RESUMO
El cáncer gástrico (CG) es la neoplasia del tubo digestivo más prevalente en el mundo, asociada a factores genéticos del hospedero y externos, como infección por Helicobacter pylori. La patogénesis incluye inflamación crónica mediada por citocinas del microambiente tumoral, detectables sistémicamente. Estudios previos reportan niveles séricos de citocinas y su contribución al diagnóstico de CG. El presente estudio analiza el perfil de citocinas del tipo de Th1(IFNγ), Th2(IL-4 e IL-10), Th17(Th-17A) y otras pro inflamatorias: IL-1ß, IL-6 y TNF-α, en plasma de 70 casos de pacientes con CG comparándolos con 132 sujetos sanos equiparables en edad y sexo. Los casos provinieron del Hospital Roosevelt e Instituto Nacional de Cancerología de Guatemala (Incan) y formaron parte de un estudio previo. Se analizó la base de datos clínicos, patológicos y epidemiológicos. Se midieron los niveles de citocinas utilizando el sistema "MSD MULTI-SPOT Assay System". La edad promedio de los casos fue 59.5 años, (DE 13.0), 51%, eran positivos para IgG anti H. pylori. Un 71% presentó adenocarcinoma grado III (Borrman), según clasificación de Lauren 55% tenían tipo intestinal. Las siete citocinas cuantificadas se encontraron significativamente elevadas (p < .05) en el plasma de los casos respecto a sus controles. Los casos de CG tipo difuso presentaron niveles de IFNγ significativa-mente elevados. Por regresión logística, las citocinas IL-6 e IL-10, están asociadas significativamente a CG (p < .05) independientemente del estatus de infección por H. pylori. Se destacan la IL-6 e IL-10 como las principales citocinas asociadas a la presencia de CG.
Gastric cancer (GC) is the most prevalent gastrointestinal neoplasm in the world, associated with host and external genetic factors, such as Helicobacter pylori infection. The pathogenesis includes chronic inflammation mediated by cytokines of the tumor microenvironment, systemically detectable. Previous studies report serum levels of cyto-kines and their contribution to the diagnosis of GC. The present study analyzes the profile of cytokines of the type Th1 (IFNγ), Th2 (IL-4 and IL-10), Th17 (Th-17A) and other pro-inflammatory: IL-1ß, IL-6 and TNF-α, in plasma of 70 cases of patients with GC compared with 132 healthy subjects comparable in age and sex. The cases came from the Roosevelt Hospital and the National Cancer Institute of Guatemala -Incan- and were part of a previous study. The clinical, pathological and epidemiological databases were analyzed. Cytokine levels were measured using the "MSD MULTI-SPOT Assay System". The average age of the cases was 59.5 years, (SD 13.0), 51% were positive for IgG anti H. pylori, 71% had grade III adenocarcinoma (Borrman), according to Laurenís classification, 55% had intestinal type. The seven cytokines quantified were found to be significantly elevated (p < .05) in the plasma of the cases compared to their controls. The diffuse GC cases presented significantly elevated IFNγ levels. By logistic regression, the cytokines IL-6 and IL-10 are significantly associated with GC (p < .05) regardless of the H. pylori infection status. IL-6 and IL-10 stand out as the main cytokines associated with the presence of GC.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Plasma/química , Neoplasias Gástricas/complicações , Citocinas/análise , Interleucina-6/análise , Interleucina-1/análise , Interleucina-10/análise , Células Th2 , Células Th17 , Imunoglobulina G/análise , Adenocarcinoma/complicações , Biomarcadores Tumorais/análise , Infecções por Helicobacter/complicações , Células Th1 , Trato Gastrointestinal/patologia , Microambiente Tumoral , Neoplasias/complicaçõesRESUMO
We aimed to determine the concentration of MMP-2 and IL-1ß in the aqueous humor of dogs with healthy eyes (n=8) and in those with mature (n=8) and hyper mature cataracts (n=8). Correlations between cytokines, cytokines, and intraocular pressure (IOP), as well as cytokines with ages of patients of each group, were also assessed. In patients with cataract, aqueous humor was collected at the end of the electroretinographic procedure. In healthy dogs, aqueous humor was collected before elective surgeries. Cytokine levels were determined using ELISA. IOP was assessed by applanation tonometry. IOP of patients with mature and hyper mature cataracts were lower than the ones measured in normal eyes (P=0.158). MMP-2 aqueous humor concentration was higher in patients with hyper mature cataracts, in comparisons with healthy patients (P=0.04). Average IL-1 ß aqueous concentration was higher in patients with cataracts (P<0.0001). Significant higher values of IL-1 ß were observed in patients with hyper mature, than in the ones with mature cataracts (P=0.0085). Correlations between MMP-2 and IL-1 ß (r=-0.38, P=0.06), MMP-2 and IOP (r=-0.149, P=0.484), and IL-1 ß and the ages of patients were not observed (P>0.05). IL-1 ß and IOP correlated negatively (r=-0.42, P=0.04). MMP-2 and the ages of patients correlated only in dogs with mature cataracts (r=0.772, P=0.02). It can be concluded that the increment in the aqueous humor concentration of IL-1 ß found in dogs with mature and hyper mature cataracts, in addition to the negative relationship of this cytokine with IOP, suggests that IL-1 ß is involved in the pathogenesis of LIU. Despite dogs with hypermature cataracts presented significant higher concentrations of MMP-2 in the aqueous humor, such cytokine did not correlate with IL-1 ß and IOP. In our study, a relationship between aqueous humor cytokines and the ages of patients was only confirmed between MMP-2 and the ages of dogs with mature cataracts.(AU)
Objetivou-se determinar as concentrações da metalloprotease-2 (MMP-2) e de interleucina-1 ß (IL-1 ß) em cães com olhos saudáveis (n=8) e naqueles com catarata madura (n=8) e hipermatura (n=8). Correlações entre ambas as citocinas, entre as citocinas e a pressão intraocular (PIO), assim como entre as citocinas e a idade dos pacientes dentro de cada grupo foram averiguadas. Nos pacientes com catarata, o humor aquoso foi colhido ao final da eletrorretinografia. Nos cães saudáveis, o humor aquoso foi colhido antes do início de cirurgias eletivas. Os níveis das citocinas foram determinados por ELISA e a PIO por tonometria de aplanação. A PIO dos pacientes com catarata madura e hipermadura foram mais baixas que aquelas dos pacientes controle (P=0.158). A concentração de MMP-2 no humor aquoso foi maior nos pacientes com catarata hipermtura, comparativamente aos pacientes saudáveis (P=0.04). A concentração de IL-1 ß no humor aquoso foi mais elevada nos cães com catarata (P<0.0001). Nos pacientes com catarata hipermatura, os valores de IL-1 ß foram significativamente mais altos que aqueles dosados nos pacientes com catarata madura (P=0.0085). Correlações entre MMP-2 e IL-1 ß (r=-0.38, P=0.06), MMP-2 e PIO (r=-0.149, P=0.484) e IL-1 ß e as idades dos pacientes não foram observadas (P>0.05). A IL-1 ß se correlacionou negativamente com a PIO (r=-0.42, P=0.04). Correlação entre MMP-2 e a idades dos pacientes foi observada apenas nos cães com catarata madura (r=0.772, P=0.02). Conclui-se que o aumento na concentração de IL-1 ß no humor aquoso de cães com catarata madura e hipermatura, associado à correlação negativa entre essa citocina e a PIO, sugerem que a mesma está envolvida na patogênese da uveíte induzida pela lente. Apesar dos cães com catarata hipermadura apresentarem concentrações significativamente maiores de MMP-2 no humor aquoso, essa citocina não se correlacionou com a IL-1 ß e a PIO. Em nosso estudo, correlação entre as citocinas dosadas no humor aquoso e a idade dos pacientes foi confirmada apenas entre MMP-2 e a idade dos cães com catarata madura.(AU)
Assuntos
Animais , Cães , Uveíte/veterinária , Catarata/veterinária , Interleucina-1/análise , Metaloproteinase 2 da Matriz/análise , Pressão IntraocularRESUMO
We aimed to determine the concentration of MMP-2 and IL-1ß in the aqueous humor of dogs with healthy eyes (n=8) and in those with mature (n=8) and hyper mature cataracts (n=8). Correlations between cytokines, cytokines, and intraocular pressure (IOP), as well as cytokines with ages of patients of each group, were also assessed. In patients with cataract, aqueous humor was collected at the end of the electroretinographic procedure. In healthy dogs, aqueous humor was collected before elective surgeries. Cytokine levels were determined using ELISA. IOP was assessed by applanation tonometry. IOP of patients with mature and hyper mature cataracts were lower than the ones measured in normal eyes (P=0.158). MMP-2 aqueous humor concentration was higher in patients with hyper mature cataracts, in comparisons with healthy patients (P=0.04). Average IL-1 ß aqueous concentration was higher in patients with cataracts (P<0.0001). Significant higher values of IL-1 ß were observed in patients with hyper mature, than in the ones with mature cataracts (P=0.0085). Correlations between MMP-2 and IL-1 ß (r=-0.38, P=0.06), MMP-2 and IOP (r=-0.149, P=0.484), and IL-1 ß and the ages of patients were not observed (P>0.05). IL-1 ß and IOP correlated negatively (r=-0.42, P=0.04). MMP-2 and the ages of patients correlated only in dogs with mature cataracts (r=0.772, P=0.02). It can be concluded that the increment in the aqueous humor concentration of IL-1 ß found in dogs with mature and hyper mature cataracts, in addition to the negative relationship of this cytokine with IOP, suggests that IL-1 ß is involved in the pathogenesis of LIU. Despite dogs with hypermature cataracts presented significant higher concentrations of MMP-2 in the aqueous humor, such cytokine did not correlate with IL-1 ß and IOP. In our study, a relationship between aqueous humor cytokines and the ages of patients was only confirmed between MMP-2 and the ages of dogs with mature cataracts.(AU)
Objetivou-se determinar as concentrações da metalloprotease-2 (MMP-2) e de interleucina-1 ß (IL-1 ß) em cães com olhos saudáveis (n=8) e naqueles com catarata madura (n=8) e hipermatura (n=8). Correlações entre ambas as citocinas, entre as citocinas e a pressão intraocular (PIO), assim como entre as citocinas e a idade dos pacientes dentro de cada grupo foram averiguadas. Nos pacientes com catarata, o humor aquoso foi colhido ao final da eletrorretinografia. Nos cães saudáveis, o humor aquoso foi colhido antes do início de cirurgias eletivas. Os níveis das citocinas foram determinados por ELISA e a PIO por tonometria de aplanação. A PIO dos pacientes com catarata madura e hipermadura foram mais baixas que aquelas dos pacientes controle (P=0.158). A concentração de MMP-2 no humor aquoso foi maior nos pacientes com catarata hipermtura, comparativamente aos pacientes saudáveis (P=0.04). A concentração de IL-1 ß no humor aquoso foi mais elevada nos cães com catarata (P<0.0001). Nos pacientes com catarata hipermatura, os valores de IL-1 ß foram significativamente mais altos que aqueles dosados nos pacientes com catarata madura (P=0.0085). Correlações entre MMP-2 e IL-1 ß (r=-0.38, P=0.06), MMP-2 e PIO (r=-0.149, P=0.484) e IL-1 ß e as idades dos pacientes não foram observadas (P>0.05). A IL-1 ß se correlacionou negativamente com a PIO (r=-0.42, P=0.04). Correlação entre MMP-2 e a idades dos pacientes foi observada apenas nos cães com catarata madura (r=0.772, P=0.02). Conclui-se que o aumento na concentração de IL-1 ß no humor aquoso de cães com catarata madura e hipermatura, associado à correlação negativa entre essa citocina e a PIO, sugerem que a mesma está envolvida na patogênese da uveíte induzida pela lente. Apesar dos cães com catarata hipermadura apresentarem concentrações significativamente maiores de MMP-2 no humor aquoso, essa citocina não se correlacionou com a IL-1 ß e a PIO. Em nosso estudo, correlação entre as citocinas dosadas no humor aquoso e a idade dos pacientes foi confirmada apenas entre MMP-2 e a idade dos cães com catarata madura.(AU)
Assuntos
Animais , Cães , Uveíte/veterinária , Catarata/veterinária , Interleucina-1/análise , Metaloproteinase 2 da Matriz/análise , Pressão IntraocularRESUMO
ABSTRACT Aims and Objectives: Polypropylene meshes have been increasingly adopted for correction of pelvic organ prolapse due to its lower recurrence rate when compared to surgeries without meshes. The study of the interaction of these materials with the host tissue may contribute to the development of materials with best biocompatibility and, consequently, less complication rates. Materials and Methods: The present study compares the inflammatory reaction of standard-weight (SW) and lightweight (LW) meshes (72 g/m216g/m2 respectively), implanted in the abdomen of 20 adult rats, which were euthanized in four or 30 days. Quantification of pro-inflammatory markers, IL-1 and TNF-α, and of metalloproteinases, MMP2 and MMP3, were carried out through immunohistochemistry with AxioVision® software. Results: There were no significant differences in the quantification of IL-1 and TNF-α in LW versus SW meshes. However, IL-1 quantification increased along time (30 days >4 days, p=0.0269). Also, MMP-2 quantification was similar to SW and LW and both presented a significant increase along time (30 days >4 days, p <0.0001). MMP-3 quantification also showed no difference between the SW and LW groups, but increased along time (30 days >4 days, p=0.02). Conclusions: Mesh's density did not influence the quantification of pro-inflammatory cytokines IL-1 and TNF-α and metalloproteinases 2 and 3. The increased expression of IL-1, MMP-2 and MMP-3 over time could represent a longstanding inflammatory response after PP mesh implantation. Possibly, the occurrence of adverse events following PP prosthetic implants can be influenced by other factors, not solely related to the amount of implanted material.
Assuntos
Animais , Feminino , Ratos , Polipropilenos/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Interleucina-1/análise , Fator de Necrose Tumoral alfa/análise , Metaloproteinase 3 da Matriz/análise , Metaloproteinase 2 da Matriz/análise , Tela Subcutânea/patologia , Fatores de Tempo , Cicatrização , Materiais Biocompatíveis/efeitos adversos , Teste de Materiais , Imuno-Histoquímica , Reprodutibilidade dos Testes , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/patologia , Colágeno/análise , Parede Abdominal/patologia , Tela Subcutânea/efeitos dos fármacosRESUMO
AIMS AND OBJECTIVES: Polypropylene meshes have been increasingly adopted for correction of pelvic organ prolapse due to its lower recurrence rate when compared to surgeries without meshes. The study of the interaction of these materials with the host tissue may contribute to the development of materials with best biocompatibility and, consequently, less complication rates. MATERIALS AND METHODS: The present study compares the inflammatory reaction of standard-weight (SW) and lightweight (LW) meshes (72 g/m216g/m2 respectively), implanted in the abdomen of 20 adult rats, which were euthanized in four or 30 days. Quantification of pro-inflammatory markers, IL-1 and TNF-α, and of metalloproteinases, MMP2 and MMP3, were carried out through immunohistochemistry with AxioVision ® software. RESULTS: There were no significant differences in the quantification of IL-1 and TNF-α in LW versus SW meshes. However, IL-1 quantification increased along time (30 days >4 days, p=0.0269). Also, MMP-2 quantification was similar to SW and LW and both presented a significant increase along time (30 days >4 days, p < 0.0001). MMP-3 quantification also showed no difference between the SW and LW groups, but increased along time (30 days >4 days, p=0.02). CONCLUSIONS: Mesh's density did not influence the quantification of pro-inflammatory cytokines IL-1 and TNF-α and metalloproteinases 2 and 3. The increased expression of IL-1, MMP-2 and MMP-3 over time could represent a longstanding inflammatory response after PP mesh implantation. Possibly, the occurrence of adverse events following PP prosthetic implants can be influenced by other factors, not solely related to the amount of implanted material.
Assuntos
Interleucina-1/análise , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 3 da Matriz/análise , Polipropilenos/efeitos adversos , Tela Subcutânea/patologia , Telas Cirúrgicas/efeitos adversos , Fator de Necrose Tumoral alfa/análise , Parede Abdominal/patologia , Animais , Materiais Biocompatíveis/efeitos adversos , Colágeno/análise , Feminino , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/patologia , Imuno-Histoquímica , Teste de Materiais , Ratos , Reprodutibilidade dos Testes , Tela Subcutânea/efeitos dos fármacos , Fatores de Tempo , CicatrizaçãoRESUMO
OBJECTIVES: To evaluate the effect of implanted S-nitrosoglutathione (GSNO) coating polypropylene mesh in foreign-body response of rats. METHODS: Thirty female rats underwent to subcutaneous implant of five polypropylene (PP) fragments: uncoated PP (control); PP polyvinylalcohol (PVA) coated and PP PVA + GSNO (1, 10 and 70 mMol) coated. After euthanasia (4 and 30 days), eight slides were prepared from each animal: hematoxylin-eosin (inflammatory response); unstained (birefringence collagen evaluation); TUNEL technique (apoptosis); and five for immunohistochemical processing: CD-31 (angiogenesis), IL-1 and TNF-α (proinflammatory cytokynes), iNOS (NO synthesis) and MMP-2 (collagen metabolism). The inflammation area, birefringence index, apoptotic index, immunoreactivity and vessel density were objectively measured. RESULTS: Inflammatory reaction area at 4 days was 11.3, 15.2, 25.1, 17.1 and 19.3% of pure PP, PVA, GSNO 1, 10 and 70 mM, respectively, p = 0.0006 (PP × Others). At 30 days lower inflammatory area was observed in GSNO 10 and 70 mM compared to pure PP (5.3, 5.2 and 11.1%, respectively, p = 0.0001). Vessel density was higher for GSNO 1 mM (25.5%) compared to pure PP (19.6%) at 30 days only, p = 0.0081. Apoptotic index at 4 days was lower for GSNO 1 mM (49.3%) than pure PVA (60.6%), p = 0.0124. GSNO 10 and 70 mM reduced their apoptotic index at 30 days compared to 4 days (49.9 vs. 36.9 and 59.1 vs. 47.5%, respectively, p = 0.0397). Birefringence index, IL-1, TNF, MMP-2 and iNOS were not different. CONCLUSIONS: Depending on concentrations, GSNO can increase angiogenesis, reduce inflammation and apoptosis compared to pure PP, without impact on cytokine, collagen organization/metabolism and endogenous NO synthesis.
Assuntos
Reação a Corpo Estranho , Neovascularização Fisiológica , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/biossíntese , S-Nitrosoglutationa/farmacologia , Telas Cirúrgicas , Animais , Apoptose/efeitos dos fármacos , Feminino , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/metabolismo , Reação a Corpo Estranho/patologia , Interleucina-1/análise , Metaloproteinase 2 da Matriz/análise , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Óxido Nítrico Sintase Tipo II/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Polipropilenos , Álcool de Polivinil/farmacologia , Ratos , Ratos Wistar , Telas Cirúrgicas/efeitos adversos , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Ideal management of sexually transmitted infections (STI) may require risk markers for pathology or vaccine development. Previously, we identified common genetic variants associated with chlamydial pelvic inflammatory disease (PID) and reduced fecundity. As this explains only a proportion of the long-term morbidity risk, we used whole-exome sequencing to identify biological pathways that may be associated with STI-related infertility. METHODS: We obtained stored DNA from 43 non-Hispanic black women with PID from the PID Evaluation and Clinical Health Study. Infertility was assessed at a mean of 84 months. Principal component analysis revealed no population stratification. Potential covariates did not significantly differ between groups. Sequencing kernel association test was used to examine associations between aggregates of variants on a single gene and infertility. The results from the sequencing kernel association test were used to choose "focus genes" (P < 0.01; n = 150) for subsequent Ingenuity Pathway Analysis to identify "gene sets" that are enriched in biologically relevant pathways. RESULTS: Pathway analysis revealed that focus genes were enriched in canonical pathways including, IL-1 signaling, P2Y purinergic receptor signaling, and bone morphogenic protein signaling. CONCLUSIONS: Focus genes were enriched in pathways that impact innate and adaptive immunity, protein kinase A activity, cellular growth, and DNA repair. These may alter host resistance or immunopathology after infection. Targeted sequencing of biological pathways identified in this study may provide insight into STI-related infertility.
Assuntos
Infecções por Chlamydia/genética , Sequenciamento do Exoma , Infertilidade/genética , Doença Inflamatória Pélvica/genética , Transdução de Sinais/genética , Adulto , Proteínas Morfogenéticas Ósseas/análise , Infecções por Chlamydia/complicações , Feminino , Humanos , Infertilidade/microbiologia , Interleucina-1/análise , Doença Inflamatória Pélvica/complicações , Doença Inflamatória Pélvica/microbiologia , Análise de Componente Principal , Receptores Purinérgicos P2Y/análiseRESUMO
The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1ß hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1ß expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1ß-positive cells in the NP group was increased, with higher integral optical density than the control group. Compared to the control group, the serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein in the newborn rats of the NP group were significantly increased. There was no significant difference in the serum level of high-density lipoprotein or cholesterol between the groups. Perinatal exposure to NP can interfere with the in vivo estrogen and progesterone levels of pregnant rats, resulting in threatened abortion, dystocia and other adverse delivery outcomes. High liver and serum NP levels of the newborn rats led to alteration of liver tissue structure and function. The NP-induced hepatotoxicity is probably mediated by inflammatory cytokines TNF-α and IL-1α.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Feminino , Interleucina-1/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análiseRESUMO
OBJECTIVES: To describe acute and sub acute aspects of histological and immunohistochemical response to PP implant in a rat subcutaneous model based on objective methods. MATERIALS AND METHODS: Thirty rats had a PP mesh subcutaneously implanted and the same dissection on the other side of abdomen but without mesh (sham). The animals were euthanized after 4 and 30 days. Six slides were prepared using the tissue removed: one stained with hematoxylin-eosin (inflammation assessment); one unstained (birefringence evaluation) and four slides for immunohistochemical processing: IL-1 and TNF-α (pro-inflammatory cytokines), MMP-2 (collagen metabolism) and CD-31 (angiogenesis). The area of inflammation, the birefringence index, the area of immunoreactivity and the number of vessels were objectively measured. RESULTS: A larger area of inflammatory reaction was observed in PP compared to sham on the 4th and on the 30th day (p=0.0002). After 4 days, PP presented higher TNF (p=0.0001) immunoreactivity than sham and no differences were observed in MMP-2 (p=0.06) and IL-1 (p=0.08). After 30 days, a reduction of IL-1 (p=0.010) and TNF (p=0.016) for PP and of IL-1 (p=0.010) for sham were observed. Moreover, area of MMP-2 immunoreactivity decreased over time for PP group (p=0.018). Birefringence index and vessel counting showed no differences between PP and sham (p=0.27 and p=0.58, respectively). CONCLUSIONS: The implantation of monofilament and macroporous polypropylene in the subcutaneous of rats resulted in increased inflammatory activity and higher TNF production in the early post implant phase. After 30 days, PP has similar cytokines immunoreactivity, vessel density and extracellular matrix organization.
Assuntos
Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/patologia , Polipropilenos/efeitos adversos , Tela Subcutânea/patologia , Telas Cirúrgicas/efeitos adversos , Animais , Materiais Biocompatíveis/efeitos adversos , Birrefringência , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/patologia , Colágeno/análise , Colágeno/metabolismo , Feminino , Imuno-Histoquímica , Interleucina-1/análise , Interleucina-1/metabolismo , Teste de Materiais , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
ABSTRACT Objectives To describe acute and sub acute aspects of histological and immunohistochemical response to PP implant in a rat subcutaneous model based on objective methods. Materials and Methods Thirty rats had a PP mesh subcutaneously implanted and the same dissection on the other side of abdomen but without mesh (sham). The animals were euthanized after 4 and 30 days. Six slides were prepared using the tissue removed: one stained with hematoxylin-eosin (inflammation assessment); one unstained (birefringence evaluation) and four slides for immunohistochemical processing: IL-1 and TNF-α (pro-inflammatory cytokines), MMP-2 (collagen metabolism) and CD-31 (angiogenesis). The area of inflammation, the birefringence index, the area of immunoreactivity and the number of vessels were objectively measured. Results A larger area of inflammatory reaction was observed in PP compared to sham on the 4th and on the 30th day (p=0.0002). After 4 days, PP presented higher TNF (p=0.0001) immunoreactivity than sham and no differences were observed in MMP-2 (p=0.06) and IL-1 (p=0.08). After 30 days, a reduction of IL-1 (p=0.010) and TNF (p=0.016) for PP and of IL-1 (p=0.010) for sham were observed. Moreover, area of MMP-2 immunoreactivity decreased over time for PP group (p=0.018). Birefringence index and vessel counting showed no differences between PP and sham (p=0.27 and p=0.58, respectively). Conclusions The implantation of monofilament and macroporous polypropylene in the subcutaneous of rats resulted in increased inflammatory activity and higher TNF production in the early post implant phase. After 30 days, PP has similar cytokines immunoreactivity, vessel density and extracellular matrix organization.
Assuntos
Animais , Feminino , Polipropilenos/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Reação a Corpo Estranho/etiologia , Reação a Corpo Estranho/induzido quimicamente , Reação a Corpo Estranho/patologia , Tela Subcutânea/patologia , Fatores de Tempo , Materiais Biocompatíveis/efeitos adversos , Birrefringência , Teste de Materiais , Imuno-Histoquímica , Celulite (Flegmão)/etiologia , Celulite (Flegmão)/patologia , Reprodutibilidade dos Testes , Colágeno/análise , Colágeno/metabolismo , Interleucina-1/análise , Interleucina-1/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Ratos Wistar , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Metaloproteinase 2 da Matriz/análise , Metaloproteinase 2 da Matriz/metabolismoRESUMO
This study aimed to investigate the expression of interleukin 1 (IL-1) system members (proteins and messenger RNA of ligands and receptors) and its distribution in ovarian follicles of cyclic cows and to evaluate the effects of IL-1ß on the survival and activation of primordial follicles in vitro. The ovaries were processed for localization of IL-1 system in preantral and antral follicles by immunohistochemical, real-time polymerase chain reaction, and Western blot analysis. For in vitro studies, ovarian fragments were cultured in α-MEM(+) supplemented with IL-1ß (0, 1, 10, 50, or 100 ng/mL), and after 6 d, the cultured tissues were processed for histologic analysis. Immunohistochemical results showed that the IL-1 system proteins IL-1ß, IL-1RA, IL-1RI, and IL-1RII were detected in the cytoplasm of oocytes and granulosa cells from all follicular categories and theca cells of antral follicles. Variable levels of messenger RNA for the IL-1 system members were observed at different stages of development. After 6 d of culture, the presence of IL-1ß (10 or 50 ng/mL) was effective in maintaining the percentage of normal follicles and in promoting primordial follicle activation. In conclusion, IL-1 system members are differentially expressed in ovarian follicles according to their stage of development. Moreover, IL-1ß promotes the development of primordial follicles. These results indicate an important role of the IL-1 system in the regulation of bovine folliculogenesis.
Assuntos
Bovinos/fisiologia , Interleucina-1/análise , Interleucina-1beta/farmacologia , Folículo Ovariano/química , Folículo Ovariano/fisiologia , RNA Mensageiro/análise , Animais , Western Blotting , Feminino , Células da Granulosa/química , Imuno-Histoquímica/veterinária , Proteína Antagonista do Receptor de Interleucina 1/análise , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1/genética , Interleucina-1beta/análise , Interleucina-1beta/genética , Oócitos/química , Folículo Ovariano/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Receptores Tipo II de Interleucina-1/análise , Receptores Tipo II de Interleucina-1/genética , Células Tecais/químicaRESUMO
The current study aimed to investigate the effects of perinatal exposure to nonylphenol (NP) on delivery outcome of pregnant rats and subsequent inflammatory hepatic injury in newborn rats. The pregnant rats were divided into 2 groups: control group (corn oil) and NP exposure group. Thirty-four pregnant rats were administered NP or corn oil by gavage from the sixth day of pregnancy to 21 days postpartum, with blood samples collected at 12 and 21 days of pregnancy and 60 days after delivery. The NP concentration was measured by HPLC, with chemiluminescence used for detection of estrogen and progesterone levels. Maternal delivery parameters were also observed. Liver and blood of the newborn rats were collected and subjected to automatic biochemical detection of liver function and blood lipid analyzer (immunoturbidimetry), and ultrastructural observation of the hepatic microstructure, with the TNF-α and IL-1β hepatic tissue levels evaluated by immunohistochemistry. Compared with the control group, the pregnant and postpartum serum NP and estradiol levels of the mother rats in the NP group were significantly increased, together with lowered progesterone level, increased number of threatened abortion and dystocia, and fewer newborn rats and lower litter weight. Serum and hepatic NP levels of the newborn rats measured 60 days after birth were significantly higher than those of the control group, as well as lower testosterone levels and increased estradiol levels. When observed under electron microscope, the hepatocyte nuclei of the control group were large and round, with evenly distributed chromatin. The chromatin of hepatocytes in the NP group presented deep staining of the nuclei, significant lipid decrease in the cytoplasm, and the majority of cells bonded with lysate. The results of immunohistochemistry showed that there was almost no TNF-α or IL-1β expression in the hepatocytes of the control group, while the number of TNF-α-, PCNA-, and IL-1β-positive cells in the NP group was increased, with higher integral optical density than the control group. Compared to the control group, the serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein in the newborn rats of the NP group were significantly increased. There was no significant difference in the serum level of high-density lipoprotein or cholesterol between the groups. Perinatal exposure to NP can interfere with the in vivo estrogen and progesterone levels of pregnant rats, resulting in threatened abortion, dystocia and other adverse delivery outcomes. High liver and serum NP levels of the newborn rats led to alteration of liver tissue structure and function. The NP-induced hepatotoxicity is probably mediated by inflammatory cytokines TNF-α and IL-1α.
Assuntos
Animais , Feminino , Ratos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fenóis/toxicidade , Animais Recém-Nascidos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Interleucina-1/análise , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/análiseRESUMO
ABSTRACT CONTEXT AND OBJECTIVE: Bacterial vaginosis occurs frequently in pregnancy and increases susceptibility to sexually transmitted infections (STI). Considering that adolescents are disproportionally affected by STI, the aim of this study was to evaluate the cervicovaginal levels of interleukin (IL)-1 beta, IL-6, IL-8 and bacterial sialidase in pregnant adolescents with bacterial vaginosis. DESIGN AND SETTING: Cross-sectional study at mother and child referral units in Belém, Pará, Brazil. METHODS: Vaginal samples from 168 pregnant adolescents enrolled were tested for trichomoniasis and candidiasis. Their vaginal microbiota was classified according to the Nugent criteria (1991) as normal, intermediate or bacterial vaginosis. Cervical infection due to Chlamydia trachomatisand Neisseria gonorrhoeae was also assessed. Cytokine and sialidase levels were measured, respectively, using enzyme-linked immunosorbent assays and MUAN conversion in cervicovaginal lavages. Forty-eight adolescents (28.6%) were excluded because they tested positive for some of the infections investigated. The remaining 120 adolescents were grouped according to vaginal flora type: normal (n = 68) or bacterial vaginosis (n = 52). Their cytokine and sialidase levels were compared between the groups using the Mann-Whitney test (P < 0.05). RESULTS: The pregnant adolescents with bacterial vaginosis had higher levels of IL-1 beta, IL-6 and IL-8 (P < 0.05). Sialidase was solely detected in 35 adolescents (67.2%) with bacterial vaginosis. CONCLUSIONS: Not only IL-1 beta and sialidase levels, but also IL-6 and IL-8 levels are higher in pregnant adolescents with bacterial vaginosis, thus indicating that this condition elicits a more pronounced inflammatory response in this population, which potentially increases vulnerability to STI acquisition.
RESUMO CONTEXTO E OBJETIVO: A vaginose bacteriana é uma condição, comum em gestantes, que aumenta a susceptibilidade a infecções sexualmente transmissíveis (IST). Considerando que adolescentes são desproporcionalmente afetadas por IST, o objetivo deste estudo foi avaliar os níveis cervicovaginais de interleucina (IL)-1 beta, IL-6, IL-8 e sialidases bacterianas em gestantes adolescentes com vaginose bacteriana. DESENHO DO ESTUDO E LOCAL: Estudo transversal em Unidade de Referência Materno Infantil (UREMIA), Belém, Pará, Brasil. MÉTODOS: Amostras vaginais das 168 gestantes adolescentes incluídas foram testadas para tricomoníase e candidíase e a microbiota vaginal foi classificada em normal, intermediária e vaginose bacteriana, segundo os critérios de Nugent (1991). Infecções cervicais por Chlamydia trachomatis eNeisseria gonorrhoeae também foram avaliadas. Os níveis de citocinas e sialidades foram quantificados, respectivamente, por método imunoenzimático e pela conversão do MUAN nos lavados cervicovaginais. Foram excluídas 48 (28,6%) adolescentes positivas para alguma das infecções investigadas. As 120 gestantes remanescentes foram agrupadas de acordo com o padrão de flora vaginal em: normal (n = 68) e vaginose bacteriana (n = 52). Níveis de citocinas e sialidases foram comparados pelo teste de Mann-Whitney, P < 0,05. RESULTADOS: As gestantes adolescentes com vaginose bacteriana entre os grupos apresentaram níveis aumentados de IL-1 beta, IL-6 and IL-8 (P < 0,05). Sialidases foram exclusivamente detectadas em 35 (67,2%) adolescentes com vaginose bacteriana. CONCLUSÕES: Não apenas a IL-1 beta e as sialidases estão aumentadas em gestantes adolescentes com vaginose bacteriana, mas também IL-6 e IL-8, indicando resposta inflamatória mais pronunciada dessa alteração de microbiota nesta população, potencializando a vulnerabilidade à aquisição de IST.
Assuntos
Adolescente , Feminino , Humanos , Gravidez , Adulto Jovem , Interleucinas/análise , Neuraminidase/análise , Vaginose Bacteriana/patologia , Colo do Útero/microbiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Interleucina-1/análise , /análise , /análise , Medição de Risco , Fatores de Risco , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Fatores Socioeconômicos , Estatísticas não Paramétricas , Vagina/microbiologiaRESUMO
CONTEXT AND OBJECTIVE: Bacterial vaginosis occurs frequently in pregnancy and increases susceptibility to sexually transmitted infections (STI). Considering that adolescents are disproportionally affected by STI, the aim of this study was to evaluate the cervicovaginal levels of interleukin (IL)-1 beta, IL-6, IL-8 and bacterial sialidase in pregnant adolescents with bacterial vaginosis. DESIGN AND SETTING: Cross-sectional study at mother and child referral units in Belém, Pará, Brazil. METHODS: Vaginal samples from 168 pregnant adolescents enrolled were tested for trichomoniasis and candidiasis. Their vaginal microbiota was classified according to the Nugent criteria (1991) as normal, intermediate or bacterial vaginosis. Cervical infection due to Chlamydia trachomatisand Neisseria gonorrhoeae was also assessed. Cytokine and sialidase levels were measured, respectively, using enzyme-linked immunosorbent assays and MUAN conversion in cervicovaginal lavages. Forty-eight adolescents (28.6%) were excluded because they tested positive for some of the infections investigated. The remaining 120 adolescents were grouped according to vaginal flora type: normal (n = 68) or bacterial vaginosis (n = 52). Their cytokine and sialidase levels were compared between the groups using the Mann-Whitney test (P < 0.05). RESULTS: The pregnant adolescents with bacterial vaginosis had higher levels of IL-1 beta, IL-6 and IL-8 (P < 0.05). Sialidase was solely detected in 35 adolescents (67.2%) with bacterial vaginosis. CONCLUSIONS: Not only IL-1 beta and sialidase levels, but also IL-6 and IL-8 levels are higher in pregnant adolescents with bacterial vaginosis, thus indicating that this condition elicits a more pronounced inflammatory response in this population, which potentially increases vulnerability to STI acquisition.
Assuntos
Interleucinas/análise , Neuraminidase/análise , Vaginose Bacteriana/patologia , Adolescente , Colo do Útero/microbiologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-1/análise , Interleucina-6/análise , Interleucina-8/análise , Gravidez , Medição de Risco , Fatores de Risco , Doenças Bacterianas Sexualmente Transmissíveis/microbiologia , Fatores Socioeconômicos , Estatísticas não Paramétricas , Vagina/microbiologia , Adulto JovemRESUMO
Células tumorais desenvolvem diversas estratégias para escapar da identificação e eliminação pelo sistema imune. Dessa forma, a investigação dos mecanismos envolvidos na comunicação celular no microambiente tumoral e na desregulação local do sistema imune é crítica para uma melhor compreensão da progressão da doença e para o desenvolvimento de alternativas terapêuticas mais eficazes. Nós aqui demonstramos que SIGIRR/IL-1R8, um importante regulador negativo de receptores de Interleucina-1 (ILRs) e receptores do tipo Toll (TLRs), apresenta expressão aumentada em uma linhagem celular epitelial mamária transformada pela superexpressão do oncogene HER2 e em tumores primários de mama, e promove o crescimento tumoral e metástase através da modulação da inflamação associada ao câncer e da atenuação da resposta imune antitumoral. Observamos que IL-1R8 tem sua expressão correlacionada com HER2 em tecidos mamários e sua alta expressão é fator de pior prognóstico em câncer de mama de baixo grau. Notavelmente, níveis aumentados de IL-1R8 foram observados especialmente nos subtipos HER2+ e Luminais de tumores de mama, e sua expressão aumentada em células epiteliais de mama transformadas por HER2 diminui a ativação da via de NF-κB e a expressão de diferentes citocinas pro-inflamatórias (IL-6, IL-8, TNF, CSF2, CSF3 e IFN-ß1). Meio condicionado de células transformadas por HER2, mas não de variantes celulares com o gene IL-1R8 silenciado, induz a polarização de macrófagos para o fenótipo M2 e inibe a ativação de células NK. Em um modelo murino transgênico de tumorigênese espontânea mediada por HER2, MMTV-neu, verificamos que a deficiência de IL-1R8 (IL-1R8-/-neu) retardou o aparecimento de tumores e reduziu a incidência, a carga tumoral e a disseminação metastática. Contudo, não foram observadas diferenças significativas no crescimento tumoral quando animais IL-1R8-/-neu receberam medula óssea de animais IL-1R8+/+, confirmando um papel importante da expressão de IL-1R8 em células não hematopoiéticas na tumorigênese da mama. Tumores IL-1R8+/+neu apresentaram maiores níveis de citocinas pró-inflamatórias como IL-1ß e VEGF, e menores níveis da citocina imunomodulatória IFN-γ. Além disso, tumores que expressavam IL-1R8 apresentaram menor infiltrado de células NK maduras, células dendríticas (DCs) e linfócitos T-CD8+ e um maior infiltrado de macrófagos M2 e linfócitos T-CD4+. Coletivamente, esses resultados indicam que a expressão de IL-1R8 em tumores de mama pode representar um novo mecanismo de escape da resposta imune e suportam IL-1R8 como potencial alvo terapêutico
Tumor cells develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. Identification of new players that regulate the cellular crosstalk within the tumor microenvironment and promote local immune dysregulation is critical to understand disease progression and to improve therapeutic strategies. Here, we demonstrate that SIGIRR/IL-1R8, a negative regulator of IL-1R and TLRs, is up-regulated in a HER2-transformed epithelial mammary cell line and in primary breast tumors and promotes tumor growth and metastasis by modulating cancer-related inflammation and impairing anti-tumor immunity. IL-1R8 expression is correlated with HER2 in mammary tissue, and higher tumor IL-1R8 expression is a poor prognostic factor in lower grade breast tumors. Notably, higher levels of IL-1R8 expression were observed in HER2+ and Luminal breast tumor subtypes and IL-1R8 up-regulation in HER2-transformed mammary epithelial cells inhibited NF-κB activation and the expression of pro-inflammatory cytokines (IL-6, IL-8, TNFα, CSF2, CSF3, IFN-ß1). Conditioned medium from HER2-transformed cells, but not from IL-1R8 knockdown variants, induced M2-macrophage polarization and inhibited natural-killer (NK) cell activation. IL-1R8 deficiency in a transgenic mouse model of breast tumorigenesis (MMTV-neu) significantly delayed tumor onset and reduced tumor incidence, burden and metastasis. No significant differences in tumor growth were observed when IL-1R8-/-neu mice were transplanted with bone marrow from IL-1R8+/+ animals, confirming an important role for IL-1R8 expression in non-hematopoietic cells during breast tumorigenesis. IL-1R8+/+neu mammary tumors presented higher levels of pro-inflammatory cytokines such as IL-1ß and VEGF, but lower levels of IFN-γ. Besides, a lower infiltrate of mature NK cells, dendritic cells (DCs) and CD8+ T cells but higher infiltrate of M2-macrophages and CD4+ T cells were present in IL-1R8 expressing tumors. Collectively, our results support IL-1R8 expression as a novel tumor immune escape mechanism in breast cancer and putative target for immunotherapy
Assuntos
Camundongos , Neoplasias da Mama/complicações , Biologia Molecular/educação , Células Neoplásicas Circulantes , Células-Tronco Hematopoéticas , Interleucina-1/análise , Carga Tumoral , Microambiente Tumoral/genéticaRESUMO
OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent for the treatment of inflammatory and angiogenesis-related diseases.
Assuntos
Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Zingiberaceae/química , Análise de Variância , Inibidores da Angiogênese/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Interleucina-1/análise , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Células U937/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...
Assuntos
Animais , Humanos , Masculino , Ratos , Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios/farmacologia , Cinamatos/farmacologia , Extratos Vegetais/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Zingiberaceae/química , Análise de Variância , Inibidores da Angiogênese/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Interleucina-1/análise , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/efeitos dos fármacos , /efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
INTRODUCTION: Root canal treatment typically involves cleaning and shaping procedures followed by treatment with antibacterial endodontic dressing between appointments and, ultimately, 3-dimensional,hermetic filling. Chlorhexidine (CHX) is effective as an irrigation solution and is used as an endodontic dressing. The aim of this study was to examine the influence of CHX on periapical cytokine expression. METHODS: Expression levels of the cytokines interferon γ, tumor necrosis factor α, interleukin (IL)-1ß, IL-17A, IL-10, and the chemokine monocyte chemoattractant protein-1 (CCL2/MCP-1) were assayed by real-time polymerase chain reaction immediately after root canal cleaning and 15 days later. RESULTS: Messenger RNA expression of IL-1ß, interferon γ, IL-10, and CCL2/MCP-1 was increased on day 15 in teeth without endodontic dressing. No statistical change was observed in the messenger RNA expression of cytokines when comparing sampling times for teeth that received endodontic dressing. CONCLUSIONS: The results show that CHX application between appointments prevented the increase of both proinflammatory and immunoregulatory cytokines 15 days after the dental procedure.
Assuntos
Clorexidina/farmacologia , Citocinas/efeitos dos fármacos , Tecido Periapical/efeitos dos fármacos , Irrigantes do Canal Radicular/farmacologia , Preparo de Canal Radicular/métodos , Dente/efeitos dos fármacos , Quimiocina CCL2/análise , Citocinas/análise , Necrose da Polpa Dentária/imunologia , Necrose da Polpa Dentária/terapia , Seguimentos , Humanos , Mediadores da Inflamação/análise , Interferon gama/efeitos dos fármacos , Interleucina-1/análise , Interleucina-10/análise , Interleucina-17/análise , Tecido Periapical/imunologia , RNA Mensageiro/efeitos dos fármacos , Dente/imunologiaRESUMO
A doença periodontal é resultado da inflamação das estruturas periodontais em resposta ao biofilme dentário presente na superfície dental e sulco gengival. Sua etiopatogenia é multifatorial e complexa. Na periodontite crônica há bacteremia freqüente durante rotinas diárias como escovação dentária e mastigação e acredita-se que esse estímulo constante ao sistema imunológico possa causar repercussões sistêmicas nos pacientes, como arterioescleroses. Uma das formas atuais de se mensurar essa alteração é pela presença de mediadores inflamatórios séricos. Sendo as proteínas de fase aguda, como as citocinas, as mais avaliadas. Assim como os trabalhos encontrados para a espécie humana, propôsse a mensuração sérica das interleucinas IL-1, IL-6, IL-10 e TNF-α em cães com doença periodontal crônica. Como grupo controle, utilizaram-se os mesmos pacientes após tratamento periodontal, mensurando as mesmas interleucinas depois de 21 dias do tratamento. Como resultado todas as interleucinas sofreram alteração, porém somente a IL-6 teve redução estatisticamente significativa após o tratamento periodontal. Todavia atenta-se para os elevados valores encontrados em alguns pacientes, o que pode demonstrar importante alteração sistêmica
Periodontal disease is the result of inflammation of the periodontal structures in response to the biofilm present on the tooth surface and the gingival sulcus. Its pathogenesis is multifactorial and complex. Bacteremia in chronic periodontitis is constant during daily routines, such as toothbrushing and chewing, and it is believed that this constant stimulus to the immune system can cause systemic effects in patients, such as arterioescleroses. One of the current ways of measuring this change is the presence of serum inflammatory mediators. The acute phase proteins, such as cytokines, are the most valued. Like the works found for the human species, the measurement of serum interleukins IL-1, IL-6, IL- 10 and TNF-α in dogs with chronic periodontal disease was proposed. As controls, we used the same patients after periodontal treatment, measuring the same interleukins after 21 days of treatment. As a result, all interleukins have been changed, but only IL-6 showed statistically significant decrease after periodontal treatment. However, the high values found in some patients, which may prove important systemic change, must be highlighted
Assuntos
Animais , Cães , Citocinas/análise , Interleucina-1/análise , /análise , /análise , Abscesso Periodontal/veterináriaRESUMO
OBJECTIVE: To compare two models of pulmonary hypertension (monocrotaline and monocrotaline+pneumonectomy) regarding hemodynamic severity, structure of pulmonary arteries, inflammatory markers (IL-1 and PDGF), and 45-day survival. METHODS: We used 80 Sprague-Dawley rats in two study protocols: structural analysis; and survival analysis. The rats were divided into four groups: control; monocrotaline (M), pneumonectomy (P), and monocrotaline+pneumonectomy (M+P). In the structural analysis protocol, 40 rats (10/group) were catheterized for the determination of hemodynamic variables, followed by euthanasia for the removal of heart and lung tissue. The right ventricle (RV) was dissected from the interventricular septum (IS), and the ratio between RV weight and the weight of the left ventricle (LV) plus IS (RV/LV+IS) was taken as the index of RV hypertrophy. In lung tissues, we performed histological analyses, as well as using ELISA to determine IL-1 and PDGF levels. In the survival protocol, 40 animals (10/group) were followed for 45 days. RESULTS: The M and M+P rats developed pulmonary hypertension, whereas the control and P rats did not. The RV/LV+IS ratio was significantly higher in M+P rats than in M rats, as well as being significantly higher in M and M+P rats than in control and P rats. There were no significant differences between the M and M+P rats regarding the area of the medial layer of the pulmonary arteries; IL-1 and PDGF levels; or survival. CONCLUSIONS: On the basis of our results, we cannot conclude that the monocrotaline+pneumonectomy model is superior to the monocrotaline model.