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1.
J Immunol ; 200(12): 3950-3961, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29712770

RESUMO

Infiltration of neutrophils into colonic mucosa has been associated with the severity of ulcerative colitis (UC). We investigated the effect of disease microenvironment on the release of neutrophil extracellular traps (NETs) as well as the involved mechanisms in NETosis and whether certain NET proteins are correlated with disease phenotype. Peripheral blood neutrophils, sera, and colonic tissue were collected from treatment-naive and mesalazine-treated patients with active UC, treatment-naive patients with active Crohn's disease, patients suffering from infectious colitis, or healthy individuals (controls). Analysis of colonic biopsy specimens and peripheral blood neutrophils for the presence of NET-related markers using immunofluorescence confocal microscopy, ELISA, immunoblotting, flow cytometry, and quantitative PCR were performed. In vitro cell and tissue culture systems were further deployed. The local inflammatory response in colon in UC, but not Crohn's disease, is characterized by the presence of NETs carrying bioactive IL-1ß and thrombogenic tissue factor. The inflammatory environment of UC is able to induce neutrophil activation, IL-1ß expression, and NET release, as shown both ex vivo and in vitro. REDD1 expression, as a mediator linking inflammation, autophagy, and NET release, was also specifically associated with the inflammatory response of UC. We show that neutrophil expression of REDD1 in colon tissue and the presence of IL-1ß in neutrophils/NETs provide candidate biomarkers for the differential diagnosis of inflammatory colitis and possible targets for the treatment of UC, suggesting that UC shares common features with autoinflammatory disorders.


Assuntos
Autofagia/fisiologia , Colite Ulcerativa/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Neutrófilos/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Autofagia/efeitos dos fármacos , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Feminino , Humanos , Inflamação/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Mesalamina/farmacologia , Pessoa de Meia-Idade , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/fisiologia , Neutrófilos/efeitos dos fármacos
2.
J Allergy Clin Immunol ; 140(5): 1378-1387.e13, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28342915

RESUMO

BACKGROUND: Familial Mediterranean fever (FMF) is an IL-1ß-dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress. OBJECTIVE: We investigated the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1ß-bearing neutrophil extracellular traps (NETs) in patients with FMF. METHODS: RNA sequencing was performed in peripheral neutrophils from 3 patients with FMF isolated both during attacks and remission, 8 patients in remission, and 8 healthy subjects. NET formation and proteins were analyzed by using confocal immunofluorescence microscopy, immunoblotting, myeloperoxidase-DNA complex ELISA, and flow cytometry. Samples from patients with Still's disease and bacterial infections were used also. RESULTS: The stress-related protein regulated in development and DNA damage responses 1 (REDD1) is significantly overexpressed during FMF attacks. Neutrophils from patients with FMF during remission are resistant to autophagy-mediated NET release, which can be overcome through REDD1 induction. Stress-related mediators (eg, epinephrine) decrease this threshold, leading to autophagy-driven NET release, whereas the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1ß and its release through NETs. REDD1 in autolysosomes colocalizes with pyrin and nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3. Mutated pyrin prohibits this colocalization, leading to higher IL-1ß levels on NETs. CONCLUSIONS: This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1ß, and might constitute an important piece in the IL-1ß-mediated inflammation puzzle.


Assuntos
Febre Familiar do Mediterrâneo/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/metabolismo , Adulto , Autofagia , Progressão da Doença , Armadilhas Extracelulares/metabolismo , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Interleucina-1beta/metabolismo , Masculino , Pirina/genética , Remissão Espontânea , Estresse Fisiológico/imunologia , Adulto Jovem
3.
Antimicrob Agents Chemother ; 60(2): 1040-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26643338

RESUMO

Macrolide antibiotics have been shown to act as immunomodulatory molecules in various immune cells. However, their effect on neutrophils has not been extensively investigated. In this study, we investigated the role of macrolide antibiotics in the generation of neutrophil extracellular traps (NETs). By assessing ex vivo and in vivo NET formation, we demonstrated that clarithromycin is able to induce NET generation both in vitro and in vivo. Clarithromycin utilizes autophagy in order to form NETs, and these NETs are decorated with antimicrobial peptide LL-37. Clarithromycin-induced NETs are able to inhibit Acinetobacter baumannii growth and biofilm formation in an LL-37-dependent manner. Additionally, LL-37 antimicrobial function depends on NET scaffold integrity. Collectively, these data expand the knowledge on the immunomodulatory role of macrolide antibiotics via the generation of LL-37-bearing NETs, which demonstrate LL-37-dependent antimicrobial activity and biofilm inhibition against A. baumannii.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Claritromicina/farmacologia , Armadilhas Extracelulares/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Neutrófilos/efeitos dos fármacos , Infecções por Acinetobacter/imunologia , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/patogenicidade , Adulto , Antibacterianos/imunologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos , Autofagia/efeitos dos fármacos , Estudos de Casos e Controles , Catelicidinas/metabolismo , Claritromicina/imunologia , Feminino , Gastrite/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Humanos , Fatores Imunológicos/imunologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/patologia
4.
Scand J Gastroenterol ; 51(8): 893-902, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27152750

RESUMO

Ischemic colitis is the result of colonic hypoperfusion and is regarded as a relatively rare condition. It can be roughly classified as occlusive and non-occlusive. Pathogenesis includes a usually transient compromise in the colonic vasculature, with a parallel activation of an inflammatory cascade caused primarily by reperfusion. Diagnosis of ischemic colitis remains often difficult and requires a combination of diagnostic techniques, whereas clinical signs are occasionally only seen late as complications. Gold standard is considered to be colonoscopy. Clinical presentation and treatment of ischemic colitis vary widely depending on the degree of ischemia. Patients of intensive care unit (ICU) with ischemic colitis are often under-diagnosed, since the parallel co-morbidities and the nonspecific nature of symptoms that mimic almost any abdominal pathology, can mislead the doctor. Moreover, sedated or ventilated patients can mask many of the characteristic features of ischemic colitis and make the diagnosis challenging. Bedside colonoscopy and diagnostic laparoscopy in ICUs are two options, which seem lately to be reliable and promising in diagnosing ischemic colitis in critically ill patients.


Assuntos
Colite Isquêmica , Colite Isquêmica/etiologia , Colite Isquêmica/terapia , Humanos , Unidades de Terapia Intensiva
5.
Surg Innov ; 21(1): 22-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23575915

RESUMO

Laparoscopic cholecystectomy is associated with attenuated acute-phase response and hypercoagulable state compared with the open procedure. Single-incision laparoscopic cholecystectomy is a new technique aiming to minimize the invasiveness of the procedure. By comparing the degree of coagulation and fibrinolysis activation after conventional multiport (CLC) and single-incision (SILC) laparoscopic cholecystectomy, we aimed to determine whether the reduced incision size induces a lower thrombophilic tendency. Thirty-two adult patients with noncomplicated symptomatic cholelithiasis were nonrandomly assigned to CLC or SILC. Prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complexes (TAT), D-dimers, fibrinogen, and von Willebrand factor levels were measured at baseline, at 1st, and 24th hour, postoperatively. Twenty-six patients were finally included in the study. Fifteen patients underwent CLC (male/female: 5/10) and 11 underwent SILC (male/female: 1/10). There were no perioperative complications. An almost similar postoperative pattern and degree of activation of coagulation and fibrinolysis pathways was noted in both groups. No statistically significant differences were found between SILC and CLC for F1 + 2, TAT, D-dimers, fibrinogen, and von Willebrand factor levels, duration of surgery, length of hospital stay, and postoperative morbidity. A similar pattern and extent of coagulation and fibrinolysis activation is present in SILC and CLC, and therefore there is no difference in tendency for thrombosis. Thromboembolic prophylaxis should be considered in SILC as recommended for CLC, pharmacologic or mechanical, considering the hemorrhagic risk and the presence of additional thromboembolism risk factors. SILC appears to be a safe, feasible technique that can be recommended for its potential advantages in cosmesis and reduced incisional pain.


Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Colecistectomia Laparoscópica/métodos , Colelitíase/sangue , Colelitíase/cirurgia , Fibrinólise , Adulto , Idoso , Antitrombina III , Estudos de Casos e Controles , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeo Hidrolases/sangue , Projetos Piloto , Estudos Prospectivos , Protrombina , Resultado do Tratamento , Fator de von Willebrand/metabolismo
6.
Eur J Dent ; 17(2): 270-282, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36400109

RESUMO

Helicobacter pylori (H. pylori) infection and periodontitis are both inflammatory conditions associated with systemic diseases. Researchers have attempted to investigate the correlation between them. This systematic review and meta-analyses were conducted to investigate the association of H. pylori infection in the stomach and/or in subgingival plaque and gingival crevicular fluid with chronic periodontitis. The protocol was created according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. The study was designed according to the Cochrane criteria. A comprehensive literature search was performed in MEDLINE, Scopus, and CENTRAL, combined with hand-searching and assessment of gray literature. The meta-analysis of the included studies was made by the Review Manager (RevMan) 5.4 software. The effect measure of the outcome was odds ratios with 95% confidence intervals. Heterogeneity was assessed by chi-square and I2. Four observational studies involving 818 subjects were included in this meta-analysis. The odds of oral H. pylori presence were higher in patients with chronic periodontitis, compared to healthy controls, with an odds ratio of 1.87 (95% confidence interval 0.85-4.10; p = 0.12). The odds of the presence of H. pylori in the stomach also were higher in patients with chronic periodontitis, with an odds ratio of 1.80 (95% confidence interval 0.82-3.95; p = 0.15). There is no evidence for an association between chronic periodontitis and the prevalence of H. pylori, detected either in subgingival plaque and gingival crevicular fluid or in the stomach.

7.
Eur J Dent ; 16(1): 145-152, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34598295

RESUMO

OBJECTIVES: This study was aimed to assess (1) the prevalence of salivary and gastric Helicobacter pylori (HP) infection in patients with and without periodontitis, (2) the prevalence of HP infection in patients with periodontitis according to its clinical classification, (3) the effect of periodontitis treatment in patients with or without gastric HP infection, and (4) if gastric HP eradication in combination with periodontitis treatment influences periodontitis clinical outcome. MATERIALS AND METHODS: Thirty-three adults with periodontitis treated by quadrant scaling and root planning (QSRP). The simplified plaque index (PI), bleeding on probing index (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were assessed pretreatment and 3 months of posttreatment. The patients were tested for oral and gastric HP. Gastric HP (+) patients received eradication therapy. A control group of 32 periodontically healthy volunteers was tested for oral and gastric HP. Saliva samples were evaluated by real-time polymerase chain reaction (rtPCR); gastric HP was detected by urea breath test (UBT). STATISTICAL ANALYSIS: Normality of variables assessed by the Kolmogorov-Smirnov test, while the differences of pre- and post-treatment were analyzed by paired samples t-test. Differences between subgroups were compared by a Student's t-test or a Mann-Whitney U-test. Comparisons of nominal variables were made by Pearson's Chi-square test. RESULTS: No saliva samples were positive for HP. Gastric HP was detected in six patients with periodontitis and seven controls (p > 0.05). HP infection affected patients with higher disease stages and grades. All HP (+) patients underwent successful eradication treatment. All clinical periodontitis indices improved following QSRP. HP (+) patients who received QSRP as adjunctive to eradication treatment showed improvement in BOP (p < 0.001), PI (p < 0.013), and CAL (p < 0.004) compared with HP (-) patients who received QSRP alone. CONCLUSION: Periodontitis was not associated with gastric HP infection. Saliva was not a gastric HP supply reservoir. Gastric HP infection was associated with advanced stages and grades of periodontitis. Although all periodontal clinical markers improved after QSRP, BOP, PI, and CAL, they were further improved when combined with eradication treatment. Periodontal evaluation and treatment combined with HP eradication are recommended in patients with HP gastric infection.

9.
Surg Endosc ; 23(2): 394-402, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18437468

RESUMO

BACKGROUND: Multiple studies have demonstrated the feasibility of peroral transgastric endoscopic procedures in porcine models. We present our experience with these procedures in a porcine survival model and expose the technical difficulties and worries about their application in humans. METHODS: We performed the following transgastric procedures in nine small pigs (20-30 kg) under general anesthesia using a double-channel therapeutic endoscope: peritoneoscopy (nine pigs), cholecystectomy (six pigs), gastrojejunal anastomosis (two pigs), and fallopian tube excision (one pig). Postsurgical complications and survival of the pigs were recorded during a 3-week follow-up. RESULTS: In six pigs, the gallbladder was successfully resected. The time of the procedure ranged from 2.5 to 3.5 hours. In one case, severe bleeding occurred from the cystic artery during dissection and was successfully managed by placement of endoscopic clips. Five pigs survived for 3 weeks after cholecystectomy. In one pig, severe peritonitis developed because of gastric contents leakage due to failure of gastric closure and the animal was euthanized 3 days after the procedure. Endoscopic transgastric gastrojejunostomy was successfully performed in two pigs without major complications. The time required for the procedure averaged about 50 min. Fallopian tube excision was also successful in one pig without any complications. The entire procedure was performed within 60 min. CONCLUSIONS: This study reports the feasibility of natural orifice transluminal endoscopic surgery (NOTES) procedures in a porcine survival model and impresses the efficacy, the safety, the complications, and some technical difficulties of transgastric NOTES procedures, which merit further evaluation in future studies.


Assuntos
Colecistectomia/métodos , Endoscopia/métodos , Tubas Uterinas/cirurgia , Derivação Gástrica/métodos , Gastroscópios , Cavidade Peritoneal/cirurgia , Animais , Estudos de Viabilidade , Feminino , Masculino , Modelos Animais , Suínos
10.
Med Sci Monit ; 15(6): CR313-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19478703

RESUMO

BACKGROUND: Synergetic activity between acid and bile has been associated with extensive esophageal mucosal damage in patients with gastro-esophageal reflux disease (GERD). Reflux of bile causes injury to gastric mucosa evaluated with an established histological index (bile reflux index, BRI). The aim of the study was to investigate the role of bile reflux in patients with GERD using the BRI. MATERIAL/METHODS: Fifteen asymptomatic subjects and 53 patients with GERD underwent upper gastrointestinal endoscopy with biopsies taken from the gastric antrum, body, cardia, and lower esophagus. The updated Sidney system was used for histological examination and BRI was calculated according to the findings in the antrum. RESULTS: BRI was elevated in 25/53 GERD patients (47%) and in 2/15 15 controls (13%) (OR: 5.8, 95%CI: 1.2-28.3). Elevated BRI was noted in 72% (13/18) of the patients with severe esophagitis (grade B or C) or Barrett's esophagus, whereas it was present in 34% (12/35) of those with mild or no lesions (OR: 5, 95%CI: 1.4-17.3). Additionally, 5 of the 6 patients detected with intestinal metaplasia (IM) at the cardia (83%) and 9 of the 12 patients with IM of the antrum (75%) had elevated BRI. CONCLUSIONS: Bile reflux gastropathy is present in a significant proportion of patients with GERD and associated with disease severity. The elevated BRI in such patients highlights the role of duodeno-gastro-esophageal reflux as an additional factor in the pathogenesis of GERD.


Assuntos
Refluxo Biliar/complicações , Refluxo Biliar/patologia , Refluxo Gastroesofágico/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Endoscopia , Feminino , Refluxo Gastroesofágico/patologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Int J Gen Med ; 12: 121-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30881087

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. However, rectal GISTs represent only 5% of this category. We report a case of a rectal GIST treated with local excision after neoadjuvant therapy. CASE PRESENTATION: A 41-year-old male patient presented with anal bleeding. Colonoscopy revealed a mass located 5 cm from the anal verge. Histological examination showed a GIST with immunohistochemical positivity for CD117 and CD34. Transanal local excision was performed after neoadjuvant therapy. CONCLUSION: Neoadjuvant immunotherapy for GISTs with unfavorable localization may facilitate local excision and avoid complications of more demanding operations.

12.
Inflamm Bowel Dis ; 24(10): 2224-2241, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29860326

RESUMO

Background: Colonic subepithelial myofibroblasts (cSEMFs) are mesenchymal cells with a pivotal role in the pathophysiology of Crohn's disease (CD) fibrosis. Here, we demonstrate for the first time a complete expression mapping of cytokine receptors, implicated in inflammatory bowel diseases, in primary human cSEMFs and how pro-inflammatory cytokines regulate this expression. Furthermore, we show the effect of Th1-, Th2-, Th17- and Treg-related cytokines on a fibrosis-related phenotype of cSEMFs. Methods: Colonic subepithelial myofibroblasts were isolated from healthy individuals' colonic biopsies. Interleukin (IL)-1α- and/or tumor necrosis factor (TNF)-α-induced mRNA and protein expression of cytokine receptors was assayed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence, respectively. Th-related cytokine effects on mRNA and protein profibrotic factor expression were analyzed by qRT-PCR and/or colorimetric assays and on the wound-healing capacity of cSEMFs by scratch test. Results: In cSEMFs, we observed basal cytokine receptor expression, which was modified by IL-1α and TNF-α. Th1-related cytokines upregulated tissue factor (TF), collagen, fibronectin and matrix metalloproteinase (MMP)-1 and downregulated α-smooth muscle actin (α-SMA), MMP-9, and wound healing rate. Th2-related cytokines upregulated collagen, TF, α-SMA, MMP-1, and wound healing rate and downregulated fibronectin and MMP-9. IL-17 and IL-23 upregulated fibronectin, and IL-22 downregulated TF. IL-17 and IL-22 decreased wound healing rate. Similar to TGF-ß, IL-23 upregulated MMP-1, tissue inhibitor of metalloproteinases-1, collagen expression, and wound healing rates. Conclusions: Our results suggest that cSEMFs have a central role in inflammation and fibrosis, as they express a great variety of Th-related cytokine receptors, making them responsive to pro-inflammatory cytokines, abundant in the inflamed mucosa of CD patients.


Assuntos
Colo/metabolismo , Citocinas/metabolismo , Fibrose/patologia , Mucosa Intestinal/patologia , Miofibroblastos/metabolismo , Receptores de Citocinas/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Células Cultivadas , Colo/citologia , Colo/imunologia , Fibrose/imunologia , Fibrose/metabolismo , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Miofibroblastos/citologia , Miofibroblastos/imunologia , Linfócitos T Reguladores/imunologia
13.
Am J Case Rep ; 19: 884-890, 2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-30054452

RESUMO

BACKGROUND The first gastric resection for stomach cancer was performed in 1879, and the first gastric resection for gastric ulcer disease was performed in 1882. During the 1990s, the first laparoscopic gastrostomies were reported. During the past decade, laparoscopic techniques have developed rapidly, gaining wide clinical acceptance. Minimally invasive surgery is now shifting the balance away from traditional open methods. We report 2 cases of endoscopically assisted laparoscopic local gastric resections for both gastric cancer and gastric ulcer disease. CASE REPORT The first case involves a 67-year-old male patient who suffered from recurrent bleeding from a gastric ulcer located 4-5 cm from the gastroesophageal junction. The patient was subjected to endoscopically assisted laparoscopic wedge resection of the affected part of the stomach, had an uneventful recovery and was discharged on the third postoperative day. The second case involves a 60-year-old female patient who was diagnosed with intramucosal gastric adenocarcinoma and was also subjected to endoscopically assisted laparoscopic wedge gastrectomy. This patient also had an uneventful recovery and was discharged on the second postoperative day. CONCLUSIONS Endoscopically assisted laparoscopic local gastric resection is a minimally invasive procedure which allows the surgeon to operate under direct visualization of the internal part of the stomach. Thus, it enables the surgeon to safely remove the affected part within healthy margins, providing the patient with all the advantages of laparoscopic surgery.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Laparoscopia/métodos , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/cirurgia , Idoso , Junção Esofagogástrica/cirurgia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Gastroscopia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Úlcera Gástrica/complicações , Resultado do Tratamento
14.
Transl Res ; 180: 118-130.e2, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27665176

RESUMO

Intestinal subepithelial myofibroblasts (SEMFs) exert a profibrotic role in Crohn's disease (CD). Tumor necrosis factor-like cytokine 1A (TL1A) and its receptors, death-domain receptor 3 (DR3) and decoy receptor 3 (DcR3), are mucosal factors with significant involvement in experimental inflammation and CD. We aimed to determine the regulation of expression of this system of proteins in SEMFs and intestinal epithelial cells. The relative amount of mRNA transcripts for TL1A, DR3, and DcR3 was measured by real-time reverse transcription polymerase chain reaction in cultured primary SEMFs, colonic myofibroblast cell line 18CO, and epithelial cell line HT29. Protein expression was determined by immunofluorescence. The effect of various proinflammatory stimuli in mRNA and protein expression was studied. TL1A mRNA and protein expression in primary SEMFs (and 18CO cells) was significantly upregulated after stimulation with interleukin 1-alpha and/or tumor necrosis factor alpha (TNF-α) (32- to 44-fold increase, P < 0.05 vs unstimulated). Following stimulation with interleukin 1-alpha + TNF-α + IFN-γ, HT-29 cells highly expressed DR3 (4.1-fold over unstimulated, P = 0.008) and DcR3 (56-fold, P = 0.009) and secreted soluble factors that led to induction of TL1A mRNA in primary SEMFs (28-fold, P = 0.008). Activated epithelial cells significantly upregulated IL-8 expression in response to stimulation with recombinant TL1A. Supernatants from mucosal cultures of patients with CD were able to stimulate the expression of TL1A in cultured primary SEMFs, in comparison to supernatants from healthy controls (3.8-fold increase, P < 0.05) or culture media alone (P < 0.05). In conclusion, we found that proinflammatory cytokines are important regulators of the expression of TL1A in SEMFs and of its receptors in intestinal epithelial cells. Our results raise the possibility for involvement of TL1A/DR3/DR3-mediated mechanisms in epithelial-mesenchymal interactions and the development of inflammation-induced intestinal fibrosis in CD.


Assuntos
Doença de Crohn/metabolismo , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Miofibroblastos/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células HT29 , Humanos , Mediadores da Inflamação/farmacologia , Interleucina-8/genética , Interleucina-8/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Solubilidade , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
15.
J Med Case Rep ; 10: 135, 2016 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-27387334

RESUMO

BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment of gallbladder disease. Post-cholecystectomy syndrome is a severe postoperative complication which can be caused by multiple mechanisms and can present with multiple disorders. The wide use of laparoscopy induces the need to understand more clearly the presentation and pathophysiology of this syndrome. Post-cholecystectomy Mirizzi syndrome is one form of this syndrome and, according to literature, this is the first report that clearly describes it. CASE PRESENTATION: We describe the case of a 62-year-old Greek woman who underwent laparoscopic cholecystectomy because of gallstone disease. A few days after surgery, post-cholecystectomy syndrome gradually developed with mild bilirubin increase in association with epigastric pain, nausea, and vomiting. After performing ultrasound, magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography, we conducted a second laparoscopic surgery to manage the obstruction, which was converted to open surgery because of the remaining inflammation from the post-endoscopic retrograde cholangiopancreatography acute pancreatitis. Four polymeric laparoscopic clips were removed because they were identified as the cause of her post-cholecystectomy syndrome. She had a quick recovery without further complications. CONCLUSIONS: Postoperative Mirizzi syndrome induced by the migration of polymer laparoscopic clips is a rare (only one case referring to polymeric clips has been published in the literature) but a well-identified complication of laparoscopic cholecystectomy which can confuse the diagnostic and therapeutic field requiring simultaneous immediate management.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Corpos Estranhos/diagnóstico , Síndrome de Mirizzi/etiologia , Síndrome Pós-Colecistectomia/complicações , Instrumentos Cirúrgicos , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Feminino , Corpos Estranhos/cirurgia , Humanos , Pessoa de Meia-Idade , Síndrome de Mirizzi/diagnóstico , Síndrome de Mirizzi/cirurgia , Síndrome Pós-Colecistectomia/diagnóstico por imagem , Instrumentos Cirúrgicos/efeitos adversos , Ultrassonografia
16.
J Invest Surg ; 29(2): 98-105, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26631974

RESUMO

PURPOSE: Complete surgical resection with negative margins without lymphadenectomy is the treatment of choice for nonmetastatic Gastrointestinal Stromal Tumors (GISTs). Laparoscopic resection of gastric GISTs <5 cm is an acceptable and oncologically feasible, safe, and effective treatment. We present our experience of an endoscopically assisted minimally invasive transumbilical single-incision laparoscopic (SILS) technique for gastric GISTs resection. METHODS: Four patients with small gastric GISTs ≤5 cm located on the greater curvature or the anterior wall were resected with SILS by using a lesion-lifting technique under the guidance of flexible gastroscopy. RESULTS: The technique was feasible and safe and offered significant advantages in locating the tumor and controlling the resection margins. There were no major intraoperative or postoperative complications, conversions, or tumor ruptures. Pathology showed low-risk GISTs resected with disease-free margins without tumor rupture. No recurrences have been observed. CONCLUSION: The endoscopically assisted SILS wedge gastrectomy is a feasible, safe, and advantageous technique for the treatment of the greater curvature or anterior wall gastric GISTs.


Assuntos
Gastrectomia/métodos , Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Gastroscopia/métodos , Laparoscopia/métodos , Gastrectomia/instrumentação , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Gastroscópios , Gastroscopia/instrumentação , Humanos , Margens de Excisão , Posicionamento do Paciente , Ferida Cirúrgica , Resultado do Tratamento , Umbigo/cirurgia
17.
Curr Med Res Opin ; 21(4): 603-10, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15899110

RESUMO

BACKGROUND: In controlled clinical trials, rabeprazole effectively improves symptoms and heals oesophageal erosions in patients with gastro-oesophageal reflux disease (GORD). AIM: To examine symptom relief during week 1 of rabeprazole therapy, in addition to GORD healing, in a clinical practice setting. METHODS: In this 8-week, prospective, multicentre, postauthorisation surveillance study conducted in Greece, patients with GORD (intent-to-treat: efficacy, 272; safety, 273) were treated with rabeprazole 20 mg once daily. The primary efficacy end point was the change from baseline in GORD symptom severity on day 1, 2, 3 and 7 using a 5-point Likert scale (1 = no symptoms; 5 = severe symptoms). Oesophageal healing was also evaluated by comparing the results of endoscopic findings at baseline and after 4 and 8 weeks of treatment. RESULTS: On day 1 of treatment, rabeprazole relieved GORD symptoms across all grades of oesophagitis, with statistically significant (p = 0.0001) improvement in heartburn, regurgitation, epigastric pain and dysphagia. Oesophageal healing was achieved in 77% of patients at week 4 and in 90% at week 8 and treatment was well tolerated. CONCLUSIONS: In a clinical practice setting, rabeprazole provided rapid relief of GORD symptoms, confirming results seen in controlled clinical trials.


Assuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/análogos & derivados , Omeprazol/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Administração Oral , Adulto , Idoso , Antiulcerosos/farmacologia , Benzimidazóis/farmacologia , Transtornos de Deglutição , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/farmacologia , Dor , Estudos Prospectivos , Rabeprazol , Resultado do Tratamento
18.
Rom J Gastroenterol ; 14(2): 117-21, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15990929

RESUMO

OBJECTIVE: To evaluate the presence of gastroesophageal reflux disease (GERD) in a Greek cohort in relationship to the body mass index (BMI), using the 3-hr postprandial esophageal pH monitoring. METHODS: Sixty-four consecutive patients (55 males, 9 females; mean age 40.7 +/- 13.7 years) with at least weekly attacks of heartburn or acid regurgitation for a period longer than one year, were screened endoscopically for esophagitis and underwent a 3-hr postprandial pH monitoring to quantify the reflux. DeMeester score was calculated. The patients were allocated to three groups: group A (reference group, n=23) with BMI < 25 kg/m(2) (normal); group B (n=25) with BMI 25-30 kg/m(2) (overweight), and group C (n=16) with BMI > 30 kg/m(2) (obese). RESULTS: A higher DeMeester score, as well as a decreased lower esophageal sphincter pressure were evidenced with increasing BMI. Moreover, there was an association between increasing BMI and the point scale of reflux symptoms. The number of cases with severe reflux symptoms increased significantly among overweight (odds ratio: 4.94, 95%CI: 0.95-25.56) and obese (odds ratio: 8.18, 95%CI: 1.19-56.00) patients. CONCLUSIONS: The shorter 3-hr postprandial test appears to be diagnostic for GERD and acceptable by patients, reducing discomfort and enhancing compliance. Our study confirms the link between obesity and GERD. BMI is strongly associated with the point scale of reflux symptoms both in overweight and obese patients.


Assuntos
Esôfago/metabolismo , Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/fisiopatologia , Obesidade/complicações , Adulto , Índice de Massa Corporal , Esofagoscopia , Feminino , Seguimentos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Grécia/epidemiologia , Humanos , Concentração de Íons de Hidrogênio , Incidência , Masculino , Monitorização Fisiológica/métodos , Obesidade/epidemiologia , Obesidade/fisiopatologia , Período Pós-Prandial/fisiologia , Índice de Gravidade de Doença
19.
J Med Case Rep ; 9: 125, 2015 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-26031291

RESUMO

INTRODUCTION: In this case report, we describe the successful treatment of a small-bowel intussusception, which was caused by a 3 cm solitary hamartomatous polyp, with single-incision laparoscopic surgery. Single-incision laparoscopic surgery is a minimally invasive surgical procedure with important advantages that allows the reduction of the intussusception and the resection of the polyp. This case report contributes to the medical literature by describing the advantages of this surgical technique that warrant its consideration as a treatment of choice in similar cases. CASE PRESENTATION: We report a case of a 19-year-old Greek woman who complained about intermittent, non-specific abdominal pain in her left lateral abdomen. She had been admitted to the hospital because of incomplete obstructive ileus. Ultrasound and computed tomography were carried out, which revealed an intussusception of the small bowel. This pathogenic situation was treated by single-incision laparoscopic surgery. Her pathology report revealed a benign, hamartomatous excised polyp of the Peutz-Jeghers type. The patient had a quick recovery without any post-operative complications. CONCLUSION: We recommend single-incision laparoscopic surgery for the safe excision of solitary hamartomatous polyps and the management of their complications, as it represents a potential advance in minimally invasive approaches.


Assuntos
Hamartoma/complicações , Intussuscepção/cirurgia , Laparoscopia/métodos , Feminino , Hamartoma/patologia , Humanos , Intestino Delgado , Intussuscepção/diagnóstico , Intussuscepção/etiologia , Síndrome de Peutz-Jeghers/complicações , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Can J Gastroenterol ; 17(4): 249-58, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12704469

RESUMO

Apoptosis is critical for organ development, tissue homeostasis, the elimination of abnormal cells and the maintenance of immune homeostasis by variable regulatory mechanisms. The death of T lymphocytes following their activation involves a series of proteases (caspases), which comprise the central executioners of apoptosis. Abnormal regulation of apoptosis results in disease. T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of the chronic inflammatory process in inflammatory bowel disease with potential tumourigenic effect. The use of antitumour necrosis factor-alpha, anti-interleukin-6R and anti-interleukin-12 antibodies suppresses colitis activity by induction of T-cell apoptosis, thereby having important implications for the design of effective therapeutic strategies in inflammatory bowel diseases. Contrary to international data, the incidence of cancer in Greek patients with inflammatory bowel disease appears to be low. A balance between cell proliferation (Ki-67 overexpression) and apoptosis (Bax protein overexpression) may partly explain the low incidence of cancer development in Greek inflammatory bowel disease patients.


Assuntos
Apoptose/imunologia , Transformação Celular Neoplásica/imunologia , Doenças Inflamatórias Intestinais/imunologia , Linfócitos T/imunologia , Animais , Anticorpos/imunologia , Anticorpos/uso terapêutico , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/prevenção & controle , Desenho de Fármacos , Saúde Global , Grécia/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Interleucina-12/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Interleucinas/antagonistas & inibidores , Interleucinas/uso terapêutico , Mucosa Intestinal/imunologia , Necrose , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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