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1.
BMC Cancer ; 20(1): 57, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992260

RESUMO

BACKGROUND: This study aimed to evaluate the safety and feasibility of self-expanding metallic stent (SEMS) followed by neoadjuvant chemotherapy prior to elective surgery for obstructing left-sided colon cancer. METHODS: Eleven consecutive patients with obstructing left-sided colon cancer between May 2014 and November 2015 were included retrospectively. All patients received SEMS followed by neoadjuvant chemotherapy. The primary outcome measure was stoma and laparoscopic surgery. RESULTS: Chemotherapy was with two cycles of CAPOX (54.5%) or three cycles mFOLFOX6 (45.5%). Median serum albumin and hemoglobin levels before surgery were significantly higher than before neoadjuvant chemotherapy (p = 0.01 and p = 0.008 respectively) and before SEMS (p = 0.01 and p = 0.003 respectively). Median bowel wall thickness proximal to the upper edge of tumor was significantly more before neoadjuvant chemotherapy than before stent (p = 0.003), and significantly less before surgery than before neoadjuvant chemotherapy (p = 0.003). No patient underwent stoma creation. Laparoscopic surgery was performed in nine (81.8%) patients. No local recurrence or metastases developed over median cancer-specific follow-up of 44 months (range, 37-55 months). CONCLUSION: SEMS followed by neoadjuvant chemotherapy prior to elective surgery appears to be safe and well tolerated in patients with obstructing left-sided colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Obstrução Intestinal/cirurgia , Laparoscopia/instrumentação , Stents Metálicos Autoexpansíveis/efeitos adversos , Adulto , Idoso , Capecitabina/uso terapêutico , Neoplasias do Colo/metabolismo , Tratamento Farmacológico , Estudos de Viabilidade , Feminino , Fluoruracila , Humanos , Obstrução Intestinal/metabolismo , Leucovorina , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Compostos Organoplatínicos , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Resultado do Tratamento
3.
Surg Endosc ; 31(1): 445-454, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27734201

RESUMO

BACKGROUND: The clinical outcomes for postoperative complications (PCs) after gastrectomy depend on early diagnosis and intensive treatment. The aim of this study was to investigate the role of C-reactive protein (CRP) as an early predictor of PCs after gastrectomy for gastric cancer. METHODS: A total of 334 consecutive patients who underwent gastrectomy for gastric cancer in 2014 were enrolled in this study. Blood samples were obtained preoperatively, and at postoperative days 1 and 4 for the measurement of inflammatory markers (white blood cell, neutrophil, and platelet counts, and CRP). Patients were classified into groups of major and minor/no PCs, which were defined as patients with PCs of more than grade III and those with grade I/II or without PCs, respectively, according to the Clavien-Dindo classification. RESULTS: Twenty-five patients developed major PCs. The CRP on postoperative day 4 provided superior diagnostic accuracy in predicting major PCs compared to the other systematic inflammatory markers. Multivariate analysis identified a CRP level of 16.8 mg/dl or greater on postoperative day 4 as a significant predictive factor for major PCs. CONCLUSIONS: Among the various systemic inflammatory markers, CRP on postoperative day 4 is the most reliable predictor of PCs after gastrectomy for gastric cancer.


Assuntos
Abscesso Abdominal/metabolismo , Fístula Anastomótica/metabolismo , Proteína C-Reativa/metabolismo , Gastrectomia , Íleus/metabolismo , Obstrução Intestinal/metabolismo , Complicações Pós-Operatórias/metabolismo , Neoplasias Gástricas/cirurgia , Abscesso Abdominal/epidemiologia , Idoso , Fístula Anastomótica/epidemiologia , Biomarcadores , Feminino , Humanos , Íleus/epidemiologia , Obstrução Intestinal/epidemiologia , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
4.
Khirurgiia (Mosk) ; (6): 55-59, 2017.
Artigo em Russo | MEDLINE | ID: mdl-28638015

RESUMO

AIM: To improve the results of treatment of patients with acute small bowel obstruction. MATERIAL AND METHODS: The research is based on the results of a comprehensive survey 202 people with acute small bowel obstruction. Reamberin was used in 102 patients treatment. RESULTS: It was established that metalloenzymes take an active part in the formation of endotoxemia in people with acute small bowel obstruction. Also, in patients as a result of an imbalance between oxidant and antioxidant systems, accumulated a significant amount of lipid peroxidation products, along with it a decrease activity of enzymes of antioxidant system. reamberin application in complex treatment of acute small bowel obstruction provided the reduction in the time correction of oxidative stress by preventing the growth and activity of lipid peroxidation products with simultaneous stimulation of the antioxidant system and contributed to the normalization of microelement homeostasis.


Assuntos
Obstrução Intestinal , Intestino Delgado , Peroxidação de Lipídeos/efeitos dos fármacos , Meglumina/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Succinatos/administração & dosagem , Doença Aguda , Adulto , Antioxidantes/administração & dosagem , Feminino , Homeostase/efeitos dos fármacos , Humanos , Obstrução Intestinal/metabolismo , Obstrução Intestinal/fisiopatologia , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Intestino Delgado/fisiopatologia , Masculino , Meglumina/administração & dosagem , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Khirurgiia (Mosk) ; (3): 17-23, 2017.
Artigo em Russo | MEDLINE | ID: mdl-28374709

RESUMO

AIM: To improve the outcomes in patients with colon cancer complicated by acute obstruction via development of combined and complex treatment strategies. MATERIAL AND METHODS: We observed 442 patients with colon cancer complicated with acute obstruction. Original classification and diagnostic algorithm were applied. RESULTS: Time of preoperative opening-up, volume and type of surgery were defined using obtained data. Also we are able to perform delayed radical surgery after correction of metabolic disorders and comorbidities, to create the conditions for combined and complex methods of treatment, to decrease the incidence of postoperative complications and mortality rate. CONCLUSION: Three-stage surgery with shortened time between interventions decreases the incidence of anastomosis failure, allows to refuse Hartmann's procedure and to avoid severe reconstructive surgical stage without prolongation of rehabilitation period.


Assuntos
Neoplasias do Colo , Procedimentos Cirúrgicos do Sistema Digestório , Obstrução Intestinal , Doenças Metabólicas , Complicações Pós-Operatórias , Idoso , Neoplasias do Colo/complicações , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Comorbidade , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Feminino , Humanos , Obstrução Intestinal/classificação , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/metabolismo , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/terapia , Estadiamento de Neoplasias , Avaliação de Processos e Resultados em Cuidados de Saúde , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/prevenção & controle , Melhoria de Qualidade , Federação Russa/epidemiologia
6.
Am J Physiol Gastrointest Liver Physiol ; 309(11): G888-99, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26428636

RESUMO

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-ß1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-ß1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-ß1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation.


Assuntos
Doença de Crohn/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Mucosa Intestinal/metabolismo , Obstrução Intestinal/metabolismo , Músculo Liso/metabolismo , Miócitos de Músculo Liso/metabolismo , Transporte Ativo do Núcleo Celular , Adulto , Processamento Alternativo , Comunicação Autócrina , Estudos de Casos e Controles , Células Cultivadas , Doença de Crohn/genética , Doença de Crohn/patologia , Feminino , Fibrose , Humanos , Hipertrofia , Fator de Crescimento Insulin-Like I/genética , Obstrução Intestinal/genética , Obstrução Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Fatores de Transcrição MEF2/genética , Fatores de Transcrição MEF2/metabolismo , Masculino , Mecanotransdução Celular , Pessoa de Meia-Idade , Proteína Quinase 7 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Músculo Liso/efeitos dos fármacos , Músculo Liso/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Fosforilação , Isoformas de Proteínas , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Mensageiro/metabolismo , Fatores de Tempo , Transfecção , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Adulto Jovem
7.
Am J Hum Genet ; 90(5): 893-9, 2012 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-22521417

RESUMO

Meconium ileus, intestinal obstruction in the newborn, is caused in most cases by CFTR mutations modulated by yet-unidentified modifier genes. We now show that in two unrelated consanguineous Bedouin kindreds, an autosomal-recessive phenotype of meconium ileus that is not associated with cystic fibrosis (CF) is caused by different homozygous mutations in GUCY2C, leading to a dramatic reduction or fully abrogating the enzymatic activity of the encoded guanlyl cyclase 2C. GUCY2C is a transmembrane receptor whose extracellular domain is activated by either the endogenous ligands, guanylin and related peptide uroguanylin, or by an external ligand, Escherichia coli (E. coli) heat-stable enterotoxin STa. GUCY2C is expressed in the human intestine, and the encoded protein activates the CFTR protein through local generation of cGMP. Thus, GUCY2C is a likely candidate modifier of the meconium ileus phenotype in CF. Because GUCY2C heterozygous and homozygous mutant mice are resistant to E. coli STa enterotoxin-induced diarrhea, it is plausible that GUCY2C mutations in the desert-dwelling Bedouin kindred are of selective advantage.


Assuntos
Obstrução Intestinal/genética , Obstrução Intestinal/metabolismo , Mecônio/metabolismo , Mutação , Receptores Acoplados a Guanilato Ciclase/genética , Receptores de Peptídeos/genética , Sequência de Aminoácidos , Animais , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidade , GMP Cíclico/metabolismo , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Diarreia/etiologia , Diarreia/metabolismo , Diarreia/fisiopatologia , Regulação para Baixo , Enterotoxinas/metabolismo , Enterotoxinas/toxicidade , Proteínas de Escherichia coli , Feminino , Hormônios Gastrointestinais/metabolismo , Genes Modificadores , Células HEK293 , Heterozigoto , Humanos , Mucosa Intestinal/metabolismo , Obstrução Intestinal/fisiopatologia , Masculino , Camundongos , Dados de Sequência Molecular , Peptídeos Natriuréticos/metabolismo , Linhagem , Fenótipo , Receptores de Enterotoxina , Receptores Acoplados a Guanilato Ciclase/metabolismo , Receptores de Peptídeos/metabolismo
8.
Am J Pathol ; 184(8): 2260-74, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24911373

RESUMO

Abnormal bacterial adherence and internalization in enterocytes have been documented in Crohn disease, celiac disease, surgical stress, and intestinal obstruction and are associated with low-level interferon (IFN)-γ production. How commensals gain access to epithelial soma through densely packed microvilli rooted on the terminal web (TW) remains unclear. We investigated molecular and ultrastructural mechanisms of bacterial endocytosis, focusing on regulatory roles of IFN-γ and myosin light chain kinase (MLCK) in TW myosin phosphorylation and brush border fanning. Mouse intestines were sham operated on or obstructed for 6 hours by loop ligation with intraluminally administered ML-7 (a MLCK inhibitor) or Y27632 (a Rho-associated kinase inhibitor). After intestinal obstruction, epithelial endocytosis and extraintestinal translocation of bacteria were observed in the absence of tight junctional damage. Enhanced TW myosin light chain phosphorylation, arc formation, and brush border fanning coincided with intermicrovillous bacterial penetration, which were inhibited by ML-7 and neutralizing anti-IFN-γ but not Y27632. The phenomena were not seen in mice genetically deficient for long MLCK-210 or IFN-γ. Stimulation of human Caco-2BBe cells with IFN-γ caused MLCK-dependent TW arc formation and brush border fanning, which preceded caveolin-mediated bacterial internalization through cholesterol-rich lipid rafts. In conclusion, epithelial MLCK-activated brush border fanning by IFN-γ promotes adherence and internalization of normally noninvasive enteric bacteria. Transcytotic commensal penetration may contribute to initiation or relapse of chronic inflammation.


Assuntos
Endocitose/fisiologia , Interferon gama/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/ultraestrutura , Quinase de Cadeia Leve de Miosina/metabolismo , Animais , Western Blotting , Linhagem Celular , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Imunofluorescência , Humanos , Hibridização in Situ Fluorescente , Obstrução Intestinal/metabolismo , Obstrução Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia Eletrônica , Microvilosidades/metabolismo , Microvilosidades/ultraestrutura , Simbiose
9.
PLoS Genet ; 8(3): e1002580, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22438829

RESUMO

Meconium ileus (MI), a life-threatening intestinal obstruction due to meconium with abnormal protein content, occurs in approximately 15 percent of neonates with cystic fibrosis (CF). Analysis of twins with CF demonstrates that MI is a highly heritable trait, indicating that genetic modifiers are largely responsible for this complication. Here, we performed regional family-based association analysis of a locus that had previously been linked to MI and found that SNP haplotypes 5' to and within the MSRA gene were associated with MI (P = 1.99 × 10(-5) to 1.08 × 10(-6); Bonferroni P = 0.057 to 3.1 × 10(-3)). The haplotype with the lowest P value showed association with MI in an independent sample of 1,335 unrelated CF patients (OR = 0.72, 95% CI [0.53-0.98], P = 0.04). Intestinal obstruction at the time of weaning was decreased in CF mice with Msra null alleles compared to those with wild-type Msra resulting in significant improvement in survival (P = 1.2 × 10(-4)). Similar levels of goblet cell hyperplasia were observed in the ilea of the Cftr(-/-) and Cftr(-/-)Msra(-/-) mice. Modulation of MSRA, an antioxidant shown to preserve the activity of enzymes, may influence proteolysis in the developing intestine of the CF fetus, thereby altering the incidence of obstruction in the newborn period. Identification of MSRA as a modifier of MI provides new insight into the biologic mechanism of neonatal intestinal obstruction caused by loss of CFTR function.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Obstrução Intestinal , Metionina Sulfóxido Redutases , Animais , Fibrose Cística/complicações , Fibrose Cística/genética , Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Estudos de Associação Genética , Células Caliciformes/patologia , Haplótipos , Humanos , Obstrução Intestinal/complicações , Obstrução Intestinal/genética , Obstrução Intestinal/metabolismo , Metionina Sulfóxido Redutases/genética , Metionina Sulfóxido Redutases/metabolismo , Camundongos , Camundongos Endogâmicos CFTR , Polimorfismo de Nucleotídeo Único
10.
Am J Physiol Gastrointest Liver Physiol ; 307(6): G642-54, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25059825

RESUMO

Effective therapies are limited for patients with parenteral nutrition-dependent short bowel syndrome. We previously showed that intestinal expression of the transcriptional coregulator tetradecanoyl phorbol acetate-induced sequence 7 (tis7) is markedly increased during the adaptive response following massive small bowel resection and tis7 plays a role in normal gut lipid metabolism. Here, we further explore the functional implications of tis7 deletion in intestinal lipid metabolism and the adaptive response following small bowel resection. Intestinal tis7 transgenic (tis7(tg)), tis7(-/-), and wild-type (WT) littermates were subjected to 50% small bowel resection. Mice were fed a control or a high-saturated-fat (42% energy) diet for 21 days. Survival, body weight recovery, lipid absorption, mucosal lipid analysis, and the morphometric adaptive response were analyzed. Quantitative real-time PCR was performed to identify tis7 downstream gene targets. Postresection survival was markedly reduced in high-fat, but not control, diet-fed tis7(-/-) mice. Decreased survival was associated with anastomotic inflammation and intestinal obstruction postresection. High-fat, but not control, diet-fed tis7(-/-) mice had increased intestinal IL-6 expression. Intestinal lipid trafficking was altered in tis7(-/-) compared with WT mice postresection. In contrast, high-fat diet-fed tis7(tg) mice had improved survival postresection compared with WT littermates. High-fat diet feeding in the setting of tis7 deletion resulted in postresection anastomotic inflammation and small bowel obstruction. Tolerance of a calorie-rich, high-fat diet postresection may require tis7 and its target genes. The presence of luminal fat in the setting of tis7 deletion promotes an intestinal inflammatory response postresection.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Enterite/etiologia , Proteínas Imediatamente Precoces/deficiência , Obstrução Intestinal/etiologia , Intestino Delgado/metabolismo , Proteínas de Membrana/deficiência , Síndrome do Intestino Curto/complicações , Anastomose Cirúrgica , Animais , Modelos Animais de Doenças , Enterite/genética , Enterite/metabolismo , Regulação da Expressão Gênica , Proteínas Imediatamente Precoces/genética , Interleucina-6/metabolismo , Absorção Intestinal , Obstrução Intestinal/genética , Obstrução Intestinal/metabolismo , Intestino Delgado/cirurgia , Metabolismo dos Lipídeos , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Síndrome do Intestino Curto/genética , Síndrome do Intestino Curto/metabolismo , Fatores de Tempo
11.
BMC Complement Altern Med ; 14: 186, 2014 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-24908398

RESUMO

BACKGROUND: Electroacupuncture (EA) is one of the techniques of acupuncture and is believed to be an effective alternative and complementary treatment in many disorders. The aims of this study were to investigate the effects and mechanisms of EA at acupoint Zusanli (ST36) on the plasticity of interstitial cells of Cajal (ICCs) in partial bowel obstruction. METHODS: A Sprague Dawley rat model of partial bowel obstruction was established and EA was conducted at Zusanli (ST36) and Yinglingquan (SP9) in test and control groups, respectively. Experiments were performed to study the effects and mechanisms of EA at Zusanli on intestinal myoelectric activity, distribution and alteration of ICCs, expression of inflammatory mediators, and c-Kit expression. RESULTS: 1) EA at Zusanli somewhat improved slow wave amplitude and frequency in the partial obstruction rats. 2) EA at Zusanli significantly stimulated the recovery of ICC networks and numbers. 3) the pro-inflammatory mediator TNF-α and NO activity were significantly reduced after EA at Zusanli, However, no significant changes were observed in the anti-inflammatory mediator IL-10 activity. 4) EA at Zusanli re-expressed c-Kit protein. However, EA at the control acupoint, SP9, significantly improved slow wave frequency and amplitude, but had no effect on ICC or inflammatory mediators. CONCLUSIONS: We concluded that EA at Zusanli might have a therapeutic effect on ICC plasticity, and that this effect might be mediated via a decrease in pro-inflammatory mediators and through the c-Kit signaling pathway, but that the relationship between EA at different acupoints and myoelectric activity needs further study.


Assuntos
Pontos de Acupuntura , Eletroacupuntura/métodos , Íleo/citologia , Células Intersticiais de Cajal/citologia , Obstrução Intestinal/terapia , Terapia por Acupuntura , Animais , Canais de Cloreto/metabolismo , Feminino , Íleo/metabolismo , Íleo/fisiopatologia , Interleucina-10/sangue , Interleucina-10/metabolismo , Células Intersticiais de Cajal/metabolismo , Obstrução Intestinal/metabolismo , Obstrução Intestinal/patologia , Masculino , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
12.
Arkh Patol ; 76(5): 61-7, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25543410

RESUMO

OBJECTIVE: To study the results of liver morphological studies in 40 Vietnamese pot belly pigs with simulated small bowel obstruction. MATERIALS AND METHODS: Liver morphofunctional changes in acute strangulation ileus were investigated in an experiment on 40 Vietnamese pot belly pigs weighing 15-20 kg. Five animals were used as a control. RESULTS: In simulated acute ileus, the found morphofunctional changes in hepatocytes were characterized by toxic dystrophy of the organ with the signs of secondary hepatitis. CONCLUSION: During the experiment, the course of the disease and surgical restoration of small bowel patency have been found to be accompanied by significant histological and ultrafine structural disorders of the liver, which is a rationale for intensive antihypoxant, antioxidant, and hepatoprotective therapy in the pre- and postoperative periods.


Assuntos
Obstrução Intestinal/tratamento farmacológico , Obstrução Intestinal/patologia , Intestino Delgado/patologia , Fígado/patologia , Animais , Antioxidantes/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Obstrução Intestinal/metabolismo , Fígado/efeitos dos fármacos , Meglumina/administração & dosagem , Meglumina/análogos & derivados , Succinatos/administração & dosagem , Suínos , Tomografia Computadorizada por Raios X
13.
Int J Colorectal Dis ; 28(3): 341-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22903297

RESUMO

PURPOSE: Anastomosis of an acutely obstructed colon is associated with an increased risk of dehiscence. In experimental models, acute obstruction decreases collagen in the colonic wall, but the time course and propagation along the colon of the biochemical changes are unknown. Furthermore, there is a paucity of information on the correlation between these biochemical changes and histological features. METHODS: Forty male Sprague Dawley rats were subjected to partial obstruction by placing a silicone ring around the left colon 30 mm above the reflection. Obstruction was maintained for 0, 1, 2, 3 or 4 days. Samples from five different locations along the colon were analysed on circumference, tissue water content, collagen concentration and histomorphology. Neutrophil and macrophage infiltration was characterized immunohistochemically. RESULTS: The colonic circumference and water content increased (p < 0.001), while the collagen concentration decreased by 48 % (p < 0.01) proximal to the obstruction already after 1 day. The degree of dilation and collagen reduction did not change significantly over the subsequent 3 days of obstruction, whereas the water content normalized by day 3. Mucosal and submucosal oedema and the relative neutrophil infiltration were highest after 1 day in the colonic segment proximal to the stenosis while the macrophage population continued to increase to day 4. Muscular necrosis in addition to ganglionitis and neuritis in the nervous plexus increased with duration of obstruction. CONCLUSIONS: The pronounced and rapid changes of the composition of cells and the extracellular matrix of the colonic wall following acute obstruction may be of guidance for present surgical treatments and future pharmacological interventions.


Assuntos
Colágeno/metabolismo , Colo/patologia , Obstrução Intestinal/metabolismo , Obstrução Intestinal/patologia , Animais , Colo/metabolismo , Imuno-Histoquímica , Obstrução Intestinal/induzido quimicamente , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Água
14.
Am J Physiol Gastrointest Liver Physiol ; 303(9): G1004-16, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22961801

RESUMO

The mechanisms underlying slow-transit constipation (STC) are unclear. In 50% of patients with STC, some form of outlet obstruction has been reported; also an elongated colon has been linked to patients with STC. Our aims were 1) to develop a murine model of STC induced by partial outlet obstruction and 2) to determine whether this leads to colonic elongation and, consequently, activation of the inhibitory "occult reflex," which may contribute to STC in humans. Using a purse-string suture, we physically reduced the maximal anal sphincter opening in C57BL/6 mice. After 4 days, the mice were euthanized (acutely obstructed), the suture was removed (relieved), or the suture was removed and replaced repeatedly (chronically obstructed, over 24-31 days). In partially obstructed mice, we observed increased cyclooxygenase (COX)-2 levels in muscularis and mucosa, an elongated impacted large bowel, slowed transit, nonpropagating colonic migrating motor complexes (CMMCs), a lack of mucosal reflexes, a depolarized circular muscle with slow-wave activity due to a lack of spontaneous inhibitory junction potentials, muscle hypertrophy, and CMMCs in mucosa-free preparations. Elongation of the empty obstructed colon produced a pronounced occult reflex. Removal of the obstruction or addition of a COX-2 antagonist (in vitro and in vivo) restored membrane potential, spontaneous inhibitory junction potentials, CMMC propagation, and mucosal reflexes. We conclude that partial outlet obstruction increases COX-2 leading to a hyperexcitable colon. This hyperexcitability is largely due to suppression of only descending inhibitory nerve pathways by prostaglandins. The upregulation of motility is suppressed by the occult reflex activated by colonic elongation.


Assuntos
Constipação Intestinal , Motilidade Gastrointestinal , Intestino Grosso , Reflexo de Estiramento/fisiologia , Animais , Constipação Intestinal/etiologia , Constipação Intestinal/metabolismo , Constipação Intestinal/fisiopatologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Modelos Animais de Doenças , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Humanos , Mucosa Intestinal/inervação , Mucosa Intestinal/metabolismo , Obstrução Intestinal/complicações , Obstrução Intestinal/metabolismo , Obstrução Intestinal/fisiopatologia , Intestino Grosso/metabolismo , Intestino Grosso/fisiopatologia , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso/inervação , Músculo Liso/metabolismo , Plexo Mientérico/metabolismo , Complexo Mioelétrico Migratório/efeitos dos fármacos
15.
J Ethnopharmacol ; 296: 115465, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35718051

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mume Fructus (MF) is a well-known traditional Chinese medicine used to treat chronic cough, prolonged diarrhea, and other inflammation-related diseases. We previously confirmed the anti-colitis effect of its ethanol extract on a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced Crohn's disease (CD) rat model. However, the active ingredients and underlying mechanisms of MF remain unknown. AIM OF THE STUDY: To clarify the material basis and potential mechanism of the ethanol extract of MF (MFE) in alleviating CD and its complications, such as lung injury and intestinal obstruction. MATERIALS AND METHODS: MF was extracted with 80% ethanol aqueous solution and separated with 0, 40, and 100% ethanol aqueous solutions. MFE and its fractions were screened in a TNBS-induced CD rat model. For the bioactive fraction, the chemical composition was identified and quantified using ultrahigh-performance liquid chromatography coupled with diode-array detection and quadrupole time-of-flight tandem mass spectrometry. Interleukin (IL)-1ß, IL-6, IL-17, transforming growth factor (TGF)-ß, and lipopolysaccharide (LPS) levels in the colon, lungs, and/or plasma were detected using enzyme-linked immunosorbent assays. The expression levels of zonula occludens-1 (ZO-1) and occludin in the colon were measured using immunohistochemical staining, and the intestinal microbiota and short-chain fatty acid (SCFA) levels were analyzed using 16S rRNA gene sequencing and gas chromatography/mass spectrometry. RESULTS: The 40% ethanol fraction of MF (MFE40), which mainly contained methyl citrate, ethyl citrate, and caffeoylquinic acid ethyl esters, was identified as the active fraction that could alleviate CD in rats. MFE40 could ameliorate inflammation and fibrosis in the colon and lung tissues by inhibiting the secretion of cytokines, such as IL-1ß, IL-6, IL-17, and TGF-ß, along with intestinal obstruction and lung injury in CD rats. The possible mechanisms of MFE40 were related to increased expression of ZO-1 and occludin in the colon, reduction in plasma LPS levels, and restoration of SCFAs via reduction in the relative abundance of Adlercreutzia, Clostridium_sensu_stricto_1, Erysipelatoclostridium, Faecalibaculum, norank_f_Erysipelotrichaceae, Phascolarctobacterium Coriobacteriaceae_UGG_002, and Allobaculum and increase in the relative abundance of Escherichia shigella, Christensenella, Acetivibrio_ethanolgignens, and Butyricicoccus. MFE40 had no significant influence on the inflammatory factors in healthy rats. CONCLUSIONS: Citrate esters and hydroxycinnamate esters are the main active constituents of MFE40. MFE40 exhibited a remission effect on CD rats and inhibited intestinal obstruction and lung injury via anti-inflammatory effects and regulation of the intestinal microbiota-gut-lung homeostasis.


Assuntos
Doença de Crohn , Obstrução Intestinal , Lesão Pulmonar , Animais , Citratos/metabolismo , Colo , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/farmacologia , Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Obstrução Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar/metabolismo , Ocludina/metabolismo , RNA Ribossômico 16S , Ratos , Ácido Trinitrobenzenossulfônico/toxicidade
16.
Am J Physiol Gastrointest Liver Physiol ; 300(1): G99-G108, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21051526

RESUMO

In gastrointestinal conditions such as bowel obstruction, pseudo-obstruction, and idiopathic megacolon, the lumen of affected bowel segments is distended and its motility function impaired. Our hypothesis is that mechanical stretch of the distended segments alters gene expression of cyclooxygenase-2 (COX-2), which impairs motility function. Partial obstruction was induced with a silicon band in the distal colon of rats for up to 7 days, and wild-type and COX-2 gene-deficient mice for 4 days. Mechanical stretch was mimicked in vitro in colonic circular muscle strips and in primary culture of colonic circular smooth muscle cells (SMC) with a Flexercell system. The rat colonic circular muscle contractility was significantly decreased in the distended segment oral to obstruction, but not in the aboral segment. This change started as early as day 1 and persisted for at least 7 days after obstruction. The expression of COX-2 mRNA and protein increased dramatically also in the oral, but not aboral, segment. The upregulation of COX-2 expression started at 12 h and the effect persisted for 7 days. At 24 h after obstruction, the COX-2 mRNA level in the oral segment increased 26-fold compared with controls. This was not accompanied by any significant increase of myeloperoxidase or inflammatory cytokines. Immunohistochemical studies showed that COX-2 was selectively induced in the colonic SMC. In vitro stretch of colonic muscle strips or cultured SMC drastically induced COX-2 expression. Incubation of circular muscle strips from obstructed segment with COX-2 inhibitor NS-398 restored the contractility. The impairment of muscle contractility in obstructed colon was attenuated in the COX-2 gene-deficient mice. In conclusion, mechanical stretch in obstruction induces marked expression of COX-2 in the colonic SMC, and stretch-induced COX-2 plays a critical role in the suppression of smooth muscle contractility in bowel obstruction.


Assuntos
Ciclo-Oxigenase 2/fisiologia , Obstrução Intestinal/fisiopatologia , Contração Muscular/fisiologia , Animais , Colo/fisiologia , Ciclo-Oxigenase 2/biossíntese , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Obstrução Intestinal/metabolismo , Masculino , Camundongos , Contração Muscular/efeitos dos fármacos , Músculo Liso/fisiologia , Nitrobenzenos/farmacologia , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Sulfonamidas/farmacologia
17.
Colorectal Dis ; 13(7): e165-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21651691

RESUMO

AIM: Our aim was to define the dynamics in collagen concentrations in the large bowel wall following decompression of experimental obstruction. METHOD: Colonic obstruction was created in 28 male rats by the placement of a silicone ring around the distal colon. The ring was removed after 4 days to mimic endoscopical decompression by stent deployment. Colon circumference and collagen concentration were measured proximal to the obstructed segment immediately and at 3 and 10 days after decompression. The corresponding colonic sites of 23 sham-operated and eight nonoperated control animals were subjected to identical analyses. RESULTS: Four days of obstruction resulted in a more than twofold increase in colonic circumference (20 vs 8 mm), with a concomitant 43% reduction (P = 0.001) in collagen concentration in the bowel wall proximal to the obstruction compared with sham animals. Three days after decompression, collagen concentrations remained reduced (P < 0.05), while there was no significant difference after 10 days with either sham-operated or nonoperated controls. Colonic circumference of the obstructed colon remained slightly distended (11 mm) on day 10 and tended to correlate (r(S) = 0.51, P = 0.053) with total matrix metalloproteinase activity. CONCLUSION: The marked reduction in collagen concentration in an experimentally obstructed colon is normalized 10 days after decompression. These findings may have clinical implications for the timing of surgical resection.


Assuntos
Colágeno/metabolismo , Doenças do Colo/metabolismo , Obstrução Intestinal/metabolismo , Animais , Doenças do Colo/enzimologia , Doenças do Colo/patologia , Doenças do Colo/cirurgia , Descompressão Cirúrgica , Obstrução Intestinal/enzimologia , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Masculino , Metaloproteinases da Matriz/metabolismo , Modelos Animais , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
Pediatr Hematol Oncol ; 28(2): 155-8, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21299343

RESUMO

Gastrointestinal stromal tumors (GISTs) are rare in the childhood period. The authors reported a case who was admitted to the neonatal intensive care unit (NICU) on a suspicion of intestinal obstruction. She was operated and a mass in a size of 6 x 4.5 x 4 cm was resected from the ileum. Histologic and immunohistochemical studies showed a GIST. CD34, small muscle actin (SMA), and desmin were positive. The baby was discharged on the 13th day after operation.


Assuntos
Neoplasias Gastrointestinais/complicações , Neoplasias do Íleo/complicações , Obstrução Intestinal/etiologia , Adulto , Biomarcadores Tumorais/metabolismo , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Neoplasias do Íleo/patologia , Recém-Nascido , Obstrução Intestinal/metabolismo , Obstrução Intestinal/cirurgia , Resultado do Tratamento
19.
Pediatr Surg Int ; 27(12): 1277-81, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21818521

RESUMO

PURPOSE: The risk of bowel injury during surgery for small bowel obstruction (SBO) has generated interest in conservative treatment modalities. Few data are available on conservative Gastrografin treatment for SBO in children. METHODS: We prospectively included patients with uncomplicated adhesive SBO managed at a pediatric center between March 2009 and September 2010. Patients who were unimproved after 48 h of conservative treatment received 50-100 ml of Gastrografin. If Gastrografin was seen in the cecum on the abdominal radiograph 4-6 h later, feeding was initiated and the patient was discharged on the same day. Each patient was matched to 2 controls on the number of previous SBO episodes. The primary outcome was length of hospital stay (>3 days), and the secondary outcome was time from admission to first feed (>2 days). Both were compared in the two groups using conditional logistic regression. RESULTS: The 8 patients admitted for SBO were matched to 16 controls. Gastrografin administration was associated with significantly lower risks of staying in the hospital longer than 3 days (P < 0.10) and waiting more than 2 days before the first feed. CONCLUSION: This preliminary study suggests that Gastrografin may be useful for managing adhesive SBO in children.


Assuntos
Diatrizoato de Meglumina/administração & dosagem , Obstrução Intestinal/tratamento farmacológico , Intestino Delgado , Aderências Teciduais/complicações , Adolescente , Criança , Pré-Escolar , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Diatrizoato de Meglumina/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Lactente , Injeções Intravenosas , Obstrução Intestinal/etiologia , Obstrução Intestinal/metabolismo , Tempo de Internação/tendências , Masculino , Estudos Prospectivos , Radiografia Abdominal , Aderências Teciduais/diagnóstico , Aderências Teciduais/tratamento farmacológico , Resultado do Tratamento
20.
Khirurgiia (Mosk) ; (6): 38-42, 2011.
Artigo em Russo | MEDLINE | ID: mdl-21716217

RESUMO

Water and electrolyte imbalance is considered to be the mainstay of preoperative treatment of patients with acute intestinal obstruction. The correct preoperative preparation defines the anaesthesia course, which requires the team work of surgeon and aneasthesiologist. The benefits of such an approach is confirmed by the retrospective analysis of 84 case histories, operated on the reason of the acute intestinal obstruction. The rational combination of colloid and crystalloid solutions was jointly selected, which allowed to decrease the need of vasopressor use and minimized the ICU and overall hospital stay.


Assuntos
Anestesia/métodos , Hemodinâmica/efeitos dos fármacos , Obstrução Intestinal/cirurgia , Equipe de Assistência ao Paciente/normas , Cuidados Pré-Operatórios , Desequilíbrio Hidroeletrolítico/terapia , Doença Aguda , Adulto , Idoso , Anestesia/efeitos adversos , Anestésicos/administração & dosagem , Anestésicos/efeitos adversos , Feminino , Humanos , Obstrução Intestinal/complicações , Obstrução Intestinal/metabolismo , Obstrução Intestinal/fisiopatologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/normas , Soluções para Reidratação/administração & dosagem , Soluções para Reidratação/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Vasoconstritores/uso terapêutico , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/metabolismo , Desequilíbrio Hidroeletrolítico/fisiopatologia
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