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1.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2496-2499, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018513

RESUMO

The small intestine is the primary site of enzymatic digestion and nutrient absorption in humans. Intestinal contractions facilitate digesta mixing, transport and contact with the absorptive surfaces. These motility patterns are regulated by an underlying electrical activity, termed slow waves. In this study, we use computational fluid dynamics simulation of flow and mixing of intestinal contents in the human duodenum with anatomically realistic geometry and contraction patterns. Parameters including the amplitude of contraction (10-50% reduction of radius) and the rheology of the digesta (Newtonian vs Non-Newtonian power law fluid) were altered in-order to study their effects on mixing. Interesting flow features such as stagnation points and reversed flow were observed with digesta. Increases in the amplitude of contraction lead to increased propulsion of digesta along the intestine and increased mixing.


Assuntos
Duodeno , Intestino Delgado , Conteúdo Gastrointestinal , Humanos , Intestinos , Reologia
2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3953-3956, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018865

RESUMO

Intestinal motility is coordinated by myogenic, neuronal and hormonal factors. Myogenic control of motility via bioelectric slow waves (SW) has been investigated using low-resolution and high-resolution (HR) electrical mapping techniques. Due to the highly conformable and irregular surface of the gut, suboptimal coverage of HR recordings may occur. In this study we designed and developed an inflatable cuff as a platform to apply even pressure across the intestinal surface to achieve consistent and reliable recordings. The inflatable cuff and a HR electrode array were applied in vivo to demonstrate the reliability of SW signal acquisition over a range of inflatable pressures (0 - 5 mm Hg). The frequency, amplitude, percentage of viable signals and signal to noise ratio metrics of the SW signals were computed and compared. Overall, with an increase in inflatable pressure from 0 to 5 mm Hg, the frequency did not change, but the amplitude of the SWs decreased from 0.10 to 0.07 mV. The noise levels were consistent across the range of inflatable pressure levels and the percentage of viable SW recordings improved significantly from 57% to 74% after application of 1 mm Hg of pressure. The inflatable and conformable cuff presented in this study provides a reliable platform for HR mapping of bioelectrical events in the intestines and other conformable organs.Clinical Relevance- This framework improves the quality and reliability of bioelectrical high-resolution recordings obtained from the small intestine. In the future, these recordings will improve our understanding of the pathophysiological mechanisms governing intestinal motility disorders and may provide clinicians with new strategies for diagnosis and treatment.


Assuntos
Motilidade Gastrointestinal , Intestino Delgado , Fenômenos Eletrofisiológicos , Reprodutibilidade dos Testes , Razão Sinal-Ruído
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 4204-4207, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018924

RESUMO

The gastrointestinal (GI) tract is in part controlled by slow wave electrical activity. Recordings of slow waves with high-resolution (HR) electrode arrays are used to characterize normal and abnormal conduction pathways. Improving the quality of these electrical recordings is important for developing a better understanding of abnormal activity. Contact pressure is one factor that can affect the quality of electrical recordings. We compared the performance of two pressure sensing devices for measuring HR electrode array contact pressure. A Velostat-based sensor array was custom designed and built in a 4 × 2 conguration (area: 30 mm2 per sensor) to be integrated into electrical recordings. Commercially available FlexiForce A201 sensors were used to compare to the Velostat-based sensors. Benchtop testing of these sensors was performed; the error of the Velostat-based sensors (14-31%) was better than that of the FlexiForce sensors (20-49%) within a range of 2666-6666 Pa. The Velostat-based sensors were also more repeatable than the FlexiForce sensors over the same pressure range. Simultaneous pressure and slow wave recordings were performed in vivo on a rabbit small intestine. The Velostat-based sensors were able to resolve spatiotemporal changes in contact pressure in the range of 0-10 000 Pa.


Assuntos
Microbioma Gastrointestinal , Trato Gastrointestinal , Animais , Eletricidade , Eletrodos , Intestino Delgado , Coelhos
4.
Chem Biol Interact ; 331: 109274, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007288

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Mutations in the adenomatous polyposis coli (APC) gene are pivotal in colorectal tumorigenesis. Recently, we demonstrated that aldehyde dehydrogenase 1B1 (ALDH1B1) knockdown dramatically reduced colon tumor growth in a mouse xenograft model. The purpose of the present preliminary study is to examine the effect of loss of ALDH1B1 in CRC development in an inducible colon-specific Apc mouse model. METHODS: ApcW/FCdx2ERT2-Cre mice develop uni-allelic inactivation of Apc specifically in colon epithelial cells following tamoxifen treatment. Aldh1b1-/- KO mice were crossed with ApcW/FCdx2ERT2-Cre mice. Six-month-old male ApcW/FCdx2ERT2-Cre/Aldh1b1-/-, and ApcW/FCdx2ERT2-Cre/Aldh1b1+/+ mice were treated with tamoxifen (50 mg/kg, i.p.) for three consecutive days. ApcW/F/Aldh1b1-/- and ApcW/F/Aldh1b1+/+ mice were treated with corn oil (i.e., tamoxifen vehicle control) for three consecutive days. Eighteen days later, mice were sacrificed and their colons examined microscopically, macroscopically and histologically for the presence of adenoma. RESULTS: All ApcW/FCdx2ERT2-Cre/Aldh1b1+/+ and ApcW/FCdx2ERT2-Cre/Aldh1b1-/- mice treated with tamoxifen developed colorectal adenoma. The ApcW/FCdx2ERT2-Cre/Aldh1b1-/- mice showed a significant decrease in the total volume of all ileal and colonic adenomas, and decreased incidence of large colonic adenoma compared to ApcW/FCdx2ERT2-Cre/Aldh1b1+/+ mice. Immunohistochemical analysis of p53 and ß-catenin showed a trend toward decreased expression score in colonic adenomas of ApcW/FCdx2ERT2-Cre/Aldh1b1-/- mice. CONCLUSION: The present preliminary study suggests that deletion of ALDH1B1 may protect against the full development of colorectal cancer. Further mechanistic studies are required to elucidate how ALDH1B1 contributes for colorectal cancer.


Assuntos
Polipose Adenomatosa do Colo/patologia , Aldeído Desidrogenase 1/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Neoplasias Colorretais/patologia , Polipose Adenomatosa do Colo/metabolismo , Aldeído Desidrogenase 1/deficiência , Aldeído Desidrogenase 1/genética , Aldeído-Desidrogenase Mitocondrial/deficiência , Aldeído-Desidrogenase Mitocondrial/genética , Animais , Neoplasias Colorretais/metabolismo , Modelos Animais de Doenças , Genótipo , Intestino Grosso/metabolismo , Intestino Grosso/patologia , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Camundongos , Camundongos Knockout , Tamoxifeno , Proteína Supressora de Tumor p53/metabolismo , beta Catenina/metabolismo
5.
Medicine (Baltimore) ; 99(44): e22741, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126311

RESUMO

Percutaneous balloon dilatation for benign biliary-enteric anastomosis stricture has been the most widely used alternative to endoscopic treatment. However, patency results from the precedent literature are inconsistent.The objective of this study was to evaluate the safety and feasibility of repeated balloon dilatation with long-term biliary drainage for the treatment of benign biliary-enteric anastomosis strictures.Data from patients with benign biliary-enteric anastomosis strictures who underwent percutaneous transhepatic cholangiography (PTC), repeated balloon dilatation with long-term biliary drainage (repeated-dilatation group; n = 23), or PTC and single balloon dilatation with long-term biliary drainage (single-dilatation group; n = 26) were reviewed. Postoperative complications, jaundice remission, and sustained anastomosis patency were compared between the groups.All procedures were successful. No severe intraoperative complications, such as biliary bleeding and perforation, were observed. The jaundice remission rate in the first week was similar in the 2 groups. During the 26-month follow-up period, 3 patients in the repeated-dilatation group had recurrences (mean time to recurrence: 22.84 ±â€Š0.67 months, range: 18-26 months). In the single-dilatation group, 15 patients had recurrences (mean time to recurrence = 15.28 ±â€Š1.63 months, range: 3-18 months). The duration of patency after dilatation was significantly better in the repeated-dilatation group (P = .01). All patients with recurrence underwent repeat PTC followed by balloon dilatation and biliary drainage.Repeated balloon dilatation and biliary drainage is an effective, minimally invasive, and safe procedure for treating benign biliary-enteric anastomosis strictures, and provides significantly higher patency rates than single dilatation.


Assuntos
Cateterismo/métodos , Dilatação/métodos , Drenagem/métodos , Complicações Pós-Operatórias/cirurgia , Estomas Cirúrgicos/efeitos adversos , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Intestino Delgado/patologia , Intestino Delgado/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Estomas Cirúrgicos/patologia , Resultado do Tratamento
6.
Sci Total Environ ; 741: 140419, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32886984

RESUMO

Fluoride (F) is largely employed in dentistry, in therapeutic doses, to control caries. However, excessive intake may lead to adverse effects in the body. Since F is absorbed mostly from the gastrointestinal tract (GIT), gastrointestinal symptoms are the first signs following acute F exposure. Nevertheless, little is known about the mechanistic events that lead to these symptoms. Therefore, the present study evaluated changes in the proteomic profile as well as morphological changes in the jejunum and ileum of rats upon acute exposure to F. Male rats received, by gastric gavage, a single dose of F containing 0 (control) or 25 mg/Kg for 30 days. Upon exposure to F, there was a decrease in the thickness of the tunic muscularis for both segments and a decrease in the thickness of the wall only for the ileum. In addition, a decrease in the density of HuC/D-IR neurons and nNOS-IR neurons was found for the jejunum, but for the ileum only nNOS-IR neurons were decreased upon F exposure. Moreover, SP-IR varicosities were increased in both segments, while VIP-IR varicosities were increased in the jejunum and decreased in the ileum. As for the proteomic analysis, the proteins with altered expression were mostly negatively regulated and associated mainly with protein synthesis and energy metabolism. Proteomics also revealed alterations in proteins involved in oxidative/antioxidant defense, apoptosis and as well as in cytoskeletal proteins. Our results, when analyzed together, suggest that the gastrointestinal symptoms found in cases of acute F exposure might be related to the morphological alterations in the gut (decrease in the thickness of the tunica muscularis) that, at the molecular level, can be explained by alterations in the gut vipergic innervation and in proteins that regulate the cytoskeleton.


Assuntos
Fluoretos , Jejuno , Animais , Íleo , Intestino Delgado , Masculino , Proteômica , Ratos
7.
Am Surg ; 86(9): 1178-1184, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32935996

RESUMO

BACKGROUND: Nonoperative management of adhesive small bowel obstruction (ASBO) results in resolution for the majority of patients. Previous studies have demonstrated that outcomes for patients with ASBO are improved when patients are admitted to a surgical service, but the effect of general surgery resident coverage is unclear. This study measures quality outcomes for patients with ASBO after the establishment of a new general surgery residency program. METHODS: An institutional review board-approved retrospective chart review of admissions for ASBO was conducted following the implementation of a protocol for ASBO nested within a newly developed resident-run emergency general surgery (EGS) service. Patients successfully treated without operative intervention were analyzed. RESULTS: During the study period, 612 patients were admitted for ASBO. After initiation of the residency, 74% of ASBO were admitted to a surgical service compared with 35% prior to residency (P < .01). Length of stay was reduced by 0.77 days (P = .016), average direct total cost per patient was reduced by 24% (P = .002), and 30-day readmissions were reduced by 35.7% (P = .046). There was no significant difference in mortality (1.4% vs 1.0%). DISCUSSION: Admission to a resident-run surgical service was associated with statistically significant improvement in outcomes for patients with ASBO. These data corroborate prior studies demonstrating the positive impact of residency programs on patient outcomes and provide additional evidence that general surgery residency programs improve outcomes for patients with surgical disease.


Assuntos
Tratamento Conservador/métodos , Educação de Pós-Graduação em Medicina/métodos , Cirurgia Geral/educação , Internato e Residência/métodos , Obstrução Intestinal/terapia , Tempo de Internação/tendências , Readmissão do Paciente/tendências , Idoso , Feminino , Humanos , Intestino Delgado , Masculino , Estudos Retrospectivos
9.
Nat Commun ; 11(1): 4791, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963229

RESUMO

The ability to absorb ingested nutrients is an essential function of all metazoans and utilizes a wide array of nutrient transporters found on the absorptive enterocytes of the small intestine. A unique population of patients has previously been identified with severe congenital malabsorptive diarrhea upon ingestion of any enteral nutrition. The intestines of these patients are macroscopically normal, but lack enteroendocrine cells (EECs), suggesting an essential role for this rare population of nutrient-sensing cells in regulating macronutrient absorption. Here, we use human and mouse models of EEC deficiency to identify an unappreciated role for the EEC hormone peptide YY in regulating ion-coupled absorption of glucose and dipeptides. We find that peptide YY is required in the small intestine to maintain normal electrophysiology in the presence of vasoactive intestinal polypeptide, a potent stimulator of ion secretion classically produced by enteric neurons. Administration of peptide YY to EEC-deficient mice restores normal electrophysiology, improves glucose and peptide absorption, diminishes diarrhea and rescues postnatal survival. These data suggest that peptide YY is a key regulator of macronutrient absorption in the small intestine and may be a viable therapeutic option to treat patients with electrolyte imbalance and nutrient malabsorption.


Assuntos
Células Enteroendócrinas/metabolismo , Absorção Intestinal/fisiologia , Transporte de Íons/fisiologia , Nutrientes/metabolismo , Animais , Enterócitos , Glucose/metabolismo , Células-Tronco Embrionárias Humanas , Humanos , Intestino Delgado , Intestinos , Camundongos , Camundongos Endogâmicos C57BL , Peptídeo YY , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Trocador 3 de Sódio-Hidrogênio , Água/metabolismo
10.
PLoS One ; 15(9): e0236964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32931498

RESUMO

BACKGROUND: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α). METHODS: We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine. RESULTS: Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine. CONCLUSIONS: Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Intestino Delgado/irrigação sanguínea , Neovascularização Fisiológica , Síndrome do Intestino Curto/cirurgia , Animais , Receptores ErbB/genética , Receptores ErbB/fisiologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Intestino Delgado/metabolismo , Masculino , Camundongos , Técnicas Analíticas Microfluídicas , Miofibroblastos , Síndrome do Intestino Curto/metabolismo
12.
Parasitol Res ; 119(11): 3649-3657, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32951143

RESUMO

Toxoplasma gondii is a protozoan parasite capable of infecting a large number of warm-blooded animals and causes serious health complications in immunocompromised patients. T. gondii infection of the feline small intestine is critical for the completion of the life cycle and transmission of T. gondii. Protein acetylation is an important posttranslational modification, which plays roles in the regulation of various cellular processes. Therefore, understanding of how T. gondii reprograms the protein acetylation status of feline definitive host can help to thwart the production and spread of T. gondii. Here, we used affinity enrichment and high-resolution liquid chromatography with tandem mass spectrometry to profile the alterations of the acetylome in cat small intestine 10 days after infection by T. gondii Prugniuad (Pru) strain. Our analysis showed that T. gondii induced significant changes in the acetylation of proteins in the cat intestine. We identified 2606 unique lysine acetylation sites in 1357 acetylated proteins. The levels of 334 acetylated peptides were downregulated, while the levels of 82 acetylated peptides were increased in the infected small intestine. The proteins with differentially acetylated peptides were particularly enriched in the bioenergetics-related processes, such as tricarboxylic acid cycle, oxidative phosphorylation, and oxidation-reduction. These results provide the first baseline of the global acetylome of feline small intestine following T. gondii infection and should facilitate further analysis of the role of acetylated protein in the pathogenesis of T. gondii infection in its definitive host.


Assuntos
Doenças do Gato/parasitologia , Intestino Delgado/metabolismo , Toxoplasma , Toxoplasmose/metabolismo , Acetilação , Animais , Doenças do Gato/metabolismo , Gatos , Cromatografia Líquida de Alta Pressão/veterinária , Feminino , Intestino Delgado/parasitologia , Lisina/metabolismo , Masculino , Processamento de Proteína Pós-Traducional , Espectrometria de Massas em Tandem/veterinária , Toxoplasma/metabolismo
13.
Zhen Ci Yan Jiu ; 45(9): 771-5, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32959563

RESUMO

Gastrointestinal motility dysfunction is not only a pathogenic factor but also a pathological manifestation. The authors summarize the recent studies on the mechanism of acupuncture and moxibustion in regulating gastrointestinal motility and analyze the effect of acupuncture and moxibustion on the brain-vagus-enteric nervous system, interstitial cells of Cajal, gastrointestinal peptides, gastrointestinal smooth muscle, and signaling pathways. The authors also put forward some suggestions for future research, including the research centering on gastrointestinal motility to explore the role of acupuncture and moxibustion in regulating gastrointestinal motility for disease prevention and treatment, specificity of acupoints, and dual-directional regulation of acupuncture and moxibustion, and the research focusing on intestinal microflora and influential factors for excitability of enteric neurons to explore the potential mechanism of acupuncture and moxibustion in regulating gastrointestinal motility, in order to provide a reference for future research.


Assuntos
Terapia por Acupuntura , Moxibustão , Motilidade Gastrointestinal , Intestino Delgado
14.
Proc Natl Acad Sci U S A ; 117(38): 23663-23673, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32900967

RESUMO

Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene that encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 chromatin immunoprecipitation (ChIP) sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes, which included Mdm2 but not p21 Global p53 activation caused a metaplastic phenotype in the pancreas that was missing in mice with acinar-specific p53 activation, suggesting non-cell-autonomous effects. The p53 cellular response at single-cell resolution in the intestine altered transcriptional cell state, leading to a proximal enterocyte population enriched for genes within oxidative phosphorylation pathways. In addition, a population of active CD8+ T cells was recruited. Combined, this study provides a comprehensive profile of the p53 transcriptional response in vivo, revealing both tissue-specific transcriptomes and a unique signature, which were integrated to induce both cell-autonomous and non-cell-autonomous responses and transcriptional plasticity.


Assuntos
Especificidade de Órgãos/genética , Análise de Célula Única , Transcriptoma/genética , Proteína Supressora de Tumor p53 , Animais , Imunoprecipitação da Cromatina , Feminino , Intestino Delgado/citologia , Intestino Delgado/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Pâncreas/citologia , Pâncreas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
18.
J Toxicol Sci ; 45(9): 539-548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879253

RESUMO

We investigated the mechanism underlying intestinal cadmium (Cd) uptake based on the mediators (metal transporters) of essential elements, such as Fe, Zn, Cu, and Ca, under normal conditions in female rats. These elements interact with Cd uptake from the intestinal tract. Cd concentration at each site of the small intestine (duodenum, jejunum, and ileum) increased as Cd exposure increased. However, Cd concentration was the highest in the duodenum. The gene expression of ZIP14, DMT1, and ATP7A increased with increase in Cd concentration. Further, Cu concentration decreased as Cd concentration increased. In contrast, Fe concentration displayed a decreasing tendency with the increase in Cd concentration. The gene expression levels of ZIP14, DMT1, and ATP7A were positively correlated with Cd concentration. Immunohistochemical staining revealed the positive sites of ZIP14 and DMT1 scattered in the area adjacent to the goblet cells, resorbable epithelial cells, and lamina propria in the duodenum tissue, according to the increase in Cd concentration. Cd is induced to synthesize and bind to metallothionein (MT-I and -II) and accumulate in the intestinal tissues, mainly in the duodenum. Such findings suggest that Cd, a contaminant element, is taken up from the intestinal tract by multiple metal transporters such as Cu, Fe, and Zn, thereby involving in the intestinal Cd absorption.


Assuntos
Cádmio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Absorção Intestinal/genética , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Cobre , ATPases Transportadoras de Cobre/genética , ATPases Transportadoras de Cobre/metabolismo , Duodeno/metabolismo , Feminino , Expressão Gênica , Ferro , Metalotioneína/metabolismo , Ratos , Zinco
19.
PLoS Negl Trop Dis ; 14(9): e0008711, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32997666

RESUMO

Environmental enteric dysfunction (EED) is an intestinal disorder common among children in low-resource settings and is associated with increased risk of growth stunting, cognitive deficits, and reduced oral vaccine immunogenicity. The Micronutrient and EED Assessment Tool (MEEDAT) is a multiplexed immunoassay that measures biomarkers previously associated with child growth faltering and/or oral vaccine immunogenicity: intestinal fatty acid-binding protein (I-FABP), soluble CD14 (sCD14), insulin-like growth factor 1 (IGF-1), and fibroblast growth factor 21 (FGF21). MEEDAT also measures systemic inflammation (α1-acid glycoprotein, C-reactive protein), ferritin, soluble transferrin receptor, retinol binding protein 4, thyroglobulin, and Plasmodium falciparum antigenemia (histidine-rich protein 2). The performance of MEEDAT was compared with commercially available enzyme-linked immunosorbent assays (ELISAs) using 300 specimens from Malian infant clinical trial participants. Regression methods were used to test if MEEDAT biomarkers were associated with seroconversion to meningococcal A conjugate vaccine (MenAV), yellow fever vaccine (YFV), and pentavalent rotavirus vaccine (PRV) after 28 days, or with growth faltering over 12 weeks. The Pearson correlations between the MEEDAT and ELISA results were 0.97, 0.86, 0.80, and 0.97 for serum I-FABP, sCD14, IGF-1, and FGF21, respectively. There were significant associations between I-FABP concentration and the probability of PRV IgG seroconversion and between IGF-1 concentration and the probability of YFV seroconversion. In multivariable models neither association remained significant, however there was a significant negative association between AGP concentration and YFV seroconversion. GLP-2 and sCD14 concentrations were significantly negatively associated with 12-week change in weight-for-age z-score and weight-for-height z-score in multivariable models. MEEDAT performed well in comparison to commercially-available ELISAs for the measurement of four analytes for EED and growth hormone resistance. Adoption of MEEDAT in low-resource settings could help accelerate the identification of interventions that prevent or treat child stunting and interventions that boost the immunogenicity of child vaccinations.


Assuntos
Imunogenicidade da Vacina/imunologia , Enteropatias/imunologia , Micronutrientes/imunologia , Vacinas/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/imunologia , Febre Amarela/prevenção & controle , Biomarcadores/sangue , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação a Ácido Graxo , Feminino , Ferritinas/sangue , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Lactente , Inflamação , Fator de Crescimento Insulin-Like I/metabolismo , Intestino Delgado , Receptores de Lipopolissacarídeos , Masculino , Mali , Proteínas Plasmáticas de Ligação ao Retinol , Fatores de Risco , Vacinação
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(8): 723-727, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32810942

RESUMO

Radiation intestinal injury (RII) refers to the intestinal complication resulting from radiation therapy of pelvic, abdominal or retroperitoneal tumor, which involves the small intestine, colon and rectum. Although the advances in radiotherapy technology have decreased the injury of adjacent tissues, 90% of the patients receiving radiotherapy have acute symptoms, the quality of life is affected due to gastrointestinal symptoms in 50% of patients, and 20%-40% of patients have moderate to severe symptoms. Based on the pathological stage, characteristics and clinical manifestations, RII can be divided into acute and chronic types, generally 3 to 6 months as the cutoff in clinical history. The main preventions of RII include reducing the radiation doses and narrowing the exposure fields. Acute RII is characterized by mucosal inflammation and self-limitation, and its treatment includes symptomatic and nutritional management. As the chronic ischemia and fibrosis in chronic RII are irreversible, bowel resection is the ideal treatment. The surgical indications for chronic RII are grade 3 and 4 intestinal injuries, including obstruction, bleeding, intestinal necrosis, perforation, and fistula. The current surgical procedure is definitive intestinal resection with stage I or II gastrointestinal reconstruction. The optimal time for definitive surgery is still controversial. Based on our experiences, 1 year after the end of radiation therapy is optimal. Under the circumstances of emergency surgery, severe malnutrition, abdominal infection, extensive intestinal injury, and abdominal adhesions that cannot be mobilized, ostomy and abdominal drainage are recommended, and definitive surgery can be considered after the return to enteral nutrition and extinction of intestinal inflammation. Preoperative setting of ureteral catheter, imaging assessment of colorectal position and iliac vascular injury, and preoperative nutritional support can reduce the risk of systemic complications effectively.


Assuntos
Enteropatias , Lesões por Radiação , Humanos , Intestino Delgado , Intestinos , Qualidade de Vida
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