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1.
Rev Esp Enferm Dig ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767017

RESUMO

Plummer-Vinson syndrome (PVS) is characterized by the classic triad of post-cricoid dysphagia, iron-deficiency anemia and esophageal webs. PVS is commonly found in women of middle age especially in the fourth and fifth decade of life. The prevalence of PVS has decreased due to early detection of iron deficiency and repletion of iron stores. We report a case of a 81-year-old female patient who had a classic presentation of PVS, treated successfully with endoscopic procedure. To our knowledge, the current case is the fourth case of dysphagia related to Plummer-Vinson syndrome reported in an octogenarian in the literature so far. Iron supplementation can resolve dysphagia in many patients, but dilation of esophageal webs may sometimes be required. PVS should be part of the differential diagnosis of sideropenic dysphagia, especially due the risk of pharyngeal and esophageal epidermoid neoplasia.

2.
Heliyon ; 10(9): e30613, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38737240

RESUMO

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

3.
Braz J Microbiol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38744770

RESUMO

OBJECTIVE: To evaluate the antimicrobial activity of Brazilian honeys against oral microorganisms. DESIGN: Organic honeys (OH-1 to OH-8) were diluted (%-w/v) and sterilized by filtration. Antimicrobial activity was defined by determining MIC and CBM against oral Streptococcus. The component responsible for the antimicrobial action was defined by a catalase assay. Antibiofilm activity was evaluated against the monospecies biofilm of Streptococcus mutans  (ATCC 700610). RESULTS: OHs showed antimicrobial activity principally OH-1, OH-2, OH-3, and OH-7 with MIC values ​​ranging between 10 and 25%. The mechanism of action occurs mainly by hydrogen peroxide produced by honey enzymes. OH-1, OH-2, and OH-7 showed total biofilm destruction at low concentrations. CONCLUSION: Brazilian honeys have promising antimicrobial and antibiofilm activity with the potential to control oral microbiota.

4.
PLoS Negl Trop Dis ; 18(5): e0012199, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38776344

RESUMO

BACKGROUND: In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD. METHODOLOGY/PRINCIPAL FINDINGS: In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells. CONCLUSION/SIGNIFICANCE: We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders.


Assuntos
Astrócitos , Doença de Chagas , Fluoxetina , Camundongos Endogâmicos C57BL , Serotonina , Trypanosoma cruzi , Animais , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/psicologia , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/fisiologia , Serotonina/metabolismo , Camundongos , Astrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Encéfalo/efeitos dos fármacos , Encéfalo/parasitologia , Encéfalo/metabolismo , Comportamento Animal/efeitos dos fármacos , Masculino , Humanos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Cognição/efeitos dos fármacos , Depressão/tratamento farmacológico , Carga Parasitária , Ansiedade/tratamento farmacológico
5.
Glob Ment Health (Camb) ; 11: e34, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572248

RESUMO

Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women's well-being and ensure healthcare system preparedness during future public health crises.

6.
NPJ Vaccines ; 9(1): 54, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459059

RESUMO

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

7.
Vaccine ; 42(8): 2065-2071, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38413280

RESUMO

OBJECTIVE: Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously. METHODS: Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively. RESULTS: Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10. CONCLUSION: Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation.


Assuntos
Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Criança , Humanos , Caxumba/prevenção & controle , Leucócitos Mononucleares , Vacina contra Sarampo-Caxumba-Rubéola , Brasil , Anticorpos Antivirais , Anticorpos Neutralizantes , Vacina contra Sarampo , Imunidade Celular , Rubéola (Sarampo Alemão)/prevenção & controle
8.
Clin Oral Investig ; 28(1): 72, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175293

RESUMO

OBJECTIVE: This study aimed to assess the effect of titanium dioxide (TiO2) and silver (Ag) nanoparticles dispersed in glycerol or water, serving as optical clearing agents nanocolloids (OCAs-NC), for improving optical coherence tomography (OCT) images and highlighting incipient lesions in ex vivo human teeth. MATERIALS AND METHODS: Twelve human teeth with incipient lesions were divided into seven groups according to the OCA-NC; they were subjected to G1 (air), G2 (glycerol), G3 (TiO2 0.1%), G4 (TiO2 0.01%), G5 (TiO2 0.001%), G6 (AgNO3 10%), and G7 (AgNO3 100%). The OCA-NC was applied to the occlusal surface, and two-dimensional images of the specimens were analyzed using OCT (930 nm central wavelength; 100 nm bandwidth; 5 mW output power; axial resolution of 7/5.3 µm in water and air, respectively; lateral resolution of 8 µm; and light penetration depth of 1.6 mm inside the sample). RESULTS: The findings demonstrated that the utilization of OCAs-NC containing metallic or dielectric nanoparticles (AgNO3 and TiO2) led to improved differentiation between sound and demineralized enamel on occlusal surfaces. Additionally, it enhanced the depth of image penetration when analyzing this hard tissue with OCT. CLINICAL RELEVANCE: In the current context of minimally invasive dentistry, the use of OCAs-NC in conjunction with OCT can provide clinicians with early diagnosis, allowing for the determination of less/more invasive therapies and consequently halting the disease before cavitation of dental tissues occurs.


Assuntos
Cárie Dentária , Nanopartículas , Humanos , Suscetibilidade à Cárie Dentária , Glicerol , Tomografia de Coerência Óptica , Cárie Dentária/diagnóstico por imagem , Água
9.
Methods Mol Biol ; 2733: 231-248, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38064036

RESUMO

Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological importance, efforts have been directed towards understanding various aspects of DENV biology, which have been facilitated by the development of different molecular strategies for engineering viral genomes, such as reverse genetics approaches. Reverse genetic systems are a powerful tool for investigating virus-host interaction, for vaccine development, and for high-throughput screening of antiviral compounds. However, stable manipulation of DENV genomes is a major molecular challenge, especially when using conventional cloning systems. To circumvent this issue, we describe a simple and efficient yeast-based reverse genetics system to recover infectious DENV clones.


Assuntos
Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Genética Reversa , Ensaios de Triagem em Larga Escala , Genoma Viral , Dengue/genética , Replicação Viral/genética
10.
J Vasc Nurs ; 41(4): 164-170, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38072568

RESUMO

BACKGROUND: Neuropathic and venous leg ulcers are chronic wounds associated with devitalized tissue and recurrent infection. Management should be guided by accurate tissue assessment, including the use of planimetry, which provides tissue types as a percentage of the total wound bed surface area. OBJECTIVE: This innovative study aimed to assess and identify the wound bed tissues, as a percentage, of neuropathic and venous ulcers using digital planimetry, providing support to nurses optimize the management of necrotic tissues and, consequently, to avoid wound infection. METHODS: This cross-sectional study enrolled 24 patients with chronic wounds who were assessed from January to March 2021 at the Wound Outpatients Clinic. The wound photographs were analyzed using Image J 1.53e and a smartphone with WoundDoc Plus® 2.8.2 via digital planimetry. Statistical analyses were performed using the binomial test, t-test, and Mann-Whitney. RESULTS: Median wound areas (p=0.3263) did not differ between the group with 2 or 3 risk factors for delayed healing (Md: 31.7) and the group with up to 1 risk factor (Md: 5.3). A low exudate level was associated with the up-to-1-risk-factor-for-delayed-healing group (p=0.0405), while a medium level was associated with the two-or-three-risk-factor group (p=0.0247). A heat map displayed the tissue percentages in the wound bed. In the group with 2 or 3 risk factors for delayed healing, 91.7% (11/12) had less than 70% granulation tissue, which was the primary factor for this group (p<0.0001). Additionally, 66.7% (8/12) of patients with 2 or 3 risk factors for delayed healing exhibited discolored and/or dark red granulation tissue as the primary factor (p=0.0130). CONCLUSION: This novel identification of wound area and tissue types as a percentage, using digital planimetry, can play a crucial role in assisting nurses in decision-making related to the appropriate management of devitalized tissues. Furthermore, this measurements may facilitate the conducting of virtual wound consultations and offer valuable support in the development of protocols aimed at preventing infection and biofilm formation in the wound bed.


Assuntos
Úlcera Varicosa , Humanos , Estudos Transversais , Cicatrização
11.
Sci Rep ; 13(1): 22695, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38123689

RESUMO

While the majority of individuals with coronavirus disease 2019 (COVID-19) recover completely, a significant percentage experience persistent symptom, which has been characterized as Long COVID and may be associated with cardiac and autonomic dysfunction. We evaluated heart rate variability (HRV) at rest and during deep-breathing (M-RSA) in patients with Long COVID. Case-control design involved 21 patients with Long COVID and 20 controls; the HRV was evaluated (POLAR system) at rest in the supine position and during M-RSA and expressed in time domain and non-linear analysis. In the supine position we found a reduction HRV measures in Long COVID' patients compared to controls for: Mean_iRR (p < 0.001), STD_iRR (p < 0.001); STD_HR (p < 0.001); SD1 (p < 0.001); SD2 (p < 0.001); alpha2 (p < 0.001). In the M-RSA we found reduction Mean_iRR (p < 0.001), STD_iRR (p < 0.001), STD_HR (p < 0.001), rMSSD (p < 0.001), RR_tri-index (p < 0.001) in Long COVID' patients except for highest Mean_HR p < 0.001. In conclusion, Long COVID reduced HRV at rest and during deep breathing. These findings may imply impairment of cardiac autonomic control when symptoms of COVID-19 persist following initial recovery.


Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Frequência Cardíaca/fisiologia , Sistema Nervoso Autônomo , Coração
12.
Open Forum Infect Dis ; 10(10): ofad490, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37869404

RESUMO

Awareness of neurological sequelae of dengue fever is increasing. However, as this case illustrates, there is a diagnostic conundrum in determining whether certain features are in keeping with dengue encephalopathy or dengue encephalitis. Further consensus is required.

13.
Ecotoxicology ; 32(7): 908-925, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37726560

RESUMO

Tropical rivers are the main destinations for tailings from urban, industrial and agricultural activities in the region studied. The present study aimed to investigate if early stages of zebrafish (Danio rerio) development is a viable biological model to assess the toxicity of surface waters of tropical rivers, and whether that toxicity could be correlated to standard water quality indexes. Embryos were exposed to samples from 55 sites from 10 hydrographic basins of rivers in Pernambuco State, northeastern Brazil. Lethality rates, sublethal toxicity based on the general morphology score (GMS) and frequencies of abnormalities were analyzed. Significant mortality was observed in samples of 7 basins. The GMS indicated significant delay in embryo-larval development in 50% of the samples. The highest toxicity was detected in basins within Recife metropolitan area, where 61% of the samples caused sublethal toxicity. Most frequent developmental abnormalities included non-inflation of the swim bladder, delayed hatching and blood stasis. The highest frequencies of blood stasis were detected in samples with highest NH3 concentrations, corroborated by a positive correlation suggesting the existence of a causal relationship. A significant correlation was detected between water quality indexes and GMS with a greater toxic effect being observed in samples collected in areas of greater urban density and greater contamination by domestic sewage. This study demonstrates that the early stages of the zebrafish is a viable ecotoxicological model to assess the toxicity of surface waters and can contribute to a better understanding between the chemical composition and the adverse effects suffered by fish early life stage fish in tropical rivers.


Assuntos
Rios , Peixe-Zebra , Animais , Brasil , Qualidade da Água , Modelos Biológicos
14.
Ann Transl Med ; 11(9): 315, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37404982

RESUMO

Background: Focal segmental glomerulosclerosis (FSGS) is frequently associated with heavy proteinuria and progressive renal failure requiring dialysis or kidney transplantation. However, primary FSGS also has a ~40% risk of recurrence of disease in the transplanted kidney (rFSGS). Multiple circulating factors have been identified to contribute to the pathogenesis of primary and rFSGS including soluble urokinase-type plasminogen activator receptor (suPAR) and patient-derived CD40 autoantibody (CD40autoAb). However, the downstream effector pathways specific to individual factors require further study. The tumor necrosis factor, TNF pathway activation by one or more circulating factors present in the sera of patients with FSGS has been supported by multiple studies. Methods: A human in vitro model was used to study podocyte injury measured as the loss of actin stress fibers. Anti-CD40 autoantibody was isolated from FSGS patients (recurrent and non-recurrent) and control patients with ESRD due to non-FSGS related causes. Two novel human antibodies-anti-uPAR (2G10) and anti-CD40 antibody (Bristol Meyer Squibb, 986090) were tested for their ability to rescue podocyte injury. Podocytes treated with patient derived antibody were transcriptionally profiled using whole human genome microarray. Results: Here we show that podocyte injury caused by sera from FSGS patients is mediated by CD40 and suPAR and can be blocked by human anti-uPAR and anti-CD40 antibodies. Transcriptomic studies to compare the molecules and pathways activated in response to CD40 autoantibody from rFSGS patients (rFSGS/CD40autoAb) and suPAR, identified unique inflammatory pathways associated with FSGS injury. Conclusions: We identified several novel and previously described genes associated with FSGS progression. Targeted blockade of suPAR and CD40 pathways with novel human antibodies showed inhibition of podocyte injury in FSGS.

15.
Viruses ; 15(7)2023 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-37515295

RESUMO

OBJECTIVES: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. METHODS: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. RESULTS: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVID-19 patients have both central memory and activated effector CD8+ T cells. Non-severe COVID-19 cases showed an increase in IL1ß, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8. CONCLUSIONS: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/genética , Interleucina-10 , Estudos de Coortes , Interleucina-6 , Brasil/epidemiologia , Imunogenética , Citocinas , Imunidade Celular
16.
Viruses ; 15(5)2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37243282

RESUMO

Interleukin-6 has been recognized as a major role player in COVID-19 severity, being an important regulator of the cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of the IL-6 pathway, namely IL6, IL6R, and IL6ST, may provide valuable prognostic/predictive markers for COVID-19. The present cross-sectional study genotyped three SNPs (rs1800795, rs2228145, and rs7730934) at IL6. IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As a control group, published data on gene and genotype frequencies were gathered from published studies before the pandemic started. Our major results point to an association of the IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion, the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidence from the literature about the association of these genotypes with mortality rates, pneumonia, and heightening of protein plasmatic levels pro-inflammatory driven effects.


Assuntos
COVID-19 , Interleucina-6 , Humanos , Interleucina-6/genética , Estudos Transversais , Receptores de Interleucina-6/genética , COVID-19/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Receptor gp130 de Citocina/genética
17.
Front Immunol ; 14: 1151058, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37138871

RESUMO

Introduction: Mannose-binding lectin (MBL) promotes opsonization, favoring phagocytosis and activation of the complement system in response to different microorganisms, and may influence the synthesis of inflammatory cytokines. This study investigated the association of MBL2 gene polymorphisms with the plasma levels of MBL and inflammatory cytokines in COVID-19. Methods: Blood samples from 385 individuals (208 with acute COVID-19 and 117 post-COVID-19) were subjected to real-time PCR genotyping. Plasma measurements of MBL and cytokines were performed by enzyme-linked immunosorbent assay and flow cytometry, respectively. Results: The frequencies of the polymorphic MBL2 genotype (OO) and allele (O) were higher in patients with severe COVID-19 (p< 0.05). The polymorphic genotypes (AO and OO) were associated with lower MBL levels (p< 0.05). IL-6 and TNF-α were higher in patients with low MBL and severe COVID-19 (p< 0.05). No association of polymorphisms, MBL levels, or cytokine levels with long COVID was observed. Discussion: The results suggest that, besides MBL2 polymorphisms promoting a reduction in MBL levels and therefore in its function, they may also contribute to the development of a more intense inflammatory process responsible for the severity of COVID-19.


Assuntos
COVID-19 , Lectina de Ligação a Manose , Humanos , Fator de Necrose Tumoral alfa/genética , Interleucina-6/genética , Citocinas/genética , Síndrome de COVID-19 Pós-Aguda , COVID-19/genética , Polimorfismo Genético , Lectina de Ligação a Manose/genética
18.
Viruses ; 15(4)2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-37112866

RESUMO

Aiming to evaluate the role of ten functional polymorphisms in long COVID, involved in major inflammatory, immune response and thrombophilia pathways, a cross-sectional sample composed of 199 long COVID (LC) patients and a cohort composed of 79 COVID-19 patients whose follow-up by over six months did not reveal any evidence of long COVID (NLC) were investigated to detect genetic susceptibility to long COVID. Ten functional polymorphisms located in thrombophilia-related and immune response genes were genotyped by real time PCR. In terms of clinical outcomes, LC patients presented higher prevalence of heart disease as preexistent comorbidity. In general, the proportions of symptoms in acute phase of the disease were higher among LC patients. The genotype AA of the interferon gamma (IFNG) gene was observed in higher frequency among LC patients (60%; p = 0.033). Moreover, the genotype CC of the methylenetetrahydrofolate reductase (MTHFR) gene was also more frequent among LC patients (49%; p = 0.045). Additionally, the frequencies of LC symptoms were higher among carriers of IFNG genotypes AA than among non-AA genotypes (Z = 5.08; p < 0.0001). Two polymorphisms were associated with LC in both inflammatory and thrombophilia pathways, thus reinforcing their role in LC. The higher frequencies of acute phase symptoms among LC and higher frequency of underlying comorbidities might suggest that acute disease severity and the triggering of preexisting condition may play a role in LC development.


Assuntos
COVID-19 , Trombofilia , Humanos , Síndrome de COVID-19 Pós-Aguda , Frequência do Gene , Marcadores Genéticos , Estudos Transversais , COVID-19/genética , Genótipo , Predisposição Genética para Doença , Trombofilia/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles
19.
Viruses ; 15(4)2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-37112878

RESUMO

The first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in Brazil was diagnosed on February 26, 2020. Due to the important epidemiological impact of COVID-19, the present study aimed to analyze the specificity of IgG antibody responses to the S1, S2 and N proteins of SARS-CoV-2 in different COVID-19 clinical profiles. This study enrolled 136 individuals who were diagnosed with or without COVID-19 based on clinical findings and laboratory results and classified as asymptomatic or as having mild, moderate or severe disease. Data collection was performed through a semistructured questionnaire to obtain demographic information and main clinical manifestations. IgG antibody responses to the S1 and S2 subunits of the spike (S) protein and the nucleocapsid (N) protein were evaluated using an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. The results showed that among the participants, 87.5% (119/136) exhibited IgG responses to the S1 subunit and 88.25% (120/136) to N. Conversely, only 14.44% of the subjects (21/136) displayed S2 subunit responses. When analyzing the IgG antibody response while considering the different proteins of the virus, patients with severe disease had significantly higher antibody responses to N and S1 than asymptomatic individuals (p ≤ 0.0001), whereas most of the participants had low antibody titers against the S2 subunit. In addition, individuals with long COVID-19 showed a greater IgG response profile than those with symptomatology of a short duration. Based on the results of this study, it is concluded that levels of IgG antibodies may be related to the clinical evolution of COVID-19, with high levels of IgG antibodies against S1 and N in severe cases and in individuals with long COVID-19.


Assuntos
COVID-19 , Humanos , Anticorpos Antivirais , Formação de Anticorpos , Imunoglobulina G , Proteínas do Nucleocapsídeo , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
20.
Viral Immunol ; 36(2): 136-143, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36745398

RESUMO

Human T lymphotropic virus 1 (HTLV-1) is a retrovirus associated with inflammatory diseases, including HTLV-1-associated myelopathy (HAM), and host genetic factors may be involved in disease evolution. The forkhead Box P3 (FOXP3) transcription factor is linked to homeostasis of the immune system, and the presence of polymorphisms in the promoter region of the FOXP3 gene should reflect its expression levels and consequent activation of regulatory T cells, which may contribute to severe inflammatory disorders, such as HAM. This study evaluated the rs2232365 polymorphism (-924 A/G) located in the promoter region of the FOXP3 gene and its association with HAM. Forty DNA samples from asymptomatic carriers and 25 samples from HAM patients were used, in addition to 130 control samples. The polymorphism was genotyped by conducting real-time polymerase chain reaction (PCR) (quantitative PCR [qPCR]) on extracted DNA. The proviral loads (PVLs) and CD4+ and CD8+ T lymphocyte counts were determined by qPCR and FACSCalibur flow cytometry, respectively. The PVLs, CD4+ T lymphocyte concentrations, and tumor necrosis factor-α dosages were considered predictive factors of the clinical profiles of HTLV-1 infection, all of which had higher levels in the HAM group. Carriers of the GG genotype for the polymorphism rs2232365 had high PVLs and CD4+ T lymphocyte concentrations.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Humanos , Paraparesia Espástica Tropical/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Polimorfismo de Nucleotídeo Único , Infecções por HTLV-I/genética , Fatores de Transcrição Forkhead/genética , Carga Viral , Provírus/genética , Provírus/metabolismo
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