RESUMO
Objectives: To determine if there is an association between the neutrophil to lymphocyte ratio (NLR) and prognosis in patients with epithelial ovarian cancer (EOC) diagnosed and treated in a Spanish population. Material and methods: Retrospective cohort of patients with epithelial ovarian cancer who had neutrophil and lymphocyte values in complete blood count before the histopathological diagnosis and survival of at least three months, in an intermediate complexity hospital. Convenience sampling. Measured variables included age, menopausal stage, parity, International Federation of Gynecology and Obstetrics (FIGO) stage, treatment type, residual tumor, lymph node involvement, presence of ascites, cytology, histologic type, differentiation grade, and CA-125 values. Additionally, outcomes, overall survival, disease/progression-free survival were also measured. Bivariate inferential and Cox regression analyses were performed. Results: Out of 78 candidates, 60 women with EOC were included. Of them, 24 (40%) had a low NLR (≤ 2,9) while 36 (60%) had a high NLR (> 2,9). An association was found between high NLR levels and suboptimal cytoreductive surgery. High NLR ratios were associated with lower overall survival (Hazard ratio (HR): 4.1; 95% CI: 1.4-11.8) and lower 5-year disease-free survival (HR: 2.6; 95% CI: 1.2-5.7). Conclusions: A plasma neutrophil to lymphocyte ratio of more than 2.9 was associated with poor prognosis in patients with epithelial ovarian cancer in our setting. There is a need to establish the optimal cut-off point and conduct prospective studies with larger patient numbers in order to support this information.
Objetivos: evaluar si hay asociación entre los valores del cociente plasmático neutrófilos/ linfocitos (NLR) y el pronóstico en pacientes con cáncer epitelial de ovario (CEO) diagnosticadas y tratadas en una población española. Materiales y métodos: cohorte retrospectiva de pacientes con cáncer epitelial de ovario que tuvieran un recuento de neutrófilos y linfocitos en hemograma previo al diagnóstico histopatológico en un hospital de nivel medio de complejidad y posterior sobrevida de, al menos, 3 meses. Muestreo por conveniencia. Se midieron: edad, estado menopáusico, paridad, estadio Federación International de Ginecología y Obstetricia (FIGO), tipo de tratamiento, tumor residual, afectación ganglionar, presencia de ascitis, citología, tipo histológico, grado de diferenciación y cifras de CA-125; como desenlaces, sobrevida global y sobrevida libre de enfermedad o progresión. Análisis inferencial bivariado y por regresión de Cox. Resultados: de 78 candidatas, ingresaron 60 mujeres con CEO. De ellas, 24 (40%) presentaron un NLR bajo (≤ 2,9) y 36 (60 %) elevado (> 2,9). Se encontró asociación entre los niveles altos de NLR y cirugía citoreductora subóptima. Los niveles altos de NLR se asociaron a menor sobrevida global (Hazard ratio (HR): 4,1; IC 95%: 1,4-11,8) y menor sobrevida libre de enfermedad a los 5 años (HR:2,6; IC 95 %: 1,2-5,7). Conclusiones: un cociente plasmático neutrófilos/linfocitos mayor de 2,9 se asoció a un mal pronóstico en pacientes con cáncer epitelial de ovario en nuestro medio. Se necesita determinar el punto de corte óptimo y realizar estudios prospectivos con mayor número de pacientes que avalen esta información.
Assuntos
Carcinoma Epitelial do Ovário , Linfócitos , Neutrófilos , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Prognóstico , Pessoa de Meia-Idade , Linfócitos/patologia , Idoso , Adulto , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Espanha/epidemiologia , Intervalo Livre de Doença , Contagem de Linfócitos , Taxa de Sobrevida , Período Pré-Operatório , Contagem de LeucócitosRESUMO
OBJECTIVE: To investigate the effects of Araucaria sp. brown propolis (ABP) against trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. METHODS: Animals received vehicle (1% DMSO, 1 ml/kg) or hydroalcoholic extract of ABP (hydroalcoholic extract of Araucaria sp. brown propolis (HEABP), 30, 100, and 300 mg/kg) orally, or dexamethasone (25 mg/kg, s.c.) for 5 days. On day 4, the animals received intracolonic TNBS (150 mg/kg), on day 6 they were euthanized. The weight of the animals, the macroscopic and microscopic colonic damage, reduced glutathione (GSH) and malondialdehyde (MDA) levels, and the activity of glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) were measured in colon homogenate. The action of HEABP and two isolated compounds in neutrophil migration was recorded. KEY FINDINGS: HEABP (100 and 300 mg/kg), but not dexamethasone, decreased colonic lesion, and increased colonic mucin staining. In parallel, HEABP decreased MDA and restored GSH levels and the activity of SOD, CAT, and GST in the colon. A dose-dependent inhibition of MPO activity was observed (LogIC50 = 1.9). Moreover, HEBPA and the junicedric and abietic acids inhibited the neutrophil chemotaxis in vitro and HEBPA reduced neutrophil migration in vivo. CONCLUSION: HEABP may be promising in the therapies for inflammatory bowel diseases, reducing oxidative and inflammatory damage, especially mediated by neutrophils.
Assuntos
Colite Ulcerativa , Malondialdeído , Estresse Oxidativo , Extratos Vegetais , Própole , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Própole/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Malondialdeído/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Colo/metabolismo , Peroxidase/metabolismo , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Modelos Animais de Doenças , Dexametasona/farmacologia , Traqueófitas/química , Catalase/metabolismo , Relação Dose-Resposta a Droga , Antioxidantes/farmacologia , Glutationa Transferase/metabolismoRESUMO
Mastitis, an inflammation of the mammary gland affecting milk production and quality in dairy herds, is often associated with Staphylococcus spp. in goats. Neutrophils are crucial in combating infections by migrating into milk and deploying various defense strategies, including the release of neutrophil extracellular traps (NETs) composed of DNA, histones, and bactericidal proteins. This study investigated whether NETs are released by goat neutrophils stimulated in vitro by Staphylococcus aureus and Staphylococcus warneri, two common pathogens of goat mastitis. PMNs were isolated from blood from healthy adult goats. We evaluated goat NET formation by stimulating cells with: phorbol 12-myristate 13-acetate (PMA) as a positive control, cytochalasin for inhibition of actin polymerization, S. aureus, and S. warneri. NET formation was observed in response to chemical stimulation and bacterial presence, effectively trapping pathogens. Variations in NET formation between S. aureus and S. warneri suggest pathogen-specific responses. These findings suggest that the formation of NETs may be an important complementary mechanism in the defense against mastitis in goats. In conclusion, this study unveils a novel defense mechanism in goats, indicating the role of NETs against S. aureus and S. warneri in mastitis.
Assuntos
Armadilhas Extracelulares , Doenças das Cabras , Cabras , Mastite , Neutrófilos , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Cabras/imunologia , Armadilhas Extracelulares/imunologia , Feminino , Mastite/veterinária , Mastite/imunologia , Mastite/microbiologia , Doenças das Cabras/imunologia , Doenças das Cabras/microbiologia , Neutrófilos/imunologia , Staphylococcus aureus/imunologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/imunologia , Staphylococcus/imunologiaRESUMO
BACKGROUND: In an aging population, there is an increasing need for easily accessible nutritional markers. AIMS: To determine whether the neutrophil-to-lymphocyte ratio (NLR) can serve as an effective nutritional indicator compared to the Mini-Nutritional Assessment Short Form (MNA-SF) or other common markers such as albumin and body mass index (BMI). METHODS: Data were obtained from the SABE study in Ecuador, which included participants aged 60 years or older. This cross-sectional study collected comprehensive data, including demographics, health-related factors, and physical assessments. Neutrophil and lymphocyte counts were measured by complete blood count. Nutritional status was assessed by MNA-SF, and BMI was calculated. Several physical tests were performed to evaluate the participants' functional status. Confounding variables such as age, sex, and comorbidities were considered. RESULTS: The final sample consisted of 1790 subjects (48.9% male). The overall median age was 68 years (IQR 64,76). BMI and lymphocytes were higher in females, while NLR was higher in males. MNA-SF showed a negative association with NLR. Similarly, lymphocyte count shows a positive association with MNA-SF. Physical tests, such as the Romberg test and the Five Times Sit-to-Stand test, also showed correlations with NLR and lymphocyte count, respectively. CONCLUSION: The study results suggest a significant relationship between NLR and lymphocytes, and nutritional status. The correlation with albumin is stronger with NLR than with BMI. The simplicity and affordability of NLR may make it suitable for routine use in several medical fields, improving our understanding of the complex relationship between nutrition, inflammation, and overall health.
Assuntos
Índice de Massa Corporal , Vida Independente , Linfócitos , Neutrófilos , Avaliação Nutricional , Estado Nutricional , Humanos , Masculino , Feminino , Idoso , Neutrófilos/citologia , Estudos Transversais , Pessoa de Meia-Idade , Contagem de Linfócitos , Equador , Avaliação Geriátrica/métodos , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de LeucócitosRESUMO
Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.
RESUMO
Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.
Assuntos
Eritema Nodoso , Perfilação da Expressão Gênica , Hanseníase Virchowiana , Ativação de Neutrófilo , Neutrófilos , Transcriptoma , Humanos , Eritema Nodoso/imunologia , Eritema Nodoso/sangue , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/diagnóstico , Hanseníase Virchowiana/sangue , Adulto , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Feminino , Pessoa de Meia-Idade , Proteínas Ligadas por GPI/genética , Talidomida , Receptores de Superfície Celular/genética , Hansenostáticos/uso terapêutico , Hansenostáticos/farmacologia , Adulto Jovem , Biomarcadores , IsoantígenosRESUMO
Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.
Assuntos
Membrana Celular , Endocitose , Canais Epiteliais de Sódio , Hipertensão , Neutrófilos , Canais Epiteliais de Sódio/metabolismo , Humanos , Neutrófilos/metabolismo , Hipertensão/metabolismo , Hipertensão/patologia , Membrana Celular/metabolismo , Lipídeos de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Masculino , Feminino , Proteínas Imediatamente Precoces/metabolismo , Pessoa de Meia-Idade , Microdomínios da Membrana/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: The isolation of neutrophils and subsequent detection of anti-human neutrophil antigens (HNA) antibodies are crucial in clinical medicine for the diagnosis of autoimmune neutropenia, neonatal alloimmune neutropenia (NAIN) and transfusion-related acute lung injury (TRALI). This study reports two cases of maternal anti-Fc-gamma-receptor-IIIb (FcγRIIIb) isoimmunization without NAIN symptoms and compares the efficiency of immunomagnetic negative selection (IMNS) with traditional dextran/Ficoll for neutrophil isolation in HNA serological assays. MATERIALS AND METHODS: Investigating two cases of maternal anti-FcγRIIIb isoimmunization, neutrophils from three donors were isolated from 8 mL of whole blood using IMNS and dextran/Ficoll. Serological assays included the granulocyte agglutination and immunofluorescence test, monoclonal antibody immobilization of granulocyte antigens and the LABScreen Multi (One Lambda). IMNS and dextran/Ficoll were compared in terms of cell yield, viability, time, cost and purity. RESULTS: Maternal anti-FcγRIIIb isoantibodies with FCGR3B gene deletion were detected in both cases. Newborns and fathers exhibited specific gene combinations: FCGR3B*02/FCGR3B*02 (Case 1) and FCGR3B*02/FCGR3B*03 (Case 2). IMNS outperformed dextran/Ficoll, yielding four times more neutrophils (average neutrophil counts: 18.5 × 103/µL vs. 4.5 × 103/µL), efficiently removing non-neutrophil cells and reducing processing time (30-40 min vs. 70-90 min), although it incurred a higher cost (2.7 times). CONCLUSION: Two cases of maternal anti-FcγRIIIb isoantibodies, unrelated to NAIN, were identified. Although neutropenia has not been described in these cases, we emphasize the importance of identifying asymptomatic cases with the potential for severe neutropenia. Additionally, IMNS is introduced as a rapid, high-yield, high-purity neutrophil isolation technique, beneficial for serological assays detecting anti-HNA antibodies.
Assuntos
Isoanticorpos , Neutrófilos , Receptores de IgG , Humanos , Neutrófilos/imunologia , Feminino , Receptores de IgG/imunologia , Isoanticorpos/imunologia , Isoanticorpos/sangue , Recém-Nascido , Proteínas Ligadas por GPI/imunologia , Masculino , Separação Imunomagnética/métodos , Adulto , Gravidez , Neutropenia/imunologia , Neutropenia/sangueRESUMO
PURPOSE: Accurate height and weight measurement can be challenging in older adults and complicates nutritional status assessment. Other parameters like the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte count (LC) could be an option to these measurements. We aimed to test these variables as subrogates of body mass index (BMI) or calf-circumference (CC) for malnutrition screening in community-dwelling older adults. METHODS: This is a secondary analysis from the Salud, Bienestar y Envejecimiento (SABE) survey from Ecuador (2009). Includes data on demographics, health-related factors, physical assessments, and complete blood count, allowing to calculate NLR and LC to be used as part of the Mini Nutritional Assessment (MNA), instead of the BMI. Consequently, 4 models were included: standard MNA, MNA-CC, MNA-NLR and MNA-LC. Finally, age, sex, and comorbidities were considered as confounding variables. RESULTS: In our analysis of 1,663 subjects, 50.81% were women. Positive correlations with standard MNA were found for MNA-NLR (Estimate = 0.654, p < 0.001) MNA-CC (Estimate = 0.875, p value < 0.001) and MNA-LC (Estimate = 0.679, p < 0.001). Bland-Altman plots showed the smallest bias in MNA-CC. Linear association models revealed varying associations between MNA variants and different parameters, being MNA-NLR strongly associated with all of them (e.g. Estimate = 0.014, p = 0.001 for albumin), except BMI. CONCLUSION: The newly proposed model classified a greater number of subjects at risk of malnutrition and fewer with normal nutrition compared to the standard MNA. Additionally, it demonstrated a strong correlation and concordance with the standard MNA. This suggests that hematological parameters may offer an accurate alternative and important insights into malnutrition.
Assuntos
Índice de Massa Corporal , Avaliação Geriátrica , Desnutrição , Neutrófilos , Avaliação Nutricional , Humanos , Feminino , Masculino , Idoso , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/sangue , Equador/epidemiologia , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Idoso de 80 Anos ou mais , Contagem de Linfócitos/métodos , Linfócitos , Estado Nutricional , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Vida Independente/estatística & dados numéricosRESUMO
The SARS-CoV-2 P.1 variant, responsible for an outbreak in Manaus, Brazil, is distinguished by 12 amino acid differences in the S protein, potentially increasing its ACE-2 affinity and immune evasion capability. We investigated the innate immune response of this variant compared to the original B.1 strain, particularly concerning cytokine production. Blood samples from three severe COVID-19 patients were analyzed post-infection with both strains. Results showed no significant difference in cytokine production of mononuclear cells and neutrophils for either variant. While B.1 had higher cytopathogenicity, neither showed viral replication in mononuclear cells. Structural analyses of the S protein highlighted physicochemical variations, which might be linked to the differences in infectivity between the strains. Our studies point to the increased infectivity of P.1 could stem from altered immunogenicity and receptor-binding affinity.
RESUMO
OBJECTIVE: To compare the relative frequencies of immune cell populations in the peripheral blood according to A. lumbricoides infection status. METHODS: Peripheral blood samples were collected from participants infected (n = 35) and uninfected with A. lumbricoides (n=27) residing in different rural municipalities of Bolívar. Infection was diagnosed using two coprological examinations and the Kato-Katz technique. Immunophenotyping was performed using two panels of markers and staining in fresh blood. The flow cytometry reading was performed on a spectral cytometer (Northern Lights, Cytek, USA). The populations identified in the first panel (Figure 1) were T lymphocytes (CD45+ CD3+), CD4+ or CD8+, B lymphocytes (CD45+ SSClow CD3- CD19+), neutrophils (CD45+ SSChi CD3- CD16+), and eosinophils (CD45+ SSChi CD3- CD16low). Monocytes were identified in another panel (Figure 2): classical (CD14++ CD16 -), intermediate (CD14++ CD16+), and non-classical (CD14+ CD16++). Dendritic cells, including CD123 + + CD303 + (plasmacytoid), HLA-DR + + CD1c + (myeloid CD1c +), and CD14-CD141 + + (myeloid CD141 +), were also identified. The study received approval from the Ethics Committee of the University of Cartagena, and participants provided informed consent. Funding was provided by the Colombian Sistema General de Regalías under BPIN2020000100405 - BPIN2020000100364. RESULTS: No significant differences were observed in age [mean cases: 35.69 (SD: 17.7) vs. controls: 37.04 (SD: 15.6) years] or sex (cases: 62.9% vs. controls: 74.1%) (Table 1). All infections were mild, with a median of 96 eggs (IQR, 48-216). A marginally significant difference was observed only in the percentage of neutrophils (45.37% in cases vs. 54.79% in controls, p=0.041) (Figure 3). Although the frequency of eosinophils was higher in the cases (8.1% vs. 6%), this difference was not significant (p=0.138) (Figure 3). No significant differences were observed in the populations of monocytes or dendritic cells between cases and controls (Figure 4). CONCLUSION: Mild A. lumbricoides infection appears to affect the number of neutrophils in peripheral blood. The low infection intensity in the studied samples may explain the lack of a significant impact on other cellular populations.
OBJETIVO: Comparar las frecuencias relativas de poblaciones de células inmunes en sangre periférica de acuerdo con el estado de infección por A. lumbricoides. MÉTODOS: Se recolectaron muestras de sangre periférica de participantes infectados (n=35) y no infectados con A. lumbricoides (n=27), residentes en distintos municipios rurales de Bolívar. La infección se diagnosticó por dos métodos coprológicos y la técnica de Kato-Katz. El inmunofenotipo se determinó con dos baterías de marcadores y tinciones en sangre fresca. La lectura fue realizada en un citómetro espectral (Northern Lights, Cytek, USA). Las poblaciones identificadas en la primera batería (Figura 1) fueron linfocitos T (CD45+ CD3+) CD4+ o CD8+, linfocitos B (CD45+ SSClow CD3- CD19+), neutrófilos (CD45+ SSChi CD3- CD16+), y eosinófilos (CD45+ SSChi CD3- CD16low). Los monocitos se identificaron en otra batería (Figura 2): clásicos (CD14++ CD16), intermedios (CD14++ CD16+), y no clásicos (CD14+ CD16++). También se identificaron células dendríticas, tales como: CD123++ CD303+ (plasmocitoides), HLA-DR++ CD1c+ (mieloides CD1c+), y CD14- CD141++ (mieloides CD141+). El estudio recibió la aprobación del Comité de Ética de la Universidad de Cartagena, y los participantes otorgaron su consentimiento informado. La financiación fue proporcionada por el Sistema General de Regalías de Colombia, bajo el BPIN2020000100405 - BPIN2020000100364. RESULTADOS: No se observaron diferencias significativas en edad [media = casos: 35,69 (DE: 17,7) vs controles: 37,04 (DE: 15,6 años] o sexo (casos: 62,9% vs. controles: 74,1%). Todas las infecciones fueron leves con una mediana de huevos de 96 (RIC: 48 - 216). Solo se encontró diferencia significativa marginal en el porcentaje de neutrófilos (45,37% en los casos vs 54,79% en controles, p=0,041). Si bien la frecuencia de eosinófilos fue más alta en los casos (8,1% vs. 6%), esta diferencia no alcanzó la significancia (p=0,138). No se observaron diferencias significativas en las poblaciones de monocitos o células dendríticas entre casos y controles (Figura 4). CONCLUSIÓN: La infección leve por A. lumbricoides parece afectar el número de neutrófilos en sangre periférica. Es posible que por la baja intensidad de la infección en la muestra estudiada, no se detecte un impacto importante de la misma sobre el resto de las poblaciones celulares. Palabras claves: Helmintos; Ascaris lumbricoides; Citometría de flujo; Inmunofenotipado; Neutrófilos.
Assuntos
Ascaríase , Humanos , Masculino , Feminino , Ascaríase/imunologia , Ascaríase/epidemiologia , Adulto , Adolescente , Animais , Adulto Jovem , Saúde da População Rural , Criança , Ascaris lumbricoides , Pessoa de Meia-Idade , ColômbiaRESUMO
OBJECTIVE: Recent studies have described a significant role for neutrophils in reproductive processes and their participation in the preparation of the cervix for childbirth and the activation of labor, in the postpartum involution of the uterus, and in the occurrence of preeclampsia. This study aimed to assess the formation of free radicals by neutrophils in the blood of women on the first day after childbirth and to characterize the adrenergic effect on this process. METHODS: Venous blood samples from 100 female volunteers aged 26-32 years who had 2 or 3 full-term deliveries were collected and analyzed. Various adrenergic compounds were considered (agonists alphaand betaadrenoreceptors, adrenoblockers). The intensity of the respiratory burst of neutrophils and the effect of adrenergic substances on them were assessed with latex-induced luminol-dependent chemiluminescence. RESULTS: Neutrophil activity depends on the stage of the woman's reproductive process: it decreases during pregnancy, reaches the lowest values during childbirth, and increases significantly in the first hours after childbirth. On the first day after childbirth, alpha-1-adrenergic receptors are highly active in neutrophils, through which NADP-H-oxidase is activated and activated oxygen species are formed. At the same time, alphaor beta-agonists inhibit the radical activity of cells. CONCLUSIONS: Latex-induced oxidative burst of female blood neutrophils correlates with the stage of the reproductive process. Stressful conditions in the postpartum period can suppress the ability of neutrophils to release reactive oxygen species, which increases the risk of postpartum infections.
Assuntos
Neutrófilos , Período Pós-Parto , Humanos , Feminino , Neutrófilos/efeitos dos fármacos , Adulto , Gravidez , Explosão Respiratória/efeitos dos fármacos , Explosão Respiratória/fisiologia , Adrenérgicos/farmacologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
The elusive nature of the liver immune system in newborns remains an important challenge, casting a shadow over our understanding of how to effectively treat and prevent diseases in children. Therefore, deeper exploration into the intricacies of neonatal immunology might be crucial for improved pediatric healthcare. Using liver intravital microscopy, we unveiled a significant population of granulocytes in the hepatic parenchyma of fetuses and newborns. Utilizing high-dimensional immunophenotyping, we showed dynamic alterations predominantly in granulocytes during neonatal development. Liver intravital microscopy from birth through adulthood captures real-time dynamics, showing a substantial presence of Ly6G + cells that persisted significantly up to 2 weeks of age. Using CyTOF, we characterized neonatal Ly6G + cells as neutrophils, confirmed by morphology and immunohistochemistry. Surprisingly, the embryonic liver hosts a distinct population of neutrophils established as early as the second gestational week, challenging conventional notions about their origin. Additionally, we observed that embryonic neutrophils occupy preferentially the extravascular space, indicating their early establishment within the liver. Hepatic neutrophils in embryos and neonates form unique cell clusters, persisting during the initial days of life, while reduced migratory capabilities in neonates are observed, potentially compensating with increased reactive oxygen species (ROS) release in response to stimuli. Finally, in vivo imaging of acute neutrophil behavior in a newborn mouse, subjected to focal liver necrosis, unveils that neonatal neutrophils exhibit a reduced migratory response. The study provides unprecedented insights into the intricate interplay of neutrophils within the liver, shedding light on their functional and dynamic characteristics during development.
RESUMO
BACKGROUND: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. METHODS: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. RESULTS: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. CONCLUSIONS: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.
Assuntos
Infecções por HIV , Vacina contra Febre Amarela , Febre Amarela , Humanos , Vacina contra Febre Amarela/efeitos adversos , Febre Amarela/prevenção & controle , Estudos Longitudinais , Viremia , Anticorpos Antivirais , Brasil , Vacinação/métodos , FígadoRESUMO
OBJECTIVE: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. INTERVENTIONS: None. MAIN VARIABLES OF INTERESTS: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. RESULTS: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65-0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77-8.85) after adjusting for confounders. CONCLUSION: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients' risk and to consider timely alternative care and management.
Assuntos
Neutrófilos , Acidente Vascular Cerebral , Humanos , Masculino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Prognóstico , Estudos Retrospectivos , Contagem de Plaquetas , Linfócitos , PlaquetasRESUMO
This study explores Neutrophil Extracellular Trap (NET) formation in equine neutrophils, which is crucial for eliminating infections and is implicated in various equine inflammatory diseases. We investigated the molecular pathways involved in NET release by equine neutrophils in response to stimuli. We use PMA, A23187, LPS, PAF, OZ, and cytokines, observing NET release in response to PMA, PAF, and A23187. In contrast, LPS, OZ, and the cytokines tested did not induce DNA release or did not consistently induce citrullination of histone 4. Peptidyl-arginine deiminase inhibition completely halted NET release, while NADPH oxidase and mitochondrial reactive oxygen species only played a role in PMA-induced NETs. Neutrophil elastase inhibition modestly affected PAF-induced NET liberation but not in PMA or A23187-induced NET, while myeloperoxidase did not contribute to NET release. We expect to provide a foundation for future investigations into the role of NETs in equine health and disease and the search for potential therapeutic targets.
Assuntos
Armadilhas Extracelulares , Neutrófilos , Animais , Cavalos , Neutrófilos/metabolismo , Armadilhas Extracelulares/metabolismo , Calcimicina/metabolismo , Lipopolissacarídeos/metabolismo , Citocinas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Neutrophil and lymphocyte ratio (NLR) has emerged as a complementary marker in intensive care. This study aimed to associate high NLR values with mortality as the primary outcome, and length of stay and need for invasive mechanical ventilation as secondary outcomes, in critically ill patients with COVID-19. A cross-sectional study encompassing 189 critically ill patients with COVID-19 was performed. The receiver operating characteristic curve was used to identify the best NLR cutoff value for ICU mortality (≥ 10.6). An NLR ≥ 10.6, compared with an NLR < 10.6, was associated with higher odds of ICU mortality (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.24-6.18), ICU length of stay ≥ 14 days (OR, 3.56; 95% CI, 1.01-12.5), and need for invasive mechanical ventilation (OR, 5.39; 95% CI, 1.96-14.81) in the fully adjusted model (age, sex, kidney dysfunction, diabetes, obesity, hypertension, deep vein thrombosis, antibiotics, anticoagulants, antivirals, corticoids, neuromuscular blockers, and vasoactive drugs). In conclusion, elevated NLR is associated with high rates of mortality, length of stay, and need for invasive mechanical ventilation in critically ill patients with COVID-19.
Assuntos
COVID-19 , Respiração Artificial , Humanos , COVID-19/terapia , Neutrófilos , Tempo de Internação , Estado Terminal , Estudos Transversais , Linfócitos , Unidades de Terapia Intensiva , Estudos RetrospectivosRESUMO
Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Hanseníase Virchowiana/imunologia , Hanseníase Virchowiana/sangue , Eritema Nodoso/imunologia , Proteínas Ligadas por GPI , Neutrófilos/imunologiaRESUMO
ABSTRACT Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]. Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5. Results: A total of 202 PLWH with CD4 > 200 cells/μL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia. Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 > 200 cells/μL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination.