Assuntos
Infecções Bacterianas , Espondiloartropatias , Testes Respiratórios , Humanos , Intestino Delgado , PrevalênciaRESUMO
Calprotectin is a heterodimeric calcium- and zinc-binding protein mainly derived from the cytoplasm of neutrophils that has direct antimicrobial functions and a role in the regulation of the innate immune response. It can be found in various biological compartments, in particular, the stool, with concentrations related to the level of mucosal inflammation. The measurement of fecal calprotectin has thus been recognized as a useful surrogate marker to distinguish patients with inflammatory bowel disease from those with irritable bowel syndrome. Moreover, it allows the monitoring of intestinal inflammation with a high negative predictive value, making it possible to exclude the diagnosis of inflammatory bowel disease for symptomatic patients. It also shows high sensitivity for the identification of patients requiring additional examinations for diagnosis, such as colonoscopy, and the evaluation of therapeutic responses, providing evidence of relapse or mucosal healing, which can lead to the intensification or reduction of treatment. As calprotectin levels are a measure of mucosal inflammation, high fecal concentrations are also found in other diseases with an inflammatory component, such as infectious enteritis or colorectal cancer. Interpretation of the concentration must therefore always take into account the clinical history and symptoms specific to each patient.
Assuntos
Doenças Inflamatórias Intestinais , Síndrome do Intestino Irritável , Humanos , Complexo Antígeno L1 Leucocitário , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/metabolismo , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Valor Preditivo dos Testes , Fezes , InflamaçãoRESUMO
BACKGROUND: Short bowel syndrome (SBS) is the main cause of intestinal failure in children. OBJECTIVES: This single-center study evaluated the safety and efficacy of teduglutide in pediatric patients with SBS-associated intestinal failure (SBS-IF). METHODS: Children with SBS followed at our center with ≥2 y on parenteral nutrition (PN) and with small bowel length <80 cm who had reached a plateau were consecutively included in the study. At baseline, participants underwent a clinical assessment including a 3-d stool balance analysis, which was repeated at the end of the study. Teduglutide was administered subcutaneously 0.05 mg/kg/d for 48 wk. PN dependence was expressed as the PN dependency index (PNDI), which is the ratio PN non-protein energy intake/REE. Safety endpoints included treatment-emergent adverse events and growth parameters. RESULTS: Median age at inclusion was 9.4 y (range: 5-16). The median residual SB length was 26 cm (IQR: 12-40). At baseline, the median PNDI was 94% (IQR: 74-119), (median PN intake: 38.9 calories/kg/d, IQR: 26.1-48.6). At week 24, 24 (96%) children experienced a reduction of >20% of PN requirements with a median PNDI = 50% (IQR: 38-81), (PN intake: 23.5 calories/kg/d IQR: 14.6-26.2), P < 0.01. At week 48, 8 children (32%) were weaned completely off PN. Plasma citrulline increased from 14 µmol/L (IQR: 8-21) at baseline to 29 µmol/L (IQR: 17-54) at week 48 (P < 0.001). Weight, height, and BMI z-scores remained stable. The median total energy absorption rate increased from 59% (IQR: 46-76) at baseline to 73% (IQR: 58-81) at week 48 (P = 0.0222). Fasting and postprandial endogenous GLP-2 concentrations increased at weeks 24 and 48 compared with baseline. Mild abdominal pain at the early phase of treatment, stoma changes, and redness at the injection site were commonly reported. CONCLUSIONS: Increased intestinal absorption and PN dependency reduction were observed with teduglutide treatment in children with SBS-IF. TRIAL REGISTRATION: ClinicalTrials.gov NCT03562130. https://clinicaltrials.gov/ct2/show/NCT03562130?term=NCT03562130&draw=2&rank=1.
Assuntos
Insuficiência Intestinal , Síndrome do Intestino Curto , Humanos , Criança , Síndrome do Intestino Curto/terapia , Intestino Delgado , Peptídeos/uso terapêutico , Fármacos Gastrointestinais/efeitos adversosRESUMO
Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.
Assuntos
Biomarcadores , Doença Ambiental , Enteropatias , Intestino Delgado , África Subsaariana , Biomarcadores/análise , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Pré-Escolar , Citrulina/análise , Estudos Transversais , Doença Ambiental/diagnóstico , Doença Ambiental/metabolismo , Transtornos do Crescimento , Humanos , Enteropatias/diagnóstico , Enteropatias/etiologia , Enteropatias/metabolismo , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Complexo Antígeno L1 LeucocitárioRESUMO
The lipoproteinogram (or lipidogram) consists in an electrophoretic separation of the main classes of serum lipoproteins. Separation was done in agarose gel using the Sebia Hydragel Lipo + Lp(a)® kit. A repeatability study (n=6) was conducted on 3 sera (1 normolipidemic, 1 hypertriglyceridemic and 1 with a high Lp(a) concentration). The reproducibility was studied on these 3 sera and on an ascites liquid containing chylomicrons, upon 6 days (n=6). A quantitative approach was made by studying areas under the curve and percentages of fractions. In both cases (repeatability and reproducibility), the revelation of the lipoproteins in the gel after electrophoretic migration was made either by staining with Sudan Black (procedure recommended by Sebia), or with Fat Red 7B. Regardless of staining, both repeatability and reproducibility studies show that all lipoprotein fractions were correctly detected at their respective positions, leading to satisfactory interpretations of lipoproteinograms. Our reproducibility study also confirmed a good stability of the fractions over 6 days (storage at +5 ± 3ÌC). In addition, the Fat Red 7B staining leads to a shorter technical time (about 40 min) for the gel drying and staining/destaining phases, which allows us to respond more quickly to certain urgent requests such as chylothorax diagnosis.
Assuntos
Compostos Azo/farmacologia , Eletroforese/métodos , Lipoproteínas/análise , Lipoproteínas/sangue , Kit de Reagentes para Diagnóstico , Coloração e Rotulagem/métodos , Líquido Ascítico/química , Compostos Azo/química , Análise Química do Sangue/métodos , Fracionamento Químico/métodos , Eletroforese em Gel de Ágar , Humanos , Lipoproteína(a)/análise , Lipoproteína(a)/sangue , Reprodutibilidade dos TestesRESUMO
A qualitative, semi-automatized method for apolipoprotein E (apoE) phenotyping by isoelectric focusing method has been evaluated on 40 serum samples from patients previously genotyped for apoE, especially as regards concordance with genotyping, but also repeatability and reproducibility of the method, and sample storage. Total concordance with genotyping and good precision criteria, together with its practicability and requirement of a little sample volume, lead to conclude to the usefulness of this method to help clinicians in the diagnosis of dyslipidemic and neurodegenerative diseases.
RESUMO
Cryptosporidium parvum is a protozoan parasite that causes intestinal malabsorptive syndrome and malnutrition. Considering the importance of di-tripeptide absorption for nutritional status, we previously investigated the regulation of PepT1 transporter in the suckling rat model of acute cryptosporidiosis and showed that PepT1 protein expression and activity were not modified in the parasitized intestine. Here we used confocal microscopy performed on intestinal villi to determine the subcellular localization of PepT1 together with f-actin and parasites. For this purpose, confocal microscopy using vibratome thick sections was developed on the distal small intestine, the preferential site of parasite implantation. Results showed major heterogeneity of apical PepT1 expression among enterocytes, which did not correlate with actin staining or parasite implantation. These results underscore the importance of considering the effect of C. parvum at the cellular scale and not only in the entire epithelium.
Assuntos
Criptosporidiose/parasitologia , Cryptosporidium parvum/fisiologia , Proteínas de Membrana Transportadoras/biossíntese , Actinas/análise , Animais , Animais Recém-Nascidos , Cryptosporidium parvum/química , Feminino , Mucosa Intestinal/parasitologia , Microscopia Confocal , Microscopia Eletrônica de Varredura , RatosRESUMO
BACKGROUND: The main cause of intestinal failure is short bowel syndrome (SBS). The management goal for children with SBS is to promote intestinal adaptation while preserving growth and development with the use of parenteral nutrition (PN). OBJECTIVES: This study evaluated the intestinal absorption rate in children with SBS, focusing on the role of the remnant colon. In addition, the relation between intestinal absorption rate, citrulline concentration, and small bowel length was studied. METHODS: Thirty-two children with SBS on PN were included. They were divided into 3 groups according to the European Society for Clinical Nutrition and Metabolism (ESPEN) anatomical classification system: type 1 SBS (n = 9), type 2 (n = 13), and type 3 (n = 10). Intestinal absorption rate was assessed by a stool balance analysis of a 3-d collection of stools. Plasma citrulline concentrations were measured and the level of PN dependency was calculated. RESULTS: The total energy absorption rate did not differ significantly between the 3 groups: 68% (61-79% ) for type 1, 60% (40-77%) for type 2, and 60% (40-77%) for type 3 ( P = 0.45). Children with type 2 or 3 SBS had significantly shorter small bowel length than children with type 1: 28 cm (19-36 cm) and 16 cm (2-29 cm), respectively, compared with 60 cm (45-78 cm) ( P = 0.04). Plasma citrulline concentrations were lower in type 3 SBS but not significantly different: 15 µmol/L (11-25 µmol/L) in type 1, 14 µmol/L (7-21 µmol/L) in type 2 , and 9 µmol/L (6-14 µmol/L) in type 3 ( P = 0.141). A multivariate analysis confirmed the role of the remnant colon in providing additional energy absorption. CONCLUSION: This study demonstrated the importance of the colon as a salvage organ in children with SBS. Plasma citrulline concentrations should be interpreted according to the type of SBS. Efforts should focus on conservative surgery, early re-establishment of a colon in continuity, and preserving the intestinal microbiota.
Assuntos
Colo/fisiopatologia , Síndrome do Intestino Curto/fisiopatologia , Criança , Pré-Escolar , Citrulina/sangue , Estudos Transversais , Feminino , Humanos , Absorção Intestinal , Intestino Delgado/crescimento & desenvolvimento , Intestino Delgado/fisiopatologia , Masculino , Nutrição Parenteral , Estudos Retrospectivos , Síndrome do Intestino Curto/sangue , Síndrome do Intestino Curto/terapiaRESUMO
BACKGROUND: Small bowel transplantation has now become a recognized treatment of irreversible, permanent, and subtotal intestinal failure. OBJECTIVE: The aim of this study was to assess intestinal absorption at the time of weaning from parenteral nutrition in a series of children after intestinal transplantation. DESIGN: Twenty-four children (age range: 14-115 mo) received intestinal transplantation, together with the liver in 6 children and the colon in 16 children. Parenteral nutrition was slowly tapered while increasing enteral tube feeding. The absorption rate was measured from a 3-d stool balance analysis performed a few days after the child had weaned from parenteral nutrition to exclusive enteral tube feeding. Results were analyzed according to the resting energy expenditure (REE; Schofield formula). RESULTS: All children were weaned from parenteral nutrition between 31 and 85 d posttransplantation. Median intakes were as follows: energy, 107 kcal · kg(-1) · d(-1) (range: 79-168 kcal · kg(-1) · d(-1)); lipids, 39 kcal · kg(-1) · d(-1) (range: 20-70 kcal · kg(-1) · d(-1)); and nitrogen, 17 kcal · kg(-1) · d(-1) (range: 11-27 kcal · kg(-1) · d(-1)). Median daily stool output was 998 mL/d (range: 220-2025 mL/d). Median absorption rates were 88% (range: 75-96%) for energy, 82% (range: 55-98%) for lipids, and 77% (range: 61-88%) for nitrogen. The ratios for ingested energy to REE and absorbed energy to REE were 2.2 (range: 1.6-3.6) and 1.8 (range: 1.3-3.3), respectively. CONCLUSION: These data indicate a suboptimal intestinal graft absorption capacity with fat malabsorption, which necessitates energy intakes of at least twice the REE.
Assuntos
Gorduras na Dieta/metabolismo , Enteropatias/cirurgia , Intestino Delgado , Nitrogênio/metabolismo , Transplante de Órgãos , Complicações Pós-Operatórias/etiologia , Síndrome do Intestino Curto/etiologia , Adolescente , Metabolismo Basal , Criança , Pré-Escolar , Defecação , Ingestão de Energia , Humanos , Lactente , Absorção Intestinal , Enteropatias/metabolismo , Enteropatias/terapia , Intestino Delgado/metabolismo , Intestino Delgado/cirurgia , Apoio Nutricional , Complicações Pós-Operatórias/metabolismo , Síndrome do Intestino Curto/metabolismoRESUMO
OBJECTIVE: Exocrine function has been described in patients with diabetes. We hypothetized that patients with exocrine dysfunction have pancreatic atrophy. METHODS: This is a cohort study of hospitalized patients. Thirty-five patients were selected after detection of impaired exocrine function in routine tests, and 17 patients were matched for age and body mass index to the previous cohort. The pancreatic volume was evaluated on sections of computed tomographic scans of the pancreas. Other investigations included a glucagon stimulation test and determination of fecal elastase-1 concentration and chymotrypsin activity. RESULTS: Fifty-two patients participated in this study, 24 with type 1 diabetes and 28 with type 2 diabetes. Duration of diabetes was 15 years (5-26 years; median [interquartile range]). The pancreatic volume, 42 cm (25-57 cm), was decreased in most patients. It did not differ in patients with type 1 diabetes compared with those with type 2 diabetes. It was decreased in patients treated with insulin and in those with low elastase-1 concentration or low chymotrypsin activity. In the multiple linear regression analysis, the pancreatic volume correlated with chymotrypsin activity and stimulated C-peptide. CONCLUSIONS: We have unraveled a link between 2 old observations in patients with diabetes: atrophy of the pancreas and exocrine deficiency. These observations give credence to the reality of the exocrine dysfunction in patients with diabetes.