RESUMEN
BACKGROUND: Chagas disease, endemic in Latin America and spreading globally due to emigration, has a significant health burden, particularly in relation to chagasic heart failure (HF). Chagasic cardiomyopathy (CCM) is characterized by chronic inflammatory myocardial disease. This study aimed to identify inflammatory parameters and biomarkers that could aid in the management of patients with chagasic HF. METHODS AND FINDINGS: A cohort study was conducted at a tertiary cardiology single-center over a mean follow-up period of 2.4 years. The study included patients with HF secondary to CCM enrolled between October 2013 and July 2017. Various clinical parameters, echocardiography findings, parasitemia status, brain natriuretic peptide (BNP) and troponin T (TnT) levels, and inflammatory biomarkers (IL-6, IL-10, IL-12p70, IL-17A, adiponectin, and IFN-γ) were assessed. The study encompassed a cohort of 103 patients, with a median age of 53 years and 70% being male. The left ventricular ejection fraction (LVEF) was 28%, with 40% of patients classified as NYHA II functional class. The median BNP level was 291 pg/ml. The observed mortality rate during the study period was 38.8%. Predictors of lower survival were identified as elevated levels of BNP, TnT, reduced LVEF, and increased adiponectin (thresholds: BNP > 309 pg/ml, TnT > 27.5 ng/ml, LVEF < 25.5%, adiponectin > 38 µg/mL). Notably, there was no evidence indicating a relationship between parasitemia and the inflammatory parameters with lower survival in these patients, including INF-γ, IL-6, IL-10, IL12-(p70), and IL17a. CONCLUSION: Despite the presence of a chronic inflammatory process, the evaluated inflammatory biomarkers in this cohort were not predictive of survival in patients with chagasic HF with reduced ejection fraction (HFrEF). However, reduced LVEF, elevated BNP, adiponectin levels, and troponin T were identified as predictors of lower survival in these patients.
Asunto(s)
Cardiomiopatía Chagásica , Insuficiencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Femenino , Insuficiencia Cardíaca/epidemiología , Volumen Sistólico , Interleucina-10 , Función Ventricular Izquierda , Estudios de Cohortes , Troponina T , Adiponectina , Interleucina-6 , Parasitemia , Biomarcadores , Péptido Natriurético Encefálico , PronósticoRESUMEN
A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.
Asunto(s)
Antiprotozoarios , Leishmaniasis Cutánea , Compuestos Organometálicos , Adulto , Antiprotozoarios/uso terapéutico , Brasil , Genitales , Humanos , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Masculino , Meglumina/uso terapéutico , Antimoniato de Meglumina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Reacción en Cadena de la PolimerasaRESUMEN
Abstract A 31-year-old male patient developed an ulcer on the glans penis that evolved for three months without healing. We diagnosed it as leishmaniasis using polymerase chain reaction. No immunosuppression or associated diseases were observed. The patient was treated with meglumine antimoniate that cured the lesion in a month post-treatment. Here, we report this case of cutaneous leishmaniasis lesion at the unusual location of glans penis in an immunocompetent individual. The lesion likely developed due to the bite of a vector, highlighting the need for considering cutaneous leishmaniasis among differential diagnosis of sexually transmitted diseases in areas endemic for leishmaniasis.
Asunto(s)
Humanos , Masculino , Adulto , Compuestos Organometálicos/uso terapéutico , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Antiprotozoarios/uso terapéutico , Brasil , Reacción en Cadena de la Polimerasa , Antimoniato de Meglumina/uso terapéutico , Genitales , Meglumina/uso terapéuticoRESUMEN
Background: Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism profiles and cardiomyopathy or T. cruzi parasitemia, as well as the impact of HIV infection on cardiopathy. Methods: Two hundred twenty-six patients and 90 control individuals were analyzed. IL1B rs1143627 T>C, IL6 rs1800795 C>G, IL17A rs2275913 G>A, IL18 rs187238 C>G, and IL18 rs1946518 C>A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by PCR. Results: Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The IL6 rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between IL17A rs2275913 AA and IL18 s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). IL18 rs1946518 AA and IL1B rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class ≥ 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for IL18 rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class ≥ 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA ≥ 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively). Conclusions: Our data support a protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the IL6 CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies.
Asunto(s)
Enfermedad de Chagas , Genotipo , Interleucina-17 , Interleucina-18 , Interleucina-1beta , Interleucina-6 , Parasitemia , Polimorfismo Genético , Trypanosoma cruzi/inmunología , Adulto , Enfermedad de Chagas/genética , Enfermedad de Chagas/inmunología , Femenino , Humanos , Interleucina-17/genética , Interleucina-17/inmunología , Interleucina-18/genética , Interleucina-18/inmunología , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Masculino , Persona de Mediana Edad , Parasitemia/genética , Parasitemia/inmunologíaRESUMEN
A study with transmission electron microscopy of mycoplasma-contaminated HeLa cells using five cell donors referred to as donors A, B, C, D and E, observations are herein presented. Experiments performed with cells from donors B, C and D, revealed the presence of Mycoplasma hyorhinis after PCR and sequencing experiments. Bacteria probably originated from a cytoplasm with compacted tiny granular particles replacing the normal cytosol territories, or from the contact with the cytoplasm through a clear semi-solid material. The compact granularity (CG) of the cytoplasm was crossed by stripes of smooth and rough endoplasmic reticulum cisternae. Among apparently normal mitochondria, it was noted, in variable proportions, mitochondria with crista-delimited lucent central regions that expand to and occupied the interior of a crista-less organelle, which can undergo fission. Other components of the scenarios of mycoplasma-induced cell demolition are villus-like structures with associated 80-200 nm vesicles and a clear, flexible semi-solid, process-sensitive substance that we named jam-like material. This material coated the cytoplasmic surface, its recesses, irregular protrusions and detached cytoplasmic fragments. It also cushioned forming bacteria. Cyst-like structures were often present in the cytoplasm. Cells, mainly apoptotic, exhibiting ample cytoplasmic sectors with characteristic net-like profile due to adjoined vacuoles, as well as ovoid or elongated profiles, consistently appeared in all cells from the last four cell donors. These cells were named "modified host cells" because bacteria arose in the vacuoles. The possibility that, in some samples, there was infection and/or coinfection of the host cell by another organism(s) cannot be ruled out.
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Citosol/microbiología , Retículo Endoplásmico/microbiología , Células HeLa/microbiología , Mitocondrias/microbiología , Mycoplasma hyorhinis/aislamiento & purificación , Vacuolas/microbiología , Células Cultivadas , Citosol/patología , ADN Bacteriano , Retículo Endoplásmico/patología , Células HeLa/patología , Humanos , Microscopía Electrónica de Transmisión , Mitocondrias/patología , Reacción en Cadena de la Polimerasa , Estaurosporina/farmacología , Vacuolas/patologíaAsunto(s)
Retículo Endoplásmico/ultraestructura , Aparato de Golgi/microbiología , Mycoplasma/fisiología , Membrana Celular/microbiología , Membrana Celular/ultraestructura , Retículo Endoplásmico/microbiología , Aparato de Golgi/ultraestructura , Células HeLa/microbiología , Células HeLa/ultraestructura , Interacciones Huésped-Parásitos/fisiología , Humanos , Microscopía Electrónica de Transmisión , Mycoplasma/ultraestructuraAsunto(s)
Humanos , Retículo Endoplásmico/ultraestructura , Aparato de Golgi/microbiología , Mycoplasma/fisiología , Membrana Celular/microbiología , Membrana Celular/ultraestructura , Retículo Endoplásmico/microbiología , Aparato de Golgi/ultraestructura , Células HeLa/microbiología , Células HeLa/ultraestructura , Interacciones Huésped-Parásitos/fisiología , Microscopía Electrónica de Transmisión , Mycoplasma/ultraestructuraRESUMEN
AIM: Modified low-density lipoprotein (mLDL), mainly upon oxidative and enzymatic modification, is the major atherogenic lipoprotein. Conversely, high-density lipoprotein (HDL) is considered antiatherogenic because of its ability to remove cholesterol. The aim of this work was to analyze both the influence of HDL on the uptake of mLDL and the expression of CD36 and Fcgamma I receptors on monocytic cell lines during cell differentiation. METHODS: Uptake of fluorescein isothiocyanate (FITC)-conjugated LDL and FITC-conjugated mLDL, i.e., copper-oxidized LDL (oxLDL) or trypsin enzyme modified LDL (enzLDL), was analyzed, as well as the expression of CD36 and FcgammaRI in THP-1 and U937 cells, using flow cytometry. RESULTS: HDL inhibited the uptake of mLDL, which varied in degree depending on the cell line or type of mLDL. Further, HDL rapidly decreased CD36 and FcgammaRI involved in the uptake of mLDL. CONCLUSIONS: We demonstrate that modified LDL promotes specific LDL receptor-independent uptake by monocytic cell lines, and that the uptake of LDL and enzLDL is less than that of oxLDL. In this process, HDL diminishes the uptake of LDL or mLDL, which may involve the down-regulation of receptors (CD36 and Fcgamma I). This regulatory process represents another way by which HDL can be anti-atherogenic and it depends on the type of modification of LDL and the stage of differentiation of monocytes to macrophages.