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1.
Artigo em Inglês | MEDLINE | ID: mdl-32872648

RESUMO

The study aimed to determine if oral hygiene influences not only oral health but also potentially metabolic disorders such as overweight or obesity. Participants were 94 patients: 40 with increased body mass and 54 with normal body mass. The methods included dental examination, a questionnaire concerning hygienic habits and an assessment of selected salivary inflammatory markers. The new parameter named "cleaning index" (describing the interaction between average time of tooth brushing in minutes and its frequency per day) significantly correlated with Body Mass Index (RSpearman = 0.300). The multivariate regression model incorporating cleaning index, approximal plaque index, receptor 1 for tumor necrosis factor-alpha (TNFα-R1) and interleukin-15 (IL-15) had a high power to predict overweight or obesity (AUC = 0.894). Patients with poor oral hygiene (approximal plaque index >40%) were more than eight times more likely to suffer from obesity than patients with good oral hygiene. Cleaning index higher than 4 decreased the odds by about 85%. Oral hygiene habits, adjusted by salivary concentrations of selected inflammatory markers may allow predicting effectively overweight or obesity risk. Early proper dental prophylaxis and treatment could lead to the better prevention of metabolic disorders.


Assuntos
Higiene Bucal , Sobrepeso , Saliva , Adulto , Índice de Massa Corporal , Quimiocina CCL2/análise , Citocinas/análise , Índice de Placa Dentária , Feminino , Humanos , Interleucina-15/análise , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/imunologia , Saúde Bucal , Índice de Higiene Oral , Sobrepeso/epidemiologia , Sobrepeso/imunologia , Doenças Periodontais/diagnóstico , Doenças Periodontais/epidemiologia , Doenças Periodontais/imunologia , Valor Preditivo dos Testes , Saliva/química , Adulto Jovem
2.
Life Sci ; 261: 118479, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32966840

RESUMO

AIMS: This study was designed to investigate the molecular mechanisms underlying the anti-inflammatory and anti-fibrosis effects of Berberine hydrochloride (BBR) following canalicular laceration (CL) surgical repair. MAIN METHODS: We used a rabbit CL model in this study. BBR and the control medicine were administered during and after the surgical operation. The degree of fibrosis in the canaliculi was evaluated using hematoxylin and eosin and Masson's trichrome staining 7 days after the operation. Inflammation inside the canaliculi was observed using a transcanalicular endoscope. Expression levels of inflammatory cell cytokines [tumor growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), intracellular adhesion molecule-I (ICAM-1), and interleukin-ß1 (IL-1ß)] were detected using immunohistochemistry. P38 and ERK1 phosphorylation and activation were determined using western blot analysis. KEY FINDINGS: The degree of inflammation and fibrosis were less in the BBR groups compared to Surgery group. The anti-inflammatory and anti-fibrosis effects of BBR were concentration-dependent. The levels of TGF-ß1, CTGF, ICAM-1, and IL-1ß were significantly lower in the BBR groups compared to Surgery group. BBR reduced the phosphorylation of P38 compared to Surgery group. SIGNIFICANCE: In conclusion, this study shows that BBR can reduce local fibrosis after CL surgical repair via its anti-inflammatory and anti-fibrosis effects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Inflamação/tratamento farmacológico , Lacerações/tratamento farmacológico , Animais , Colágeno/análise , Citocinas/análise , Fibrose , Inflamação/patologia , Lacerações/patologia , Masculino , Coelhos
3.
J Environ Pathol Toxicol Oncol ; 39(3): 225-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865914

RESUMO

Asthma is marked by chronic irritation in the airway lumen of the lungs due to the accretion of inflammatory cells that influence the regular inhalation process. An extended buildup of inflammation leads to oxidative pressure and the repression of antioxidant functions. In the current study, a potential compound, boldine, was tested for the containment of provocative markers along the path of antiasthmatic activity in an ovalbumin (OVA)-induced asthmatic mice model. As an effect, the boldine (10 and 20 mg/kg) treatment suppressed inflammatory cells such as eosinophil, macrophage, neutrophil, lymphocyte, and other inflammatory markers in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. Likewise, immunoglobulin E (IgE) levels were drastically condensed in the serum of boldine-treated animals. Levels of enzymatic and nonenzymatic antioxidants, such as superoxide dismutase (SOD) and glutathione (GSH), were upregulated in the boldine treatment group compared to the asthmatic control group, which displays the antioxidant effects of boldine on asthmatic animals. Interestingly, the reactive oxygen species (ROS) and malonaldehyde (MDA) levels were repressed in the BALF of boldine-treated mice groups. Therefore, the effects of boldine are significant for the management of asthma, reducing the accrual of inflammatory cells, along with other inflammatory markers, while improving antioxidant markers and containing ROS. Hence, boldine may be an option for clinical trials of chronic asthma management.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Aporfinas/uso terapêutico , Asma/tratamento farmacológico , Animais , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Aporfinas/administração & dosagem , Asma/imunologia , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/análise , Modelos Animais de Doenças , Eosinófilos/citologia , Imunoglobulina E/sangue , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Espécies Reativas de Oxigênio/metabolismo , Testes de Função Respiratória
4.
Respir Res ; 21(1): 245, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962703

RESUMO

BACKGROUND: The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. METHODS: We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1ß, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. RESULTS: Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1ß and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). CONCLUSIONS: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/análise , Mortalidade Hospitalar , Mediadores da Inflamação/sangue , Pandemias/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Fatores Etários , Análise de Variância , Área Sob a Curva , Técnicas de Laboratório Clínico/métodos , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Universitários , Humanos , Incidência , Masculino , Pandemias/prevenção & controle , Fenótipo , Pneumonia Viral/fisiopatologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Reino Unido
5.
Vet Pathol ; 57(5): 642-652, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32880235

RESUMO

In the small intestine, localized innate mucosal immunity is critical for intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) infection induces villus injury and impairs digestive function. Moreover, the infection might comprise localized innate mucosal immunity. This study investigated specific enterocyte subtypes and innate immune components of weaned pigs during PEDV infection. Four-week-old pigs were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24). At day post inoculation (DPI) 2, 4, and 6, lysozyme expression in Paneth cells, cellular density of villous and Peyer's patch microfold (M) cells, and the expression of polymeric immunoglobulin receptor (pIgR) were assessed in the jejunum and ileum by immunohistochemistry, and interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the jejunum by ELISA. PEDV infection led to a decrease in the ratios of villus height to crypt depth (VH-CD) in jejunum at DPI 2, 4, and 6 and in ileum at DPI 4. The number of villous M cells was reduced in jejunum at DPI 4 and 6 and in ileum at DPI 6, while the number of Peyer's patch M cells in ileum increased at DPI 2 and then decreased at DPI 6. PEDV-infected pigs also had reduced lysozyme expression in ileal Paneth cells at DPI 2 and increased ileal pIgR expression at DPI 4. There were no significant changes in IL-1ß and TNF-α expression in PEDV-infected pigs compared to controls. In conclusion, PEDV infection affected innate mucosal immunity of weaned pigs through alterations in Paneth cells, villous and Peyer's patch M cells, and pIgR expression.


Assuntos
Infecções por Coronavirus/veterinária , Imunidade Inata , Mucosa Intestinal/imunologia , Vírus da Diarreia Epidêmica Suína , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Citocinas/análise , Íleo/imunologia , Íleo/patologia , Íleo/virologia , Mucosa Intestinal/química , Mucosa Intestinal/patologia , Mucosa Intestinal/virologia , Jejuno/imunologia , Jejuno/patologia , Jejuno/virologia , Receptores de Imunoglobulina Polimérica/metabolismo , Suínos , Desmame
6.
J Vet Sci ; 21(4): e59, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32735097

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. To understand AD, there have been many trials establishing AD animal models. Although various trials to establish AD animal models have been existed, even the mechanisms of AD in animal models are not enough clarified. OBJECTIVES: This study assessed AD characteristics induced in Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice following trinitrochlorobenzene (TNCB) treatment for different periods and house dust mite (HDM) treatment to compare each model's immunological patterns, especially with cytokine antibody array tool. METHODS: In this study, we exposed Nc/Nga mice to TNCB or HDM extract to induce AD. Nc/Nga mice were divided into 4 groups: control, TNCB 2 weeks-treated, TNCB 8 weeks-treated, and HDM-treated groups. After AD induction, all mice were evaluated by serum immunoglobulin E (IgE) concentration and serum cytokine antibody assays, scoring of skin lesions, scoring of scratching frequency, and histological analysis. RESULTS: The results showed significant differences between groups in serum IgE concentration, skin lesion scores, and scratching frequency. The analysis results for serum cytokine antibody arrays showed that in the TNCB 8 weeks- and HDM-treated groups, but not in the TNCB 2 weeks-treated group, expressions of genes related to the immune response were enriched. Among the histological results, the skin lesions in the HDM-treated group were most similar to those of AD. CONCLUSIONS: We confirmed that immunological pattern of AD mice was markedly different between HDM and TNCB treated groups. In addition, the immunological pattern was quietly different dependent on TNCB treated duration.


Assuntos
Citocinas/análise , Dermatite Atópica/imunologia , Cloreto de Picrila/efeitos adversos , Pyroglyphidae/fisiologia , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/parasitologia , Modelos Animais de Doenças , Feminino , Camundongos , Fatores de Tempo
7.
Nature ; 584(7821): 463-469, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32717743

RESUMO

Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4. However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses. By contrast, patients with severe COVID-19 maintained these elevated responses throughout the course of the disease. Moreover, severe COVID-19 was accompanied by an increase in multiple type 2 (anti-helminths) effectors, including interleukin-5 (IL-5), IL-13, immunoglobulin E and eosinophils. Unsupervised clustering analysis identified four immune signatures, representing growth factors (A), type-2/3 cytokines (B), mixed type-1/2/3 cytokines (C), and chemokines (D) that correlated with three distinct disease trajectories. The immune profiles of patients who recovered from moderate COVID-19 were enriched in tissue reparative growth factor signature A, whereas the profiles of those with who developed severe disease had elevated levels of all four signatures. Thus, we have identified a maladapted immune response profile associated with severe COVID-19 and poor clinical outcome, as well as early immune signatures that correlate with divergent disease trajectories.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citocinas/análise , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Citocinas/imunologia , Eosinófilos/imunologia , Feminino , Humanos , Imunoglobulina E/análise , Imunoglobulina E/imunologia , Interleucina-13/análise , Interleucina-13/imunologia , Interleucina-5/análise , Interleucina-5/imunologia , Masculino , Pessoa de Meia-Idade , Pandemias , Linfócitos T/citologia , Linfócitos T/imunologia , Carga Viral , Adulto Jovem
8.
Med Hypotheses ; 143: 110124, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721813

RESUMO

Utilising biomarkers for COVID-19 diagnosis, prediction of treatment response and overall prognostication have been investigated recently. However, these ventures have only considered the use of blood-based molecular markers. Saliva is another biofluid that warrants being applied in similar fashion with major advantages that centres on its non-invasive and repeatable collection as well as cost-efficiency. To this end, this article presents a hypothesis for the sources of biomarkers useful clinically for COVID-19 disease outcome estimation and identify the likely implications of their detection in saliva.


Assuntos
Betacoronavirus , Biomarcadores/análise , Infecções por Coronavirus/metabolismo , Modelos Imunológicos , Pandemias , Pneumonia Viral/metabolismo , Saliva/química , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Citocinas/análise , Testes Diagnósticos de Rotina , Vesículas Extracelulares , Líquido do Sulco Gengival/química , Humanos , MicroRNAs/análise , Doenças da Boca/complicações , Doenças da Boca/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Saliva/imunologia , Saliva/virologia , Glândulas Salivares/metabolismo , Glândulas Salivares/virologia , Proteínas e Peptídeos Salivares/análise
9.
ACS Chem Neurosci ; 11(13): 1909-1913, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525657

RESUMO

Studies have found increased rates of dysosmia in patients with Novel Coronavirus disease 2019 (COVID-19). However, the mechanism that causes olfactory loss is unknown. The primary objective of this study was to explore local proinflammatory cytokine levels in the olfactory epithelium in patients with COVID-19. Biopsies of the olfactory epithelium were taken from patients with confirmed COVID-19 as well as uninfected controls. Levels of tumor necrosis factor α (TNF-α) and interleukin-1-beta (IL-1ß) were assessed using ELISA and compared between groups. Average TNF-α levels were significantly increased in the olfactory epithelium of the COVID-19 group compared to the control group (P < 0.05). However, no differences in IL-1ß were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Transtornos do Olfato/metabolismo , Mucosa Olfatória/metabolismo , Pneumonia Viral/metabolismo , Adulto , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Citocinas/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Fator de Necrose Tumoral alfa/metabolismo
10.
Respir Res ; 21(1): 154, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552811

RESUMO

Electronic cigarette (e-cig) vaping is increasing rapidly in the United States, as e-cigs are considered less harmful than combustible cigarettes. However, limited research has been conducted to understand the possible mechanisms that mediate toxicity and pulmonary health effects of e-cigs. We hypothesized that sub-chronic e-cig exposure induces inflammatory response and dysregulated repair/extracellular matrix (ECM) remodeling, which occur through the α7 nicotinic acetylcholine receptor (nAChRα7). Adult wild-type (WT), nAChRα7 knockout (KO), and lung epithelial cell-specific KO (nAChRα7 CreCC10) mice were exposed to e-cig aerosol containing propylene glycol (PG) with or without nicotine. Bronchoalveolar lavage fluids (BALF) and lung tissues were collected to determine e-cig induced inflammatory response and ECM remodeling, respectively. Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor. Interestingly, matrix metalloproteinases (MMPs), such as MMP2, MMP8 and MMP9, were altered both at the protein and mRNA transcript levels in female and male KO mice, but WT mice exposed to PG alone showed a sex-dependent phenotype. Moreover, MMP12 was increased significantly in male mice exposed to PG with or without nicotine in a nAChRα7-dependent manner. Additionally, sub-chronic e-cig exposure with or without nicotine altered the abundance of ECM proteins, such as collagen and fibronectin, significantly in a sex-dependent manner, but without the direct role of nAChRα7 gene. Overall, sub-chronic e-cig exposure with or without nicotine affected lung inflammation and repair responses/ECM remodeling, which were mediated by nAChRα7 in a sex-dependent manner.


Assuntos
Infecções por Coronavirus/epidemiologia , Sistemas Eletrônicos de Liberação de Nicotina , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia/metabolismo , Vaping/efeitos adversos , Receptor Nicotínico de Acetilcolina alfa7/genética , Animais , Gasometria , Western Blotting , Líquido da Lavagem Broncoalveolar , Citocinas/análise , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pandemias , Pneumonia/fisiopatologia , Distribuição Aleatória , Valores de Referência , Papel (figurativo) , Síndrome Respiratória Aguda Grave/epidemiologia , Transdução de Sinais/genética
11.
ACS Sens ; 5(6): 1506-1513, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32482077

RESUMO

The global COVID-19 pandemic has oversaturated many intensive care units to the point of collapse, leading to enormous spikes in death counts. Before critical care becomes a necessity, identifying patients who are likely to become critically ill and providing prompt treatment is a strategy to avoid ICU oversaturation. There is a consensus that a hyperinflammatory syndrome or a "cytokine storm" is responsible for poor outcomes in COVID-19. Measuring cytokine levels at the point of care is required in order to better understand this process. In this Perspective, we summarize the main events behind the cytokine storm in COVID-19 as well as current experimental treatments. We advocate for a new biosensor-enabled paradigm to personalize the management of COVID-19 and stratify patients. Biosensor-guided dosing and timing of immunomodulatory therapies could maximize the benefits of these anti-inflammatory treatments while minimizing deleterious effects. Biosensors will also be essential in order to detect complications such as coinfections and sepsis, which are common in immunosuppressed patients. Finally, we propose the ideal features of these biosensors using some prototypes from the recent literature as examples. Multisensors, lateral flow tests, mobile biosensors, and wearable biosensors are seen as key players for precision medicine in COVID-19.


Assuntos
Betacoronavirus , Técnicas Biossensoriais/métodos , Infecções por Coronavirus/terapia , Citocinas/análise , Imunomodulação , Inflamação , Pneumonia Viral/terapia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Humanos , Interleucina-6/análise , Interleucina-6/imunologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Medicina de Precisão , Sepse
12.
PLoS One ; 15(6): e0235220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584885

RESUMO

BACKGROUND: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied. EXPERIMENTAL APPROACH: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. RESULTS: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP. DISCUSSION: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.


Assuntos
Pinos Ortopédicos/efeitos adversos , Fraturas do Fêmur/cirurgia , Traumatismo Múltiplo/patologia , Miocárdio/patologia , Actinina/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular , Conexina 43/metabolismo , Citocinas/análise , Citocinas/metabolismo , Desmina/metabolismo , Fraturas do Fêmur/patologia , Proteína HMGB1/análise , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Inflamação , Masculino , Camundongos , Traumatismo Múltiplo/metabolismo , Traumatismo Múltiplo/veterinária , Miocárdio/metabolismo , Estresse Nitrosativo , Suínos , Troponina I/análise
14.
BMC Infect Dis ; 20(1): 444, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576149

RESUMO

BACKGROUND: The syphilis epidemic continues to cause substantial morbidity and mortality worldwide, particularly in low- and middle-income countries, despite several recent disease control initiatives. Though our understanding of the pathogenesis of this disease and the biology of the syphilis agent, Treponema pallidum subsp. pallidum has improved over the last two decades, further research is necessary to improve clinical diagnosis and disease management protocols. Additionally, such research efforts could contribute to the identification of possible targets for the development of an effective vaccine to stem syphilis spread. METHODS: This study will recruit two cohorts of participants with active syphilis infection, one with de novo infection, one with repeat infection. Whole blood specimens will be collected from each study participant at baseline, 4, 12, 24, 36, and 48 weeks, to track specific markers of their immunological response, as well as to compare humoral reactivity to Treponema pallidum antigens between the two groups. Additionally, we will use serum specimens to look for unique cytokine patterns in participants with early syphilis. Oral and blood samples, as well as samples from any syphilitic lesions present, will also be collected to sequence any Treponema pallidum DNA found. DISCUSSION: By furthering our understanding of syphilis pathogenesis and human host immune response to Treponema pallidum, we will provide important data that will help in development of new point-of-care tests that could better identify active infection, leading to improved syphilis diagnosis and management. Findings could also contribute to vaccine development efforts.


Assuntos
Vacinas Bacterianas/uso terapêutico , Sífilis/epidemiologia , Sífilis/prevenção & controle , Treponema pallidum/imunologia , Vacinação , Antígenos de Bactérias/imunologia , Sequência de Bases , Estudos de Coortes , Citocinas/análise , DNA Bacteriano/genética , Seguimentos , Humanos , Tipagem Molecular , Peru/epidemiologia , Sífilis/sangue , Sífilis/imunologia , Treponema pallidum/genética
15.
PLoS One ; 15(6): e0231882, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544178

RESUMO

Gestations at the extremes of reproductive age are characterized as high-risk pregnancies, conditions that might influence colostrum composition. This first milk secretion contains nutrients necessary for the development and immunity of the newborn; therefore, this study aims to compare adolescent and advanced maternal age mothers regarding sociodemographic, gestational, and perinatal characteristics and the colostrum levels of pro-inflammatory cytokines in these groups of study. This cross-sectional study has compared sociodemographic, gestational and perinatal data from adolescent mothers (between 10 and 24 years old) (n = 117), advanced maternal age mothers (over 35 years of age) (n = 39) and mothers considered a control group (25 to 34 years old) (n = 58). Additionally, colostrum samples were obtained from the studied and control group subjects by manual milking, between 48 and 72 hours postpartum, and the samples were analyzed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). The majority of the studied mothers reported living a stable union, and 81.2% of the adolescent mothers did not carry out any paid activity. Mothers with advanced maternal age mainly delivered by cesarean section and presented a higher body mass index (BMI). Neonatal weight and Apgar score were not different between the groups. The concentrations of interleukin (IL)-1ß and IL-6 were higher in the colostrum of mothers with advanced age compared to adolescent mothers, but did not differ from the control group. The concentrations of IL-8 and tumor necrosis factor alpha did not differ between the three groups. Therefore, our data demonstrated that maternal age influenced the sociodemographic and gestational characteristics as well as the composition of colostrum cytokines.


Assuntos
Colostro/metabolismo , Citocinas/análise , Ensaio de Imunoadsorção Enzimática , Adolescente , Adulto , Peso ao Nascer , Índice de Massa Corporal , Cesárea , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Interleucina-1beta/análise , Interleucina-6/análise , Período Pós-Parto , Gravidez , Adulto Jovem
16.
J Infect ; 81(2): 205-212, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32579986

RESUMO

A subgroup of COVID-19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper-activation, hyper-inflammation, cytokine storm development. Furthermore, organ-specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.


Assuntos
Infecções por Coronavirus/diagnóstico , Inflamação/virologia , Pneumonia Viral/diagnóstico , Betacoronavirus , Biomarcadores/análise , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Citocinas/análise , Progressão da Doença , Humanos , Inflamação/complicações , Pulmão/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Medição de Risco
17.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: covidwho-165371

RESUMO

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina , Citocinas/análise , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Pandemias , Pneumonia Viral/patologia , Sistema Respiratório/patologia
18.
Cell Host Microbe ; 27(6): 883-890.e2, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: covidwho-125388

RESUMO

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina , Citocinas/análise , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Pandemias , Pneumonia Viral/patologia , Sistema Respiratório/patologia
19.
Arch Pathol Lab Med ; 144(10): 1230-1233, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401053

RESUMO

CONTEXT.­: The measurement of cytokines in clinical laboratories is becoming an increasingly routine part of immune monitoring when administering biologic and cell-based immunotherapies and also for clinical assessment of inflammatory conditions. While a number of commercial assays and platforms are available for cytokine measurement, there is currently little standardization among these analytical methods. OBJECTIVE.­: To characterize the variability and comparability among cytokine testing platforms that are commonly used in clinical laboratories. DESIGN.­: We analyzed data for 4 cytokines (interleukin [IL]-1, IL-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) from 6 College of American Pathologists cytokine surveys administered from 2015 to 2018. Analyses interrogated variability between testing methods and variability within each laboratory across the mailings. RESULTS.­: Significant variability was noted across methods with analysis of IL-1 showing the least variability and IL-6, IL-8, and TNF-α varying between methods to a greater extent. Intralab variability was also significant with TNF-α measurements again showing the greatest variability. CONCLUSIONS.­: This retrospective analysis of College of American Pathologists proficiency testing data for cytokine measurement is the largest method comparison to date, and this study provides a description of the variation of cytokine measurement across methods, across laboratories, and within laboratories. Serial monitoring of cytokines should preferentially be performed by the same method within the same laboratory.


Assuntos
Citocinas/análise , Ensaio de Proficiência Laboratorial/normas , Patologia Clínica/normas , Humanos , Laboratórios/normas , Melhoria de Qualidade , Estudos Retrospectivos
20.
Artigo em Inglês | MEDLINE | ID: mdl-32407669

RESUMO

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Sistema Respiratório/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina , Citocinas/análise , Interações Hospedeiro-Patógeno , Humanos , Interferons/metabolismo , Pandemias , Pneumonia Viral/patologia , Sistema Respiratório/patologia
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