C when compared to group A. As for the levels of receptors and their relationship with the degree of lung involvement, we found higher values of sTNFR1 in patients in group 1 (pulmonary involvement < 25%), suggesting that inflammatory processes related to TNF are not necessarily associated with the primary site of infection. When we analysed the patients who passed away compared to those who recovered, both receptors significantly increased the mortality numbers. These findings suggest a relevant influence of soluble receptors in the inflammatory processes involved in the pathogenesis of COVID-19. Wherefore, we suggest using these receptors as biomarkers of severity and mortality of the disease.
Asunto(s)
COVID-19 , Receptores Tipo I de Factores de Necrosis Tumoral , Humanos , Receptores Tipo II del Factor de Necrosis Tumoral , SARS-CoV-2 , Citocinas , Factor de Necrosis Tumoral alfaRESUMEN
ABSTRACT Introduction: HIV/AIDS is considered one of the great cases of public health, but it is seen that patients who use antiretroviral therapy (ART) and practice strength training promote a promotion of their health. Objectives: Assess the impact of strength and resistance training on cytokines and body composition in people living with HIV/AIDS. Methods: Randomized clinical trial, the sample consisted of 12 patients, 7 from the Strength Group (GF) and 5 from Group 2, Muscular Resistance (MGR). We compared the levels of IL-2, IL-4, IL-6, IL-10 and TNF-α cytokines and body composition in the first and last sessions. The patients completed 36 strength and resistance training sessions over 12 weeks. Results: After 36 sessions of GRM resistance training, there was a significant increase from 4,734 pg/mL to 5,050 pg/mL of IL-10 (p=0.002). Regarding the GFR, no significant results were found. For body composition, there were significant differences in GFR due to the increase in lean mass of the arms from 6,441g to 7,014g (p=0.04), legs from 16,379g to 17,281g (p=0.02) and whole body of 45,640g to 47,343g (p=0.01). In G2 there was a significant decrease in the percentage of fat in the arms from 23,160% to 20,750% (p = 0.04). To assess quality of life, the WHOQOL-HIV-Bref questionnaire was used, where significant improvement was found in all domains, except for the level of independence domain. Conclusion: We conclude that muscular resistance training is effective in increasing IL-10 and decreasing the percentage of fat in the arms, whereas strength training increases lean mass in arms, legs, and the whole body. Level of Evidence I; Randomized Clinical Trial.
RESUMEN Introducción: El VIH/SIDA es considerado uno de los grandes casos de salud pública, sin embargo, está comprobado que pacientes que hacen uso de la terapia antirretroviral (TARV) y practican entrenamiento de fuerza provoca una promoción de su salud. Objetivos: Evaluar el impacto del entrenamiento de fuerza en la resistencia a las citoquinas y en la composición corporal de las personas que viven con VIH/SIDA. Métodos: Ensayo clínico aleatorizado, la muestra estuvo compuesta por 12 pacientes, siete del Grupo de Fuerza (TFG) y cinco del Grupo de Resistencia Muscular (GRM). Se compararon los niveles de las citocinas IL-2, IL-4, IL-6, IL-10 y TNF-α y la composición corporal en la primera y la última sesión. Los pacientes completaron 36 sesiones de entrenamiento de fuerza y resistencia durante 12 semanas. Resultados: Tras 36 sesiones de entrenamiento de resistencia GRM, se produjo un aumento significativo de 4.734 pg/mL a 5.050 pg/mL de IL-10 (p=0,002). En cuanto a la TFG, no se encontraron resultados significativos. En cuanto a la composición corporal, hubo diferencias significativas en la TFG debido al aumento de la masa magra en brazos de 6.441g a 7.014g (p=0,04), piernas de 16.379g a 17.281g (p=0,02) y cuerpo entero de 45.640g a 47.343g (p=0,01). En el GRM hubo una disminución significativa del porcentaje de grasa en los brazos de 23.160% a 20.750% (p = 0,04). Para la evaluación de la calidad de vida se utilizó el cuestionario WHOQOL-HIV-Bref, donde se encontró una mejoría significativa en todos los dominios, excepto en el dominio nivel de independencia. Conclusión: Concluimos que el entrenamiento de resistencia muscular es eficaz para aumentar la IL-10 y disminuir el porcentaje de grasa en los brazos, mientras que el entrenamiento de fuerza aumenta la masa magra total. Nivel de Evidencia I; Ensayo clínico aleatorizado.
RESUMO Introdução: O HIV/AIDS é considerado um dos grandes casos de saúde pública, porém verifica-se que pacientes que fazem uso de terapia antirretroviral (TARV) e praticam treinamento de força provocam uma promoção de sua saúde. Objetivos: Avaliar o impacto do treinamento de força sobre a resistência nas citocinas e a composição corporal de pessoas vivendo com HIV/AIDS. Métodos: Ensaio clínico randomizado, a amostra foi composta por 12 pacientes, sendo sete do Grupo Força (TFG) e cinco do Grupo Resistência Muscular (GRM). Comparou-se os níveis das citocinas IL-2, IL-4, IL-6, IL-10 e TNF-α e a composição corporal na primeira e na última sessão. Os pacientes completaram 36 sessões de treinamento de força e resistência ao longo de 12 semanas. Resultados: Após 36 sessões de treinamento resistido GRM, houve um aumento significativo de 4.734 pg/mL para 5.050 pg/mL de IL-10 (p=0,002). Em relação à TFG, não foram encontrados resultados significativos. Para composição corporal, houve diferenças significativas na TFG devido ao aumento da massa magra dos braços de 6.441g para 7.014g (p=0,04), pernas de 16.379g para 17.281g (p=0,02) e corpo inteiro de 45.640g para 47.343g (p=0,01). No GRM houve diminuição significativa do percentual de gordura nos braços de 23.160% para 20.750% (p = 0,04). Para avaliação da qualidade de vida foi utilizado o questionário WHOQOL-HIV-Bref, onde foi encontrada uma melhora significativa em todos os domínios, exceto no domínio nível de independência. Conclusão: Conclui-se que o treinamento de resistência muscular é eficaz em aumentar a IL-10 e diminuir o percentual de gordura nos braços, enquanto o treinamento de força aumenta a massa magra geral. Nível de Evidência I; Ensaio Clínico Randomizado.
RESUMEN
Probiotics contribute to the integrity of the intestinal mucosa and preventing dysbiosis caused by opportunistic pathogens, such as intestinal helminths. Bacillus cereus GM obtained from Biovicerin® was cultured to obtain spores for in vivo evaluation on experimental schistosomiasis. The assay was performed for 90 days, where all animals were infected with 50 cercariae of Schistosoma mansoni on the 15th day. Three experimental groups were formed, as follows: G1-saline solution from the 1st until the 90th day; G2-B. cereus GM (105 spores in 300 µL of sterile saline) from the 1st until the 90th day; and G3-B. cereus GM 35th day (onset of oviposition) until the 90th day. G2 showed a significant reduction of 43.4% of total worms, 48.8% of female worms and 42.5% of eggs in the liver tissue. In G3, the reduction was 25.2%, 29.1%, and 44% of the total number of worms, female worms, and eggs in the liver tissue, respectively. G2 and G3 showed a 25% (p < 0.001) and 22% (p < 0.001) reduction in AST levels, respectively, but ALT levels did not change. ALP levels were reduced by 23% (p < 0.001) in the G2 group, but not in the G3. The average volume of granulomas reduced (p < 0.0001) 65.2% and 46.3% in the liver tissue and 83.0% and 53.2% in the intestine, respectively, in groups G2 and G3. Th1 profile cytokine (IFN-γ, TNF-α, and IL-6) and IL-17 were significantly increased (p < 0.001) stimulated with B. cereus GM in groups G2 and G3. IL-4 showed significant values when the stimulus was mediated by ConA. By modulating the immune response, B. cereus GM reduced the burden of worms, improved some markers of liver function, and reduced the granulomatous inflammatory reaction in mice infected with S. mansoni, especially when administered before infection.
Asunto(s)
Probióticos , Esquistosomiasis mansoni , Esquistosomiasis , Femenino , Animales , Ratones , Esquistosomiasis mansoni/parasitología , Bacillus cereus , Schistosoma mansoni , Esquistosomiasis/parasitología , Hígado/parasitologíaRESUMEN
Anti-Ascaris lumbricoides (Asc) IgE and IgG can immunomodulate the allergy; however, the influence of these isotypes has not been investigated in the giardiasis and allergy. Therefore, the frequency of respiratory allergy (RA) symptoms in Giardia lamblia-infected children, with or without anti-Asc IgE, IgG1, or IgG4 and Th1, Th2/Treg, and Th17 cytokine production, was evaluated. We performed a case-control study with children aged 2-10 years old selected by questionnaire and stool exams to form the groups: infected or uninfected with RA (G-RA, n = 55; nG-RA, n = 43); infected and uninfected without RA (G-nRA, n = 59; nG-nRA, n = 54). We performed blood leukocyte counts and in vitro culture. Cytokine levels in the supernatants (CBA), serum total IgE and anti-Asc IgE (ImmunoCAP), IgG1, IgG4, and total IgA (ELISA) were measured. Infection was not associated with allergy. Infected children showed increased levels of anti-Asc IgG1, IL-2, IFN-γ, IL-4, and IL-10. There was a lower frequency of allergy-related symptoms in anti-Asc IgG1-positive children than IgG1-negative (OR = 0.38; CI = 0.17-0.90, p = 0.027) and few eosinophils in G-RA than in G-nRA and more in G-nRA than in nG-nRA, whereas TNF-α levels were higher in the G-RA than in the nG-nRA group. For infected and positive anti-Asc IgG1, there was higher TNF-α and IL-10 production than G/-IgG1. IL-10 levels were lower in nG/ + IgG1 than in infected or non-infected, and both were negative for anti-Asc IgG1. Th1/Th2/IL-10 profiles were stimulated in the infected patients, and in those with circulating anti-Asc IgG1, the TNF-α production was strengthened with a lower risk for respiratory allergy symptoms.
Asunto(s)
Giardia lamblia , Hipersensibilidad , Animales , Humanos , Niño , Preescolar , Interleucina-10 , Ascaris , Factor de Necrosis Tumoral alfa , Estudios de Casos y Controles , Hipersensibilidad/complicaciones , Citocinas , Inmunoglobulina G , Inmunoglobulina ERESUMEN
BACKGROUND: Trypanosoma cruzi, which causes Chagas disease (CD), is a versatile haemoparasite that uses several strategies to evade the host's immune response, including adipose tissue (AT), used as a reservoir of infection. As it is an effective barrier to parasite evasion, the effectiveness of the drug recommended for treating CD, Benznidazole (BZ), may be questionable. OBJECTIVE: To this end, we evaluated the parasite load and immunomodulation caused by BZ treatment in the culture of adipocytes differentiated from human adipose tissue-derived stem cells (ADSC) infected with T. cruzi. METHODS: The ADSC were subjected to adipogenic differentiation. We then carried out four cultures in which we infected the differentiated AT with trypomastigote forms of the Y strain of T. cruzi and treated them with BZ. After the incubation, the infected AT was subjected to quantitative polymerase chain reaction (qPCR) to quantify the parasite load and transmission electron microscopy (TEM) to verify the infection. The supernatant was collected to measure cytokines, chemokines, and adipokines. FINDINGS: We found elevated secretion of IL-6, CXCL-10/IP-10, CCL2/MCP-1, CCL5/RANTES, and leptin in infected fat cells. However, treatment with BZ promoted a decrease in IL-6. MAIN CONCLUSION: Therefore, we believe that BZ has a beneficial role as it reduces inflammation in infected fat cells.
Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Humanos , Interleucina-6 , Enfermedad de Chagas/parasitología , Nitroimidazoles/farmacología , Nitroimidazoles/uso terapéutico , Tejido Adiposo , Adipocitos , Diferenciación Celular , Tripanocidas/farmacología , Tripanocidas/uso terapéuticoRESUMEN
Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co-cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA-4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+ , CD86+ and HLA-DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN-γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL-10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.
Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Humanos , Leucocitos Mononucleares , Colombia , Nitroimidazoles/farmacología , Nitroimidazoles/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Tripanocidas/farmacología , Tripanocidas/uso terapéuticoRESUMEN
Post-chikungunya virus (CHIKV) chronic arthritis shares several immunopathogenic mechanisms with rheumatoid arthritis (RA), which has led to discussions about the probable relationship between the two diseases. Indeed, some studies have suggested a role for CHIKV infection in RA development. However, to the best of our knowledge, the influence of CHIKV on previous RA has not yet been demonstrated. Herein, we analyzed the potential synergism between CHIKV infection and RA on cytokine and chemokine levels. For this, we compared the IL-1ß, IL-6, IL-10, IL-17A, CCL2, CXCL8, CXCL9 and CXCL10 levels, in addition to rheumatoid factor (RF) and C-reactive protein (CRP), in patients with post-CHIKV chronic arthritis (named CHIKV group), patients with RA (RA group), and patients with previous RA who were later infected by CHIKV (RA-CHIKV). History of CHIKV infection was confirmed by serology (IgG, ELISA). Cytokines/chemokines were quantified by flow cytometry. RF, CRP, age and sex data were obtained from medical records. IL-1ß, IL-6, IL-10 and IL-17A levels were significantly higher in RA-CHIKV compared to the other groups. CXCL8 levels were higher in the CHIKV group than in RA. CXCL9 was higher in CHIKV than in the RA-CHIKV group. CXCL10 was higher in CHIKV than in the other groups. FR levels were higher in RA than in the CHIKV group, and in RA-CHIKV than in CHIKV. No significant difference was observed in CCL2 and CRP, as well as in age and sex. Finally, our findings suggest an interplay between CHIKV infection and RA, which must be analyzed for its possible clinical impact.
Asunto(s)
Artritis Reumatoide , Fiebre Chikungunya , Virus Chikungunya , Humanos , Citocinas , Interleucina-10 , Interleucina-17 , Interleucina-6 , QuimiocinasRESUMEN
Background and objectives: surgical site infections (SSI) continue to be a major concern in orthopedic oncology and pose as great a challenge as cancer recurrence, despite the preventive potential of surgery. SSI can be avoided if evidence-based measures are taken. The objective was to assess the frequency of infections in oncological orthopedic surgeries and associated risk factors and inflammatory markers in a reference hospital in the state of Pernambuco. Methods: the frequency of SSI, the identification of isolated microorganisms, the risk factors and the profile of Th1 and Th2 inflammatory markers (IL-2, IL-4, IL-6, IL-10, TNF and IFN-Ƴ) in patients with musculoskeletal cancer were analyzed. Results: SSI were found in 9.1% of patients undergoing orthopedic surgery. Bivariate analysis revealed that a surgical team comprising more than five members (p=0.041) and the need for intraoperative transfusion (p=0.012) were correlated with a higher risk of SSI. The measurement of ultrasensitive C-reactive protein levels to assess the inflammatory response after SSI showed results that were superior to the reference values for each sample, ranging from >5 to >200mg/dl by the immunoturbidimetric method. Of the IL-2, INFγ and TNF (Th1) and IL-4, IL-6, IL-10 (Th2) levels, only interleukin 6 showed high levels, between 6.68 and 58.76 pg/mL. Conclusion: the study found that surgical team with five or more members and blood transfusion were factors associated with the development of SSI in orthopedic surgery in patients with musculoskeletal cancer. Among the inflammatory markers, interleukin 6 (IL-6) showed the highest correlation with the outcome.(AU)
Justificativa e objetivos: as infecções do sítio cirúrgico (ISC) continuam sendo uma grande preocupação na oncologia ortopédica e representam um desafio tão grande quanto a recorrência do câncer, apesar do potencial preventivo da cirurgia. As ISC podem ser evitadas se forem tomadas medidas baseadas em evidências. O objetivo foi avaliar a frequência de infecções em cirurgias ortopédicas oncológicas e os fatores de risco e marcadores inflamatórios associados em um hospital de referência no estado de Pernambuco. Métodos: foram analisados a frequência de ISC, a identificação de microrganismos isolados, os fatores de risco e o perfil de marcadores inflamatórios Th1 e Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) em pacientes portadores de câncer musculoesquelético. Resultados: as ISC foram encontradas em 9,1% dos pacientes submetidos à cirurgia ortopédica. A análise bivariada revelou que uma equipe cirúrgica composta por mais de cinco membros (p=0,041) e a necessidade de transfusão intraoperatória (p=0,012) foram correlacionadas com maior risco de ISC. A dosagem dos níveis de proteína C reativa ultrassensível para avaliação da resposta inflamatória após ISC apresentou resultados superiores aos valores de referência para cada amostra, variando de >5 a >200mg/dl pelo método imunoturbidimétrico. Dos níveis de IL-2, INFγ e TNF (Th1) e IL-4, IL-6, IL-10 (Th2), apenas a interleucina 6 apresentou níveis elevados, entre 6,68 e 58,76 pg/mL. Conclusão: o estudo constatou que equipe cirúrgica com cinco ou mais membros e transfusão sanguínea foram fatores associados ao desenvolvimento de ISC em cirurgia ortopédica em pacientes com câncer musculoesquelético. Entre os marcadores inflamatórios, interleucina 6 (IL-6) apresentou maior correlação com o desfecho.(AU)
Justificación y objetivos: las infecciones del sitio quirúrgico (ISQ) siguen siendo una preocupación importante en la oncología ortopédica y representan un desafío tan grande como la recurrencia del cáncer, a pesar del potencial preventivo de la cirugía. Las ISQ se pueden prevenir si se toman medidas basadas en la evidencia. El objetivo fue evaluar la frecuencia de infecciones en cirugías ortopédicas oncológicas y los factores de riesgo y marcadores inflamatorios asociados en un hospital de referencia en el estado de Pernambuco. Métodos: se analizaron la frecuencia de ISQ, la identificación de microorganismos aislados, los factores de riesgo y el perfil de marcadores inflamatorios Th1 y Th2 (IL-2, IL-4, IL-6, IL-10, TNF e IFN-Ƴ) en pacientes con cáncer musculoesquelético. Resultados: se encontraron ISQ en el 9,1% de los pacientes sometidos a cirugía ortopédica. El análisis bivariado reveló que un equipo quirúrgico compuesto por más de cinco miembros (p=0,041) y la necesidad de transfusión intraoperatoria (p=0,012) se correlacionaron con un mayor riesgo de ISQ. La medición de los niveles de proteína C reactiva ultrasensible para evaluar la respuesta inflamatoria después de la ISQ presentó resultados superiores a los valores de referencia para cada muestra, variando de >5 a >200 mg/dl por el método inmunoturbidimétrico. De los niveles de IL-2, INFγ y TNF (Th1) e IL-4, IL-6, IL-10 (Th2), solo la interleucina 6 mostró niveles elevados, entre 6,68 y 58,76 pg/mL. Conclusión: el estudio encontró que el equipo quirúrgico con cinco o más miembros y la transfusión el estudio encontró que un equipo quirúrgico con cinco o más miembros y transfusión de sangre fueron factores asociados con el desarrollo de ISQ en cirugía ortopédica en pacientes con cáncer musculoesquelético. Entre los marcadores inflamatorios, la interleucina 6 (IL-6) mostró la mayor correlación con el resultado.(AU)
Asunto(s)
Humanos , Infección de la Herida Quirúrgica , Neoplasias Óseas/complicaciones , Factores de Riesgo , Neoplasias de los Músculos/complicacionesRESUMEN
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), affects millions of people worldwide. Polymerase Chain Reaction (PCR) and real-time quantitative PCR (qPCR) have been used as tools to monitor parasitic levels in the bloodstream of individuals exposed to infection, thus enabling the monitoring of relapses and the effectiveness of therapy, for example. The aim of this study was to evaluate the TcSAT-IAM system, developed by our research group, on samples from patients with suspected Chagas disease infection. Initially, primer systems were developed for the detection of the nuclear DNA (SAT-DNA) from T. cruzi (TcSAT-IAM). The Cruzi system, predicted in the literature, and TcSAT-IAM were then evaluated in relation to their analytical sensitivity, specificity and efficiency. Afterwards, the applicability of the qPCR technique using both systems (separately) for the diagnosis of acute CD was evaluated in samples from 77 individuals exposed to the outbreak that occurred in Pernambuco-Brazil, relating the results obtained to those of the classical diagnostic methods recommended for this stage of the infection. TcSAT-IAM and Cruzi had a detection limit of 1 fg of target DNA (0,003 parasites). Thirty-eight cases were recorded, 28 by laboratory criteria and 10 by clinical and epidemiological criteria. Blood samples from 77 subjects were submitted to qPCR by both systems, reaching an agreement of 89.61% between them. After analyzes between systems and diagnostic criteria, the TcSAT-IAM showed sensitivity and specificity of 52.36% (CI 37.26-67.52) and 92.31% (CI 79.68-97.35), respectively, accuracy of 72.73% and moderate agreement. The TcSAT-IAM showed an accuracy of 72.58% and 75% in relation to parasitological and serological tests (IgM anti-T. cruzi), respectively. Therefore, quantitative PCR should be incorporated into the diagnosis of suspected acute cases of Chagas disease.
Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Humanos , Brasil/epidemiología , Patología Molecular , ADN Protozoario/genética , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/tratamiento farmacológico , Trypanosoma cruzi/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Brotes de EnfermedadesRESUMEN
Due to the limitations of Chagas disease therapy, microalgae can be promising in the search of new trypanocidal compounds, since these organisms produce bioactive compounds with large pharmaceutical applications, including antiparasitic effects. In this work, trypanocidal activity of aqueous extract of Tetradesmus obliquus and, for the first time, aqueous extract of Chlorella vulgaris, were evaluated against trypomastigote forms of Trypanosoma cruzi. In addition, cytotoxic activity in Vero cells was evaluated. Our results showed that C. vulgaris and T. obliquus present trypanocidal activity (IC50 = 32.9 µg ml-1 and 36.4 µg ml-1, respectively), however, C. vulgaris did not present cytotoxic effects in Vero cells (CC50 > 600 µg ml-1) and displayed a higher selectivity against trypomastigotes forms of T. cruzi (SI > 18). Thus, microalgae extracts, such as aqueous extract of C. vulgaris, are promising potential candidates for the development of natural antichagasic drugs.