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2.
Nature ; 585(7823): 102-106, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32848245

RESUMO

Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis1. Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)2,3, as well as human studies4-6, have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4+ T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain of Lactobacillus reuteri that possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.


Assuntos
Encefalomielite Autoimune Experimental/microbiologia , Microbioma Gastrointestinal/imunologia , Inflamação/patologia , Medula Espinal/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Animais , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/prevenção & controle , Feminino , Vida Livre de Germes , Inflamação/imunologia , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , Intestino Delgado/patologia , Lactobacillus reuteri/química , Lactobacillus reuteri/imunologia , Lactobacillus reuteri/patogenicidade , Masculino , Camundongos , Esclerose Múltipla/imunologia , Esclerose Múltipla/microbiologia , Esclerose Múltipla/patologia , Glicoproteína Mielina-Oligodendrócito/química , Glicoproteína Mielina-Oligodendrócito/imunologia , Medula Espinal/imunologia , Células Th17/imunologia , Células Th17/patologia
3.
PLoS One ; 15(8): e0237101, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817686

RESUMO

Mutations in the genes encoding for voltage-gated sodium channels cause profound sensory disturbances and other symptoms dependent on the distribution of a particular channel subtype in different organs. Humans with the gain-of-function mutation p.Leu811Pro in SCN11A (encoding for the voltage-gated Nav1.9 channel) exhibit congenital insensitivity to pain, pruritus, self-inflicted injuries, slow healing wounds, muscle weakness, Charcot-like arthropathies, and intestinal dysmotility. As already shown, knock-in mice (Scn11a+/L799P) carrying the orthologous mutation p.Leu799Pro replicate reduced pain sensitivity and show frequent tissue lesions. In the present study we explored whether Scn11a+/L799P mice develop also pruritus, muscle weakness, and changes in gastrointestinal transit time. Furthermore, we analyzed morphological and functional differences in nerves, skeletal muscle, joints and small intestine from Scn11a+/L799P and Scn11a+/+ wild type mice. Compared to Scn11a+/+ mice, Scn11a+/L799P mice showed enhanced scratching bouts before skin lesions developed, indicating pruritus. Scn11a+/L799P mice exhibited reduced grip strength, but no disturbances in motor coordination. Skeletal muscle fiber types and joint architecture were unaltered in Scn11a+/L799P mice. Their gastrointestinal transit time was unaltered. The small intestine from Scn11a+/L799P showed a small shift towards less frequent peristaltic movements. Similar proportions of lumbar dorsal root ganglion neurons from Scn11a+/L799P and Scn11a+/+ mice were calcitonin gene-related peptide (CGRP-) positive, but isolated sciatic nerves from Scn11a+/L799P mice exhibited a significant reduction of the capsaicin-evoked release of CGRP indicating reduced neurogenic inflammation. These data indicate important Nav1.9 channel functions in several organs in both humans and mice. They support the pathophysiological relevance of increased basal activity of Nav1.9 channels for sensory abnormalities (pain and itch) and suggest resulting malfunctions of the motor system and of the gastrointestinal tract. Scn11a+/L799P mice are suitable to investigate the role of Nav1.9, and to explore the pathophysiological changes and mechanisms which develop as a consequence of Nav1.9 hyperactivity.


Assuntos
Mutação com Ganho de Função , Debilidade Muscular/genética , Canal de Sódio Disparado por Voltagem NAV1.9/genética , Prurido/genética , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Feminino , Trânsito Gastrointestinal , Força da Mão , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Movimento , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Canal de Sódio Disparado por Voltagem NAV1.9/metabolismo , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
4.
Front Immunol ; 11: 1311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32676080

RESUMO

Chimeric antigen receptor T cell (CART) therapy, administration of certain T cell-agonistic antibodies, immune check point inhibitors, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) and Toxic shock syndrome (TSS) caused by streptococcal as well as staphylococcal superantigens share one common complication, that is T cell-driven cytokine release syndrome (CRS) accompanied by multiple organ dysfunction (MOD). It is not understood whether the failure of a particular organ contributes more significantly to the severity of CRS. Also not known is whether a specific cytokine or signaling pathway plays a more pathogenic role in precipitating MOD compared to others. As a result, there is no specific treatment available to date for CRS, and it is managed only symptomatically to support the deteriorating organ functions and maintain the blood pressure. Therefore, we used the superantigen-induced CRS model in HLA-DR3 transgenic mice, that closely mimics human CRS, to delineate the immunopathogenesis of CRS as well as to validate a novel treatment for CRS. Using this model, we demonstrate that (i) CRS is characterized by a rapid rise in systemic levels of several Th1/Th2/Th17/Th22 type cytokines within a few hours, followed by a quick decline. (ii) Even though multiple organs are affected, small intestinal immunopathology is the major contributor to mortality in CRS. (iii) IFN-γ deficiency significantly protected from lethal CRS by attenuating small bowel pathology, whereas IL-17A deficiency significantly increased mortality by augmenting small bowel pathology. (iv) RNA sequencing of small intestinal tissues indicated that IFN-γ-STAT1-driven inflammatory pathways combined with enhanced expression of pro-apoptotic molecules as well as extracellular matrix degradation contributed to small bowel pathology in CRS. These pathways were further enhanced by IL-17A deficiency and significantly down-regulated in mice lacking IFN-γ. (v) Ruxolitinib, a selective JAK-1/2 inhibitor, attenuated SAg-induced T cell activation, cytokine production, and small bowel pathology, thereby completely protecting from lethal CRS in both WT and IL-17A deficient HLA-DR3 mice. Overall, IFN-γ-JAK-STAT-driven pathways contribute to lethal small intestinal immunopathology in T cell-driven CRS.


Assuntos
Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Interferon gama/genética , Interleucina-17/genética , Inibidores de Janus Quinases/uso terapêutico , Pneumonia Viral/patologia , Pirazóis/uso terapêutico , Animais , Células Cultivadas , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Citocinas/imunologia , Antígeno HLA-DR3/genética , Intestino Delgado/imunologia , Intestino Delgado/patologia , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Knockout , Pandemias , Pneumonia Viral/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/imunologia
5.
Nat Commun ; 11(1): 2759, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32488028

RESUMO

Human noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.


Assuntos
Células Enteroendócrinas/imunologia , Células Epiteliais/imunologia , Norovirus/fisiologia , Doença Aguda , District of Columbia , Células Enteroendócrinas/metabolismo , Gastroenterite/virologia , Genótipo , Humanos , Intestino Delgado/patologia , Intestino Delgado/virologia , Norovirus/genética , RNA Viral , Replicação Viral
6.
Am J Surg Pathol ; 44(8): 1130-1136, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32590456

RESUMO

The absence of neuroendocrine (NE) cells in the intestinal mucosa in autoimmune enteropathy (AIE) has been occasionally reported. However, the status of NE cells has not been studied in detail in AIE. Small bowel and colonic biopsies were retrospectively retrieved from 18 AIE patients (26 baseline [18 small bowel and 8 colon]; and 15 follow-up [11 duodenum and 4 colon] biopsies in 11 patients). Thirty-three common variable immunodeficiency (CVID) patients (30 small bowel and 16 colon), 15 inflammatory bowel disease patients (5 duodenum and 10 colon), 13 immunoglobulinA deficiency patients (13 duodenum and 5 colon), and 10 normal controls (5 colon and 5 duodenum) were selected as control groups. Histologic features (villous atrophy, intraepithelial lymphocytosis, acute inflammation, crypt apoptosis, and absence or presence of goblet cells, Paneth cells and plasma cells) were recorded. Chromogranin immunostain was performed and chromogranin-positive NE cells were counted per 10 consecutive, well-oriented crypts. On the basis of the number of chromogranin-positive NE cells, cases were graded as being absent (≤3 NE cells), markedly decreased (≤15), and intact (>15). The NE cell status correlated with histologic features. The median age of 18 AIE patients was 38.5 years (range: 11 to 74 y) and 14 patients were male. Fourteen of 18 (78%) patients showed loss (absent or markedly decreased) of NE cells in the small bowel and/or colon in the baseline biopsies including 12 (of 18) small bowel and 6 (of 8) colon biopsies. Follow-up biopsy was available in 11 patients. Six of 7 (85%) patients who showed loss of NE cells in the baseline biopsies regained NE cells in the follow-up biopsies, and 1 patient continued to show loss of NE cells. Four patients who showed intact NE cells in the baseline remained unchanged in the follow-up. Among the control groups, 3 of 33 (9%) CVID patients showed loss of NE cells. NE cells were not lost in the biopsies of all 15 and 13 patients with inflammatory bowel disease and immunoglobulinA deficiency, respectively, or the 10 normal controls. In all 41 biopsies (26 baseline plus 15 follow-up) with AIE, NE cell loss was significantly associated with increased crypt apoptosis and loss of goblet cells (P=0.001, both) but not with other histologic findings. In conclusion, our study suggests that NE cells may also be the target cells in AIE and commonly lost in the intestinal crypts in AIE, and consequently loss of NE cells can be used as an adjunct histologic feature for diagnosis of AIE.


Assuntos
Colo/patologia , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Células Neuroendócrinas/patologia , Poliendocrinopatias Autoimunes/patologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biópsia , Criança , Cromograninas/análise , Colo/química , Colo/imunologia , Bases de Dados Factuais , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/química , Mucosa Intestinal/imunologia , Intestino Delgado/química , Intestino Delgado/imunologia , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/química , Células Neuroendócrinas/imunologia , Poliendocrinopatias Autoimunes/imunologia , Poliendocrinopatias Autoimunes/metabolismo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
Ann R Coll Surg Engl ; 102(8): 571-576, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32538120

RESUMO

INTRODUCTION: Intertwining of bowel loops to form a knot is very rare cause of intestinal obstruction. Among intestinal knots, ileoileal knotting is the most rare, with only a handful of cases reported in literature. We present a rare case of ileoileal knotting and review of small bowel knots. The aim of this review was to summarise the existing evidence on small bowel knots and to postulate the possible mechanisms for knotting. METHODS: A systematic search was conducted for literature published up to December 2019 using MEDLINE, PubMed and Google Scholar databases, together with the references of the full-text articles retrieved. Papers with case reports of small bowel knots were considered to be eligible for inclusion in the review. FINDINGS: A total of 14 case reports were evaluated. There was no clear predilection for age or sex. Mostly cases were from Asia and Africa with no cases from the West. The presenting complaints were abdominal pain (93%), vomiting (64%), abdominal distention (57 %) and obstipation (43%). The bowel was gangrenous in 78% of cases. All underwent exploration, with the majority requiring resection and anastomosis of the involved segment. CONCLUSION: Ileoileal knotting is a very rare cause of intestinal obstruction. Possible mechanisms include loaded bowel with longer mesentery, vigorous peristalsis, single bulky meal, pregnancy and intussusception. The condition is extremely difficult to diagnose preoperatively and it is usually diagnosed intraoperatively. The standard of treatment is resection of gangrenous part and anastomosis.


Assuntos
Obstrução Intestinal , Intestino Delgado , Dor Abdominal , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gangrena , Humanos , Lactente , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/patologia , Obstrução Intestinal/fisiopatologia , Obstrução Intestinal/cirurgia , Volvo Intestinal , Intestino Delgado/patologia , Intestino Delgado/fisiopatologia , Intestino Delgado/cirurgia , Intussuscepção , Masculino , Pessoa de Meia-Idade , Vômito , Adulto Jovem
8.
Int J Exp Pathol ; 101(3-4): 80-86, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32567731

RESUMO

ApcMin/+ mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expression in intestinal adenomas and determine whether TNS4 is upregulated by Wnt signalling. ApcMin/+ mice (n = 11) were sacrificed at approximately 120 days old at the onset of anaemia signs. Small intestines were harvested, and Swiss roll preparations were tested for TNS4 expression by immunohistochemistry (IHC). Individual polyps were also separately collected (n = 14) and tested for TNS4 mRNA expression and Kras mutation. The relationship between Wnt signalling and TNS4 expression was tested by Western blotting in the human CRC cell line HCT116 after inhibition of ß-catenin activity with MSAB or its increase by transfection with a Flag ß-catenin expression vector. Overall, 135/148 (91.2%) of the total intestinal polyps were positive for TNS4 expression by IHC, whilst adjacent normal areas were negative. RT-qPCR analysis showed approximately 5-fold upregulation of TNS4 mRNA in the polyps compared to adjacent normal tissue and no Kras mutations were detected. In HCT116, ß-catenin inhibition resulted in reduced TNS4 expression, and conversely, ß-catenin overexpression resulted in increased TNS4 expression. In conclusion, this is the first report linking aberrant Wnt signalling to upregulation of TNS4 both during initiation of intestinal adenomas in mice and in in vitro models. The exact contribution of TNS4 to adenoma development remains to be investigated, but the ApcMin/+ mouse represents a good model to study this.


Assuntos
Pólipos Adenomatosos/metabolismo , Genes APC , Neoplasias Intestinais/metabolismo , Intestino Delgado/metabolismo , Tensinas/metabolismo , Via de Sinalização Wnt , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/patologia , Animais , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Tensinas/genética , Regulação para Cima , beta Catenina/metabolismo
9.
Clin Imaging ; 67: 74-85, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32526662

RESUMO

Computerized tomography (CT) and magnetic resonance imaging (MRI), particularly MR Enterography, are the standard cross-sectional imaging modalities used to study small bowel involvement in a context of multiorgan disease. Clinical symptoms are generally nonspecific in such cases. Moreover, imaging findings of the different conditions often overlap. However, analysis of the location, distribution of the lesions on the small bowel wall, as well as of the rest of the bowel and of distant organs, may help narrow the spectrum of diagnoses of multiorgan conditions involving both the small bowel and other organs. The purpose of this presentation is to review and illustrate the CT and MRI features of small bowel involvement in systemic disease. Based on the underlying mechanism, we will categorize them as follows: congenital/hereditary, immunologic, infiltrative, vascular, infectious and miscellaneous.


Assuntos
Intestino Delgado/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Intestino Delgado/patologia , Intestinos/patologia
11.
Surg Clin North Am ; 100(3): 635-648, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32402306
12.
Medicine (Baltimore) ; 99(20): e20288, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443374

RESUMO

BACKGROUND: As one of the complications after abdominal operation, early postoperative inflammatory small bowel obstruction (EPISBO) is a great trouble for many patients. The use of somatostatin in treating this disease had been widely reported, but its efficacy and safety were controversial. Therefore, the present research carried out a systematic review of the clinical efficacy and safety of somatostatin in treating EPISBO. METHODS: Computer retrieval was conducted in foreign databases (including PubMed, The Cochrane Library, and Embase) and Chinese database (including Sino Med, CNKI, VIP, and WangFang Data), supplementary search for the literatures included was performed, and manual retrieval was performed in abstracts, books, and non-electronic magazines related to the present research to ensure the recall rate. Among all republished relevant experimental studies in Chinese and English from January 1, 1996 to February 1, 2020, randomized controlled trials on the curative efficacy of somatostatin for EPISBO were collected. The evaluation measures included patients' total effective rate, peristaltic sound recovery time, time of disappearance of abdominal pain, time of first defecation after operation, drainage of gastrointestinal decompression and length of stay after treatment. The literatures were selected by two investigators independently to extract data according to the inclusion and exclusion criteria, Bias Risk Assessment Tool recommended by Cochrane Review Hand book 5.2 was used to assess literature quality, and meta-analysis was carried out by using soft Stata 12.0. RESULTS: This study will scientifically and effectively analyze the clinical efficacy and safety of somatostatin in the treatment of EPISBO through systematic review and meta-analysis. ETHICS AND DISSEMINATION: The results of this study will be published in a peer-reviewed SCI journal to provide evidence-based medical evidence for the clinical treatment of early postoperative inflammatory bowel obstruction. PROTOCOL AND REGISTRATION: Open Science Framework (https://osf.io, OSF), registration number: ryd2g.


Assuntos
Inflamação/tratamento farmacológico , Obstrução Intestinal/tratamento farmacológico , Intestino Delgado/patologia , Complicações Pós-Operatórias/tratamento farmacológico , Somatostatina/uso terapêutico , Dor Abdominal/epidemiologia , Defecação , Humanos , Inflamação/epidemiologia , Obstrução Intestinal/epidemiologia , Tempo de Internação , Peristaltismo/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores de Tempo
13.
PLoS One ; 15(5): e0233208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428030

RESUMO

To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer.


Assuntos
Adenocarcinoma/enzimologia , Neoplasias do Colo/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Intestino Delgado/enzimologia , NADPH Oxidase 1/biossíntese , Proteínas de Neoplasias/biossíntese , Adenocarcinoma/genética , Adenocarcinoma/patologia , Células CACO-2 , Neoplasias do Colo/genética , Células HT29 , Humanos , Intestino Delgado/patologia , Modelos Biológicos , NADPH Oxidase 1/genética , Proteínas de Neoplasias/genética
14.
Int J Clin Oncol ; 25(8): 1441-1449, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32448950

RESUMO

BACKGROUND: There is no standard chemotherapy available for unresectable or metastatic small bowel adenocarcinoma (SBA) because of its rarity. This systematic review aims to assess the efficacy and safety of chemotherapy for patients with unresectable or metastatic SBA. METHODS: In accordance with the PRISMA statements, literature search was conducted using PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. The included studies were prospective randomized, nonrandomized, or observational studies. Risk of bias was assessed the ROBINS-I tool. RESULTS: Seven prospective single-arm Phase II studies were included in this review. Six of them were assessed as having a moderate risk of bias and one as having a serious risk of bias. A meta-analysis was not performed, because the studies were single-arm. Systemic chemotherapy based on fluoropyrimidine regimens achieved favorable outcomes with acceptable adverse effects as a first therapy; however, the regimens differed in each study. The object response rate was 18-50%, and the disease control rate was 29-87%. With 5-fluorouracil, adriamycin, and mitomycin-C regimen, one treatment-related death occurred. A second line of therapy including chemotherapy with nab-paclitaxel also showed favorable efficacy. The object response rate was 20%, and the disease control rate was 50%. CONCLUSIONS: Systemic chemotherapy based on fluoropyrimidine regimens was mainly used for unresectable or metastatic SBA. While it may achieve favorable outcomes with acceptable adverse effects, further evidence is needed.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Intestinais/tratamento farmacológico , Intestino Delgado/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Albuminas/administração & dosagem , Doxorrubicina/administração & dosagem , Fluoruracila/administração & dosagem , Humanos , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Intestino Delgado/efeitos dos fármacos , Paclitaxel/administração & dosagem , Estudos Prospectivos , Resultado do Tratamento
16.
Pol J Pathol ; 71(1): 30-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32429652

RESUMO

Most neuroendocrine neoplasms (NEN) are characterized by the presence of somatostatin receptors (SSTR) which we use in location diagnostics and treatment. The aim of this study was to evaluate the expression of somatostatin receptors by immunohistochemistry in tissue obtained after surgery of the primary focus in the small intestine. The group of patients consisted of 41 people, in 18 cases the primary tumor was in the jejunum and in 23 in the ileum. The immunohistochemical method was used to visualize the receptors, using polyclonal antibodies in a two-stage peroxidase method. In patients with NEN of the small intestine, the SSTR2a and SSTR5 receptors are most commonly expressed, followed by SSTR2b and 3. In statistical analysis, it was shown that the expression of somatostatin receptors was not dependent on the primary site of the tumor (p > 0.05). The dependence of SSTR expression on histological maturity is evident. SSTR1, SSTR2b, SSTR3 and SSTR5 are more common in tumors with grading G1 (p < 0.05). In the study group, the exception was SSTR2a, whose incidence was comparable in both groups (p = 0.35). In NEN of the small intestine, the expression SSTR2a and SSTR5 is the most common.


Assuntos
Neoplasias Intestinais/diagnóstico , Intestino Delgado/patologia , Tumores Neuroendócrinos/diagnóstico , Receptores de Somatostatina/genética , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/genética , Tumores Neuroendócrinos/genética
17.
BMC Surg ; 20(1): 111, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448270

RESUMO

BACKGROUND: Laparoscopy induces adhesion due to ischemia-reperfusion injury. However, the detail pathomechanism is poorly understood. This study aimed to investigate the impact of laparoscopy on mast cell and mesothelium morphological changes in the rat. METHODS: Forty-nine males of Sprague-Dawley Rattus norvegicus were divided into four groups: a) control and b) intervention groups P1, P2, and P3 that underwent 60 min laparoscopic using carbon dioxide (CO2) insufflation at 8, 10, and 12 mmHg groups, respectively. Serum hydrogen peroxide (H2O2), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress index (OSI) levels were determined 24 h after laparoscopy. Histopathological analyses of mast cell infiltration and degranulation and mesothelium thickness in the liver, greater omentum, mesenterium, small intestine, and peritoneum were performed 7 days after the procedure. RESULTS: H2O2, MDA, and OSI levels were significantly increased in the intervention groups compared with the control (p<0.05), while the SOD and CAT levels were decreased in the intervention groups compared with the control (p<0.05). Mast cell infiltration and degranulation were higher in the intervention groups than in control (p<0.05), while the mesothelium thickness was significantly lower in the laparoscopic groups than in control (p<0.05). Interestingly, the decrease in mesothelium thickness was strongly associated with the increase in mast cell infiltration and degranulation (p<0.01). CONCLUSIONS: Our study shows that laparoscopy in rats increases mast cell infiltration and degranulation, which also results in and correlates with a decrease in mesothelial thickness.


Assuntos
Degranulação Celular/fisiologia , Laparoscopia/efeitos adversos , Mastócitos/patologia , Traumatismo por Reperfusão/etiologia , Animais , Epitélio/patologia , Peróxido de Hidrogênio/sangue , Intestino Delgado/patologia , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
18.
BMC Surg ; 20(1): 113, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450834

RESUMO

BACKGROUND: Ewing's sarcoma usually presents in paediatric patients with its primary location being bone tissue. Nevertheless, we present such an adult case which arises from the small intestine. We registered thirty one cases of such origin published so far excluding ours. CASE PRESENTATION: We report a case of 30 year old female who was admitted due to the persistent anaemia. Whole body computed tomography scan revealed abdominal mass in her left upper abdominal compartment. Surgery on the mass originating from jejunum was performed, although due to extremely complicated postoperative period and rapid dissemination no additional therapy had been performed. The tumour was positive for CD99, ERG, CD56, Synaptophysin, PanCK, Cam5.2. CONCLUSION: Extraosseus Ewing's sarcoma is extremely rare entity, with poor prognosis.


Assuntos
Intestino Delgado/patologia , Sarcoma de Ewing/diagnóstico , Antígeno 12E7/metabolismo , Adulto , Feminino , Humanos , Tomografia Computadorizada por Raios X
19.
Khirurgiia (Mosk) ; (3): 85-88, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32271743

RESUMO

A case of two-stage minimally invasive surgical treatment of an elderly patient with bilateral inguinal hernia is presented: a recurrent oblique on the left, combined (femoral, obturator, oblique and direct inguinal) on the right with incarceration and necrosis of the small intestine in the femoral canal. Previously, the patient underwent closure of perforated ulcer of duodenum from upper-midline laparotomy, epicystostomy, transvesical adenomectomy from the lower-midline laparotomy. The first stage we performed diagnostic laparoscopy, minilaparotomy, reduction and resection of necrotic small intestine loop. The second stage was carried endovideoscopic total extraperitoneal allohernioplasty by the method of Extended-View Totally Extraperitoneal (e-TEP) on two sides. The positive results of the treatment indicate a high efficiency of video endoscopic alloplasty of occult hernias in a complex case. To diagnose and perform adequate surgical intervention with a combined femoral hernia, when the obturator and inguinal hernias are formed, but clinically do not manifest themselves, it is possible only with endoscopic examination of potential sites of hernia formation in the inguinal region, which is not possible with open plastic hernia of the inguinal region.


Assuntos
Hérnia Femoral/cirurgia , Hérnia Inguinal/cirurgia , Hérnia do Obturador/cirurgia , Herniorrafia/métodos , Intestino Delgado/cirurgia , Necrose/cirurgia , Idoso , Endoscopia , Hérnia Femoral/complicações , Hérnia Inguinal/complicações , Hérnia do Obturador/complicações , Humanos , Intestino Delgado/irrigação sanguínea , Intestino Delgado/patologia , Laparoscopia , Necrose/etiologia
20.
Mutat Res ; 850-851: 503136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247553

RESUMO

Tumorigenesis induced by oxidative stress is thought to be initiated by mutagenesis, but via an indirect mechanism. The dose-response curves for agents that act by this route usually show a threshold, for unknown reasons. To gain insight into these phenomena, we have analyzed the dose response for mutagenesis induced by the oral administration of potassium bromate, a typical oxidative-stress-generating agent, to gpt delta mice. The agent was given orally for 90 d to either Nrf2+ or Nrf2-knockout (KO) mice and mutants induced in the small intestine were analyzed. In Nrf2+mice, the mutant frequency was significantly greater than in the vehicle controls at a dose of 0.6 g/L but not at 0.2 g/L, indicating that a practical threshold for mutagenesis lies between these doses. At 0.6 g/L, the frequencies of G-to-T transversions (landmark mutations for oxidative stress) and G-to-A transitions were significantly elevated. In Nrf2-KO mice, too, the total mutant frequency was increased only at 0.6 g/L. G-to-T transversions are likely to have driven tumorigenesis in the small intestine. A site-specific G-to-T transversion at guanine (nucleotide 406) in a 5'-TGAA-3' sequence in gpt, and our primer extension reaction showed that formation of the oxidative DNA base modification 8-oxo-deoxyguanosine (8-oxo-dG) at nucleotide 406 was significantly increased at doses of 0.6 and 2 g/L in the gpt delta mice. In the Apc oncogene, guanine residues in the same or similar sequences (TGAA or AGAA) are highly substituted by thymine (G-to-T transversions) in potassium bromate-induced tumors. We propose that formation of 8-oxo-dG in the T(A)GAA sequence is an initiating event in tumor formation in the small intestine in response to oxidative stress.


Assuntos
Bromatos/toxicidade , Mutagênese/genética , Estresse Oxidativo/genética , Pentosiltransferases/genética , 8-Hidroxi-2'-Desoxiguanosina/genética , Administração Oral , Animais , Bromatos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , DNA/efeitos dos fármacos , DNA/genética , Relação Dose-Resposta a Droga , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Camundongos , Camundongos Knockout , Mutagênese/efeitos dos fármacos , Mutação , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos
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