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1.
Physiol Int ; 106(3): 225-235, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560236

RESUMO

OBJECTIVES: Impaired intestinal barrier function has been demonstrated in the pathophysiology of diarrhea-predominant irritable bowel syndrome (IBS-D). This study aimed to describe the intestinal ultrastructural findings in the intestinal mucosal layer of IBS-D patients. METHODS: In total, 10 healthy controls and 10 IBS-D patients were analyzed in this study. The mucosa of each patient's rectosigmoid colon was first assessed by confocal laser endomicroscopy (CLE); next, biopsied specimens of these sites were obtained. Intestinal tissues of IBS-D patients and healthy volunteers were examined to observe cellular changes by transmission electron microscopy (TEM). RESULTS: CLE showed no visible epithelial damage or inflammatory changes in the colonic mucosa of IBS-D compared with healthy volunteers. On transmission electron microscopic examination, patients with IBS-D displayed a larger apical intercellular distance with a higher proportion of dilated (>20 nm) intercellular junctional complexes, which was indicative of impaired mucosal integrity. In addition, microvillus exfoliation, extracellular vesicle as well as increased presence of multivesicular bodies were visible in IBS-D patients. Single epithelial cells appeared necrotic, as characterized by cytoplasmic vacuolization, cytoplasmic swelling, and presence of autolysosome. A significant association between bowel habit, frequency of abdominal pain, and enlarged intercellular distance was found. CONCLUSION: This study showed ultrastructural alterations in the architecture of intestinal epithelial cells and intercellular junctional complexes in IBS-D patients, potentially representing a pathophysiological mechanism in IBS-D.


Assuntos
Diarreia/patologia , Mucosa Intestinal/ultraestrutura , Síndrome do Intestino Irritável/patologia , Dor Abdominal/patologia , Colo Sigmoide/ultraestrutura , Citoplasma/patologia , Citoplasma/ultraestrutura , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Feminino , Humanos , Junções Intercelulares/ultraestrutura , Masculino , Pessoa de Meia-Idade , Reto/patologia , Reto/ultraestrutura
2.
Res Vet Sci ; 126: 127-130, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31479828

RESUMO

The aim of the present study was to investigate whether abnormalities in plasma diamine oxidase (DAO) activity reflect the degree of intestinal mucosal disorder in calves with diarrhea. A total of 50 Holstein calves were enrolled. Thirty-six of the 50 calves presented diarrhea and were sub-classified by severity based on fecal status (0: firm, 1: pasty, 2: loose, and 3: watery) and blood pH (acidemia: blood pH <7.25) as follows: Seventeen calves exhibiting watery diarrhea and/or fall into acidemia were sub-categorized into the severe group. The other nineteen calves exhibiting pasty or loose diarrhea and not fall into acidemia were sub-categorized into the moderate group. The remaining 14 calves without diarrhea were assigned to the control group. The plasma DAO activity was significantly lower (p < .01) in the calves with severe or moderate diarrhea than in the control group. In addition, the plasma DAO activity was significantly lower (p < .05) in the severe group than in the moderate group. The relationship between plasma DAO activity and fecal score (r = -0.55, p < .01) in calves with diarrhea were found to have significantly and negatively correlated by Spearman's rank test in this study. Our results suggested that plasma DAO activity reflect the degree of intestinal mucosal disorder due to diarrhea.


Assuntos
Doenças dos Bovinos/sangue , D-Aminoácido Oxidase/sangue , Diarreia/veterinária , Mucosa Intestinal/patologia , Acidose , Animais , Biomarcadores/sangue , Bovinos , Diarreia/sangue , Diarreia/patologia , Fezes
3.
Eur J Haematol ; 103(5): 519-522, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31389104

RESUMO

We present a case series of 3 patients to highlight the fact that PTLD post-transplant can mimic GVHD, and should be part of the differential diagnosis for diarrhea post allo-HCT. Awareness of this presentation has important therapeutic implications, as increased immune suppression for the management of GVHD, can worsen clinical features of PTLD. Diagnostic imaging and tissue biopsies should be undertaken early in post-transplant patients presenting with diarrhea or hepatic abnormalities, especially with atypical presentations like fever, and EBV PCR monitoring can expedite clinical decision-making in such complicated scenarios while awaiting results of gut biopsies.


Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Transtornos Linfoproliferativos , Doença Aguda , Aloenxertos , Biópsia , Tomada de Decisão Clínica , Diarreia/diagnóstico , Diarreia/patologia , Diarreia/terapia , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/patologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Hepatopatias/diagnóstico , Hepatopatias/patologia , Hepatopatias/terapia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade
4.
Virus Genes ; 55(6): 795-801, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31463771

RESUMO

Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus that causes intestinal diseases in neonatal piglets with diarrhea, vomiting, dehydration, and post-infection mortality of 50-100%. Currently, there are no effective treatments or vaccines available to control PDCoV. To study the potential of RNA interference (RNAi) as a strategy against PDCoV infection, two short hairpin RNA (shRNA)-expressing plasmids (pGenesil-M and pGenesil-N) that targeted the M and N genes of PDCoV were constructed and transfected separately into swine testicular (ST) cells, which were then infected with PDCoV strain HB-BD. The potential of the plasmids to inhibit PDCoV replication was evaluated by cytopathic effect, virus titers, and real-time quantitative RT-PCR assay. The cytopathogenicity assays demonstrated that pGenesil-M and pGenesil-N protected ST cells against pathological changes with high specificity and efficacy. The 50% tissue culture infective dose showed that the PDCoV titers in ST cells treated with pGenesil-M and pGenesil-N were reduced 13.2- and 32.4-fold, respectively. Real-time quantitative RT-PCR also confirmed that the amount of viral RNA in cell cultures pre-transfected with pGenesil-M and pGenesil-N was reduced by 45.8 and 56.1%, respectively. This is believed to be the first report to show that shRNAs targeting the M and N genes of PDCoV exert antiviral effects in vitro, which suggests that RNAi is a promising new strategy against PDCoV infection.


Assuntos
Infecções por Coronavirus/genética , Coronavirus/genética , Proteínas Virais/genética , Replicação Viral/genética , Animais , Coronavirus/patogenicidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Diarreia/genética , Diarreia/patologia , Diarreia/veterinária , Diarreia/virologia , Masculino , Plasmídeos/genética , Interferência de RNA , RNA Interferente Pequeno/genética , RNA Viral/genética , Suínos/virologia , Doenças dos Suínos/genética , Doenças dos Suínos/virologia , Testículo/crescimento & desenvolvimento , Testículo/virologia
6.
EBioMedicine ; 45: 456-463, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31229436

RESUMO

BACKGROUND: Children with severe acute malnutrition (SAM), with or without diarrhoea, often have enteropathy, but there are few molecular data to guide development of new therapies. We set out to determine whether SAM enteropathy is characterised by specific transcriptional changes which might improve understanding or help identify new treatments. METHODS: We collected intestinal biopsies from children with SAM and persistent diarrhoea. mRNA was extracted from biopsies, sequenced, and subjected to a progressive set of complementary analytical approaches: NOIseq, Gene Set Enrichment Analysis (GSEA), and correlation analysis of phenotypic data with gene expression. FINDINGS: Transcriptomic profiles were generated for biopsy sets from 27 children of both sexes, under 2 years of age, of whom one-third were HIV-infected. NOIseq analysis, constructed from phenotypic group extremes, revealed 66 differentially expressed genes (DEGs) out of 21,386 mapped to the reference genome. These DEGs include genes for mucins and mucus integrity, antimicrobial defence, nutrient absorption, C-X-C chemokines, proteases and anti-proteases. Phenotype - expression correlation analysis identified 1221 genes related to villus height, including increased cell cycling gene expression in more severe enteropathy. Amino acid transporters and ZIP zinc transporters were specifically increased in severe enteropathy, but transcripts for xenobiotic metabolising enzymes were reduced. INTERPRETATION: Transcriptomic analysis of this rare collection of intestinal biopsies identified multiple novel elements of pathology, including specific alterations in nutrient transporters. Changes in xenobiotic metabolism in the gut may alter drug disposition. Both NOIseq and GSEA identified gene clusters similar to those differentially expressed in pediatric Crohn's disease but to a much lesser degree than those identified in coeliac disease. FUND: Bill & Melinda Gates Foundation OPP1066118. The funding agency had no role in study design, data collection, data analysis, interpretation, or writing of the report.


Assuntos
Diarreia/genética , Enteropatias/genética , Desnutrição Aguda Grave/genética , Transcriptoma/genética , Biópsia , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Enteropatias/epidemiologia , Enteropatias/patologia , Mucosa Intestinal/metabolismo , Masculino , Análise de Sequência de RNA , Desnutrição Aguda Grave/epidemiologia , Desnutrição Aguda Grave/patologia , Zâmbia/epidemiologia
7.
Acta Vet Scand ; 61(1): 26, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182127

RESUMO

BACKGROUND: Pre-weaning diarrhea (PWD) is a severe syndrome, with world-wide occurrence, affecting farmed mink (Neovison vison) kits during the lactation period. Kits affected by PWD often display clinical signs such as: yellow-white diarrhea, greasy skin, and dehydration. In severe cases the kits eventually die. It is common practice to treat PWD using antimicrobials; however the effect is not well documented. Due to the multifactorial etiology of PWD vaccine development is not feasible. The role played by the immune status of the mink kits with respect to their susceptibility to PWD is not well studied. To elucidate the possible association between PWD and total IgG serum concentration in young kits we analyzed blood collected from kits from 100 litters on two mink farms during the same breeding period, one farm being a case farm with high prevalence of PWD, and the other being a control farm with no cases of PWD. RESULTS: Kits affected by PWD had a significantly reduced weight gain compared to unaffected control kits. Litters born later in the breeding period came down with PWD at an earlier age than litters born at the start of the breeding period. We found that PWD affected kits had significantly lower concentrations of serum IgG compared to unaffected kits at 13-15 days of age (the last blood sampling point of the study). CONCLUSION: The results in this study suggest that PWD affected kits less efficiently absorbed IgG from maternal milk or had a lower intake of maternal milk, potentially contributing to the exacerbation of disease. A lower intake of IgG and/or less absorption from maternal milk could also pre-dispose kits for PWD. Future studies will be needed to elucidate if the circulating level of IgG is directly related to protection against disease and to investigate if administration of IgG could be helpful in alleviating and/or preventing PWD in mink kits.


Assuntos
Animais Lactentes/imunologia , Diarreia/veterinária , Imunoglobulina G/sangue , Vison/imunologia , Animais , Animais Lactentes/sangue , Diarreia/sangue , Diarreia/imunologia , Diarreia/patologia , Vison/sangue , Desmame , Ganho de Peso
8.
Cell Host Microbe ; 26(1): 135-146.e5, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31231045

RESUMO

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here, we derive an in vivo model of Cryptosporidium infection in immunocompetent C57BL/6 mice by isolating parasites from naturally infected wild mice. Similar to human cryptosporidiosis, this infection causes intestinal pathology, and interferon-γ controls early infection while T cells are critical for clearance. Importantly, mice that controlled a live infection were resistant to secondary challenge and vaccination with attenuated parasites provided protection equal to live infection. Both parasite and host are genetically tractable and this in vivo model will facilitate mechanistic investigation and rational vaccine design.


Assuntos
Imunidade Adaptativa , Criptosporidiose/imunologia , Diarreia/imunologia , Modelos Animais de Doenças , Interações Hospedeiro-Patógeno , Imunidade Inata , Animais , Criptosporidiose/patologia , Cryptosporidium/crescimento & desenvolvimento , Cryptosporidium/imunologia , Diarreia/patologia , Resistência à Doença , Camundongos , Camundongos Endogâmicos C57BL
9.
Mol Med Rep ; 20(1): 787-794, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180516

RESUMO

Irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD) overlap. It is not clear whether GERD is caused by non­erosive esophagitis, or erosive esophagitis. The Rome criteria are not widely used for the diagnosis of IBS in the clinic. In total, 1,489 IBS patients without red flags were included in the present retrospective study. They comprised of 1,331 females and 158 males with a mean age of 51 years. The diagnosis of IBS was verified by endoscopic and histopathological examinations. Whereas erosive esophagitis occurred in 97% of patients, only 66% had GERD symptoms. Endoscopy and histopathological examinations revealed that 1.4% of the IBS patients with diarrhea as the predominant symptom had other organic gastrointestinal diseases: 0.3% with celiac disease, 0.2% with Crohn's disease, 0.07% with ulcerative colitis, 0.6% with microscopic colitis, and 0.2% with colon cancer. Applying the Rome III criteria produced a sensitivity of 100% [95% confidence intervals (CI)=99.8­100.0%] a specificity of 98.7% (95% CI=98.0­99.2%), a positive likelihood ratio of 76.9%, and a negative likelihood ratio of 0%. IBS is associated with erosive esophagitis. Applying Rome III criteria without red flags and history, was effective in diagnosing IBS. Celiac disease and microscopic colitis should be considered as alternative diagnoses.


Assuntos
Esofagite/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Diarreia/diagnóstico , Diarreia/patologia , Esofagite/patologia , Feminino , Humanos , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Microb Pathog ; 134: 103557, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31153984

RESUMO

Escherichia coli (E. coli) O1-induced diarrhea is associated with intestinal microbial imbalance, however, the results of using oral antibiotics still remain poor. To overcome such problem, our study investigates the role of metabolites from stable flies (MSF) in the occurrence of diarrhea. The amino acid composition and molecular weight analysis of MSF by RP-HPLC and GPC, respectively. Besides the normal control group, SPF mice in other group were inoculated with E. coli O1 received treatment as follows over a period of 7 days saline solution (E. coli control), ciprofloxacin (0.13 g/kg; positive control) and MSF (2, 4 and 8 mg/kg) dosage. Throughout the experiment, defecation and body weights were examined and recorded. On the eighth day, after administering anesthesia, blood, tissue of small intestine samples were obtained for immunological and anti-oxidant. Small intestinal tissues and cecum contents samples were used for histopathological and 16S rDNA sequencing analysis. Our showed that MSF was rich in isoleucine, and its molecular weight less than 400 Da is 60.03%. MSF (4 and 8 mg/kg) and ciprofloxacin, significantly decreased IL-6, IL-8 and TNF-α levels, whereas, increased IL-2, IL-4, IL-10, INF-γ, IgA and IgG levels in mice having diarrhea. These treatments also reversed intestinal flora imbalance as indicated by the increased in Firmicutes-to-Bacteroidetes ratio and Clostridium levels (P < 0.05) and improved 5-HT, CAT and SOD levels. MSF favored diarrhea management as compared to ciprofloxacin, suggesting that MSF can be used in the management of E. coli O1-induced diarrhea, in normal gut microbiota and normal intestinal antioxidant function.


Assuntos
Diarreia/tratamento farmacológico , Sistema Imunitário/imunologia , Muscidae/química , Animais , Antioxidantes/uso terapêutico , Peso Corporal , Ceco , Ciprofloxacino/farmacologia , Citocinas/sangue , Citocinas/metabolismo , Diarreia/patologia , Diarreia/prevenção & controle , Modelos Animais de Doenças , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestino Delgado , Intestinos/efeitos dos fármacos , Intestinos/patologia , Larva/química , Masculino , Camundongos
11.
Life Sci ; 231: 116529, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31173781

RESUMO

AIMS: The present study investigated the effect of Escherichia coli Nissle 1917 (EcN) on irinotecan-induced intestinal barrier dysfunction and gut microbial dysbiosis in a mouse model and in the human colonic cells lines Caco-2. MATERIALS AND METHODS: Male BALB/c mice received irinotecan intraperitoneal injection with or without EcN administration intragastrically. Body weight, diarrhea severity, intestinal permeability and histopathological analysis of ileum epithelia of mice from different groups were assessed. The expression and localization of tight junction proteins were examined using western blot and immunofluorescence. Gut microbiota structure and diversity were measured with 16 S rRNA sequencing. Caco-2 monolayers were incubated with EcN culture supernatant (EcNsup) or SN-38 and the monolayer barrier function was assessed by transepithelial electrical resistance (TER) and FITC-dextran 4000 Da (FD-4) flux. KEY FINDINGS: Pretreatment with EcN significantly attenuated irinotecan-induced weight loss and diarrhea in mice. In addition, EcN inhibited the increased intestinal permeability and decreased Claudin-1 expression in irinotecan-treated mice. Furthermore, irinotecan treatment decreased the diversity of gut microbiota and increased the relative abundance of Proteobacteria compared to control group. EcN administration ameliorated the gut microbiota dysbiosis. In Caco-2 monolayers, EcNsup ameliorated the decreased TER and increased FD-4 flux elicited by SN-38. Moreover, EcNsup attenuated SN-38-induced altered localization and distribution of Claudin-1 in Caco-2 monolayers. SIGNIFICANCE: Our results indicated that the administration of EcN protected against irinotecan-induced intestinal injury by regulating intestinal barrier function and gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Animais , Células CACO-2 , Claudina-1/metabolismo , Diarreia/patologia , Disbiose/tratamento farmacológico , Escherichia coli/metabolismo , Gastroenteropatias/metabolismo , Microbioma Gastrointestinal/genética , Humanos , Enteropatias/metabolismo , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Irinotecano/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Probióticos/farmacologia , Proteínas de Junções Íntimas/metabolismo
12.
Chin Med J (Engl) ; 132(13): 1524-1532, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31205078

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is characterized by cytokine imbalance. Previously, decreased plasma interleukin 10 (IL-10) level was reported in patients with IBS, which may be due to genetic polymorphisms. However, there are no reports correlating the IL-10 polymorphisms with IL-10 production in patients with IBS. This study aimed to analyze the effect of IL-10 polymorphisms on IL-10 production and its correlation with the clinical symptoms in Chinese patients with diarrhea-predominant IBS (IBS-D). METHODS: Two IL-10 single nucleotide polymorphisms (rs1800871 and rs1800896) were detected in 120 patients with IBS-D and 144 healthy controls (HC) using SNaPshot. IBS symptom severity score, Bristol scale, hospital anxiety, and depressive scale (HADS) were used to evaluate the clinical symptoms, as well as the psychological status and visceral sensitivity of the subjects. IL-10 levels in the plasma and peripheral blood mononuclear cell (PBMC) culture supernatant were measured using enzyme-linked immunosorbent assay, while those in ileal and colonic mucosal biopsies were measured using immunohistochemistry. RESULTS: The frequency of rs1800896 C allele was significantly lower in the patients with IBS-D than that in the HC (odds ratio: 0.49, 95% confidence interval: 0.27-0.92, P = 0.0240). The IL-10 levels in the plasma (P = 0.0030) and PBMC culture supernatant (P = 0.0500) of the CT genotype subjects were significantly higher than those in the TT genotype subjects. The CT genotype subjects exhibited a higher pain threshold in the rectal distention test than the TT genotype subjects. Moreover, IL-10 rs1800871 GG genotype subjects showed an increase in the HADS score compared to other genotype subjects. CONCLUSIONS: IL-10 rs1800896 C allele is correlated with higher IL-10 levels in the plasma and the PBMC culture supernatant, which is associated with a higher pain threshold in the Chinese patients with IBS-D. This study provides an explicit relationship of IL-10 polymorphisms with IL-10 production, which might help in understanding the pathogenesis of IBS-D.


Assuntos
Diarreia/sangue , Diarreia/genética , Interleucina-10/sangue , Interleucina-10/genética , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/genética , Adolescente , Adulto , Idoso , Diarreia/patologia , Genótipo , Humanos , Síndrome do Intestino Irritável/patologia , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
14.
Semin Diagn Pathol ; 36(3): 187-192, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31036328

RESUMO

Knowledge of the pathogenic roles of certain bacterial agents in gastroenteritis has been growing over the past few decades. With the increasing use of multiplex molecular-based syndromic stool pathogen panels, the roles of Plesiomonas shigelloides and some of the diarrheagenic pathotypes of Escherichia coli (enterotoxigenic E. coli [ETEC], enteropathogenic E. coli [EPEC], enteroinvasive E. coli [EIEC], and enteroaggregative E. coli [EAEC]) have been better understood. Although not currently targeted on Food and Drug Administration (FDA)-cleared commercial multiplex stool panels, Aeromonas has also emerged as a possible cause of bacterial gastroenteritis. The clinical presentation, pathophysiology, and diagnostic approaches to these pathogens in stool specimens are reviewed. Variability in inclusion of these pathogens on multiplex molecular panels and difficulties in detection by stool culture techniques utilized by clinical microbiology laboratories have contributed to an unclear understanding of the pathogenic role of several of these pathogens. Nonetheless, most evidence points towards a clear pathogenic role for P. shigelloides and ETEC, and possibly EPEC and EIEC. The contribution of Aeromonas spp. and EAEC to bacterial gastroenteritis has not been fully established. Further studies of pathogenicity of these pathogens are needed.


Assuntos
Aeromonas/isolamento & purificação , Infecções Bacterianas/patologia , Doenças Transmissíveis Emergentes/patologia , Diarreia/patologia , Escherichia coli/isolamento & purificação , Gastroenterite/patologia , Plesiomonas/isolamento & purificação , Infecções Bacterianas/diagnóstico , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/microbiologia , Diarreia/diagnóstico , Diarreia/microbiologia , Fezes/microbiologia , Gastroenterite/diagnóstico , Gastroenterite/microbiologia , Humanos
15.
Rev Gastroenterol Peru ; 39(1): 21-26, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31042233

RESUMO

INTRODUCTION: Functional dyspepsia (FD) is a complex symptom. Currently there are multiple therapeutic options that are used for the management of these patients; however, FD therapies are based on symptomatic control and do not address the pathophysiological pathways involved in its development. The duodenum has been proposed as a key site to understand the complex pathophysiology involved in FD. OBJECTIVE: The aim of the study is to determine duodenal eosinophilia in patients with FD and establish the clinical-pathological correlation with the cardinal symptoms of dyspepsia. MATERIAL AND METHODS: Case-control study. Patients older than 18 years with dyspepsia according to the Rome IV criteria, and upper gastrointestinal endoscopy normal (FD group).Patients with iron deficiency anemia and chronic diarrhea (control group). Biopsies were taken in the stomach, duodenal bulb and second portion of duodenum. A sample size of 140 patients (70 patients in the FD group and 70 patients in the control group) was calculated. The collected information was described and analyzed by conventional statistical techniques. RESULTS: 243 patients were recruited. 84 patients were included in the FD group and 84 patients in the control group. 135 patients were women (80.3%). The mean age was 53.6 years (SD 14.9). Duodenal eosinophilia was found with significant difference in patients with early satiety (p=0.01). There was no difference in patients with postprandial fullness (p=0.63), epigastric pain or burning (p=0.26), gastroesophageal reflux symptoms (p=0.13), allergy and food intolerance (p=0.42) and smoking (p=0.28). There was no relationship between duodenal mastocytosis and early satiety (p=0.98), postprandial fullness (p=0.78), and epigastric pain or burning (p=0.82). CONCLUSIONS: Duodenal eosinophilia was similar in FD and controls. In subgroup analysis, duodenal eosinophilia occurs in patients with early satiety.


Assuntos
Duodenopatias/epidemiologia , Dispepsia/epidemiologia , Eosinofilia/epidemiologia , Dor Abdominal/epidemiologia , Adulto , Anemia Ferropriva/patologia , Estudos de Casos e Controles , Doença Crônica , Comorbidade , Diarreia/patologia , Duodenopatias/patologia , Dispepsia/patologia , Eosinofilia/patologia , Feminino , Intolerância Alimentar/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Humanos , Masculino , Mastocitose/epidemiologia , Saciação , Fumar/epidemiologia , Avaliação de Sintomas
16.
Biomed Res Int ; 2019: 4530203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073525

RESUMO

Effects of the microbiome associated with diarrhea-predominant irritable bowel syndrome (IBS-D) on the gut have been reported, but no study has reported the effects of the IBS-D gut microbiome on the liver. We transplanted the fecal microbiota from an IBS-D patient and from a healthy volunteer to GF rats. The hepatic inflammation, serum biochemical parameters and metabolome, fecal microbiota profile, fecal short-chain fatty acids (SCFAs), and correlations among them before and after berberine intervention were assessed. Compared with the healthy control fecal microbiome transplantation (FMT) rats, the fecal microbiota of IBS-D patients induces significant Kupffer cell hyperplasia, hepatic sinusoid hypertrophy, and elevated levels of hepatic tumor necrosis factor-α and interferon-γ and decreases the synthesis of ALB in GF rats. This is possibly related to Faecalibacterium and Bifidobacterium attributable to fecal formate, acetate, and propionate levels, which are associated with the host linoleic acid pathway. Berberine can partially reverse the Kupffer cell hyperplasia, Faecalibacterium, fecal formate, acetate, and propionate by modulating the gut microbiome composition. These results may imply that IBS-D not only is an intestinal functional disorder but can cause liver inflammation, thus providing some implications regarding the clinical cognition and treatment of IBS-D.


Assuntos
Berberina/administração & dosagem , Diarreia/tratamento farmacológico , Inflamação/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Animais , Bifidobacterium/efeitos dos fármacos , Bifidobacterium/patogenicidade , Diarreia/microbiologia , Diarreia/patologia , Modelos Animais de Doenças , Faecalibacterium/efeitos dos fármacos , Faecalibacterium/patogenicidade , Transplante de Microbiota Fecal , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Humanos , Inflamação/microbiologia , Inflamação/patologia , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/patologia , Macrófagos do Fígado/efeitos dos fármacos , Macrófagos do Fígado/patologia , Fígado/microbiologia , Fígado/patologia , Ratos
17.
Animal ; 13(11): 2463-2472, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31084646

RESUMO

Dietary protein restriction is one of the effective ways to reduce post-weaning diarrhoea and intestinal fermentation in piglets, but it may also reduce growth performance. The compensatory growth induced by subsequent protein realimentation may solve the issue. However, little research has been done on the impact of protein realimentation on the gut. In this study, the effects of protein restriction and realimentation on ileal morphology, ileal microbial composition and metabolites in weaned piglets were investigated. Thirty-six 28-day-old weaned piglets with an average body weight of 6.47 ± 0.04 kg were randomly divided into a control group and a treatment group. The CP level in the diet of the control group was 18.83% for the entire experimental period. The piglets in the treatment group were fed 13.05% CP between days 0 and 14 and restored to a diet of 18.83% CP for days 14 to 28. On day 14 and 28, six pigs from each group were sacrificed and sampled. It was found that the abundance of Lactobacillus and Salmonella in the ileal digesta was significantly lower in the treatment group than the control group on day 14, whereas the abundance of Clostridium sensu stricto 1, Streptococcus, Halomonas and Pseudomonas significantly increased in the ileal digesta of the treatment group on day 14 compared with the control group. In addition, reduced concentrations of lactic acid, total short-chain fatty acids (total SCFAs), total branched chain fatty acids, ammonia and impaired ileal morphology and mucosal barrier were observed in the treatment group on day 14. However, diarrhoea levels decreased in the treatment group throughout the experiment. During the succedent protein realimentation stage, the treatment group demonstrated compensatory growth. Compared with the control group, the treatment group showed increased abundance of Lactobacillus and reduced abundance of Salmonella, Halomonas and Pseudomonas in the ileum on day 28. The concentrations of lactic acid and total SCFAs increased significantly, whereas the concentration of ammonia remained at a lower level in the treatment group on day 28 compared with the control group. Overall, protein realimentation could improve ileal morphology and barrier functions and promote ileal digestive and absorptive functions. In conclusion, ileal microbial composition and metabolites could change according to dietary protein restriction and realimentation and eventually influence ileal morphology and barrier functions.


Assuntos
Ração Animal/análise , Diarreia/veterinária , Dieta com Restrição de Proteínas/veterinária , Doenças dos Suínos/microbiologia , Suínos/fisiologia , Amônia/análise , Animais , Diarreia/microbiologia , Diarreia/patologia , Dieta/veterinária , Proteínas na Dieta/metabolismo , Digestão , Ácidos Graxos/análise , Ácidos Graxos Voláteis/análise , Íleo/microbiologia , Íleo/patologia , Ácido Láctico/análise , Lactobacillus/isolamento & purificação , Distribuição Aleatória , Salmonella/isolamento & purificação , Suínos/microbiologia , Doenças dos Suínos/patologia , Desmame
18.
Nat Commun ; 10(1): 1826, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015451

RESUMO

The bacterial pathogen Shigella flexneri causes 270 million cases of bacillary dysentery (blood in stool) worldwide every year, resulting in more than 200,000 deaths. A major challenge in combating bacillary dysentery is the lack of a small-animal model that recapitulates the symptoms observed in infected individuals, including bloody diarrhea. Here, we show that similar to humans, infant rabbits infected with S. flexneri experience severe inflammation, massive ulceration of the colonic mucosa, and bloody diarrhea. T3SS-dependent invasion of epithelial cells is necessary and sufficient for mediating immune cell infiltration and vascular lesions. However, massive ulceration of the colonic mucosa, bloody diarrhea, and dramatic weight loss are strictly contingent on the ability of the bacteria to spread from cell to cell. The infant rabbit model features bacterial dissemination as a critical determinant of S. flexneri pathogenesis and provides a unique small-animal model for research and development of therapeutic interventions.


Assuntos
Diarreia/patologia , Disenteria Bacilar/patologia , Hemorragia Gastrointestinal/patologia , Shigella flexneri/patogenicidade , Sistemas de Secreção Tipo III/imunologia , Animais , Animais Recém-Nascidos/microbiologia , Colo/microbiologia , Colo/patologia , Diarreia/microbiologia , Modelos Animais de Doenças , Disenteria Bacilar/microbiologia , Células Epiteliais/microbiologia , Feminino , Hemorragia Gastrointestinal/microbiologia , Células HT29 , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Gravidez , Coelhos
19.
Int J Oncol ; 54(4): 1376-1386, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30968152

RESUMO

Irinotecan (CPT­11) is a DNA topoisomerase I inhibitor which is widely used in clinical chemotherapy, particularly for colorectal cancer treatment. However, late­onset diarrhea is one of the severe side­effects of this drug and this restricts its clinical application. The present study aimed to investigate the protective effects of curcumin treatment on CPT­11­induced intestinal mucosal injury both in vitro and in vivo and to elucidate the related mechanisms involved in these effects. For this purpose, mice were intraperitoneally injected with CPT­11 (75 mg/kg) for 4 days to establish a model of late­onset diarrhea. Curcumin (100 mg/kg) was intragastrically administered 8 days before the injection of CPT­11. Injury to small intestinal tissues was examined by H&E staining. The protein expression of prolyl 4­hydroxylase subunit beta (P4HB) and peroxiredoxin 4 (PRDX4) was detected by immunohistochemistry, as well as western blot analysis. IEC­6 cell viability was detected by MTT assay. Flow cytometry was performed to examine the cell apoptotic rate, mitochondrial membrane potential and reactive oxygen species (ROS) generation. Immunofluorescence was used to observe the localization of nuclear factor (NF)­κB. The levels of cleaved caspase­3, glucose­regulated protein, 78 kDa (GRP78), P4HB, PRDX4 and CHOP were detected by western blot analysis. The results revealed that in vivo, curcumin effectively attenuated the symptoms of diarrhea and abnormal intestinal mucosa structure induced by CPT­11 in nude mice. Treatment with curcumin also increased the expression of P4HB and PRDX4 in the tissue of the small intestine. In vitro, curcumin, exhibited little cytotoxicity when used at concentrations <2.5 µg/ml for 24 h in IEC­6 cells. At this concentration, curcumin also improved cell morphology, inhibited apoptosis, maintained mitochondrial membrane potential and reduced the elevated levels of ROS induced by CPT­11 (20 µg/ml). Furthermore, curcumin abolished NF­κB signal transduction and protected the cells from CPT­11­induced apoptosis by upregulating the expression of molecular chaperones, such as GRP78, P4HB and PRDX4, and suppressing the levels of the apoptosis­related proteins, CHOP and cleaved caspase­3. On the whole, our data indicate that curcumin exerted protective effects against CPT­11­induced intestinal mucosa injury. The protective effects of curcumin are mediated by inhibiting the activation of NF­κB, and suppressing oxidative stress and endoplasmic reticulum stress.


Assuntos
Curcumina/farmacologia , Diarreia/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Irinotecano/efeitos adversos , Inibidores da Topoisomerase I/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Neoplasias Colorretais/tratamento farmacológico , Curcumina/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais , Humanos , Injeções Intraperitoneais , Mucosa Intestinal/citologia , Mucosa Intestinal/patologia , Irinotecano/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Inibidores da Topoisomerase I/administração & dosagem , Resultado do Tratamento
20.
Biomed Pharmacother ; 113: 108751, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30870717

RESUMO

A rising amount of evidences show that gut microbiota is an important factor in mediating the growth of ulcerative colitis (UC), the major product of colon bacteria fermentation butyrate as mediator have effects on the mucosal immune system by expanding regulatory T cells (Treg) in the colon. Turkish galls, an insect gall parasitized on the tree branches of Quercus infectoria Oliv., exhibiting the promising prospect in treating the remedy of UC by regulating the bacteria, whereas its mechanism remains unclear. Here, this work found that three types of gut bacteria collaborating to improve DSS-induced UC in mice after Turkish galls intervention, including putative SCFAs-producing bacteria (PCPB), anti-inflammatory bacteria and harmful bacteria. The Helicobacter, Bilophila, Acinetobacter and Odoribacter, which belong to the harmful bacteria were dramatically increased in UC group, whereas the harmful bacteria were reduced after treatment with Turkish galls. The Allobaculum, Bacteriodes, Blautia, Butyricimonas, belonging to PCPB, were significantly increased after Turkish galls and butyrate intervention, and we also observed that the concentration of butyrate increased with the grows of PCPB. The Bifidobacterium, Lactococcus, which belong to the anti-inflammatory bacteria, were also significantly increased after Turkish galls intervention. Meanwhile, rectal administration of Turkish galls and butyrate could increase mucosa inflammation and diarrhea. The expression of cytokines in the colon was improved by butyrate and Turkish galls treatment group. The percentage of Treg out of CD4+ population was evaluated by flow cytometry after Turkish galls and butyrate intervention. The results suggested that Turkish galls alleviated UC by modulating three types of the gut microbiota, and butyrate may be used to relieve inflammatory. This study may help us to understand the mechanism of Turkish galls in treating UC from the perspective of intestinal flora and also offered a mechanism reference for UC treatment using an insect gall in rich of polyphenolic compounds.


Assuntos
Colite Ulcerativa/terapia , Enema , Microbioma Gastrointestinal , Medicina Tradicional Chinesa/métodos , Animais , Butiratos/metabolismo , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Sulfato de Dextrana/toxicidade , Diarreia/patologia , Diarreia/terapia , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Inflamação/patologia , Inflamação/terapia , Insetos , Masculino , Camundongos , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Quercus/parasitologia , Linfócitos T Reguladores/imunologia
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