RESUMO
Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition associated with altered bowel habits and recurrent abdominal pain, often triggered by food intake. Current treatments focus on improving stool pattern, but effective treatments for pain in IBS are still lacking due to our limited understanding of pathophysiological mechanisms. Visceral hypersensitivity (VHS), or abnormal visceral pain perception, underlies abdominal pain development in IBS, and mast cell activation has been shown to play an important role in the development of VHS. Our work recently revealed that abdominal pain in response to food intake is induced by the sensitization of colonic pain-sensing neurons by histamine produced by activated mast cells following a local IgE response to food. In this review, we summarize the current knowledge on abdominal pain and VHS pathophysiology in IBS, we outline the work leading to the discovery of the role of histamine in abdominal pain, and we introduce antihistamines as a novel treatment option to manage chronic abdominal pain in patients with IBS.
RESUMO
Aim: Testing the effect of Fluoride, chlorhexidine, and molecular iodine applications on the mean micro-shear bond strength (SBS) of enamel in an attempt to preserve enamel integrity during the bonding process. Materials and Methods: The study was an observational case-control one in which 150 human teeth were classified into 10 groups according to the product kind and the prescribed treatment. Each group consisted of 15 teeth. Group C was the control group. Groups FP, FV, and OS utilized products that could be utilized in a professional dental setting. Group FP was treated with 1.23% NaF prophy paste, Group FV was treated with 5% NaF varnish, and Group OS was treated with Opal® Seal Fluoride releasing primer and sealant. Groups L, LF, CHX, and I were treated with mouth rinses. Group L was treated with Listerine Zero Fluoride-Free Mouthwash, Group LF with Listerine Zero 0.02% NaF Mouth Rinse, Group CHX with 0.12% chlorhexidine gluconate, and Group I with ioRinse RTU 100 ppm molecular iodine rinse. Groups TP and G utilized alternative remineralization products. Group TP was treated with Fluoro Calcium Phosphosilicate bioglass containing toothpaste, and Group G was treated with Curodont Protect remineralizing tooth gel. One-way ANOVA test was utilized to perform all statistical analysis in this study. Results: For mean micro-SBS, no significant difference (P > 0.05) between any of the experimental groups was observed when compared to the control group. There was a significant difference (P < 0.05) between Opal Seal versus Listerine Total, Opal Seal versus Peridex, Listerine versus Listerine Total, and Listerine versus Peridex. All other experimental group comparisons revealed a nonsignificant difference (P > 0.05). Conclusions: As the null hypothesis (H0) assumes that changes observed in an experiment are due to chance, hence, the outcomes of this study are coherent with (H0) since the aforementioned application methods did not significantly impact the SBS of orthodontic resin cement to enamel.
RESUMO
OBJECTIVE: To investigate the accuracy of gingival crevicular fluid (GCF) E-cadherin and total antioxidant capacity (TAC) to discriminate periodontal health from disease. SUBJECTS AND METHODS: GCF samples were collected from participants with periodontal health (control), gingivitis, and periodontitis (n = 25 each group). The latter group was further subdivided according to stage (S) and grade. Periodontal parameters were recorded then levels of biomarkers were assayed using ELISA and antioxidant status by use of the Total Antioxidant Capacity Assay for E-cadherin and TAC, respectively. RESULTS: All periodontal parameters were significantly higher in periodontally diseased groups than controls. The GCF E-cadherin significantly increased in gingivitis and periodontitis (S2 to S4) cases as compared to controls. Level of this protein in GCF samples from periodontitis S3 was significantly higher than in gingivitis and S2 groups. The GCF-TAC level was significantly higher in controls than in periodontally diseased groups. No significant differences were observed in the levels of these proteins between grade B and C periodontitis. Both molecules could discriminate periodontal health from gingivitis and periodontitis stages and differentiating periodontitis S3 from gingivitis and other periodontitis stages. CONCLUSIONS: Levels of TAC and unbounded E-cadherin in GCF samples exhibited promising diagnostic abilities to differentiate periodontal health and disease.
RESUMO
OBJECTIVES: To determine the potential of gingival crevicular fluid (GCF) volume, E-cadherin and total antioxidant capacity (TAC) levels to predict the outcomes of nonsurgical periodontal therapy (NSPT) for periodontitis patients. BACKGROUND: NSPT is the gold-standard treatment for periodontal pockets < 6 mm in depth, however, successful outcomes are not always guaranteed due to several factors. Periodontitis-associated tissue destruction is evidenced by the increased level of soluble E-cadherin and reduced antioxidants in oral fluids which could be used as predictors for success/failure of NSPT. MATERIALS AND METHODS: Patients with periodontitis (n = 24) were included in this clinical trial and full-mouth periodontal charting was recorded for each patient. GCF samples from periodontal pockets with probing pocket depth (PPD) 4-6 mm from the interproximal surfaces of anterior and premolar teeth were obtained. These sites subsequently received NSPT and were clinically re-evaluated after 1 and 3 months. Levels of GCF E-cadherin and TAC levels were assayed using ELISA. RESULTS: All clinical periodontal parameters were significantly improved 3 months after completion of NSPT. These outcomes were associated with a significant decrease in E-cadherin levels and GCF volume, while TAC levels were significantly increased in samples obtained in follow-up appointments. Binary regression model analysis showed that PPD, GCF volume, E-cadherin, and TAC levels could significantly (p < .05) predict the outcomes of NSPT. The cut-off points for PPD, GCF volume, E-cadherin and TAC were 5 mm, 4 × 10-3, 1267.97 pg/mL and 0.09 µmol/g, respectively. CONCLUSION: NSPT improved clinical parameters along with increased antioxidants capacity and epithelial pocket lining integrity. Discrimination of favorable/unfavorable responsiveness of periodontally diseased sites to NSPT could be possible by using GCF volume, PPD, E-cadherin and TAC level assessments.
Assuntos
Antioxidantes , Periodontite , Humanos , Caderinas , Líquido do Sulco Gengival , Bolsa PeriodontalRESUMO
STATEMENT OF PROBLEM: Worn denture teeth are a common reason for replacing complete dentures. However, clinical studies on the amount of denture tooth wear are lacking. PURPOSE: The purpose of this clinical study was to compare the clinical wear of denture teeth made from double cross-linked (DCL) versus highly cross-linked (HCL) materials after 1 year in service. MATERIAL AND METHODS: Fourteen participants received maxillary and mandibular removable complete dentures (RCDs). The participants randomly received either DCL or HCL teeth. Each RCD was scanned with an intraoral scanner 1 week after finishing any occlusal adjustment and after 1 year. Occlusal contact marks were recorded using articulating paper, and photographs were made in centric and eccentric movements. The generated 1-week and 1-year standard tessellation language (STL) files of the scans were obtained and trimmed using the Geomagic X software program. After merging the files, the depth of the wear facets was measured using the software program tool that measures the vertical gap distance in micrometers at 100 points distributed on the contact areas. These areas were identified by using the segment tools in the software program. Repeated measures ANOVA was used to analyze the differences between the collected data (α=.05). RESULTS: The DCL had higher mean ±standard deviation wear (62.7 ±40 µm) than the HCL (37 ±31 µm) after 1 year in service (P<.001). CONCLUSIONS: Both DCL and HCL denture teeth showed acceptable clinical wear after 1 year of clinical use. HCL denture teeth showed more resistance to occlusal wear than DCL denture teeth.
RESUMO
OBJECTIVES: Clinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA). DESIGN: We developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity. RESULTS: Prenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance of Ligilactobacillus murinus, in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs. CONCLUSION: PS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.
Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Masculino , Feminino , Camundongos , Animais , Síndrome do Intestino Irritável/microbiologia , Disbiose , Fezes/microbiologia , InflamaçãoRESUMO
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and an altered defecation pattern. Depending on the criteria used, it affects between 5 and 10% of the general population and has a serious impact on quality of life. Most patients with IBS show an induction or exacerbation of their symptoms, particularly abdominal pain, after eating certain foods. This raises the question of the role played by food in IBS pathophysiology. In this review, we describe the multiple risk factors of IBS, and we give an overview of the role of food as a trigger of IBS, distinguishing between immune and non-immune reactions to food. We finally highlight recent findings identifying an immune-mediated mechanism underlying food-induced abdominal pain in IBS.
Assuntos
Gastroenteropatias , Síndrome do Intestino Irritável , Dor Abdominal/complicações , Doença Crônica , Alimentos/efeitos adversos , Humanos , Qualidade de VidaRESUMO
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that is characterized by abdominal pain and an altered defecation pattern. It affects between 5 and 20% of the general population and can seriously impact quality of life. The pathophysiology of IBS is rather complex and multifactorial including, for example, altered signalling by the gut-brain axis, dysbiosis, abnormal visceral pain signalling and intestinal immune activation. The latter has gained particular interest in recent years, with growing insight into the bidirectional communication between the nervous system and the immune system. In this Review, we detail the current evidence suggesting that immune activation contributes to the pathology seen in patients with IBS and discuss the potential mechanisms involved. Moreover, we describe how immune mediators, particularly those released by mast cells, can directly activate or sensitize pain-transmitting nerves, leading to increased pain signalling and abdominal pain. Finally, we discuss the potential of interventions targeting immune activation as a new therapeutic strategy for patients suffering from IBS.
Assuntos
Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Qualidade de Vida , Dor Abdominal/etiologia , Disbiose , MastócitosRESUMO
The oxygen sensor prolyl hydroxylase domain 2 (PHD2) plays an important role in cell hypoxia adaptation by regulating the stability of HIF proteins (HIF1α and HIF2α) in numerous cell types, including T lymphocytes. The role of oxygen sensor on immune cells, particularly on regulatory T cell (Treg) function, has not been fully elucidated. The purpose of our study was to evaluate the role of PHD2 in the regulation of Treg phenotype and function. We demonstrate herein that selective ablation of PHD2 expression in Treg (PHD2ΔTreg mice) leads to a spontaneous systemic inflammatory syndrome, as evidenced by weight loss, development of a rectal prolapse, splenomegaly, shortening of the colon, and elevated expression of IFN-γ in the mesenteric lymph nodes, intestine, and spleen. PHD2 deficiency in Tregs led to an increased number of activated CD4 conventional T cells expressing a Th1-like effector phenotype. Concomitantly, the expression of innate-type cytokines such as Il1b, Il12a, Il12b, and Tnfa was found to be elevated in peripheral (gut) tissues and spleen. PHD2ΔTreg mice also displayed an enhanced sensitivity to dextran sodium sulfate-induced colitis and toxoplasmosis, suggesting that PHD2-deficient Tregs did not efficiently control inflammatory response in vivo, particularly those characterized by IFN-γ production. Further analysis revealed that Treg dysregulation was largely prevented in PHD2-HIF2α (PHD2-HIF2αΔTreg mice), but not in PHD2-HIF1α (PHD2-HIF1αΔTreg mice) double KOs, suggesting an important and possibly selective role of the PHD2-HIF2α axis in the control of Treg function. Finally, the transcriptomic analysis of PHD2-deficient Tregs identified the STAT1 pathway as a target of the PHD2-HIF2α axis in regulatory T cell phenotype and in vivo function.
Assuntos
Colite , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Linfócitos T Reguladores , Animais , Colite/induzido quimicamente , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos , Oxigênio , Pró-Colágeno-Prolina Dioxigenase , Prolil HidroxilasesRESUMO
OBJECTIVES: The objective of this study is to test the wear of dual-cured bulkfill and flowable bulkfill composites. MATERIALS AND METHODS: Six dual-cured bulkfill composites, Cention, Cention-Exp, Activa, Fill-up, Hyperfil Injectafill, and two flowable bulkfill composites Tetric Evoflow BulkFill and G-aenial Universal Flo were tested in this study (n = 8). Each composite was applied into an aluminum sample holder and cured with a Valo Grand (1230 mW/cm2 ) or self-cured according to manufacturer's recommendations, and stored in water for 3 weeks. The samples were subjected to 120 000 load cycles of 49 N (CS-4) against spherical steatite antagonists and simultaneously subjected to 4440 thermocycles (5°C-55°C). At intervals between load cycles, polyvinyl siloxane impressions were taken and scanned with a True Definition Laser Scanner. The volumetric wear was calculated using image software (Geomagic). Microscopic images of selected wear facets and their corresponding worn antagonists were obtained using SEM. All data were analyzed using analysis of variance (ANOVA) and Tukey post hoc test for multiple comparison (α = .05; ß = .2). RESULTS: The load cycles volumetric wear-increase was linear. Two-way ANOVA showed significant main effects (material and light-cured) and significant interactions. Self-cured materials (mean = 0.38 mm3 ) showed more wear than light-cured materials (mean = 0.35mm3 ). CONCLUSIONS: The bioactive materials except Activa light-cured showed significantly more wear than the flowable composites. CLINICAL SIGNIFICANCE: This study demonstrated that most of the dual-cured composites, if light-cured, showed the same wear as the flowable composites used as control. Therefore, to obtain adequate wear resistance the dual-cured composites should be routinely light-cured.
Assuntos
Resinas Compostas , Teste de Materiais , Propriedades de SuperfícieRESUMO
Beyond its well-admitted role in development and organogenesis, it is now clear that the transcription factor c-Maf has owned its place in the realm of immune-related transcription factors. Formerly introduced solely as a Th2 transcription factor, the role attributed to c-Maf has gradually broadened over the years and has extended to most, if not all, known immune cell types. The influence of c-Maf is particularly prominent among T cell subsets, where c-Maf regulates the differentiation as well as the function of multiple subsets of CD4 and CD8 T cells, lending it a crucial position in adaptive immunity and anti-tumoral responsiveness. Recent research has also revealed the role of c-Maf in controlling Th17 responses in the intestine, positioning it as an essential factor in intestinal homeostasis. This review aims to present and discuss the recent advances highlighting the particular role played by c-Maf in T lymphocyte differentiation, function, and homeostasis.
Assuntos
Tolerância Imunológica , Proteínas Proto-Oncogênicas c-maf/fisiologia , Linfócitos T/imunologia , Diferenciação Celular , Humanos , Interleucina-10/biossíntese , Intestinos/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/análise , Proteínas Proto-Oncogênicas c-maf/genética , Linfócitos T/citologia , Linfócitos T/fisiologiaRESUMO
RORγt-expressing Tregs form a specialized subset of intestinal CD4+ Foxp3+ cells which is essential to maintain gut homeostasis and tolerance to commensal microbiota. Recently, c-Maf emerged as a critical factor in the regulation of RORγt expression in Tregs. However, aside from c-Maf signaling, the signaling pathways involved in the differentiation of RORγt+ Tregs and their possible interplay with c-Maf in this process are largely unknown. We show that RORγt+ Treg development is controled by positive as well as negative signals. Along with c-Maf signaling, signals derived from a complex microbiota, as well as IL-6/STAT3- and TGF-ß-derived signals act in favor of RORγt+ Treg development. Ectopic expression of c-Maf did not rescue RORγt expression in STAT3-deficient Tregs, indicating the presence of additional effectors downstream of STAT3. Moreover, we show that an inflammatory IFN-γ/STAT1 signaling pathway acts as a negative regulator of RORγt+ Treg differentiation in a c-Maf independent fashion. These data thus argue for a complex integrative signaling network that finely tunes RORγt expression in Tregs. The finding that type 1 inflammation impedes RORγt+ Treg development even in the presence of an active IL-6/STAT3 pathway further suggests a dominant negative effect of STAT1 over STAT3 in this process.
Assuntos
Diferenciação Celular/genética , Diferenciação Celular/imunologia , Expressão Gênica , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Imunofenotipagem , Camundongos , Camundongos Transgênicos , Proteínas Proto-Oncogênicas c-maf/genética , Proteínas Proto-Oncogênicas c-maf/metabolismo , Fator de Transcrição STAT3/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/citologia , Fator de Crescimento Transformador beta/metabolismoRESUMO
Follicular helper T cells (Tfh) have been identified as the primary cell subpopulation regulating B cell responses in germinal centers, thus supporting high-affinity antibody production. Among the transcription factors orchestrating Tfh cell differentiation and function, the role played by the proto-oncogene c-Maf remains poorly characterized. We report herein that selective loss of c-Maf expression in the T cell compartment results in defective development of Tfh cells in response to both antigen/adjuvant vaccinations and commensal intestinal bacteria. Accordingly, c-Maf expression in T cells was essential for the development and high-affinity antibody secretion in vaccinated animals. c-Maf was expressed early, concomitantly to BCL6, in Tfh cell precursors and found to regulate Tfh fate in a cell-autonomous fashion. Altogether, our findings reveal a novel, non-redundant, function for c-Maf in the differentiation of Tfh cells and the regulation of humoral immune responses to T-cell-dependent antigens.
RESUMO
Prenatal ultrasound, magnetic resonance imaging and matching postnatal computer tomography imaging findings are presented in a neonate with histologically proven congenital hepatoblastoma. Familiarity with the prenatal imaging findings of a hepatoblastoma are essential to make a reliable, specific diagnosis facilitating decision-making about the pre-, peri- and postnatal management.