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1.
Anticancer Res ; 40(11): 6029-6037, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109541

RESUMO

BACKGROUND: Tongue cancer is more common in men than in women. Yet the effects of sex steroid hormones on the behaviour of oral tongue squamous cell carcinoma (OTSCC) are not well known. Matrix metalloproteinase 8 (MMP8) is expressed in OTSCC and can degrade estrogen receptors (ERs). MATERIALS AND METHODS: Western blot was used to examine the levels of ERß in OTSCC cell lines (HSC-3 and SCC-25). We evaluated the effects of estradiol and dihydrotestosterone (DHT) on HSC-3 and SCC-25 cell migration, invasion and viability. The effect of estradiol on the invasion of MMP8-overexpressing (MMP8+) and empty vector HSC-3 cells was examined using 3D spheroid invasion assay. RESULTS: Both HSC-3 and SCC-25 cells expressed ERß. In scratch assay, estradiol, but not DHT, reduced the migration and invasion of HSC-3 and SCC-25 cells. MMP8+ HSC-3 cells showed weaker invasion than empty vector cells, in line with previous reports. However, MMP8 overexpression did not alter the effect of estradiol on HSC-3 cell invasion in spheroid assay. CONCLUSION: Estradiol inhibited the migration and invasion of OTSCC cells, whereas DHT had no effect. Our data suggest that MMP8 does not modulate the effect of estradiol in OTSCC cells. However, the sex difference in OTSCC incidence might partly be due to protective actions of estradiol in epithelial cell carcinogenesis.


Assuntos
Hormônios Esteroides Gonadais/uso terapêutico , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/uso terapêutico , Estradiol/farmacologia , Estradiol/uso terapêutico , Receptor beta de Estrogênio/metabolismo , Hormônios Esteroides Gonadais/farmacologia , Humanos , Metaloproteinase 8 da Matriz/metabolismo , Invasividade Neoplásica
2.
Life Sci ; 259: 118191, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32777302

RESUMO

Numerous population studies conducted worldwide indicate that the prevalence of asthma is higher in obese versus lean individuals. It has been reported that sensitized lean mice has a better recovery of lung inflammation in asthma. Extracellular matrix (ECM) plays an essential role in the structural support of the lungs regulating the airways diameter, thus preventing its collapse during expiration. ECM renewal by metalloproteinase (MMPs) enzymes is critical for pulmonary biology. There seems to be an imbalance of MMPs activity in asthma and obesity, which can impair the lung remodeling process. In this study, we characterized the pulmonary ECM of obese and lean mice, non-sensitized and sensitized with ovalbumin (OVA). Pharmacological intervention was performed by using anti-TNF-α, and MMP-8 and MMP-9 inhibitors in obese and lean sensitized mice. Activity of MMPs was assessed by gelatinase electrophorese, western blotting and zymogram in situ. Unbalance of MMP-2, MMP-8, MMP-9 and MMP-12 was detected in lung tissue of OVA-sensitized obese mice, which was accompanied by high degradation, corroborating an excessive deposition of types I and III collagen in pulmonary matrix of obese animals. Inhibitions of TNF-α and MMP-9 reduced this MMP imbalance, clearly suggesting a positive effect on pulmonary ECM. Obese and lean mice presented diverse phenotype of asthma regarding the ECM compounds and the inhibition of MMPs pathway could be a good alternative to regulate the activity in ECM lungs of asthmatic obese individuals.


Assuntos
Asma/etiologia , Asma/metabolismo , Metaloproteases/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/citologia , Matriz Extracelular/metabolismo , Inflamação/metabolismo , Pulmão/patologia , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Inibidores de Proteases/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores
3.
Mol Cell Biochem ; 467(1-2): 107-116, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32108279

RESUMO

Hepatic stellate cells (HSCs) are known to play a key role in the progression of liver fibrosis by producing excessive extracellular matrix (ECM). Matrix metalloproteinases (MMPs) belong to a family of endopeptidases, which have a well-established role in the degradation of ECM. Our study suggests that, besides the degradation of the extracellular matrix, matrix metalloproteinase-8 (MMP-8) has a non-canonical role in activating the quiescent HSCs to myofibroblasts by regulating the expression of Col1A1 and αSMA. We have identified that MMP-8 secreted from macrophages as a response to LPS stimulation activates HSCs via ERK1/2-dependent pathway. In addition to this, we determined that MMP-8 may regulate the homodimerization of c-Jun in LX-2 cells, during the trans-differentiation process from quiescent HSC to activate myofibroblasts. Macrophage-released MMP-8 plays a master role in activating the dormant HSCs to activate myofibroblasts through the Erk-mediated pathway and Jun cellular translocation leading to liver fibrosis. Significance MMP-8 can be used as a therapeutic target against liver fibrosis.


Assuntos
Células Estreladas do Fígado/citologia , Lipopolissacarídeos/efeitos adversos , Sistema de Sinalização das MAP Quinases , Metaloproteinase 8 da Matriz/metabolismo , Técnicas de Cultura de Células , Transdiferenciação Celular , Colágeno Tipo I/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Multimerização Proteica , Proteínas Proto-Oncogênicas c-jun/química , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Células THP-1
4.
Int J Mol Sci ; 21(2)2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31963361

RESUMO

BACKGROUND: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. MATERIALS AND METHODS: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. RESULTS: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. CONCLUSION: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.


Assuntos
Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Gengiva/efeitos dos fármacos , Hiperplasia Gengival/tratamento farmacológico , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Gengiva/metabolismo , Hiperplasia Gengival/metabolismo , Humanos , Metaloproteinase 11 da Matriz/metabolismo , Metaloproteinase 15 da Matriz/metabolismo , Metaloproteinase 16 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinases da Matriz Associadas à Membrana/metabolismo , Metaloproteinases da Matriz Secretadas/metabolismo
5.
Clin Oral Investig ; 24(5): 1837-1844, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31444693

RESUMO

OBJECTIVES: The aim of this study is to investigate the expression of sTREM-1 and its ligand PGLYRP1, as well as the expression of MMP-8 and its inhibitor TIMP-1, in peri-implant diseases. As a secondary aim, we analyzed the influence of the concomitant existence of periodontitis in the expression of these biomarkers. MATERIALS AND METHODS: This study included 77 patients (29 males and 48 females; mean age 55.0 ± 11.5), 18 having gingivitis, 16 having periodontitis, 20 having mucositis, and 23 having peri-implantitis. Patients were clinically examined, and unstimulated whole saliva was collected. sTREM-1, PGLYRP1, MMP-8, TIMP-1, and MMP-8/TIMP1 ratio were determined by ELISA. RESULTS: The periodontitis group presented higher probing depth (PD) mean, and higher clinical attachment loss, compared with the other groups. The peri-implantitis group presented higher PD mean in implants compared to the mucositis group. Patients with PD ≥ 6 mm showed significantly higher levels of PGLYRP1, MMP-8, and MMP-8/TIMP-1 ratio than patients with PD < 6 mm. When all four markers were assessed, there were no significant differences between mucositis and peri-implantitis groups. Concomitant periodontitis resulted in higher significant levels of MMP-8 in patients with peri-implant disease. CONCLUSION: We did not observe significant differences in the levels of the sTREM-1/PGLYRP1/MMP-8 axis between patients with periodontal and peri-implant diseases, suggesting that these markers are also involved in the inflammatory process around implants. Besides, the presence of periodontitis may affect the levels of MMP-8 in patients with peri-implant disease. CLINICAL RELEVANCE: The sTREM-1/PGLYRP1/MMP-8 axis could be useful as potent markers in periodontal and peri-implant diseases.


Assuntos
Citocinas/metabolismo , Implantes Dentários , Metaloproteinase 8 da Matriz/metabolismo , Peri-Implantite/metabolismo , Periodontite/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor Tecidual de Metaloproteinase-1/metabolismo
6.
J Formos Med Assoc ; 119(2): 652-659, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31543299

RESUMO

BACKGROUND/PURPOSE: It is still challengeable to treat periodontal pockets refractory to mechanical debridement. This study is to evaluate the potential of indocyanine green (ICG)-diode laser-based photothermal therapy (PTT) for solving this dilemma. METHODS: Bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament cells (PDLCs) were incubated with phosphate-buffered saline, chlorhexidine, or ICG, non-irradiated or irradiated with 810-nm diode lasers, and the cell viability was evaluated. Patients with teeth refractory to mechanical periodontal debridement on different quadrants were recruited. At baseline (T0), all examined teeth received scaling and root planing, and those on the test quadrant (PTT group) received ICG-diode laser treatment. The outcome was evaluated using clinical parameters and cytokines in the gingival crevicular fluids at 4-6 weeks (T1) and 6 months (T2). RESULTS: In ICG-treated cultures, the viability of BMSCs and PDLCs was recovered on day 4, and laser irradiation inhibited the metabolic activities of BMSCs. 22 patients with 30 control teeth and 35 PTT-treated teeth were examined. All examined teeth showed modest reductions in probing pocket depth (PPD), clinical attachment loss (CAL), bleeding upon probing (BOP), and plaque score at T1 and T2 and significant reductions in IL-1ß and MMP-8 at T2. Compared with controls, BOP was reduced more prominently, IL-1ß and MMP-8 were significantly lower, and reductions in PPD and CAL were slightly greater in the PTT group at T1 (0.05-0.19 mm). CONCLUSION: ICG-diode laser-based PTT is compatible to periodontium and assists in faster resolution of gingival inflammation in periodontal pockets refractory to mechanical debridement.


Assuntos
Periodontite Crônica/radioterapia , Verde de Indocianina/uso terapêutico , Lasers Semicondutores , Bolsa Periodontal/radioterapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Líquido do Sulco Gengival/metabolismo , Humanos , Interleucina-1beta/metabolismo , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Pessoa de Meia-Idade , Índice Periodontal , Taiwan , Resultado do Tratamento
7.
Clin Oral Investig ; 24(1): 343-350, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31102041

RESUMO

OBJECTIVES: The aim of this study was to investigate in vitro the effect of clodronate on interleukin-1ß (IL-1ß)-stimulated human periodontal ligament fibroblasts (HPdLFs) with the focus on inflammatory factors of orthodontic tooth movement with and without compressive force. MATERIALS AND METHODS: HPdLFs were incubated with 5 µM clodronate and 10 ng/mL IL-1ß. After 48 h, cells were exposed to 3 h of compressive force using a centrifuge. The gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase 8 (MMP-8), and the tissue inhibitor of MMP (TIMP-1) was analyzed using RT-PCR. Prostaglandin E2 (PGE-2), IL-6, and TIMP-1 protein syntheses were quantified via ELISA. RESULTS: Compressive force and IL-1ß induced an overexpression of COX-2 gene expression (61.8-fold; p < 0.05 compared with control), diminished by clodronate (41.1-fold; p < 0.05 compared with control). Clodronate slowed down the compression and IL-1ß induced IL-6 gene expression (161-fold vs. 85.6-fold; p < 0.05 compared with control). TNF-α was only slightly affected without statistical significance. Clodronate reduced IL-1ß-stimulated MMP-8 expression with and without compressive force. TIMP-1 on gene and protein level was downregulated in all groups. Analyzing the MMP-8/TIMP-1 ratio, the highest ratio was detected in IL-1ß-stimulated HPdLFs with compressive force (21.2-fold; p < 0.05 compared with control). Clodronate diminished IL-1ß-induced upregulation of MMP-8/TIMP-1 ratio with (11.5-fold; p < 0.05 compared with control) and without (12.5-fold; p < 0.05 compared with control) compressive force. CONCLUSION: Our study demonstrates a slightly anti-inflammatory effect by clodronate under compressive force in vitro. Additionally, the periodontal remodeling presented by the MMP-8/TIMP-1 ratio seems to be diminished by clodronate. CLINICAL RELEVANCE: Reduction of pro-inflammatory factors and reduction of periodontal remodeling might explain reduced orthodontic tooth movement under clodronate intake.


Assuntos
Ácido Clodrônico , Interleucina-1beta , Ligamento Periodontal , Fenômenos Biomecânicos , Células Cultivadas , Ácido Clodrônico/farmacologia , Dinoprostona , Fibroblastos , Humanos , Interleucina-1beta/fisiologia , Metaloproteinase 8 da Matriz/metabolismo , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Técnicas de Movimentação Dentária
8.
Cardiovasc Res ; 116(1): 211-225, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30778537

RESUMO

AIMS: Emerging evidence has suggested that adventitia stem/progenitor cells (AdSPCs) migrate into the intima of arteries in response to injury, where they differentiate towards smooth muscle cells (SMCs) and participate in neointimal hyperplasia. We have previously identified matrix metalloproteinase-8 (MMP8) as a key player in atherogenesis. In this study, we aimed to investigate the functional roles of macrophage-derived MMP8 in AdSPC differentiation and injury-induced arterial remodelling. METHODS AND RESULTS: We first observed an important role for MMP8 in SMC differentiation from embryonic stem cells, but this effect was not seen in AdSPCs. Instead, through macrophages/AdSPCs co-culture and macrophage conditional culture medium studies, we have demonstrated that the MMP8 protein secreted from macrophages promotes SMC differentiation from AdSPCs. Mechanistically, we showed that macrophage-derived MMP8 promotes SMC differentiation from AdSPCs through modulating transforming growth factor-ß activity and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)/Notch1 signalling. We further demonstrated that the binding site for CBF1, Suppressor of Hairless, and Lag-1 (CSL) within SMC gene promoters is responsible for Notch1 mediated SMC differentiation. Finally, we demonstrated that macrophage-derived MMP8 increased injury-induced neointimal SMC hyperplasia by activating ADAM10/Notch1 signalling. CONCLUSIONS: We have identified macrophage-derived MMP8 as a regulator in SMC differentiation from AdSPCs and neointimal SMC hyperplasia in response to injury. Our data provide new insights into the roles of MMP8 in AdSPC differentiation and the pathogenesis of neointima formation in the context of angiographic restenosis, and therefore may aid in the development of novel therapeutic agents for the prevention of this disease.


Assuntos
Túnica Adventícia/enzimologia , Lesões das Artérias Carótidas/enzimologia , Diferenciação Celular , Proliferação de Células , Macrófagos/enzimologia , Metaloproteinase 8 da Matriz/metabolismo , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Neointima , Células-Tronco/enzimologia , Proteína ADAM10/genética , Proteína ADAM10/metabolismo , Túnica Adventícia/patologia , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Macrófagos/patologia , Metaloproteinase 8 da Matriz/deficiência , Metaloproteinase 8 da Matriz/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Comunicação Parácrina , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais , Células-Tronco/patologia , Remodelação Vascular
9.
Acta Odontol Scand ; 78(3): 210-216, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31726911

RESUMO

Objective: Odontoblasts are thought to be involved in innate immunity but their precise role in this process is not fully understood. Here, we assess effects of lipopolysaccharide (LPS) and lipoteichoic acid (LTA), produced by Gram-negative and Gram-positive bacteria, respectively, on matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and cathelin-related antimicrobial peptide (CRAMP) expression in odontoblast-like MDPC-23 cells.Material and methods: Gene activity and protein production was determined by quantitative real-time RT-PCR and ELISA, respectively. Cellular expression of CRAMP was determined by immunocytochemistry.Results: Stimulation with LTA (5 and 25 µg/ml) but not LPS (1 and 5 µg/ml) for 24 h enhanced IL-6 mRNA expression. The LTA-induced up-regulation of IL-6 mRNA levels was associated with increased IL-6 protein levels. Stimulation with either LPS or LTA for 24 h lacked effect on both MMP-8 transcript and protein expression. Immunocytochemistry disclosed that MDPC-23 cells expressed immunoreactivity for CRAMP. MDPC-23 cells showed mRNA expression for CRAMP, but stimulation with either LPS or LTA did not modulate CRAMP transcript expression.Conclusions: We show that MDPC-23 cells possess immune-like cell properties such as LTA-induced IL-6 production and expression of the antimicrobial peptide CRAMP, suggesting that odontoblasts may modulate innate immunity via these mechanisms.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-6/genética , Lipopolissacarídeos/farmacologia , Metaloproteinase 8 da Matriz/genética , Odontoblastos/metabolismo , Ácidos Teicoicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Interleucina-6/metabolismo , Lipopolissacarídeos/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Odontoblastos/imunologia , Odontoblastos/patologia , Reação em Cadeia da Polimerase em Tempo Real
10.
Int J Pediatr Otorhinolaryngol ; 128: 109700, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606684

RESUMO

OBJECTIVES: The aim of the current study was to assess the levels of MMP-8, MMP-9 and TIMP-1 in the group of children with adenoids who suffered from exudative otitis media. METHODS: The study included 20 patients (10 females and 10 males) with adenoid hypertrophy coexisting with otitis media with effusion. The reference group included 24 patients (10 females and 14 males) with adenoid hypertrophy without otitis media. The levels of MMP-8, MMP-9 and TIMP-1 were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated cell cultures of the tonsils, using commercial enzyme-linked immunosorbent assay kits (R@D Systems, USA). RESULTS: The median MMP-8, MMP-9 and TIMP-1 concentrations (220.8 ng/mL, 311.1 ng/mL, 53.5 ng/mL, respectively) in the study group were significantly higher (p = 0.000, p = 0.000, p = 0.048, respectively) than those in the reference group (93.5 ng/mL, 112.5 ng/mL, 36.95 ng/mL, respectively). ROC analysis revealed that the area under a curve (AUC) for both metalloproteinases MMP-8 and MMP-9 was 1 with a diagnostic sensitivity of 100% and diagnostic specificity of 95.8%, as compared to 0.690 for TIMP-1. Significant differences were found between the AUC for MMP-8 and TIMP-1 and MMP-9 and TIMP-1 (p < 0.001 for both comparisons). CONCLUSIONS: The changes in the concentrations of MMP-8, MMP-9 and TIMP-1 may indicate an increased remodeling of the extracellular matrix in children with adenoid hypertrophy and otitis media with effusion. The findings can have clinical as well as diagnostic utility. Determination of MMP-8 and MMP-9 may help qualify a child for adenoidectomy and differentiate pediatric patients affected by adenoid hypertrophy with and without otitis media.


Assuntos
Tonsila Faríngea/metabolismo , Tonsila Faríngea/patologia , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Otite Média com Derrame/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adenoidectomia , Tonsila Faríngea/cirurgia , Área Sob a Curva , Células Cultivadas , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Hipertrofia/complicações , Hipertrofia/cirurgia , Masculino , Otite Média com Derrame/complicações , Otite Média com Derrame/diagnóstico , Curva ROC
11.
Molecules ; 25(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881666

RESUMO

Nowadays, saliva is a subject of growing scientific interest because of its definite advantages as diagnostic medium. The aim of our study was to investigate the diagnostic potential and reliability of messenger RNAs (mRNAs) of selected genes-interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glutathione synthetase (GSS)-as salivary markers in children with diagnosed pyelonephritis and to correlate their levels with typical urine para-clinical indicators of the disease. Analysis of the mRNA levels for IL-6, MMP-8 and GSS in 28 children hospitalized with the diagnosis of pyelonephritis was conducted applying the method of quantitative reverse transcription polymerase chain reaction (RT-qPCR). In the study group (n = 28), IL-6 mRNA levels demonstrated 64-fold increase (p < 0.001). MMP-8 and GSS mRNA levels were increased in 12 samples in patients with pyelonephritis 3.27 (p < 0.01) and 1.94 (p < 0.001) times, respectively. We found a strong and significant correlation (p < 0.001) between the investigated mRNA for IL-6 and MMP-8, IL-6 and GSS, MMP-8 and GSS. Moderate degree of correlation was established between IL-6 and the typical para-clinical indicator of leucocytes (0.43, p < 0.05) and between GSS and leucocytes (0.54, p < 0.01). Salivary IL-6, MMP-8 and GSS mRNA levels in combination with urine test analysis could be useful diagnostic tool for the very distributed disorder of pyelonephritis in childhood.


Assuntos
Glutationa Sintase/genética , Interleucina-6/genética , Metaloproteinase 8 da Matriz/genética , Pielonefrite/genética , Saliva/metabolismo , Biomarcadores/urina , Criança , Pré-Escolar , Feminino , Glutationa Sintase/metabolismo , Humanos , Interleucina-6/metabolismo , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Pielonefrite/diagnóstico , Pielonefrite/urina , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Mediators Inflamm ; 2019: 7436932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780869

RESUMO

Background: Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods: Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996-2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results: MPO correlated positively with MMP-8 (rho 0.496, P < 0.001) and MMP-9 (rho 0.153, P = 0.02) but negatively with TIMP-1 (rho -0.361, P < 0.001). MMP-8 emerged as the best predictor of disease outcomes: a CSF MMP-8 concentration above the median increased the odds of death 4.9-fold (95% confidence interval 1.8-12.9). Conclusions: CSF MMP-8 presented as an attractive prognostic marker in children with bacterial meningitis.


Assuntos
Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Meningites Bacterianas/enzimologia , Meningites Bacterianas/patologia , Peroxidase/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Estudos Retrospectivos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto Jovem
13.
mBio ; 10(5)2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641087

RESUMO

In many impoverished regions of the world, it may not be possible to assess two major risk factors for preterm birth: a short cervical length and the depletion of vaginal lactobacilli. We determined whether measuring specific compounds in vaginal fluid might be a simple, noninvasive, and cost-effective way to predict the bacteria that dominate the vaginal microbiome and indicate the presence of a shortened cervix (<25 mm). Vaginal fluid samples were prospectively collected from mid-trimester pregnant women, and the concentrations of d- and l-lactic acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, matrix metalloproteinases MMP-2 and MMP-8, the 70-kDa heat shock protein, a2 isoform of vacuolar ATPase, and sequestrome-1 were quantified by an enzyme-linked immunosorbent assay (ELISA). The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography. The vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of d-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject's age and race, were significantly associated with cervical length. Using piecewise structural equation modeling, we established a causal network that links CST to cervical length via biomarkers. We concluded that measuring levels of TIMP-1 and d-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition.IMPORTANCE Premature birth and its complications are the largest contributors to infant death in the United States and globally. A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. However, in many resource-poor areas of the world, the technology to test for their occurrence is unavailable, and pregnant women with these risk factors are neither identified nor treated. In this study, we used path analysis to gain an unprecedented understanding of interactions between vaginal microbiome composition, the concentrations of various compounds in vaginal secretions, and cervical length. We identified low-cost point-of-care measures that might be used to identify pregnant women at risk for preterm birth. The use of these measures coupled with appropriate preventative or treatment strategies could reduce the incidence of preterm births in poor areas of the world that lack access to more sophisticated diagnostic methods.


Assuntos
Colo do Útero/metabolismo , Colo do Útero/microbiologia , Microbiota/genética , Vagina/metabolismo , Vagina/microbiologia , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Lactobacillus/genética , Lactobacillus/metabolismo , Lactobacillus crispatus/genética , Lactobacillus crispatus/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Gravidez , RNA Ribossômico 16S/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Adulto Jovem
14.
Transpl Immunol ; 57: 101244, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31526865

RESUMO

BACKGROUND: Obliterative bronchiolitis (OB) is the major complication limiting the long-term survival of allografts after lung transplantation. In this study, we investigated the effect of tacrolimus (FK506) combined with GM6001,a matrix metalloproteinase (MMP) inhibitor, on the formation of OB using a mouse heterotopic tracheal transplantation model. METHODS: Syngeneic tracheal grafts were transplanted heterotopically from BALB/c mice to BALB/c mice. Allografts from C57BL/6 mice were transplanted to BALB/c mice. Isograft group, allograft group, allograft+FK506 group, allograft +GM6001 group and allograft+FK506 + GM6001 group was given respectively intraperitoneal injection of saline, saline, FK506, GM6001 and FK506 + GM6001 once a day. At 28 day after transplantation, OB incidence was determined by hematoxylin-eosin staining and the expressions of MMPs and cytokines were assessed using enzyme linked immunosorbent assay, immunohistochemical assays and western blot assay. RESULTS: The tracheal occlusion rates of isograft group, allograft group, allograft+FK506 group, allograft+GM6001 group and allograft+FK506 + GM6001 group were 0, 74.1 ±â€¯9.79%, 34.4 ±â€¯6.04%, 40.3 ±â€¯8.77% and 26.5 ±â€¯5.73% respectively. There were significant differences between the latter two groups (P < .001). The serum MMP-8 and MMP-9 levels of allograft group were significantly higher than those of isograft group (P < .05) and had no significant decrease when treated by FK506. The serum MMP-8 and MMP-9 levels of allograft+FK506 + GM6001 group were significantly lower than those of allograft+FK506 group (P < .05). MMP-8 and MMP-9 protein expression in the grafts of allograft+FK506 + GM6001 group were lower than those of allograft+FK506 group verified by immunohistochemical staining and western blotting. CONCLUSION: FK506 combined with GM6001 could alleviate tracheal obliteration in mouse heterotopic tracheal transplantation model, due to its inhibitory effect on MMPs.


Assuntos
Obstrução das Vias Respiratórias/prevenção & controle , Bronquiolite Obliterante/prevenção & controle , Dipeptídeos/uso terapêutico , Transplante de Pulmão , Complicações Pós-Operatórias/prevenção & controle , Tacrolimo/uso terapêutico , Traqueia/patologia , Animais , Bronquiolite Obliterante/etiologia , Modelos Animais de Doenças , Quimioterapia Combinada , Sobrevivência de Enxerto , Humanos , Masculino , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Traqueia/transplante , Transplante Heterotópico , Transplante Homólogo
15.
Biomolecules ; 9(10)2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31546991

RESUMO

The spatial and temporal availability of cytokines, and the microenvironments this creates, is critical to tissue development and homeostasis. Creating concentration gradients in vitro using soluble proteins is challenging as they do not provide a self-sustainable source. To mimic the sustained cytokine secretion seen in vivo from the extracellular matrix (ECM), we encapsulated a cargo protein into insect virus-derived proteins to form nanoparticle co-crystals and studied the release of this cargo protein mediated by matrix metalloproteinase-2 (MMP-2) and MMP-8. Specifically, when nerve growth factor (NGF), a neurotrophin, was encapsulated into nanoparticles, its release was promoted by MMPs secreted by a PC12 neuronal cell line. When these NGF nanoparticles were spotted onto a cover slip to create a uniform circular field, movement and alignment of PC12 cells via their extended axons along the periphery of the NGF nanoparticle field was observed. Neural cell differentiation was confirmed by the expression of specific markers of tau, neurofilament, and GAP-43. Connections between the extended axons and the growth cones were also observed, and expression of connexin 43 was consistent with the formation of gap junctions. Extensions and connection of very fine filopodia occurred between growth cones. Our studies indicate that crystalline protein nanoparticles can be utilized to generate a highly stable cytokine gradient microenvironment that regulates the alignment and differentiation of nerve cells. This technique greatly simplifies the creation of protein concentration gradients and may lead to therapies for neuronal injuries and disease.


Assuntos
Citocinas/metabolismo , Metaloproteinases da Matriz/metabolismo , Fator de Crescimento Neural/farmacologia , Neurônios/citologia , Proteínas de Matriz de Corpos de Inclusão/genética , Reoviridae/fisiologia , Animais , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Preparações de Ação Retardada , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Nanopartículas , Fator de Crescimento Neural/química , Fator de Crescimento Neural/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas de Matriz de Corpos de Inclusão/metabolismo , Células PC12 , Tamanho da Partícula , Ratos , Reoviridae/genética , Reoviridae/metabolismo , Transdução de Sinais
16.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514474

RESUMO

Matrix metalloproteinases (MMPs) have traditionally been considered as tumor promoting enzymes as they degrade extracellular matrix components, thus increasing the invasion of cancer cells. It has become evident, however, that MMPs can also cleave and alter the function of various non-matrix bioactive molecules, leading to both tumor promoting and suppressive effects. We applied systematic review guidelines to study MMP8 in cancer including the use of MMP8 as a prognostic factor or as a target/anti-target in cancer treatment, and its molecular mechanisms. A total of 171 articles met the inclusion criteria. The collective evidence reveals that in breast, skin and oral tongue cancer, MMP8 inhibits cancer cell invasion and proliferation, and protects patients from metastasis via cleavage of non-structural substrates. Conversely, in liver and gastric cancers, high levels of MMP8 worsen the prognosis. Expression and genetic alterations of MMP8 can be used as a prognostic factor by examination of the tumor and serum/plasma. We conclude, that MMP8 has differing effects on cancers depending on their tissue of origin. The use of MMP8 as a prognostic factor alone, or with other factors, seems to have potential. The molecular mechanisms of MMP8 in cancer further emphasize its role as an important regulator of bioactive molecules.


Assuntos
Metaloproteinase 8 da Matriz/metabolismo , Neoplasias/enzimologia , Animais , Biomarcadores Tumorais/metabolismo , Epigênese Genética , Humanos , Metaloproteinase 8 da Matriz/sangue , Neoplasias/sangue , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Prognóstico
17.
J Biol Chem ; 294(26): 10266-10277, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31110047

RESUMO

The collagenase subfamily of matrix metalloproteinases (MMPs) have important roles in the remodeling of collagenous matrices. The proteinase-activated receptor (PAR) family has a unique mechanism of activation requiring proteolysis of an extracellular domain forming a neo-N terminus that acts as a tethered ligand, a process that has been associated with the development of arthritis. Canonical PAR2 activation typically occurs via a serine proteinase at Arg36-Ser37, but other proteinases can cleave PARs downstream of the tethered ligand and "disarm" the receptor. To identify additional cleavage sites within PAR2, we synthesized a 42-amino-acid peptide corresponding to the extracellular region. We observed that all three soluble MMP collagenases, MMP-1, MMP-8, and MMP-13, cleave PAR2 and discovered a novel cleavage site (Ser37-Leu38). Metalloproteinases from resorbing bovine nasal cartilage and recombinant human collagenases could cleave a quenched fluorescent peptide mimicking the canonical PAR2 activation region, and kinetic constants were determined. In PAR2-overexpressing SW1353 chondrocytes, we demonstrated that the activator peptide SLIGKV-NH2 induces rapid calcium flux, inflammatory gene expression (including MMP1 and MMP13), and the phosphorylation of extracellular signal-regulated kinase (ERK) and p38 kinase. The corresponding MMP cleavage-derived peptide (LIGKVD-NH2) exhibited no canonical activation; however, we observed phosphorylation of ERK, providing evidence of biased agonism. Importantly, we demonstrated that preincubation with active MMP-1 reduced downstream PAR2 activation by a canonical activator, matriptase, but not SLIGKV-NH2 These results support a role for collagenases as proteinases capable of disarming PAR2, revealing a mechanism that suppresses PAR2-mediated inflammatory responses.


Assuntos
Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Receptor PAR-2/antagonistas & inibidores , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Condrossarcoma/genética , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 8 da Matriz/genética , Fragmentos de Peptídeos/metabolismo , Fosforilação , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas
18.
PLoS One ; 14(4): e0215218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30970007

RESUMO

Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38-66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16-24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach.


Assuntos
Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/farmacologia , Adulto , Idoso , Transporte Biológico/efeitos dos fármacos , Cartilagem/citologia , Sobrevivência Celular , Colágeno/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Técnicas In Vitro , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Pessoa de Meia-Idade , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia
19.
Am J Obstet Gynecol ; 221(2): 142.e1-142.e22, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30928566

RESUMO

BACKGROUND: Intra-amniotic infection is present in 10% of patients with an episode of preterm labor, and is a risk factor for impending preterm delivery and neonatal morbidity/mortality. Intra-amniotic inflammation is often associated with intra-amniotic infection, but is sometimes present in the absence of detectable microorganisms. Antibiotic treatment of intra-amniotic infection has traditionally been considered to be ineffective. Intra-amniotic inflammation without microorganisms has a prognosis similar to that of intra-amniotic infection. OBJECTIVE: To determine whether antibiotics can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. MATERIALS AND METHODS: The study population consisted of women who met the following criteria: 1) singleton gestation between 20 and 34 weeks; 2) preterm labor and intact membranes; 3) transabdominal amniocentesis performed for the evaluation of the microbiologic/inflammatory status of the amniotic cavity; 4) intra-amniotic infection and/or intra-amniotic inflammation; and 5) received antibiotic treatment that consisted of ceftriaxone, clarithromycin, and metronidazole. Follow-up amniocentesis was performed in a subset of patients. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed for Ureaplasma spp. Intra-amniotic infection was defined as a positive amniotic fluid culture or positive polymerase chain reaction, and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count or a positive result of a rapid test for matrix metalloproteinase-8. For this study, the final diagnosis of intra-amniotic inflammation was made by measuring the interleukin-6 concentration in stored amniotic fluid (>2.6 ng/mL). These results were not available to managing clinicians. Treatment success was defined as eradication of intra-amniotic infection and/or intra-amniotic inflammation or delivery ≥37 weeks. RESULTS: Of 62 patients with intra-amniotic infection and/or intra-amniotic inflammation, 50 received the antibiotic regimen. Of those patients, 29 were undelivered for ≥7 days and 19 underwent a follow-up amniocentesis. Microorganisms were identified by culture or polymerase chain reaction of amniotic fluid obtained at admission in 21% of patients (4/19) who had a follow-up amniocentesis, and were eradicated in 3 of the 4 patients. Resolution of intra-amniotic infection/inflammation was confirmed in 79% of patients (15/19), and 1 other patient delivered at term, although resolution of intra-amniotic inflammation could not be confirmed after a follow-up amniocentesis. Thus, resolution of intra-amniotic inflammation/infection or term delivery (treatment success) occurred in 84% of patients (16/19) who had a follow-up amniocentesis. Treatment success occurred in 32% of patients (16/50) with intra-amniotic infection/inflammation who received antibiotics. The median amniocentesis-to-delivery interval was significantly longer among women who received the combination of antibiotics than among those who did not (11.4 days vs 3.1 days: P = .04). CONCLUSION: Eradication of intra-amniotic infection/inflammation after treatment with antibiotics was confirmed in 79% of patients with preterm labor, intact membranes, and intra-amniotic infection/inflammation who had a follow-up amniocentesis. Treatment success occurred in 84% of patients who underwent a follow-up amniocentesis and in 32% of women who received the antibiotic regimen.


Assuntos
Antibacterianos/uso terapêutico , Corioamnionite/tratamento farmacológico , Trabalho de Parto Prematuro , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Amniocentese , Líquido Amniótico/metabolismo , Líquido Amniótico/microbiologia , Biomarcadores/metabolismo , Ceftriaxona/uso terapêutico , Corioamnionite/microbiologia , Claritromicina/uso terapêutico , Parto Obstétrico , Feminino , Humanos , Interleucina-6/metabolismo , Contagem de Leucócitos , Metaloproteinase 8 da Matriz/metabolismo , Metronidazol/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Estudos Retrospectivos
20.
Am J Obstet Gynecol ; 221(2): 140.e1-140.e18, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30928565

RESUMO

BACKGROUND: Cervical insufficiency is a risk factor for spontaneous midtrimester abortion or early preterm birth. Intra-amniotic infection has been reported in 8-52% of such patients and intra-amniotic inflammation in 81%. Some professional organizations have recommended perioperative antibiotic treatment when emergency cervical cerclage is performed. The use of prophylactic antibiotics is predicated largely on the basis that they reduce the rate of complications during the course of vaginal surgery. However, it is possible that antibiotic administration can also eradicate intra-amniotic infection/inflammation and improve pregnancy outcome. OBJECTIVE: To describe the outcome of antibiotic treatment in patients with cervical insufficiency and intra-amniotic infection/inflammation. STUDY DESIGN: The study population consisted of 22 women who met the following criteria: (1) singleton pregnancy; (2) painless cervical dilatation of >1 cm between 16.0 and 27.9 weeks of gestation; (3) intact membranes and absence of uterine contractions; (4) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity; (5) presence of intra-amniotic infection/inflammation; and (6) antibiotic treatment (regimen consisted of ceftriaxone, clarithromycin, and metronidazole). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction for Ureaplasma spp. was performed. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms or a positive polymerase chain reaction for Ureaplasma spp., and intra-amniotic inflammation was suspected when there was an elevated amniotic fluid white blood cell count (≥19 cells/mm3) or a positive rapid test for metalloproteinase-8 (sensitivity 10 ng/mL). For the purpose of this study, the "gold standard" for diagnosis of intra-amniotic inflammation was an elevated interleukin-6 concentration (>2.6 ng/mL) using an enzyme-linked immunosorbent assay. The results of amniotic fluid interleukin-6 were not available to managing clinicians. Follow-up amniocentesis was routinely offered to monitor the microbiologic and inflammatory status of the amniotic cavity and fetal lung maturity. Treatment success was defined as resolution of intra-amniotic infection/inflammation or delivery ≥34 weeks of gestation. RESULTS: Of 22 patients with cervical insufficiency and intra-amniotic infection/inflammation, 3 (14%) had microorganisms in the amniotic fluid. Of the 22 patients, 6 (27%) delivered within 1 week of amniocentesis and the remaining 16 (73%) delivered more than 1 week after the diagnostic procedure. Among these, 12 had a repeat amniocentesis to assess the microbial and inflammatory status of the amniotic cavity; in 75% (9/12), there was objective evidence of resolution of intra-amniotic inflammation or intra-amniotic infection demonstrated by analysis of amniotic fluid at the time of the repeat amniocentesis. Of the 4 patients who did not have a follow-up amniocentesis, all delivered ≥34 weeks, 2 of them at term; thus, treatment success occurred in 59% (13/22) of cases. CONCLUSION: In patients with cervical insufficiency and intra-amniotic infection/inflammation, administration of antibiotics (ceftriaxone, clarithromycin, and metronidazole) was followed by resolution of the intra-amniotic inflammatory process or intra-amniotic infection in 75% of patients and was associated with treatment success in about 60% of cases.


Assuntos
Antibacterianos/uso terapêutico , Corioamnionite/tratamento farmacológico , Incompetência do Colo do Útero/microbiologia , Adulto , Amniocentese , Líquido Amniótico/metabolismo , Líquido Amniótico/microbiologia , Biomarcadores/metabolismo , Candida albicans/isolamento & purificação , Ceftriaxona/uso terapêutico , Cerclagem Cervical , Corioamnionite/microbiologia , Claritromicina/uso terapêutico , Parto Obstétrico , Feminino , Humanos , Interleucina-6/metabolismo , Leucócitos/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metronidazol/uso terapêutico , Gravidez , Estudos Retrospectivos , Streptococcus anginosus/isolamento & purificação , Ureaplasma/isolamento & purificação
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