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1.
Medicine (Baltimore) ; 101(35): e30098, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107510

RESUMO

BACKGROUND: A jejunal gastrointestinal stromal tumor (GIST) is a rare neoplasm of the gastrointestinal (GI) tract. Massive bleeding due to a jejunal GIST is a diagnostic and therapeutic challenge. It may be a life-threatening GIST complication that requires urgent intervention. Acute GI bleeding, which requires urgent surgical intervention, is a very rare clinical manifestation of GIST. A jejunal GIST with massive hemorrhage with coronavirus disease 2019 in a male patient in older age with many comorbidities has been not reported in the worldwide literature. METHODS: In this case report, we present an 80-year-old man who was admitted to surgery due to abdominal pain, melena, and hematochezia for several hours. An upper endoscopy and colonoscopy were inconclusive. A multidetector contrast-enhanced computed tomography (CT) of the abdominal and pelvic cavity showed concentric irregular thickening in the distal jejunum.The histopathological finding showed a GIST measuring 6 cm with a mitotic index 2/50 high power fields. The patient's hemodynamic condition deteriorated despite initial conservative treatment including a blood transfusion. Therefore, patient underwent the emergency surgery 24 hours after admission: partial jejunal resection with the tumor followed by primary end-to-end anastomosis. RESULTS: The mass was removed completely. There were no surgical complications in the postoperative course. On the first postoperative day, a severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test was performed due to a persistent dry cough, which yielded a positive result. After 14 days, the patient died due to pneumonia and circulatory failure. CONCLUSIONS: This case indicates that jejunal GIST can present as massive lower gastrointestinal bleeding and urgent surgery can successfully stop bleeding and save the patient's life. The CT scan was the most effective investigation to find the source of GI bleeding in this case. Therefore, we suggest performing CT in patients with acute massive lower gastrointestinal bleeding when the source of bleeding is not visible on endoscopy, and urgent surgical jejunal resection to stop life-threatening bleeding caused by a jejunal GIST.


Assuntos
COVID-19 , Tumores do Estroma Gastrointestinal , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal/efeitos adversos , Hemorragia Gastrointestinal/complicações , Hemorragia Gastrointestinal/cirurgia , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Jejuno/patologia , Jejuno/cirurgia , Masculino
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(7): 888-894, 2022 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36039585

RESUMO

OBJECTIVES: Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects. METHODS: A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (n=22) or FJ (n=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method. RESULTS: In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (P=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (P=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (P=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (P=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (P=0.066). CONCLUSIONS: There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.


Assuntos
Neoplasias Esofágicas , Fístula , Retalhos de Tecido Biológico , Procedimentos Cirúrgicos Reconstrutivos , Constrição Patológica/etiologia , Neoplasias Esofágicas/cirurgia , Fístula/etiologia , Retalhos de Tecido Biológico/patologia , Retalhos de Tecido Biológico/cirurgia , Humanos , Hipofaringe/patologia , Hipofaringe/cirurgia , Jejuno/patologia , Jejuno/cirurgia , Necrose , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Estudos Retrospectivos , Coxa da Perna/patologia , Coxa da Perna/cirurgia
3.
BMC Gastroenterol ; 22(1): 300, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725375

RESUMO

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition of unknown prevalence characterized by an excessive amount of bacteria in the small bowel, typically resulting in vague gastrointestinal symptoms with bloating being most commonly reported. Here we describe a severe case of SIBO leading to small bowel necrosis requiring surgical intervention. CASE PRESENTATION: A 55-year-old Hispanic female with gastric outlet obstruction secondary to a newly diagnosed gastric adenocarcinoma, receiving neoadjuvant chemotherapy, developed bloody gastrostomy output and rapidly progressing nausea and abdominal distention 3 days after jejunostomy tube placement and initiation of jejunal enteral nutrition. Imaging revealed diffuse pneumatosis and portal venous gas. Surgical exploration confirmed segmental bowel necrosis requiring resection. Histologic findings were consistent with SIBO. CONCLUSIONS: Presentation of severe SIBO in the setting of intestinal stasis secondary to gastric outlet after initiation of enteral feeds is a rare phenomenon. Early recognition and diagnosis of SIBO is critical in minimizing patient morbidity and mortality.


Assuntos
Síndrome da Alça Cega , Gastroenteropatias , Enteropatias , Síndrome da Alça Cega/etiologia , Feminino , Gastroenteropatias/patologia , Humanos , Jejunostomia , Jejuno/patologia , Pessoa de Meia-Idade , Necrose
4.
J Gastrointest Surg ; 26(9): 1917-1929, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35689008

RESUMO

PURPOSE: The number of neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes. RESULTS: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes. CONCLUSIONS: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs.


Assuntos
Tumores Neuroendócrinos , Humanos , Íleo/patologia , Jejuno/patologia , Linfonodos/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Nomogramas , Prognóstico , Programa de SEER
5.
Nihon Shokakibyo Gakkai Zasshi ; 119(5): 452-458, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35545544

RESUMO

Intraductal papillary mucinous carcinoma (IPMC) arising from the heterotopic pancreas is rare. A case of IPMC metastasis from the jejunal heterotopic pancreas was described. The heterotopic pancreas could be the source of the submucosal tumor-like lesion found in the small intestine with an elevated carbohydrate antigen (CA) 19-9 level. A 60-year-old woman was admitted to the hospital with pulmonary thromboembolism and anemia. The level of CA19-9, a tumor marker, was found to be 211.8U/ml. A tumor in the jejunum was discovered using contrast-enhanced computed tomography. There were also a number of hepatic tumors found. A submucosal tumor-like lesion in the jejunum was discovered during an enteroscopy, and a biopsy revealed it to be an adenocarcinoma. Partial resection of the jejunum was performed to control hemorrhage. Histopathology revealed an invasive IPMC arising from a heterotopic pancreas (Heinrich type II) and chemotherapy with gemcitabine and nab-paclitaxel was initiated. There have only been three cases of invasive IPMC from a heterotopic pancreas reported, and this is the first one to include chemotherapeutic treatment of distant metastasis.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma Papilar , Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Papilar/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Jejuno/patologia , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia
6.
Nihon Shokakibyo Gakkai Zasshi ; 119(4): 342-350, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35400687

RESUMO

During a medical health check, a 29-year-old man was presented to our hospital with iron deficiency anemia. He had no significant medical history in his family. Despite being diagnosed with ocular sarcoidosis 5 years ago, he had no vision problems. Physical examination revealed normal vital signs and a nontender abdomen;however, his eyelid conjuvitis was pale, and he became aware of fatigue when moving vigorously. He had upper gastrointestinal endoscopy and colonoscopy, but there was no evidence of bleeding detected. A contrasted mass 30mm in size was discovered on abdominal contrast-enhanced computed tomography at the dorsal wall of the proximal jejunum. Positron emission tomography showed an accumulation image in the bilateral hilar lymph and upper jejunum. A 30-mm submucosal tumor with a central depression in the upper jejunum was discovered using a double-balloon enteroscopy. We performed biopsies from the depression margin and tattoo marking on the oral side of the tumor. Even though the biopsies specimen revealed granulation tissue, the patient was referred to surgery and underwent a partial jejunum resection because the tumor was diagnosed as the cause of anemia. The operation went smoothly, and the patient was discharged on the seventh postoperative day. Histological examination showed a proliferation of densely packed spindle cells with prominent nuclear palisading. The immunohistochemical examination revealed that c-kit and CD34 were highly expressed, whereas desmin and S-100 proteins were not. Ki-67 expression demonstrated a very low proliferative index (2%). We discovered gastrointestinal stromal tumors (GIST), as well as an ectopic pancreas. GIST is extremely rare in young people, and the coexistence of ectopic pancreas and sarcoidosis has never been reported.


Assuntos
Anemia , Tumores do Estroma Gastrointestinal , Sarcoidose , Adolescente , Adulto , Anemia/complicações , Anemia/patologia , Colonoscopia , Enteroscopia de Duplo Balão , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Jejuno/patologia , Masculino , Pâncreas , Sarcoidose/complicações
7.
Am Surg ; 88(7): 1541-1542, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35282706

RESUMO

Multiple gastrointestinal stromal tumors (GISTs) of the small intestine is an uncommon finding but can be a marker for underlying neurofibromatosis type 1 (NF1). We present the case of the 38-year-old male without prior NF1 diagnosis who presented with a small bowel obstruction. His physical exam was notable for cutaneous nodules and café-au-lait spots. He progressed to peritonitis and underwent an exploratory laparotomy, which revealed a 6-cm hemorrhagic mass along the antimesenteric border of the jejunum, causing obstruction and perforation. Pathology was consistent with GISTs. NF1-associated GISTs differ from wild-type GISTs in that they are unlikely to have C-KIT and PDGFRA mutations and therefore do not respond to imatinib. Treatment is largely limited to surgical resection; however, there is evidence that MEK inhibitors may prove an additional treatment strategy.


Assuntos
Tumores do Estroma Gastrointestinal , Obstrução Intestinal , Neurofibromatose 1 , Adulto , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Jejuno/patologia , Masculino , Mutação , Neurofibromatose 1/complicações , Proteínas Proto-Oncogênicas c-kit/genética
8.
Front Immunol ; 13: 835686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281029

RESUMO

Angiotensin converting enzyme-2 (ACE2) and associated proteins play a pivotal role in various physiological and pathological events, such as immune activation, inflammation, gut barrier maintenance, intestinal stem cell proliferation, and apoptosis. Although many of these clinical events are quite significant in SIV/HIV infection, expression profiling of these proteins has not been well reported. Considering the different pathological consequences in the gut after HIV infection, we hypothesized that the expression of ACE2 and associated proteins of the Renin-angiotensin system (RAS) could be compromised after SIV/HIV infection. We quantified the gene expression of ACE2 as well as AGTR1/2, ADAM17, and TMPRSS2, and compared between SIV infected and uninfected rhesus macaques (Macaca mulatta; hereafter abbreviated RMs). The gene expression analysis revealed significant downregulation of ACE2 and upregulation of AGTR2 and inflammatory cytokine IL-6 in the gut of infected RMs. Protein expression profiling also revealed significant upregulation of AGTR2 after infection. The expression of ACE2 in protein level was also decreased, but not significantly, after infection. To understand the entirety of the process in newly regenerated epithelial cells, a global transcriptomic study of enteroids raised from intestinal stem cells was performed. Interestingly, most of the genes associated with the RAS, such as DPP4, MME, ANPEP, ACE2, ENPEP, were found to be downregulated in SIV infection. HNFA1 was found to be a key regulator of ACE2 and related protein expression. Jejunum CD4+ T cell depletion and increased IL-6 mRNA, MCP-1 and AGTR2 expression may signal inflammation, monocyte/macrophage accumulation and epithelial apoptosis in accelerating SIV pathogenesis. Overall, the findings in the study suggested a possible impact of SIV/HIV infection on expression of ACE2 and RAS-associated proteins resulting in the loss of gut homeostasis. In the context of the current COVID-19 pandemic, the outcome of SARS-CoV-2 and HIV co-infection remains uncertain and needs further investigation as the significance profile of ACE2, a viral entry receptor for SARS-CoV-2, and its expression in mRNA and protein varied in the current study. There is a concern of aggravated SARS-CoV-2 outcomes due to possible serious pathological events in the gut resulting from compromised expression of RAS- associated proteins in SIV/HIV infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Linfócitos T CD4-Positivos/imunologia , Jejuno/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/metabolismo , Vírus da Imunodeficiência Símia/fisiologia , Animais , Células Cultivadas , Citocinas/metabolismo , Dipeptidil Peptidase 4/metabolismo , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação , Jejuno/patologia , Macaca mulatta , Receptor Tipo 2 de Angiotensina/metabolismo
9.
Nat Commun ; 13(1): 234, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017515

RESUMO

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.


Assuntos
Intestino Grosso/patologia , Intestino Delgado/patologia , Macaca mulatta/crescimento & desenvolvimento , Animais , Duodeno/patologia , Feminino , Trato Gastrointestinal , Expressão Gênica , Transtornos do Crescimento/patologia , Humanos , Íleo/patologia , Inflamação , Enteropatias , Mucosa Intestinal , Jejuno/patologia , Masculino , Desnutrição
10.
Gastroenterology ; 162(3): 877-889.e7, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861219

RESUMO

BACKGROUND & AIMS: Excessive shedding of apoptotic enterocytes into the intestinal lumen is observed in inflammatory bowel disease and is correlated with disease relapse. Based on their cytolytic capacity and surveillance behavior, we investigated whether intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IELs) are actively involved in the shedding of enterocytes into the lumen. METHODS: Intravital microscopy was performed on GFP γδ T cell reporter mice treated with intraperitoneal lipopolysaccharide (10 mg/kg) for 90 minutes to induce tumor necrosis factor-mediated apoptosis. Cell shedding in various knockout or transgenic mice in the presence or absence of blocking antibody was quantified by immunostaining for ZO-1 funnels and cleaved caspase-3 (CC3). Granzyme A and granzyme B release from ex vivo-stimulated γδ IELs was quantified by enzyme-linked immunosorbent assay. Immunostaining for γδ T cell receptor and CC3 was performed on duodenal and ileal biopsies from controls and patients with Crohn's disease. RESULTS: Intravital microscopy of lipopolysaccharide-treated mice revealed that γδ IELs make extended contact with shedding enterocytes. These prolonged interactions require CD103 engagement by E-cadherin, and CD103 knockout or blockade significantly reduced lipopolysaccharide-induced shedding. Furthermore, we found that granzymes A and B, but not perforin, are required for cell shedding. These extracellular granzymes are released by γδ IELs both constitutively and after CD103/E-cadherin ligation. Moreover, we found that the frequency of γδ IEL localization to CC3-positive enterocytes is increased in Crohn's disease biopsies compared with healthy controls. CONCLUSIONS: Our results uncover a previously unrecognized role for γδ IELs in facilitating tumor necrosis factor-mediated shedding of apoptotic enterocytes via CD103-mediated extracellular granzyme release.


Assuntos
Antígenos CD/metabolismo , Doença de Crohn/metabolismo , Enterócitos/fisiologia , Granzimas/metabolismo , Cadeias alfa de Integrinas/metabolismo , Linfócitos Intraepiteliais/fisiologia , Adolescente , Adulto , Animais , Antígenos CD/genética , Apoptose , Caderinas/metabolismo , Caspase 3/metabolismo , Doença de Crohn/patologia , Duodeno/patologia , Enterócitos/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Humanos , Íleo/patologia , Cadeias alfa de Integrinas/genética , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Linfócitos Intraepiteliais/enzimologia , Linfócitos Intraepiteliais/patologia , Microscopia Intravital , Jejuno/imunologia , Jejuno/patologia , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
11.
Clin J Gastroenterol ; 15(1): 107-111, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34792784

RESUMO

Clear cell sarcoma-like tumour of the gastrointestinal tract (CCSLGT) is a rare entity which has been recently described as late as 2003. Only around 70 cases have been reported in the English literature till date. CCSLGT is mostly seen in young adults in the late 20 s and early 30 s. CCSLGT are aggressive tumours. They are similar to the clear cell sarcoma of the soft tissue but lack melanocytic differentiation, retain neuroendocrine differentiation, and have osteoclastic giant cells. EWSR1-CREB1 fusion is characteristic of these tumours. Complete surgical excision is the best treatment option available. They have a high recurrence rate and poor prognosis. Currently, effective chemotherapy or a targeted agent is not available for the management of these tumours. Here, we describe a case of clear cell sarcoma-like tumour of jejunum encountered by us in a young man. The immunohistochemical and genetic profiling of these tumours are also discussed.


Assuntos
Neoplasias Gastrointestinais , Sarcoma de Células Claras , Neoplasias Gastrointestinais/patologia , Perfil Genético , Humanos , Intestino Delgado/patologia , Jejuno/patologia , Jejuno/cirurgia , Masculino , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/patologia
12.
Int J Surg Pathol ; 30(5): 539-542, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34955063

RESUMO

Solitary Peutz-Jeghers type polyps are characterized by a hamartomatous polyp of the gastrointestinal (GI) tract in a patient without mucocutaneous pigmentation, family history of Peutz-Jeghers syndrome, or STK11/LKB1 mutations. Histologically identical to the polyps in Peutz-Jeghers syndrome, these sporadic polyps can arise anywhere along the GI tract, with typical arborizing smooth muscles extending from the muscularis mucosa. While the lining mucosa is generally the same as the organ in which it arises, gastric pyloric and osseous metaplasia have been reported in intestinal polyps in Peutz-Jeghers syndrome. Herein, the authors report the first case of a small intestinal solitary Peutz-Jeghers type polyp with gastric antral and fundic gland lining mucosa. A 43-year-old male was admitted for small bowel obstruction. Diagnostic laparoscopy revealed jejuno-jejunal intussusception with an associated polyp measuring 7.2 cm. Histological examination showed a hamartomatous polyp with arborizing smooth muscle bundles extending from the muscularis mucosae. The polyp was lined by non-dysplastic gastric antral and fundic gland mucosa, and was sharply demarcated from the adjacent non-polypoid intestinal mucosa. Colonoscopy, esophagogastroduodenoscopy and small bowel enteroscopy revealed no additional polyps or masses. Thorough investigation of the patient's family history was negative for Peutz-Jeghers syndrome or mucocutaneous pigmentation. Molecular analysis of the lesion was negative for STK11/LKB1 mutations. A diagnosis of solitary Peutz-Jeghers type polyp of the small bowel with gastric antral and fundic gland mucosal lining was rendered.


Assuntos
Hamartoma , Síndrome de Peutz-Jeghers , Adulto , Mucosa Gástrica/patologia , Hamartoma/patologia , Humanos , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/patologia , Pólipos Intestinais/cirurgia , Jejuno/patologia , Masculino , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/genética
13.
PLoS Genet ; 17(12): e1009250, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34860830

RESUMO

Epigenetic mechanisms are gatekeepers for the gene expression patterns that establish and maintain cellular identity in mammalian development, stem cells and adult homeostasis. Amongst many epigenetic marks, methylation of histone 3 lysine 4 (H3K4) is one of the most widely conserved and occupies a central position in gene expression. Mixed lineage leukemia 1 (MLL1/KMT2A) is the founding mammalian H3K4 methyltransferase. It was discovered as the causative mutation in early onset leukemia and subsequently found to be required for the establishment of definitive hematopoiesis and the maintenance of adult hematopoietic stem cells. Despite wide expression, the roles of MLL1 in non-hematopoietic tissues remain largely unexplored. To bypass hematopoietic lethality, we used bone marrow transplantation and conditional mutagenesis to discover that the most overt phenotype in adult Mll1-mutant mice is intestinal failure. MLL1 is expressed in intestinal stem cells (ISCs) and transit amplifying (TA) cells but not in the villus. Loss of MLL1 is accompanied by loss of ISCs and a differentiation bias towards the secretory lineage with increased numbers and enlargement of goblet cells. Expression profiling of sorted ISCs revealed that MLL1 is required to promote expression of several definitive intestinal transcription factors including Pitx1, Pitx2, Foxa1, Gata4, Zfp503 and Onecut2, as well as the H3K27me3 binder, Bahcc1. These results were recapitulated using conditional mutagenesis in intestinal organoids. The stem cell niche in the crypt includes ISCs in close association with Paneth cells. Loss of MLL1 from ISCs promoted transcriptional changes in Paneth cells involving metabolic and stress responses. Here we add ISCs to the MLL1 repertoire and observe that all known functions of MLL1 relate to the properties of somatic stem cells, thereby highlighting the suggestion that MLL1 is a master somatic stem cell regulator.


Assuntos
Células-Tronco Adultas/fisiologia , Diferenciação Celular/genética , Histona-Lisina N-Metiltransferase/genética , Mucosa Intestinal/patologia , Proteína de Leucina Linfoide-Mieloide/genética , Animais , Transplante de Medula Óssea , Metilação de DNA , Modelos Animais de Doenças , Epigênese Genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Mucosa Intestinal/citologia , Jejuno/citologia , Jejuno/patologia , Camundongos , Camundongos Transgênicos , Mutagênese , Mutação , Proteína de Leucina Linfoide-Mieloide/metabolismo , Nicho de Células-Tronco
14.
Nutrients ; 13(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34836133

RESUMO

Bulbs from the Alliaceae family have been well-known and valued spices for thousands of years, not only for their unique flavor and aroma features, but also for their high nutritional and health-promoting values. Long-term or excessive consumption of these vegetables, especially raw garlic, can have side effects in the body (including in the digestive tract), causing a number of pathological changes in the intestinal wall; these changes lead, in turn, to its damage, dysfunction, and disorder development. Therefore, the aim of this study was to investigate the effect of the addition of freeze-dried vegetables from the Alliaceae family, i.e., garlic (Allium sativum L.), white onion, and red onion (Allium cepa L.) on the morphometric parameters (intestinal villi length, crypt depth, thickness of tunica mucosa, and the thickness of tunica muscle) of the jejunum of rats fed a semi-synthetic atherogenic diet (1% dietary cholesterol). In freeze-dried vegetables administered to rats, the contents of selected bioactive ingredients and their antioxidant potentials were determined. The effect of the onion vegetable supplements on growth parameters, serum lipid profile, plasma antioxidant potential, and the intestinal morphological parameters of rats loaded with cholesterol was determined. In an animal experiment, 30 male Wistar rats were divided into 5 diet groups, diet consumption and FER were studied. Supplementation of the atherogenic diet with vegetables improved the blood plasma lipid profiles and atherogenic indices, in a manner that was dependent on the type of supplementation used, with the best hypolipidemic and anti-atherosclerotic effects found in garlic use. The atherogenic diet, as well as the supplementation of this diet with the tested vegetables from the Alliaceae family, influenced the histological changes in the epithelium of the jejunum of rats. The damage to the intestinal mucosa was the greatest in animals fed an atherogenic diet supplemented with garlic. Bearing in mind that the desired beneficial therapeutic or prophylactic effects of onion vegetables (in particular garlic) in the course of various metabolic ailments (including atherosclerosis) are achieved during long-term supplementation, it is important to remember their possible cytotoxic effects (e.g., on the digestive tract) in order to achieve real benefits related to the supplementation with vegetables from the Alliaceae family.


Assuntos
Allium/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Alho/efeitos adversos , Mucosa Intestinal/patologia , Jejuno/patologia , Animais , Dieta Aterogênica/efeitos adversos , Masculino , Ratos , Ratos Wistar , Verduras/efeitos adversos
15.
Int J Mol Sci ; 22(21)2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34769369

RESUMO

Competition for the amino acid arginine by endothelial nitric-oxide synthase (NOS3) and (pro-)inflammatory NO-synthase (NOS2) during endotoxemia appears essential in the derangement of the microcirculatory flow. This study investigated the role of NOS2 and NOS3 combined with/without citrulline supplementation on the NO-production and microcirculation during endotoxemia. Wildtype (C57BL6/N background; control; n = 36), Nos2-deficient, (n = 40), Nos3-deficient (n = 39) and Nos2/Nos3-deficient mice (n = 42) received a continuous intravenous LPS infusion alone (200 µg total, 18 h) or combined with L-citrulline (37.5 mg, last 6 h). The intestinal microcirculatory flow was measured by side-stream dark field (SDF)-imaging. The jejunal intracellular NO production was quantified by in vivo NO-spin trapping combined with electron spin-resonance (ESR) spectrometry. Amino-acid concentrations were measured by high-performance liquid chromatography (HPLC). LPS infusion decreased plasma arginine concentration in control and Nos3-/- compared to Nos2-/- mice. Jejunal NO production and the microcirculation were significantly decreased in control and Nos2-/- mice after LPS infusion. No beneficial effects of L-citrulline supplementation on microcirculatory flow were found in Nos3-/- or Nos2-/-/Nos3-/- mice. This study confirms that L-citrulline supplementation enhances de novo arginine synthesis and NO production in mice during endotoxemia with a functional NOS3-enzyme (control and Nos2-/- mice), as this beneficial effect was absent in Nos3-/- or Nos2-/-/Nos3-/- mice.


Assuntos
Arginina/metabolismo , Citrulina/administração & dosagem , Endotoxemia/patologia , Microcirculação , NADPH Oxidase 2/fisiologia , NADPH Oxidases/fisiologia , Óxido Nítrico/metabolismo , Animais , Endotoxemia/tratamento farmacológico , Endotoxemia/etiologia , Intestinos/efeitos dos fármacos , Intestinos/metabolismo , Intestinos/patologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Mediators Inflamm ; 2021: 2752265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34602857

RESUMO

METHODS: The mice were randomly distributed into four groups: (a) control (CTRL) group, (b) ETEC group, (c) IQW-ETEC group, and (d) IRW-ETEC group. Villus length and crypt depth were measured after hematoxylin and eosin staining. The inflammatory reaction was analyzed via inflammatory cytokines (i.e., TNF-α, IL-1ß, IL-6, and IL-10) using the enzyme-linked immunosorbent assay (ELISA). The microbiota in the colon was sequenced using 16S ribosomal RNA. RESULTS: The villus length decreased, the crypt depth decreased, and the expression of inflammatory cytokines (i.e., TNF-α, IL-1ß, IL-6, and IL-10) increased due to ETEC. In the IRW-ETEC and IQW-ETEC groups, the Shannon index decreased (P < 0.05). IQW and IRW increased the abundance of Firmicutes, Proteobacteria, Clostridiales, Lachnospiraceae, and Alloprevotella; contrastingly, it decreased the abundance of Epsilonproteobacteria, Erysipelotrichales, Prevotellaceae, and Flavobacteriaceae compared to the ETEC group (P <0.05). CONCLUSION: This study ascertained that the addition of IQW and IRW could alleviate jejunal inflammation and increase microbiota community diversity.


Assuntos
Diarreia/microbiologia , Escherichia coli Enterotoxigênica/patogenicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/tratamento farmacológico , Oligopeptídeos/farmacologia , Animais , Colo/microbiologia , Citocinas/análise , Microbioma Gastrointestinal/fisiologia , Jejuno/patologia , Masculino , Camundongos
17.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639101

RESUMO

A well-functional intestinal mucosal barrier can be compromised as a result of various diseases, chemotherapy, radiation, and chemical exposures including surfactants. Currently, there are no approved drugs targeting a dysfunctional intestinal barrier, which emphasizes a significant medical need. One candidate drug reported to regulate intestinal mucosal permeability is melatonin. However, it is still unclear if its effect is primarily receptor mediated or antioxidative, and if it is associated with enteric neural pathways. The aim of this rat intestinal perfusion study was to investigate the mechanisms of melatonin and nicotinic acetylcholine receptors on the increase in intestinal mucosal clearance of 51Cr-labeled ethylenediaminetetraacetate induced by 15 min luminal exposure to the anionic surfactant, sodium dodecyl sulfate. Our results show that melatonin abolished the surfactant-induced increase in intestinal permeability and that this effect was inhibited by luzindole, a melatonin receptor antagonist. In addition, mecamylamine, an antagonist of nicotinic acetylcholine receptors, reduced the surfactant-induced increase in mucosal permeability, using a signaling pathway not influenced by melatonin receptor activation. In conclusion, our results support melatonin as a potentially potent candidate for the oral treatment of a compromised intestinal mucosal barrier, and that its protective effect is primarily receptor-mediated.


Assuntos
Permeabilidade da Membrana Celular , Mucosa Intestinal/efeitos dos fármacos , Doenças do Jejuno/prevenção & controle , Jejuno/efeitos dos fármacos , Melatonina/farmacologia , Receptores de Melatonina/metabolismo , Tensoativos/toxicidade , Animais , Antioxidantes/farmacologia , Motilidade Gastrointestinal , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Doenças do Jejuno/induzido quimicamente , Doenças do Jejuno/metabolismo , Doenças do Jejuno/patologia , Jejuno/metabolismo , Jejuno/patologia , Masculino , Ratos , Ratos Wistar , Receptores de Melatonina/genética , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo
18.
Oxid Med Cell Longev ; 2021: 6867962, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594475

RESUMO

The purpose of this research is to explore the positive effects of Lactobacillus plantarum and Lactobacillus brevis on the tissue damage and microbial community in mice challenged by Enterotoxigenic Escherichia coli (ETEC). Twenty-four mice were divided into four groups randomly: the CON group, ETEC group, LP-ETEC group and LB-ETEC group. Our results demonstrated that, compared with the ETEC group, the LP-ETEC and LB-ETEC groups experienced less weight loss and morphological damage of the jejunum. We measured proinflammatory factors of colonic tissue and found that L. plantarum and L. brevis inhibited the expression of proinflammatory factors such as IL-ß, TNF-α, and IL-6 and promoted that of the tight junction protein such as claudin-1, occludin, and ZO-1. Additionally, L. plantarum and L. brevis altered the impact of ETEC on the intestinal microbial community of mice, significantly increased the abundance of probiotics such as Lactobacillus, and reduced that of pathogenic bacteria such as Proteobacteria, Clostridia, Epsilonproteobacteria, and Helicobacter. Therefore, we believe that L. plantarum and L. brevis can stabilize the intestinal microbiota and inhibit the growth of pathogenic bacteria, thus protecting mice from the gut inflammation induced by ETEC.


Assuntos
Infecções por Escherichia coli/terapia , Jejuno/patologia , Lactobacillus brevis/fisiologia , Lactobacillus plantarum/fisiologia , Probióticos/uso terapêutico , Animais , Claudina-1/genética , Claudina-1/metabolismo , Modelos Animais de Doenças , Escherichia coli Enterotoxigênica/patogenicidade , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Microbioma Gastrointestinal , Interleucina-1beta/metabolismo , Jejuno/metabolismo , Jejuno/microbiologia , Camundongos , Camundongos Endogâmicos ICR , Fator de Necrose Tumoral alfa/metabolismo
19.
Physiol Rep ; 9(15): e14960, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34337895

RESUMO

Ionizing radiation causes dramatic change in the transport and barrier functions of the intestine. The degree of radiation damage rate depends primarily on the absorbed dose and post-irradiation time. Variety of experimental protocols providing different time points and doses exist, with the lack of a common approach. In this study, to develop a unified convenient experimental scheme, dose and time dependence of barrier and transport properties of rat jejunum following ionizing radiation exposure were examined. Male Wistar rats were exposed to total body X-ray irradiation (2, 5, or 10 Gy). The control group was subjected to sham irradiation procedure. Samples of rat jejunum were obtained at 24, 48, or 72 h post-irradiation. Transepithelial resistance, short circuit current (Isc ), and paracellular permeability for sodium fluorescein of jejunum samples were measured in an Ussing chamber; a histological examination was also performed. These parameters were significantly disturbed only 72 h after irradiation at a dose of 10 Gy, which was accompanied by loss of crypt and villi, inflammatory infiltrations, and disintegration of enterocytes. This suggests that found experimental point (72 h after 10 Gy exposure) is the most appropriate for future study using rat jejunum as a model.


Assuntos
Fluoresceína/metabolismo , Mucosa Intestinal/patologia , Jejuno/patologia , Raios X/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Jejuno/metabolismo , Jejuno/efeitos da radiação , Masculino , Permeabilidade , Ratos , Ratos Wistar , Fatores de Tempo
20.
Eur J Pharmacol ; 909: 174408, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364877

RESUMO

The cellular and tissue damage induced by oxidative stress (OS) contribute to a variety of human diseases, which include gastrointestinal diseases. Salvianolic acid B (Sal B), which is a natural polyphenolic acid in Salvia miltiorrhiza, exhibits prominent antioxidant properties. However, its precise function and molecular mechanisms in protecting normal intestine epithelium from OS-induced damage are still poorly defined. In this study, we tried to clarify this relationship. Here, we found Sal B addiction in the rat intestinal epithelial cell, IEC-6, prevented H2O2-induced cell viability decrease and apoptosis induction, ameliorated H2O2-induced intestinal epithelial barrier dysfunction and mitochondrial dysfunction, and suppressed H2O2-induced production of ROS to varying degrees, ranging from 10% to 30%. Moreover, by employing an ischemia reperfusion model of rats, we also discovered that Sal B treatment reversed ischemia and a reperfusion-caused decrease in villus height and crypt depth, decreased proliferation of enterocytes, and increased the apoptotic index in the jejunum and ileum. Mechanistically, Sal B treatment up-regulated the phosphorylated level of Akt and GSK3ß in enterocytes in vitro and in vivo, and PI3K inhibitor LY294002 treatment abrogated the protective effects of Sal B. Meanwhile, the inactivation of GSK3ß reversed the oxidative stress-induced apoptosis and mitochondrial dysfunction in IEC-6 cells. Together, our results demonstrated that the damage of intestinal epithelial cells in in vitro and in vivo models were both attenuated by Sal B treatment, and such antioxidant activity might very possibly be attributed to the activation of Akt/GSK3ß signaling.


Assuntos
Antioxidantes/farmacologia , Benzofuranos/farmacologia , Enteropatias/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Benzofuranos/uso terapêutico , Linhagem Celular , Modelos Animais de Doenças , Enterócitos/efeitos dos fármacos , Enterócitos/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Íleo/citologia , Íleo/efeitos dos fármacos , Íleo/patologia , Enteropatias/patologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Jejuno/citologia , Jejuno/efeitos dos fármacos , Jejuno/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos
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