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1.
Artigo em Inglês | MEDLINE | ID: mdl-38558411

RESUMO

BACKGROUND: In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. METHODS: A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. RESULTS: Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). CONCLUSION: A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. CLINICALTRIALS: gov NCT03508193.

2.
Am J Clin Pathol ; 161(2): 149-154, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788094

RESUMO

OBJECTIVES: To assess if the distribution of villous intraepithelial lymphocytes (IELs) in a pediatric cohort with Marsh I histopathology is specific to celiac disease (CeD). METHODS: Multicenter, retrospective case-control study between January 2001 and December 2019 in children (<18 years) with and without CeD with intraepithelial lymphocytosis and normal villous architecture. Pathology specimens were reviewed by 2 study pathologists who were blinded to the final diagnosis. Morphologic features (villous height to crypt depth ratio [Vh:Cd]) and IELs in the villous tip, top, or bottom half of the villus were quantified. RESULTS: Of the 97 children with Marsh I histopathology identified during the study period, 63 were excluded due to an insufficient number of well-oriented villous-crypt complexes or a Vh:Cd less than 2. Villous IELs were measured in 34 cases (14 CeD, 20 non-CeD controls). There was no difference between the non-CeD and CeD groups in the mean IELs at the villous tip (14.0 ± 7.1 vs 11.7 ± 6.0, P = .31), top (46.4 ± 18.4 vs 38.3 ± 10.8, P = .11), or bottom (29.8 ± 16.8 vs 28.5 ± 12.8, P = .80) half of each villus, respectively. CONCLUSIONS: The distribution of IELs in Marsh I lesions is not specific for CeD.


Assuntos
Doença Celíaca , Linfócitos Intraepiteliais , Linfocitose , Humanos , Criança , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Estudos Retrospectivos , Estudos de Casos e Controles , Linfócitos Intraepiteliais/patologia , Cádmio , Áreas Alagadas , Linfocitose/diagnóstico , Linfócitos/patologia , Duodeno/patologia , Mucosa Intestinal/patologia , Biópsia
3.
J Pediatr Gastroenterol Nutr ; 77(6): 698-702, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37608439

RESUMO

Gluten challenge is an essential clinical tool that involves reintroducing or increasing the amount of gluten in the diet to facilitate diagnostic testing in celiac disease (CD). Nevertheless, there is no consensus regarding the applications of gluten timing, dosing, and duration in children. This review aims to summarize the current evidence, discuss practical considerations, and proposes a clinical algorithm to help guide testing in pediatric patients. Childhood development, social circumstances, and long-term health concerns must be considered when identifying a candidate for gluten challenge. Based on previous studies, the authors suggest baseline serology followed by a minimum of 3-6 grams of gluten per day for over 12 weeks to optimize diagnostic accuracy for evaluation of CD. A formal provider check-in at 4-6 weeks is essential so the provider and family can adjust dosing or duration as needed. Increasing the dose of gluten further may improve diagnostic yield if tolerated, although in select cases a lower dose and shorter course (6-12 weeks) may be sufficient. There is consensus that mild elevations in celiac serology (<10 times the upper limit of normal) or symptoms, while supportive are not diagnostic for CD. Current North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines recommend histologic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy as the accurate and most appropriate endpoint for gluten challenge.


Assuntos
Doença Celíaca , Glutens , Humanos , Criança , Desenvolvimento Infantil , Mucosa Intestinal/patologia , Dieta Livre de Glúten
6.
Dig Dis Sci ; 68(5): 1944-1949, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36585541

RESUMO

BACKGROUND: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. AIMS: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). METHODS: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. RESULTS: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). CONCLUSION: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study.


Assuntos
Doença Celíaca , Humanos , Criança , Doença Celíaca/epidemiologia , Aditivos Alimentares/efeitos adversos , Glutens , Dieta Livre de Glúten , Alimentos
7.
Clin Chim Acta ; 531: 382-385, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35550816

RESUMO

BACKGROUND: We assessed the diagnostic utility of deamidated gliadin peptide immunoglobulin G (DGP-IgG) in pediatric patients without immunoglobulin A deficiency who underwent tissue transglutaminase immunoglobulin A (TTG-IgA) screening and biopsy. METHODS: Patients who had TTG-IgA performed in our laboratory had sample frozen over 1.5 y. If a patient underwent biopsy within 6 months of serology, DGP-IgG was performed on frozen sample. All testing was performed on the BioPlex 2200. Biopsies were assigned a modified Marsh-Oberhuber score. The sensitivity, specificity, and positive and negative predictive values were calculated for TTG-IgA and DGP-IgG for values ≥ 15 u/ml, 15-149 u/ml, and ≥ 150 u/ml using biopsy as gold standard. RESULTS: A total of 458 patients were included. Sensitivity and specificity for DGP-IgG ≥ 15 u/ml and Marsh ≥ 2 was 76% and 87.5% and TTG-IgA ≥ 15 was notably higher at 93.3% and 92.2%. Sensitivity and specificity of DGP-IgG were 66% and 88.9% at moderate and 29.3% and 98.4% at high increases. The positive predictive value of DGP-IgG for celiac disease in TTG-IgA negative patients was 2.8%. CONCLUSIONS: Our study suggests DGP-IgG does not add significant value in patients screened for celiac disease.


Assuntos
Doença Celíaca , Neoplasias Cutâneas , Autoanticorpos , Doença Celíaca/diagnóstico , Criança , Gliadina , Humanos , Imunoglobulina A , Imunoglobulina G , Proteína 2 Glutamina gama-Glutamiltransferase , Sensibilidade e Especificidade , Transglutaminases
8.
Am J Gastroenterol ; 117(6): 902-917, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35442220

RESUMO

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant's baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7-18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was <1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was -0.3 (95% credible interval -1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness.


Assuntos
Colite Ulcerativa , Doença de Crohn , Complexo Antígeno L1 Leucocitário , Adolescente , Teorema de Bayes , Criança , Colite Ulcerativa/complicações , Colite Ulcerativa/dietoterapia , Doença de Crohn/complicações , Doença de Crohn/dietoterapia , Dieta , Fezes/química , Humanos , Inflamação/complicações , Inflamação/dietoterapia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/dietoterapia , Complexo Antígeno L1 Leucocitário/análise , Medicina de Precisão
9.
JPGN Rep ; 3(2): e203, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-37168898

RESUMO

Acute gastrointestinal graft-versus-host disease (GI GVHD) is a complication after hematopoietic stem cell transplant with high morbidity and mortality. In particular, steroid-refractory GI GVHD can be difficult to treat. Recent investigations have revealed that patients after transplant can experience intestinal dysbiosis contributing to the progression of GVHD. Modulation of the gut microbiome through dietary intake could potentially improve the intestinal dysbiosis in GI GVHD. In this case series, we present 3 patients where dietary therapy was used in conjunction with immunosuppression to achieve clinical remission of GI GVHD.

10.
Biomed Pharmacother ; 146: 112486, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34891113

RESUMO

BACKGROUND AND AIMS: Many epidemiological studies suggest an association between antibiotic exposure and the development of inflammatory bowel disease [IBD]. However, the majority of these studies are observational and still the question remains, "Does the specific antibiotic administration regimen play a role in the development of colitis?" This study aimed to compare the possible effects of continuous and intermittent antibiotic exposure on the development of colitis using a colitis-susceptible IL-10 knockout [IL-10-/-] mouse model. METHODS: IL-10-/- mice [C57BL/6] were randomly assigned to a non-antibiotic group, continuous antibiotic group and intermittent antibiotic group, and observed for 30 weeks. The antibiotic cocktail was given via the drinking water. The differential response to antibiotics was assessed. RESULTS: Intermittent antibiotic treatment resulted in severe colitis with early disease onset in IL-10-/- mice. Higher unit colon weight and spleen weight were observed in intermittent antibiotic-treated mice but not in the continuous antibiotic group. Moreover, intermittent antibiotic treatment aggravated epithelial damage and colonic inflammation, mucosal barrier dysfunction and colonic allergic sensitization in IL-10-/- mice, whereas continuous antibiotic treatment ameliorated these symptoms. Male IL-10-/- mice with intermittent antibiotic exposure were more susceptible to colonic inflammation and allergic response than females. CONCLUSIONS: In summary, intermittent antibiotic exposure accelerated the development of severe colitis more than continuous antibiotic exposure in IL-10-/- male mice. In addition to the colonic damage and impaired barrier function, stimulation of allergic response may play a role in accelerating the development of colitis in genetically susceptible mice.


Assuntos
Ampicilina/efeitos adversos , Antibacterianos/efeitos adversos , Colite/induzido quimicamente , Interleucina-10/genética , Neomicina/efeitos adversos , Animais , Colite/metabolismo , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Feminino , Hipersensibilidade Alimentar , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos Knockout , Mucina-2/metabolismo , Permeabilidade
11.
Dig Dis Sci ; 67(6): 2029-2038, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33974186

RESUMO

BACKGROUND: Widespread variation in the diagnosis and treatment of eosinophilic esophagitis (EoE) has previously been reported among adult gastroenterologists; however, variation in EoE practice in among pediatric populations is poorly characterized. The study objectives were to describe guideline adherence and understand reasons for variation in EoE practice among pediatric gastroenterologists following publication of the updated 2018 international EoE guidelines. METHODS: We developed and administered a 28-item survey to pediatric gastroenterologists via an email listserv using the PEDGI Bulletin Board from 03/2019 to 04/2019. The survey was developed using evidence-based review, expert validation, and cognitive interviews. Survey domains included respondent knowledge of and adherence to published guidelines, diagnostic and management approach and rationale, and participant demographics. Analysis included descriptive statistics and tests for association. RESULTS: A total of 288 pediatric gastroenterologists completed the survey, most of whom practiced in an academic center (73%). More than half (63%) reported knowledge of the 2018 updated guidelines; however, only 52% agreed with them and 50% reported adherence. Respondents who reported not agreeing with updated guidelines cited concerns regarding increasing number of endoscopies (72%), misdiagnosing eosinophilia from reflux (56%), and insufficient data (23%). The most common drivers of decision making with respect to therapy choice were patient/family preference, evidence/guidelines, and symptom burden. CONCLUSIONS: Many physicians are not adherent to current guidelines for reasons which include lack of knowledge of updated guidelines and concern regarding the strength of the supporting evidence. This study elucidates several areas to enhance education regarding these guidelines to promote widespread adherence.


Assuntos
Esofagite Eosinofílica , Gastroenterologistas , Adulto , Criança , Enterite , Eosinofilia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/terapia , Gastrite , Gastroenterologistas/psicologia , Fidelidade a Diretrizes , Humanos , Inquéritos e Questionários
12.
Am J Clin Pathol ; 157(1): 136-139, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34542555

RESUMO

OBJECTIVES: Forgoing biopsy for the diagnosis of celiac disease in children with tissue transglutaminase immunoglobulin A (tTG-IgA) levels greater than or equal to 10 times the upper limit of normal (≥10×ULN) has been advocated by the European Society of Paediatric Gastroenterology, Hepatology and Nutrition. METHODS: Our retrospective study tested the specificity and positive predictive value (PPV) of the BioPlex 2200 assay (Bio-Rad Laboratories) in diagnosing celiac disease at the ≥10×ULN tTG-IgA threshold, which is ≥150 U/mL (negative <15 U/mL). We used the tTG-IgA and duodenal biopsy results within 6 months following tTG-IgA measurements from 542 patients who had any number of duodenal biopsy fragments, of whom 165 patients had 5 or more tissue fragments. Sensitivity and specificity of the test were calculated using histology as the gold standard for Marsh class 2 and above. RESULTS: For histopathologic findings in the duodenum with Marsh 2 and higher, the specificity and PPV of the BioPlex 2200 at ≥10×ULN tTG-IgA were 99.5% and 95.4% using all biopsies and 97.9% and 94.9% for biopsies with 5 or more tissue fragments. CONCLUSIONS: Should clinical considerations preclude endoscopy, the BioPlex 2200 assay at ≥10×ULN TTG-IgA could be considered highly suggestive of disease.


Assuntos
Doença Celíaca , Autoanticorpos , Biópsia , Doença Celíaca/diagnóstico , Criança , Humanos , Imunoglobulina A , Polímeros , Proteína 2 Glutamina gama-Glutamiltransferase , Estudos Retrospectivos , Sensibilidade e Especificidade , Transglutaminases
13.
Mol Nutr Food Res ; 65(24): e2100152, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34633750

RESUMO

SCOPE: Anthocyanin-containing potatoes exert anti-inflammatory activity in colitic mice. Gut bacterial dysbiosis plays a critical role in ulcerative colitis. This study examined the extent to which the anti-colitic activity of anthocyanin-containing red/purple-fleshed potatoes depends on the gut bacteria using a chemically-induced rodent model of colitis with the intact and antibiotic-ablated microbiome. METHODS AND RESULTS: Four-week-old male mice (C57BL6) are randomly assigned to the control diet or 20% purple-/red-fleshed potatoes supplemented diet group. The microbiota-ablated group received an antibiotic cocktail in drinking water. At week nine, colitis is induced by 2% dextran sulfate sodium (DSS) in drinking water for five days. Administration of antibiotics resulted in a 95% reduction in gut bacterial load and fecal SCFAs. DSS-induced elevated gut permeability and body weight loss are more pronounced in antibiotic mice compared to non-antibiotic mice. Purple- or red-fleshed potato supplementation (20% w/w) ameliorated DSS-induced reduction in colon length and mucin 2 expression levels, and increase in permeability, spleen weight, myeloperoxidase (MPO) activity, and inflammatory cytokines (IL-6, IL-17, and IL1-ß) expression levels in non-antibiotic mice, but not in gut microbiota ablated mice. CONCLUSIONS: Anthocyanin-containing potatoes are potent in alleviating colitis, and the gut microbiome is critical for the anti-colitic activity of anthocyanin-containing potatoes.


Assuntos
Colite , Microbioma Gastrointestinal , Solanum tuberosum , Animais , Antocianinas/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Pediatr Gastroenterol Hepatol Nutr ; 24(5): 432-442, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34557396

RESUMO

PURPOSE: The aim of this study was to evaluate the nutrient content consumed by children and adolescents on home-prepared versus chef-prepared specific carbohydrate diets (SCD) as therapy for inflammatory bowel disease (IBD). METHODS: Dietary intake of two cohorts with active IBD initiating the SCD over 12 weeks was assessed. The home-prepared cohort received detailed guidance from dietitians on implementation of the SCD. The chef in the other cohort was knowledgeable in the SCD and prepared meals from a fixed set of recipes. Data from 3-day diet diaries at 4 different time points were collected. US Recommended Daily Allowances (RDA) were calculated for macronutrients, vitamins, and minerals. RESULTS: Eight participants on the homemade SCD and 5 participants on the chef-prepared SCD were included in analysis. Mean % RDA for energy intake was 115% and 87% for homemade and chef-prepared groups (p<0.01). Mean % RDA for protein intake was 337% for homemade SCD and 216% for chef-prepared SCD (p<0.01). The homemade SCD group had higher mean % RDA values for vitamin A and iron, while the chef-prepared SCD group had higher intake of vitamins B1, B2, D, phosphorus and zinc (p<0.01 for all). CONCLUSION: The SCD implemented homemade versus chef-prepared can result in significantly different intake of nutrients and this may influence efficacy of this dietary therapy. Meal preparation dynamics and the motivation of families who pursue dietary treatment may play an important role on the foods consumed and the outcomes on dietary therapy with the SCD.

15.
Paediatr Drugs ; 23(2): 131-141, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33761130

RESUMO

Tumor necrosis factor alpha inhibitors (TNFi) are widely used in children with autoimmune and autoinflammatory conditions. Although TNFi are approved to treat psoriasis, they have also been shown to paradoxically induce psoriasiform lesions. In this review, we aim to focus on the clinical presentation and management of paradoxical psoriasis after exposure to TNFi in children with juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), or chronic nonbacterial osteomyelitis (CNO). A narrative review of the literature was performed given the limited number of publications on this topic. Children with IBD, CNO, and JIA have a higher risk of developing psoriasis at baseline, which increases after TNFi use in those with JIA and IBD. Risk factors for paradoxical psoriasis remain incompletely defined, and patients with IBD and/or CNO develop paradoxical psoriasis more commonly than those with JIA. Sex, race, and family history were not significantly associated with paradoxical psoriasis. The most commonly implicated TNFi include infliximab and adalimumab. Paradoxical psoriasis occurs in a similar distribution on the body to isolated psoriatic lesions and is morphologically indistinguishable. In many instances, topical therapies are effective in treating psoriasis and children can continue on TNFi for their primary disease. If lesions are severe or unacceptable to patients, TNFi may be switched or discontinued. Further research is needed to better characterize risk factors and understand the mechanism of disease pathogenesis. Pediatric health care providers who prescribe TNFi should counsel families regarding the risk of paradoxical psoriasis prior to starting the medication and monitor for new cutaneous eruptions.


Assuntos
Psoríase/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Criança , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/efeitos adversos , Masculino , Fatores de Risco
16.
Pediatr Dev Pathol ; 24(3): 206-212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33538229

RESUMO

OBJECTIVES: The goal of our study was to determine whether visual assessment of the esophagus and stomach could predict abnormal histology and determine the frequency of interventions based on biopsies in patients undergoing endoscopy for elevated tissue transglutaminase immunoglobulin A antibody (TTG). METHODS: Pathology records were searched for patients with biopsy performed for elevated TTG. Pathology report, endoscopy report, and follow-up were obtained and slides from the duodenum reviewed. Pathology was considered gold standard for sensitivity and specificity calculations. RESULTS: 240 patients were included. 215 patients had esophageal biopsies performed. Esophageal endoscopic visual assessment had sensitivity of 47% and specificity of 93% for abnormal histology. 16(7%) patients had therapy or referral related to results and, of these, 6(38%) had visually normal endoscopy. 237 biopsies were performed of stomach. Gastric endoscopic visual assessment had a sensitivity and specificity of 20% and 87%. 24(10%) patients had therapy based on findings and, of these, 12 (50%) had visually normal endoscopy. CONCLUSIONS: Endoscopic assessment of esophagus and stomach has low sensitivity and high specificity for pathologic abnormalities when indication for endoscopy is elevated TTG. When endoscopy is visually normal clinical interventions based on biopsy are rare, and foregoing biopsy may be considered.


Assuntos
Autoanticorpos , Doença Celíaca/diagnóstico , Esofagoscopia/métodos , Gastroscopia/métodos , Autoantígenos/imunologia , Biópsia , Doença Celíaca/imunologia , Doença Celíaca/patologia , Criança , Feminino , Proteínas de Ligação ao GTP/imunologia , Humanos , Imunoglobulina A , Masculino , Proteína 2 Glutamina gama-Glutamiltransferase , Sensibilidade e Especificidade , Transglutaminases/imunologia
17.
Exp Dermatol ; 30(3): 384-389, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33205489

RESUMO

Inherited or acquired blockade of distal steps in the cholesterol synthetic pathway results in ichthyosis, due to reduced cholesterol production and/or the accumulation of toxic metabolic precursors, while inhibition of epidermal cholesterol synthesis compromises epidermal permeability barrier homeostasis. We showed here that 3ß-hydroxysteroid-δ8, δ7-isomerase-deficient mice (TD), an analog for CHILD syndrome in humans, exhibited not only lower basal transepidermal water loss rates, but also accelerated permeability barrier recovery despite the lower expression levels of mRNA for epidermal differentiation marker-related proteins and lipid synthetic enzymes. Moreover, TD mice displayed low skin surface pH, paralleled by increased expression levels of mRNA for sodium/hydrogen exchanger 1 (NHE1) and increased antimicrobial peptide expression, compared with wild-type (WT) mice, which may compensate for the decreased differentiation and lipid synthesis. Additionally, in comparison with WT controls, TD mice showed a significant reduction in ear thickness following challenges with either phorbol ester or oxazolone. However, TD mice exhibited growth retardation. Together, these results demonstrate that 3ß-hydroxysteroid-δ8, δ7-isomerase deficiency does not compromise epidermal permeability barrier in mice, suggesting that alterations in epidermal function depend on which step of the cholesterol synthetic pathway is interrupted. But whether these findings in mice could be mirrored in humans remains to be determined.


Assuntos
Dermatite Alérgica de Contato/fisiopatologia , Epiderme/metabolismo , Fenômenos Fisiológicos da Pele/genética , Esteroide Isomerases/genética , Animais , Peptídeos Antimicrobianos/metabolismo , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/genética , Epiderme/ultraestrutura , Feminino , Expressão Gênica , Homeostase/genética , Concentração de Íons de Hidrogênio , Camundongos , Microscopia Eletrônica , Mutação , Oxazolona , Permeabilidade , RNA Mensageiro/metabolismo , Trocador 1 de Sódio-Hidrogênio/genética , Esteroide Isomerases/deficiência , Acetato de Tetradecanoilforbol , Perda Insensível de Água/genética
18.
Nutrients ; 12(12)2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33291229

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory intestinal disorder associated with intestinal dysbiosis. Diet modulates the intestinal microbiome and therefore has a therapeutic potential. The aim of this study is to determine the potential efficacy of three versions of the specific carbohydrate diet (SCD) in active Crohn's Disease. METHODS: 18 patients with mild/moderate CD (PCDAI 15-45) aged 7 to 18 years were enrolled. Patients were randomized to either SCD, modified SCD(MSCD) or whole foods (WF) diet. Patients were evaluated at baseline, 2, 4, 8 and 12 weeks. PCDAI, inflammatory labs and multi-omics evaluations were assessed. RESULTS: Mean age was 14.3 ± 2.9 years. At week 12, all participants (n = 10) who completed the study achieved clinical remission. The C-reactive protein decreased from 1.3 ± 0.7 at enrollment to 0.9 ± 0.5 at 12 weeks in the SCD group. In the MSCD group, the CRP decreased from 1.6 ± 1.1 at enrollment to 0.7 ± 0.1 at 12 weeks. In the WF group, the CRP decreased from 3.9 ± 4.3 at enrollment to 1.6 ± 1.3 at 12 weeks. In addition, the microbiome composition shifted in all patients across the study period. While the nature of the changes was largely patient specific, the predicted metabolic mode of the organisms increasing and decreasing in activity was consistent across patients. CONCLUSIONS: This study emphasizes the impact of diet in CD. Each diet had a positive effect on symptoms and inflammatory burden; the more exclusionary diets were associated with a better resolution of inflammation.


Assuntos
Doença de Crohn/dietoterapia , Dieta , Carboidratos da Dieta , Disbiose/tratamento farmacológico , Quimioterapia de Indução , Adolescente , Proteína C-Reativa , Carboidratos , Criança , Doença de Crohn/terapia , Método Duplo-Cego , Feminino , Humanos , Doenças Inflamatórias Intestinais , Masculino , Metabolômica , Metagenômica , Microbiota , Proteômica
19.
Exp Dermatol ; 29(10): 1027-1032, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32794261

RESUMO

Nitric oxide (NO) regulates a variety of epidermal functions, including epidermal proliferation, differentiation and cutaneous wound healing. However, whether nitric oxide (NO) and its synthetic enzymes regulate epidermal permeability barrier homeostasis is not clear. In the present study, we employed inducible nitric oxide synthase (iNOS) KO mice to explore the role of iNOS in epidermal permeability barrier homeostasis. Our results showed that iNOS mice displayed a comparable levels of basal transepidermal water loss rates, stratum corneum hydration and skin surface pH to their wild-type mice, but epidermal permeability barrier recovery was significantly delayed both 2 and 4 hours after acute barrier disruption by tape stripping. In parallel, expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes were lower in iNOS KO mice versus wild-type controls. Topical applications of two structurally unrelated NO donors to iNOS KO mice improved permeability barrier recovery kinetics and upregulated expression levels of mRNA for epidermal differentiation-related proteins and lipid synthetic enzymes. Together, these results indicate that iNOS and its product regulate epidermal permeability barrier homeostasis in mice.


Assuntos
Epiderme/fisiologia , Homeostase , Óxido Nítrico Sintase Tipo II/fisiologia , Óxido Nítrico/metabolismo , Animais , Diferenciação Celular , Epiderme/química , Epiderme/enzimologia , Proteínas Filagrinas , Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Proteínas de Filamentos Intermediários/genética , Queratinócitos/fisiologia , Metabolismo dos Lipídeos/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo II/genética , Permeabilidade/efeitos dos fármacos , Precursores de Proteínas/genética , RNA Mensageiro/metabolismo , S-Nitroso-N-Acetilpenicilamina/farmacologia , Fenômenos Fisiológicos da Pele , Perda Insensível de Água
20.
Pediatr Dev Pathol ; 23(5): 380-386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511053

RESUMO

BACKGROUND: Multiple prior studies have looked at clinical and laboratory parameters in ulcerative colitis to predict prognosis, but individual histologic features of inflammation and their prognostic significance have not been well studied. The purpose of our study was to determine whether histologic features at presentation with acute severe colitis predict colectomy in pediatric patients. METHODS: Patients were identified retrospectively through the gastroenterology and pathology databases. Demographic information, duration of disease, laboratory data, endoscopic appearance at scope, and histologic features of inflammation were reviewed along with medical therapies. Patients who underwent surgery within 90 days of hospitalization were compared to those who did not. RESULTS: Fifty patients with acute severe colitis, defined as Pediatric Ulcerative Colitis Activity Index ≥65, were included. Sixteen patients had colectomies performed within 90 days of presentation. No statistically significant difference was found between the surgery and no-surgery groups for patient age, albumin, hemoglobin, or C-reactive protein, though hemoglobin trended toward significance, P = .05. The endoscopic Mayo score and histologic features of inflammation (architectural changes, chronic inflammation, eosinophils, neutrophils within the lamina propria, neutrophils in epithelium, crypt destruction, and ulceration) were similar between groups. CONCLUSION: In pediatric patients presenting for hospitalization with acute severe colitis, no histologic features of inflammation predicted colectomy within 90 days.


Assuntos
Colectomia , Colite Ulcerativa/patologia , Colite Ulcerativa/cirurgia , Colo/patologia , Mucosa Intestinal/patologia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Colite Ulcerativa/diagnóstico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença
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