Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.983
Filtrar
1.
PLoS One ; 15(7): e0234659, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614834

RESUMO

BACKGROUND: The relationship between poor oral health conditions and cognitive decline is unclear. OBJECTIVE: To examine the association between oral health and cognition in humans and rats. METHODS: In humans: a cross-sectional study was conducted. Cognitive levels were evaluated by the Mini Mental State Examination (MMSE); oral conditions were reflected by the number of missing index teeth, bleeding on probing, and probing pocket depth (PD). In rats: a ligature-induced (Lig) periodontitis model and Aß25-35-induced model of Alzheimer's disease (AD) were established; tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and C-reactive protein levels in the hippocampus and cerebral cortex were detected. RESULTS: MMSE scores for the number of missing index teeth ≥ 7 group were significantly lower than those in the ≤ 6 group. A negative relationship (correlation coefficient ρ = -0.310, P = 0.002) was observed between MMSE scores and number of missing index teeth. More missing index teeth and lower education levels were independent risk factors for cognitive decline. A negative relationship (correlation coefficient ρ = -0.214, P = 0.031) was observed between MMSE scores and average PD. TNF-α and IL-6 levels in the hippocampus of the Lig+AD group were significantly higher than those of the AD group. IL-1 and IL-6 levels in the cerebral cortex of the Lig+AD group were significantly higher than those of the AD group. CONCLUSION: Poor oral health conditions including more missing index teeth and higher average PD may be risk factors for cognitive decline. Periodontitis may increase inflammatory cytokines in rat models of AD.


Assuntos
Transtornos Cognitivos/etiologia , Saúde Bucal , Periodontite/complicações , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/toxicidade , Animais , Proteína C-Reativa/análise , Causalidade , Córtex Cerebral/química , China/epidemiologia , Transtornos Cognitivos/epidemiologia , Comorbidade , Estudos Transversais , Índice CPO , Modelos Animais de Doenças , Feminino , Hipocampo/química , Humanos , Interleucina-1/análise , Masculino , Aprendizagem em Labirinto , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Fragmentos de Peptídeos/toxicidade , Índice Periodontal , Periodontite/epidemiologia , Periodontite/etiologia , Periodontite/fisiopatologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Risco , Fator de Necrose Tumoral alfa/análise
2.
Int. j. morphol ; 38(3): 558-564, June 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1098287

RESUMO

Chronic hepatotoxicity is a debilitating and frequently life-threatening disease resulting in progressive liver failure. The toxic chemical, thioacetamide (TAA) is used to evaluate hepatoprotective agents, and the polyphenolic compound, resveratrol was proposed as a novel treatment for diseases with hyperactivation of the mammalian target of rapamycin (mTOR) cell signaling pathway. This analysis sought to investigate the potential protective effect of resveratrol against liver injury induced by TAA via the inhibition of hepatic mTOR. Model group rats received several injections of TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed at week 10 and the protective group was pretreated with resveratrol (20 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment. Harvested liver tissues were examined using light microscopy and liver homogenates were assayed for biomarkers of inflammation and assessed the levels of mTOR protein in all animal groups. In addition, blood samples were assayed for biomarkers of liver injury enzyme. TAA substantially damaged the hepatic tissue of the model group such as infiltration of inflammatory cells, vacuolated cytoplasm, dark pyknotic nuclei, and dilated congested blood vessel that were effectively protected by resveratrol. Resveratrol also significantly (p<0.05) inhibited TAA-induced mTOR, high sensitivity c-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in harvested liver homogenates and blood samples. Thus, we conclude that resveratrol effectively protects against TAA-induced hepatotoxicity in rats, possibly due to the inhibition of mTOR and inflammation.


La hepatotoxicidad crónica es una enfermedad debilitante y potencialmente mortal que produce insuficiencia hepática progresiva. La toxicidad del químico de la tioacetamida (TAA) se utiliza para evaluar los agentes hepatoprotectores y el compuesto polifenólico, resveratrol, se propuso como un nuevo tratamiento para enfermedades con hiperactivación de la vía de señalización celular mTOR (mammalian Target of Rapamycin). Aquí buscamos investigar el posible efecto protector del resveratrol contra la lesión hepática inducida por TAA a través de la inhibición de la vía de señalización mTOR en hepatocitos. Las ratas del grupo modelo recibieron varias inyecciones de TAA (200 mg / kg; dos veces por semana durante 8 semanas) antes de ser sacrificadas en la semana 10 y el grupo protector se trató previamente con resveratrol (20 mg / kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuó recibiendo ambos agentes hasta el final del experimento. Se examinaron los tejidos hepáticos recolectados usando microscopía óptica y se analizaron los homogeneizados hepáticos para detectar biomarcadores de inflamación y se evaluaron los niveles de proteína mTOR en todos los grupos de animales. Además, se analizaron muestras de sangre para detectar biomarcadores de la enzima de lesión hepática. TAA dañó sustancialmente el tejido hepático del grupo modelo, con infiltración de células inflamatorias, citoplasma vacuolado, núcleos picnóticos oscuros y vasos sanguíneos congestionados dilatados que estaban efectivamente protegidos por el resveratrol. El resveratrol también inhibió significativamente (p <0.05) mTOR, proteína C-reactiva (hs-CRP), factor de necrosis tumoral alfa (TNF-α), interleucina-6 (IL-6), alanina aminotransferasa (ALT ) y aspartato aminotransferasa (AST) en las muestras de sangre y de hígados recolectados. En conclusión, el resveratrol protege eficazmente contra la hepatotoxicidad inducida por TAA en ratas, posiblemente debido a la inhibición de mTOR y de la inflamación.


Assuntos
Animais , Masculino , Camundongos , Tioacetamida/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Resveratrol/administração & dosagem , Aspartato Aminotransferases/análise , Proteína C-Reativa/análise , Fator de Necrose Tumoral alfa/análise , Alanina Transaminase/análise , Modelos Animais de Doenças
3.
Acta Cir Bras ; 35(4): e202000404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555936

RESUMO

PURPOSE: To analyze the effect of calcitriol treatment on acute colitis in an experimental rat model. METHODS: A total of 24 adult Sprague Dawley albino rats were randomly separated into 3 equal groups: control group (n:8), colitis group (n:8), calcitriol administered group (n:8). A single dose of acetic acid (1 ml of 4% solution) was administered intrarectally to induce colitis. Group 1 was given 1 ml/kg 0.9% NaCl intraperitoneally; rats belonging to Group 2 were administered calcitriol 1 µg/kg for 5 days. RESULTS: Plasma tumor necrosis factor alpha, Pentraxin 3, and malondialdehyde levels were significantly lower in the calcitriol administered colitis group than in the standard colitis group (p<0.01). In the Calcitriol group, there was a significant histological improvement in hyperemia, hemorrhage and necrotic areas in the epithelium compared to the placebo group (p <0.000). CONCLUSION: The findings suggest that calcitriol may be an agent that could be used in acute colitis treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Calcitriol/uso terapêutico , Colite/tratamento farmacológico , Doença Aguda , Animais , Proteína C-Reativa/análise , Colite/sangue , Colite/patologia , Modelos Animais de Doenças , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Estresse Oxidativo/genética , Distribuição Aleatória , Ratos Sprague-Dawley , Valores de Referência , Reprodutibilidade dos Testes , Componente Amiloide P Sérico/análise , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
4.
PLoS One ; 15(6): e0234731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544181

RESUMO

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.


Assuntos
Alternaria/patogenicidade , Rinite/patologia , Sinusite/patologia , Alternaria/imunologia , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Interleucina-10/análise , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/análise , Interleucina-4/genética , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal/química , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/metabolismo , Rinite/imunologia , Sinusite/imunologia , Baço/metabolismo , Baço/microbiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
5.
Nat Commun ; 11(1): 2607, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451375

RESUMO

Quantification of pathogen and host biomarkers is essential for the diagnosis, monitoring, and treatment of infectious diseases. Here, we demonstrate sensitive and rapid quantification of bacterial load and cytokines from human biological samples to generate actionable hypotheses. Our digital assay measures IL-6 and TNF-α proteins, gram-negative (GN) and gram-positive (GP) bacterial DNA, and the antibiotic-resistance gene blaTEM with femtomolar sensitivity. We use our method to characterize bronchoalveolar lavage fluid from patients with asthma, and find elevated GN bacteria and IL-6 levels compared to healthy subjects. We then analyze plasma from patients with septic shock and find that increasing levels of IL-6 and blaTEM are associated with mortality, while decreasing IL-6 levels are associated with recovery. Surprisingly, lower GN bacteria levels are associated with higher probability of death. Applying decision-tree analysis to our measurements, we are able to predict mortality and rate of recovery from septic shock with over 90% accuracy.


Assuntos
Citocinas/sangue , DNA Bacteriano/sangue , Choque Séptico/imunologia , Choque Séptico/microbiologia , Asma/imunologia , Asma/microbiologia , Carga Bacteriana , Biomarcadores/análise , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Estudos de Casos e Controles , Citocinas/análise , DNA Bacteriano/genética , Árvores de Decisões , Genes Bacterianos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/genética , Bactérias Gram-Positivas/isolamento & purificação , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Interleucina-6/análise , Interleucina-6/sangue , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Multiplex/estatística & dados numéricos , Prognóstico , Sensibilidade e Especificidade , Choque Séptico/mortalidade , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangue , Resistência beta-Lactâmica/genética
6.
An Acad Bras Cienc ; 92(1): e20190261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401838

RESUMO

Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Citarabina/efeitos adversos , Edema Pulmonar/tratamento farmacológico , Rutina/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Masculino , NF-kappa B/análise , Oxidantes/sangue , Estresse Oxidativo/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/patologia , Ratos , Ratos Wistar , Rutina/farmacologia , Fator de Necrose Tumoral alfa/análise
7.
Neurology ; 94(23): e2412-e2423, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32461282

RESUMO

OBJECTIVE: To measure exosomal and plasma levels of candidate blood biomarkers in veterans with history of mild traumatic brain injury (mTBI) and test their relationship with chronic symptoms. METHODS: Exosomal and plasma levels of neurofilament light (NfL) chain, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and vascular endothelial growth factor (VEGF) were measured using an ultrasensitive assay in a cohort of 195 veterans, enrolled in the Chronic Effects of Neurotrauma Consortium Longitudinal Study. We examined relationships between candidate biomarkers and symptoms of postconcussive syndrome (PCS), posttraumatic stress disorder (PTSD), and depression. Biomarker levels were compared among those with no traumatic brain injury (TBI) (controls), 1-2 mTBIs, and repetitive (3 or more) mTBIs. RESULTS: Elevated exosomal and plasma levels of NfL were associated with repetitive mTBIs and with chronic PCS, PTSD, and depression symptoms. Plasma TNF-α levels correlated with PCS and PTSD symptoms. The total number of mTBIs correlated with exosomal and plasma NfL levels and plasma IL-6. Increased number of years since the most recent TBI correlated with higher exosomal NfL and lower plasma IL-6 levels, while increased number of years since first TBI correlated with higher levels of exosomal and plasma NfL, as well as plasma TNF-α and VEGF. CONCLUSION: Repetitive mTBIs are associated with elevated exosomal and plasma levels of NfL, even years following these injuries, with the greatest elevations in those with chronic PCS, PTSD, and depression symptoms. Our results suggest a possible neuroinflammatory and axonal disruptive basis for symptoms that persist years after mTBI, especially repetitive.


Assuntos
Concussão Encefálica/sangue , Exossomos/química , Proteínas de Neurofilamentos/sangue , Saúde dos Veteranos , Veteranos , Adulto , Biomarcadores , Traumatismos por Explosões/sangue , Traumatismos por Explosões/complicações , Concussão Encefálica/complicações , Estudos Transversais , Depressão/sangue , Depressão/etiologia , Feminino , Seguimentos , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Concussão/sangue , Síndrome Pós-Concussão/etiologia , Prognóstico , Degeneração Retrógrada , Índice de Gravidade de Doença , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/etiologia , Fator de Necrose Tumoral alfa/análise , Fator A de Crescimento do Endotélio Vascular/sangue , Guerra
8.
J Appl Oral Sci ; 28: e20190519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348444

RESUMO

Natural products have emerged as a rich source of bioactive compounds for adjunctive treatments of many infectious and inflammatory conditions, including periodontitis. Among the monoterpenes with significant biological properties, there is the perillyl alcohol (POH), which can be found in several essential oils and has shown immunomodulatory properties in recent studies, which may be interesting in the treatment of non-neoplastic inflammatory disorders. Objective To determine the antibacterial and immune modulatory activities of the POH. Methodology The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the POH for two significant Gram-negative periodontal pathogens were determined by macrodilution and subculture, respectively. Cell proliferation and cytotoxicity in RAW 264.7 macrophages were determined by Trypan Blue and mitochondrial enzymatic activity assay. The modulation of reactive oxygen species (ROS) was analyzed by flow cytometry and expression of TNF and arginase-1 by real-time PCR. Results The POH was effective against P. gingivalis (ATCC 33277) and F. nucleatum (ATCC 25586) with MIC= MBC=1600 µM. No cytotoxicity up to 100 µM was observed on macrophages. The cell proliferation was inhibited from 48 hours at 100 µM (p<0.05) and 250 µM (p<0.01). The POH increased ROS production at both 10 µM and 100 µM (p<0.05) in unstimulated cells. The PMA-induced ROS production was not affected by POH, whereas 100 µM significantly reduced lipopolysaccharide-induced (LPS-induced) ROS. The expression of TNF was not affected by POH in unstimulated cells or in cells polarized to M1 phenotype, whereas both concentrations of POH reduced (p<0.05) the expression of arginase-1 in M2-polarized macrophages. Conclusion The POH has antibacterial activity against periodontal pathogens and reduced proliferation of murine macrophages without significant cytotoxicity at concentrations up to 100 µM. In addition, the POH reduced the LPS-induced ROS and the expression of arginase-1 in M2-polarized macrophages.


Assuntos
Antibacterianos/farmacologia , Fusobacterium nucleatum/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Monoterpenos/farmacologia , Porphyromonas/efeitos dos fármacos , Espécies Reativas de Oxigênio/análise , Animais , Arginase/análise , Produtos Biológicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Fusobacterium nucleatum/crescimento & desenvolvimento , Expressão Gênica , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Porphyromonas/crescimento & desenvolvimento , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise
9.
Braz Oral Res ; 34: e015, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130362

RESUMO

We sought to compare the characteristics and clinical significance of neutrophil extracellular traps in gingival samples from patients with periodontitis and those with gingivitis. The clinical indexes of gingival samples from patients with periodontitis and gingivitis were measured; the expression of TNF-alpha and IL-8 was measured by real-time fluorescent quantitative PCR; and the expression of TLR-8 and MMP-9 was measured by western blotting assays. Chemotaxis, phagocytosis and phagocytic activity of neutrophils were measured. Compared with the healthy group, the expression of TNF-α and IL-8 in the periodontitis group and the gingivitis group increased significantly (p < 0.05), and TNF-α in the gingivitis group was significantly lower than that in the healthy group (p < 0.05). The expression of IL-8 in the periodontitis group was significantly higher than that in the periodontitis group (p < 0.05). Furthermore, the expression of TLR-8 and MMP-9 in the periodontitis group was different from that in the gingivitis group and the healthy group, and the expression of TLR-8 and MMP-9 in the gingivitis group was significantly different from that in the healthy group (p < 0.05). In addition, the neutrophil mobility index in healthy people was 3.02 ± 0.53, that in the periodontitis group was 2.21 ± 0.13, and that in the gingivitis group was 2.31 ± 0.12. In conclusion, the chemotaxis of neutrophils in gingival samples of patients with periodontitis and gingivitis was decreased, the phagocytotic ability and activity of neutrophils were reduced, and the release of the extracellular trap-releasing inducible factors TNF-alpha and IL-8 also declined.


Assuntos
Armadilhas Extracelulares , Gengivite/patologia , Neutrófilos/patologia , Periodontite/patologia , Actinas/análise , Adulto , Western Blotting , Estudos de Casos e Controles , Eletroforese em Gel de Ágar , Feminino , Humanos , Interleucina-8/análise , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Índice Periodontal , RNA/análise , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Receptor 8 Toll-Like/análise , Fator de Necrose Tumoral alfa/análise , Adulto Jovem
10.
An Bras Dermatol ; 95(2): 144-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32146009

RESUMO

BACKGROUND: Anogenital warts are the leading sexually transmitted infection in patients seeking care at specialized clinics. They may display a vast array of forms, according to the interaction of the virus with the host's immunity. Cellular immunity is the epithelium's main form of defense against the virus, involving an active participation of the Langerhans cells and pro-inflammatory cytokines such as TNF-α. OBJECTIVE: To assess the epithelial immune response of anogenital warts in males, according to the number of lesions presented. METHODS: This is a prospective, cross-sectional study carried out at the dermatology outpatient clinic in a tertiary hospital. We included male patients over 18 years of age without comorbidities who had anogenital condylomata and no previous treatments.In order to evaluate the local epithelial immunity, the lesions were quantified, then removed and employed in CD1a immunohistochemistry assays for assessing the morphometry and morphology of Langerhans cells; TNF-α; reaction was used for determining cytokine positivity in the epithelium. RESULTS: 48 patients were included in the study. There was no statistically significant difference as to the number of Langerhans cells, in their morphology, or the presence of TNF-α. However, patients presenting with more Langerhans cells in the lesions had cells with a star-like and dendritic morphology, whereas in those with a lower cell count had cells with a rounded morphology and no dendrites (p<0.001). STUDY LIMITATIONS: Small number of patients analyzed. CONCLUSION: There was no difference in epithelial immunity between patients having few or many anogenital condyloma lesions as measured by the morphology and morphometry of Langerhans cells and TNF-α; positivity. Such an assessment employing immunity markers differing from the usual ones is expected to yield useful results.


Assuntos
Doenças do Ânus/imunologia , Condiloma Acuminado/imunologia , Doenças dos Genitais Masculinos/imunologia , Células de Langerhans/patologia , Fator de Necrose Tumoral alfa/análise , Doenças do Ânus/patologia , Condiloma Acuminado/patologia , Estudos Transversais , Células Dendríticas/imunologia , Células Dendríticas/patologia , Doenças dos Genitais Masculinos/patologia , Humanos , Imuno-Histoquímica , Células de Langerhans/imunologia , Masculino , Estudos Prospectivos , Valores de Referência , Fator de Necrose Tumoral alfa/imunologia
11.
PLoS Negl Trop Dis ; 14(3): e0008093, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176691

RESUMO

Human leishmaniasis is a public health problem worldwide for which the development of a vaccine remains a challenge. T cell-mediated immune responses are crucial for protection. Peptide vaccines based on the identification of immunodominant T cell epitopes able to induce T cell specific immune responses constitute a promising strategy. Here, we report the identification of human leukocyte antigen class-I (HLA-I) and -II (HLA-II)-restricted multi-epitope peptides from Leishmania proteins that we have previously described as vaccine candidates. Promastigote Surface Antigen (PSA), LmlRAB (L. major large RAB GTPase) and Histone (H2B) were screened, in silico, for T cell epitopes. 6 HLA-I and 5 HLA-II-restricted multi-epitope peptides, able to bind to the most frequent HLA molecules, were designed and used as pools to stimulate PBMCs from individuals with healed cutaneous leishmaniasis. IFN-γ, IL-10, TNF-α and granzyme B (GrB) production was evaluated by ELISA/CBA. The frequency of IFN-γ-producing T cells was quantified by ELISpot. T cells secreting cytokines and memory T cells were analyzed by flow cytometry. 16 of 25 peptide pools containing HLA-I, HLA-II or HLA-I and -II peptides were able to induce specific and significant IFN-γ levels. No IL-10 was detected. 6 peptide pools were selected among those inducing the highest IFN-γ levels for further characterization. 3/6 pools were able to induce a significant increase of the percentages of CD4+IFN-γ+, CD8+IFN-γ+ and CD4+GrB+ T cells. The same pools also induced a significant increase of the percentages of bifunctional IFN-γ+/TNF-α+CD4+ and/or central memory T cells. We identified highly promiscuous HLA-I and -II restricted epitope combinations from H2B, PSA and LmlRAB proteins that stimulate both CD4+ and CD8+ T cell responses in recovered individuals. These multi-epitope peptides could be used as potential components of a polytope vaccine for human leishmaniasis.


Assuntos
Antígenos de Protozoários/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Leishmania/imunologia , Leishmaniose Cutânea/imunologia , Proteínas Recombinantes de Fusão/imunologia , Adulto , Antígenos de Protozoários/genética , Ensaio de Imunoadsorção Enzimática , Epitopos de Linfócito T/genética , Feminino , Citometria de Fluxo , Granzimas/análise , Antígenos de Histocompatibilidade Classe I/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Interferon gama/análise , Interleucina-10/análise , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fator de Necrose Tumoral alfa/análise , Voluntários , Adulto Jovem
12.
Medicine (Baltimore) ; 99(10): e19359, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150077

RESUMO

Monitoring anti-TNF agents in inflammatory bowel disease (IBD) patients may be helpful in optimizing outcomes. We aimed to evaluate potential correlations among demographic, clinical, laboratory, or imaging parameters, as well as serum levels of infliximab (IFX) and adalimumab (ADA) and their respective antibodies, in the clinical management of IBD patients.A cross-sectional study of 95 patients with Crohn's disease (CD) or ulcerative colitis (UC) in maintenance therapy with infliximab or adalimumab was performed. Drug trough levels and anti-drug levels were determined using ELISA-based assays.Regarding the serum IFX dosage, patients with higher relative C-reactive protein (CRP) levels had significantly lower relative serum IFX levels (<3 µg/mL) (P = .028). In contrast, higher concentrations of anti-IFX antibodies were found in patients who were not on concomitant immunomodulators (P = .022) and who had more biological-related adverse events (P = .001) and higher levels of CRP (P = .042). Serum CRP levels were also negatively correlated with IFX (CC = -0.315; P = .033) but positively correlated with the presence of IFX antibodies (CC = 0.327; P = .027). Serum albumin dosage showed a positive correlation with levels of both IFX (CC = 0.379; P = .004) and ADA (CC = 0.699; P = .003).Although anti-TNF-α trough levels and immunogenicity do not show a significant correlation with disease outcome, our results reinforce the use of combination therapy for patients treated with infliximab. Moreover, we confirmed the presence of significant associations between anti-TNF-α trough levels and immunogenicity with body mass index (BMI), the concomitant use of immunomodulators, the rates of side effects, and laboratory markers, including serum albumin and CRP.


Assuntos
Doenças Inflamatórias Intestinais/sangue , Fator de Necrose Tumoral alfa/análise , Adalimumab/análise , Adalimumab/sangue , Adalimumab/uso terapêutico , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Infliximab/análise , Infliximab/sangue , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
13.
Allergol. immunopatol ; 48(1): 48-55, ene.-feb. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-186591

RESUMO

Background: Several pro-inflammatory and anti-inflammatory mediators play a role in the immunopathogenesis of food allergy (FA). The aim of this study was to investigate the utility of serum biomarkers like interleukin (IL)-10, TNF-alfa, and IL-6 in the diagnosis and/or follow-up of FA. Methods: Sixty (25 females, 41.6%) newly diagnosed FA patients [IgE mediated (group-1, n = 37), non-IgE (group-2, n = 23)] with a median age of nine (1-33) months were enrolled. Twenty-four healthy children with a median age of eight (1-36) months constituted the control group (CG). In all the subjects, serum TNF-alfa, IL-6 and IL-10 levels were evaluated at the time of diagnosis and reassessed four weeks after therapeutic elimination diet (TED). Results: The mean white blood cell count and median absolute eosinophile count of the CG were significantly lower than group-1 (p values were 0.019 and 0.006, respectively). The mean absolute neutrophile count and the median IL-6 were significantly higher in group-1 when compared with group-2 (p values were 0.005 and 0.032, respectively. Median TNF-alfa and IL-6 levels were significantly higher in the pre-TED among all patients (p values were 0.005 and 0.018, respectively). In group-1, median TNF-α and IL-6 levels decreased significantly after TED (p values were 0.01 and 0.029, respectively). Conclusions: Our findings support the role of inflammation in the pathogenesis of FA. Serum TNF-alfa and IL-6 levels may be useful markers for follow-up in FA, especially among IgE-mediated FA patients. Evaluation of IL-10 results was not sufficient for an interpretation of clinical tolerance


No disponible


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Interleucina-10/sangue , Interleucina-6/sangue , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Imediata/diagnóstico , Fator de Necrose Tumoral alfa/sangue , Mucosa Intestinal/imunologia , Algoritmos , Alérgenos , Anafilaxia/imunologia , Biomarcadores , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/análise
14.
Braz Oral Res ; 34: e014, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074214

RESUMO

Although dental implants and bone regenerative procedures are important approaches for the reestablishment of esthetics and function in young patients with a history of generalized aggressive periodontitis (GAP), no predictable outcomes have been reported, and the host osteo-immunoinflammatory response may play a relevant role in this context. In view of the lack of molecular investigations into the bone tissue condition of young patients with periodontitis, the aim of this study was to evaluate the gene expression of bone-related factors in this population. Bone biopsies were obtained from the posterior mandible in 16 individuals previously diagnosed with GAP and on periodontal support therapy and from 17 periodontally healthy (PH) patients. The gene expression of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, receptor activator of the NF-κB ligand (RANKL), osteoprotegerin (OPG), osteocalcin (OC), bone sialoprotein (BSP), and type I collagen (COL-I), important biomarkers of bone turnover, was evaluated by qRT-PCR. Lower TGF-ß and OPG mRNA levels were observed in GAP patients compared to PH individuals (p ≤ 0.05). There were no between-group differences in levels of TNF-α, BSP, RANKL, OC, or COL-I mRNA (p>0.05). In young adults, a history of periodontal disease can negatively modulate the gene expression of important bone-related factors in alveolar bone tissue. These molecular outcomes may contribute to the future development of therapeutic approaches to benefit bone healing in young patients with history of periodontitis via modulation of osteo-immuno-inflammatory biomarkers.


Assuntos
Periodontite Agressiva/genética , Expressão Gênica , Adulto , Periodontite Agressiva/metabolismo , Processo Alveolar/química , Biomarcadores , Colágeno Tipo I/análise , Colágeno Tipo I/genética , Estudos Transversais , Feminino , Humanos , Sialoproteína de Ligação à Integrina/análise , Sialoproteína de Ligação à Integrina/genética , Masculino , Osteocalcina/análise , Osteocalcina/genética , Osteoprotegerina/análise , Osteoprotegerina/genética , Ligante RANK/análise , Ligante RANK/genética , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Método Simples-Cego , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
15.
Acta Cir Bras ; 34(12): e201901205, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049185

RESUMO

PURPOSE: To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia. METHODS: Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined. RESULTS: Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1ß levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). CONCLUSION: HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.


Assuntos
Alcaloides/farmacologia , Anestésicos Inalatórios/efeitos adversos , Hipocampo/efeitos dos fármacos , Isoflurano/efeitos adversos , Fatores de Crescimento Neural/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Sesquiterpenos/farmacologia , Anestesia/efeitos adversos , Animais , Ensaio de Imunoadsorção Enzimática , Hipocampo/metabolismo , Humanos , Interleucina-1beta/análise , Interleucina-6/análise , Masculino , Aprendizagem em Labirinto , Fatores de Crescimento Neural/análise , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
16.
Acta Cir Bras ; 34(12): e201901206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049186

RESUMO

PURPOSE: To evaluate the effects of prednisolone against sodium diclofenac both with ciprofloxacin compared to artificial tears on the symptoms and signs of acute viral conjunctivitis. METHODS: Study included 37 patients diagnosed with acute conjunctivitis and distributed by three groups: A (1% prednisolone acetate + ciprofloxacin (0.3%); B (Sodium diclofenac (0.1%) + ciprofloxacin (0.3%) and C (artificial tears + ciprofloxacin (0.3%). Patients received medication 6/6 hours daily. Signs and symptoms (e.g. lacrimation, burning, photophobia, etc.) were scored at baseline and on the first, third, fifth and seventh days and in the end of treatment using a standardized questionnaire and slit lamp anterior segment examination. RESULTS: All three groups demonstrated an improvement in the signs and symptoms of conjunctivitis in their follow-up visits. There was no significant difference in symptom and sign scores between Group A and B and B and C in the study visits ( p >0.05). However, the comparison between groups A and C showed a clinical trend (p=0.05) on third evaluation suggesting better clinical action using the corticosteroids. CONCLUSION: The prednisolone acetate was not superior to the use of sodium diclofenac or artificial tears in relieving the signs and symptoms of viral conjunctivitis.


Assuntos
Corticosteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Ciprofloxacino/administração & dosagem , Conjuntivite Viral/tratamento farmacológico , Diclofenaco/administração & dosagem , Prednisolona/análogos & derivados , Doença Aguda , Adolescente , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Interferon gama , Interleucinas/análise , Lubrificantes Oftálmicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/análise , Soluções Oftálmicas/administração & dosagem , Prednisolona/administração & dosagem , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Adulto Jovem
17.
Acta Cir Bras ; 34(12): e201901204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074166

RESUMO

PURPOSE: To examine the therapeutic effect of external adenosine on an acetic acid-induced acute ulcerative colitis model in rats. METHODS: Thirty male mature rats were divided into three groups as control, acute colitis (AC) and AC+adenosine group (AC+AD). AC was induced by rectal administration of 4% acetic acid (AA). 5mg/kg/day adenosine was performed i.p for 4 weeks to AC+AD group. Rectum and colon were excised for microscopic and histopathological histopathologic evaluations, and immunohistochemical analysis of nuclear factor kappa B (NF-kB). Blood samples were collected for biochemical detection of TNF-α, Pentraxin-3 and malondialdehyde (MDA) levels. RESULTS: AC group had generalized hyperemia and hemorrhage with increased macroscopic and histopathological scores compared with control (P <0.0001) while adenosine treatment decreased these scores significantly (P <0.001), with reduced distribution of disrupted epithelium, leukocyte infiltrates, and focal hemorrhage. AC group showed significantly increased immunoexpression of NF-kB in rectum, plasma and tissue levels of TNF-α, plasma Pentraxin-3 and MDA levels (P <0.0001) while adenosine reduced these levels (P < 0.05). CONCLUSION: Adenosine appears to promote healing of colon and rectum exposed to AA-induced AC, suggesting a boosting effect of adenosine on the intestinal immune system to cure ulcerative colitis.


Assuntos
Adenosina/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ácido Acético , Doença Aguda , Animais , Proteína C-Reativa/análise , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colo/patologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Masculino , Malondialdeído/sangue , NF-kappa B/análise , Ratos Sprague-Dawley , Reto/patologia , Valores de Referência , Reprodutibilidade dos Testes , Componente Amiloide P Sérico/análise , Substâncias Reativas com Ácido Tiobarbitúrico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise
18.
J Pediatr Hematol Oncol ; 42(3): 185-192, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032240

RESUMO

Although aplastic anemia has been extensively investigated, little is known about their circulating cytokine pattern. The present study was done to evaluate the severity of the disease with the 3 major anti-hematopoietic cytokines interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ). This study is ethically cleared. A total of 102 bone marrow plasma and peripheral blood plasma paired samples were collected from the confirmed acquired aplastic anemia (AAA) patients and 10 control cases after taking written consent and analyzed by the quantitative enzyme-linked immunosorbent assay. The Mann-Whitney U test was used for statistical analysis. Considerably increased levels of IL-2, TNF-α, and IFN-γ were found in the peripheral blood plasma and bone marrow plasma of AAA patients as compared with controls, that is, 45.76±20.61 versus 1.99±1.25, P<0.00001; 26.51±15.62 versus 11.7±3.67, P=0.00188; 17.04±11.64 versus 5.27±1.92, P=0.00034 and 70.54± 37.57 versus 3.12±1.82, P<0.00001; 251.82±243.80 versus 15.66±6.35, P<0.00001; 39.35±22.58 versus 11.12±2.41, P=0.00012, respectively. The IL-2, TNF-α, and IFN-γ levels were observed to be extraordinarily elevated in AAA, but were very low in the control cases. The results confirm that IL-2, TNF-α, and IFN-γ may have an imperative association with the disaster in the bone marrow compartment of AAA patients. The levels and ranges of the observed cytokines can also be predicted by the severity basis of this study.


Assuntos
Anemia Aplástica/imunologia , Interferon gama/análise , Interleucina-2/análise , Fator de Necrose Tumoral alfa/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
J Med Food ; 23(2): 191-197, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32017647

RESUMO

Fructus mume was recorded in the Chinese Pharmacopoeia and traditional Chinese medical books for chronic cough, but the effect and related constituents are still unknown. Thus, we investigated the protect effects and the relevant constituents of F. mume in a guinea pig model with chronic cough induced by cigarette smoke (CS). The organic acids and polysaccharides in F. mume were detected by high performance liquid chromatography, gel permeation chromatography, and gas chromatography-mass spectrometry. The guinea pigs were orally administrated with vehicle or the water extract of Fructus mume (FW) during the 14 days of CS exposure. Citric acid induced coughs were automatically measured by Buxco system. The differential cells in bronchoalveolar lavage fluid (BALF) and histopathological changes in lung tissue were assessed by hematoxylin and eosin staining. The tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8) levels in lung tissue were detected via enzyme-linked immunosorbent assay. The mucus productions in tracheas were determined with Alcian blue-periodic acid Schiff staining. The results suggested relatively high concentration of citric acid, chlorogenic acid, and neochlorogenic acid in F. mume, and high proportion of galactose and glucose and lower molecular weight of polysaccharides. Administration of FW significantly reduced the cough frequency, decreased inflammatory cells in BALF and lung tissue, and attenuated the thickening of airway epithelium and submucosa compared with CS-exposure group. Moreover, the overproduction of TNF-α and IL-8 in lung tissues, and mucus in central airways of CS-induced guinea pigs was markedly inhibited by FW. The extract could also protect against CS exposure-induced chronic cough in guinea pigs by reducing coughs, airways inflammation, and mucus overproduction.


Assuntos
Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Frutas/química , Prunus/química , Poluição por Fumaça de Tabaco/efeitos adversos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Doença Crônica , Ácido Cítrico , Tosse/induzido quimicamente , Cobaias , Interleucina-8/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Muco , Extratos Vegetais/uso terapêutico , Fator de Necrose Tumoral alfa/análise
20.
Clin Oral Investig ; 24(10): 3623-3631, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32060657

RESUMO

OBJECTIVE: This study aimed to evaluate the levels of interleukin-18 and tumor necrosis factor-alpha in gingival crevicular fluid of diabetic children with gingivitis. METHODOLOGY: Eighty-eight children (44 with type 1 diabetes mellitus and 44 systemically healthy) were recruited for the study. The children were divided into four subgroups based on their periodontal and systemic condition: (1) systemically and periodontally healthy children (H), (2) systemically healthy children with gingivitis (G), (3) periodontally healthy children with T1DM (T1DM + H), and (4) children with T1DM and gingivitis (T1DM + G). The plaque index, gingival index, probing pocket depth, and GCF volume were recorded. The IL-18 and TNF-α levels in GCF were determined by ELISA. RESULTS: The clinical periodontal parameters, GCF IL-18 level, and TNF-α level were similar between diabetic and systemically healthy children (p > 0.05). The gingivitis subgroups had a significantly higher GI, PI, PPD, GCF volume, and TNF-α total amounts than the H subgroups (p < 0.0001). The IL-18 concentrations in the gingivitis subgroups were significantly lower than in the periodontally healthy subgroups. CONCLUSIONS: In diabetic children with good metabolic control, T1DM did not affect the GCF levels of IL-18 and TNF-α in the presence of gingivitis. However, increased GCF TNF-α levels in children with gingivitis confirm that TNF-α is closely related to gingival inflammation. CLINICAL RELEVANCE: Type 1 diabetes mellitus is not associated with GCF interleukin-18 and tumor necrosis factor-alpha levels in children with gingivitis.


Assuntos
Diabetes Mellitus Tipo 1 , Gengivite , Interleucina-18/farmacocinética , Fator de Necrose Tumoral alfa/análise , Criança , Diabetes Mellitus Tipo 1/complicações , Líquido do Sulco Gengival , Gengivite/complicações , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA