RESUMO
Human defensins are cysteine-rich peptides (Cys-rich peptides) of the innate immune system. Defensins contain an ancestral structural motif (i.e., γ-core motif) associated with the antimicrobial activity of natural Cys-rich peptides. In this study, low concentrations of human α- and ß-defensins showed microbicidal activity that was not associated with cell membrane permeabilization. The cell death pathway was similar to that previously described for human lactoferrin, also an immunoprotein containing a γ-core motif. The common features were (1) cell death not related to plasma membrane (PM) disruption, (2) the inhibition of microbicidal activity via extracellular potassium, (3) the influence of cellular respiration on microbicidal activity, and (4) the influence of intracellular pH on bactericidal activity. In addition, in yeast, we also observed (1) partial K+-efflux mediated via Tok1p K+-channels, (2) the essential role of mitochondrial ATP synthase in cell death, (3) the increment of intracellular ATP, (4) plasma membrane depolarization, and (5) the inhibition of external acidification mediated via PM Pma1p H+-ATPase. Similar features were also observed with BM2, an antifungal peptide that inhibits Pma1p H+-ATPase, showing that the above coincident characteristics were a consequence of PM H+-ATPase inhibition. These findings suggest, for the first time, that human defensins inhibit PM H+-ATPases at physiological concentrations, and that the subsequent cytosolic acidification is responsible for the in vitro microbicidal activity. This mechanism of action is shared with human lactoferrin and probably other antimicrobial peptides containing γ-core motifs.
Assuntos
Membrana Celular , ATPases Translocadoras de Prótons , Humanos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , ATPases Translocadoras de Prótons/metabolismo , ATPases Translocadoras de Prótons/antagonistas & inibidores , Permeabilidade da Membrana Celular/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Defensinas/farmacologia , Defensinas/metabolismo , Concentração de Íons de Hidrogênio , Saccharomyces cerevisiae/metabolismo , beta-Defensinas/metabolismo , beta-Defensinas/farmacologia , Lactoferrina/farmacologia , Lactoferrina/metabolismo , Potássio/metabolismo , Testes de Sensibilidade Microbiana , Candida albicans/efeitos dos fármacosRESUMO
BACKGROUND: COVID-19-induced diabetes is a novel and enigmatic disease. Our aim was to evaluate a possible relationship between post-COVID-19 syndrome (PCS) and increased insulin resistance (IR) in non-diabetic outpatients after mild COVID-19. METHODS: Repeated measures design. Three evaluations [1E (pre-COVID, baseline), 2E (3 months post-COVID) and 3E (21 months post-COVID)] were performed, directed to PCS+ and PCS- subjects. Triglyceride-glucose (TyG) index ≥8.74 was considered IR, and albumin-to-globulin ratio (AGR) <1.50, inflammation. RESULTS: We analyzed 112 individuals (median [IQR] age=44 [20] years, 58% women, 36 PCS+, 76 PCS-). PCS+ with very low basal IR (TyG <7.78, lowest quartile) showed a reduced inflammatory burden (basal AGR=1.81 [0.4] vs. 1.68 [0.2] in 2E; P=0.23), and increased TyG across evaluations (from basal 7.62 [0.2] to 8.29 [0.5]; P=0.018]. Conversely, PCS+ subjects with high basal TyG (TyG ≥8.65, highest quartile) did not show significant variations in TyG, but a greater inflammatory load (basal AGR=1.69 [0.3] vs. 1.44 [0.3] in 2E; P=0.10). In multivariable models addressing groups with reduced basal IR (TyG <8.01), PCS has been a consistent predictor for TyG, after adjusting for confounders. Partial correlation and multivariable analyses showed similarities involving acute polysymptomatic COVID-19 and PCS regarding IR. CONCLUSIONS: PCS was associated with increased IR, being more evident when the baseline degree of IR was very low. PCS and increased IR were separately associated with inflammation. Acute polysymptomatic COVID-19 and PCS could be clinical expressions of underlying inflammatory state, which in turn may also trigger IR.
RESUMO
INTRODUCTION/OBJECTIVES: DISH has traditionally been considered a non-inflammatory rheumatic disorder. Currently, an inflammatory component has been theorized in the early phases of this condition (EDISH). The study is aimed at investigating a possible relationship between EDISH and chronic inflammation. METHOD: Analytical-observational study: participants from the Camargo Cohort Study were enrolled. We collected clinical, radiological, and laboratory data. C-reactive protein (CRP), albumin-to-globulin ratio (AGR), and triglyceride-glucose (TyG) index were assessed. EDISH was defined by Schlapbach's scale grades I or II. A fuzzy matching with tolerance factor = 0.2 was performed. Subjects without ossification (NDISH), sex- and age-matched with cases (1:4), acted as controls. Definite DISH was an exclusion criterion. Multivariable analyses were performed. RESULTS: We evaluated 987 persons (mean age 64 ± 8 years; 191 cases with 63.9% women). EDISH subjects presented more frequently obesity, T2DM, MetS, and the lipid pattern [↑TG ↓TC]. TyG index and alkaline phosphatase (ALP) were higher. Trabecular bone score (TBS) was significantly lower (1.310 [0.2] vs. 1.342 [0.1]; p = 0.025). CRP and ALP showed the highest correlation (r = 0.510; p = 0.0001) at lowest TBS level. AGR was lower, and its correlations with ALP (r = - 0.219; p = 0.0001) and CTX (r = - 0.153; p = 0.022), were weaker or non-significant in NDISH. After adjustment for potential confounders, estimated CRP means for EDISH and NDISH were 0.52 (95% CI: 0.43-0.62) and 0.41 (95% CI: 0.36-0.46), respectively (p = 0.038). CONCLUSIONS: EDISH was associated with chronic inflammation. Findings revealed an interplay between inflammation, trabecular impairment, and the onset of ossification. Lipid alterations were similar to those observed in chronic-inflammatory diseases. Key Points ⢠An inflammatory component has been theorized in early stages of DISH (EDISH) ⢠In EDISH group compared to non-DISH, we observed significantly higher correlations between biomarkers and some relevant variables. In particular, with alkaline phosphatase (ALP) and with trabecular bone score (TBS) ⢠EDISH has shown to be associated with chronic inflammation ⢠The lipid alterations observed in the EDISH group were similar to those observed in chronic-inflammatory diseases.
Assuntos
Hiperostose Esquelética Difusa Idiopática , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Hiperostose Esquelética Difusa Idiopática/diagnóstico por imagem , Hiperostose Esquelética Difusa Idiopática/complicações , Estudos de Coortes , Fosfatase Alcalina , Inflamação/complicações , LipídeosRESUMO
BACKGROUND: ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association. METHODS: Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed. RESULTS: We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p = .036), and number of symptoms of PCS (p = .017) were noted in group O. Concerning biomarkers, PCS + and PCS- showed no differences in A, B, and AB groups. In contrast, group O PCS + patients had significantly lower albumin-to-globulin ratio and higher lymphocyte count, fibrinogen, CRP levels, and higher percentages of 3 composite indices, than PCS- subjects. Group O showed a 6-fold increased risk of PCS, compared to non-O (adjusted OR = 6.25 [95%CI, 1.6-23]; p = .007). CONCLUSIONS: Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.
Assuntos
COVID-19 , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , COVID-19/epidemiologia , Sistema ABO de Grupos Sanguíneos , Estudos de Casos e Controles , Pacientes Ambulatoriais , Estudos Retrospectivos , SARS-CoV-2 , Anticorpos Antivirais , Comorbidade , Imunoglobulina G , Biomarcadores , Fibrinogênio , Albuminas , Síndrome de COVID-19 Pós-AgudaRESUMO
OBJECTIVE: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS: We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.
Assuntos
Ageusia , COVID-19 , Anosmia , Biomarcadores , Proteína C-Reativa/análise , COVID-19/complicações , Estudos Transversais , Fadiga , Feminino , Fibrinogênio/análise , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Mialgia , Neutrófilos/metabolismo , Síndrome de COVID-19 Pós-AgudaRESUMO
Se realiza un estudio retrospectivo para evaluar los detalles clínicos y de tratamiento en 90 pacientes con seminoma de testículo tratados en el departamento de radioterapia del Instituto Nacional de Cancerología en un período comprendido entre 1974 a 1983. La mortalidad de acuerdo al estadio clínico inicial es descrita. Los resultados de sobrevida global a 10 años fueron de 66% con un 92% para el estadio clinico I, de un 85% en el lla y de 64% en el E.C.IIb (enfermedad voluminosa palpable infradiafragmática). El estadió clínico III tuvo una sobrevida del 50 % a 5 años y ningún paciente del E.C.IV estaba vivo en 2 años. Las recaidas se presentaron de manera temprana en los estadios IIb, III y IV, en el E.C. I hubo 2 recaidas (el 7%) y de 3 años. Se trataron de identificar factores pronósticos clínicos encontrando sólo significativamente el del volumen inicial de la enfermedad al momento del diagnóstico. Se define la conducta actual en el manejo de estos tumores. La tolerancia al tratamiento es muy buena no encontrándose complicaciones en nuestro reporte
Assuntos
Humanos , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Masculino , Disgerminoma , Neoplasias Testiculares , Estudos Retrospectivos , Testículo/fisiopatologiaRESUMO
De acuerdo a Leksell, el término radiocirugía se refiere a una dosis alta de radiación aplicada a un tumor intracerebral de pequeño tamaño. En la actualidad, el desarrollo de esta técnica requiere de: 1. Métodos estereotáxicos para la localización precisa del tumor; 2. Acelerador lineal adaptado para el tratamiento y 3. Equipo especializado constituido por un radioterapeuta, un neurocirujano con entrenamiento en estereotaxia y un físico-médico. En este artículo se presenta un estudio preliminar para el desarrollo de la radiocirugía en el Instituto Nacional de Cancerología.