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1.
Pharmacol Res ; 149: 104464, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31553934

RESUMO

Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC. Colonic inflammation was induced in mice by dinitrobenzenesulfonic acid (DNBS). The effect of orally administered CBDV on macroscopic and microscopic damage, inflammatory parameters (i.e. myeloperoxidase activity, intestinal permeability and cytokine production) and faecal microbiota composition, was evaluated 3 days after DNBS administration. TRPA1 expression was studied by RT-PCR in inflamed colons of mice as well as in mucosal colonic biopsies of children with active UC, whose response to incubation with CBDV was also investigated. CBDV attenuates, in a TRPA1-antagonist sensitive manner, DNBS-induced signs of inflammation including neutrophil infiltration, intestinal permeability, and cytokine (i.e. IL-1ß, IL-6 and the chemokine MCP-1) production. CBDV also alters the dysregulation of gut microbiota associated to colitis. Finally, CBDV lessens cytokine expression in colonic biopsies from pediatric patients with ulcerative colitis, a condition in which TRPA1 was up-regulated. Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC. Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.


Assuntos
Anti-Inflamatórios/uso terapêutico , Canabinoides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Citocinas/análise , Inflamação/tratamento farmacológico , Animais , Criança , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Humanos , Inflamação/genética , Inflamação/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Masculino , Camundongos , Canal de Cátion TRPA1/genética , Regulação para Cima/efeitos dos fármacos
2.
Eur J Clin Nutr ; 70(1): 23-7, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26173865

RESUMO

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.


Assuntos
Índice de Massa Corporal , Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Estado Nutricional , Aumento de Peso , Tecido Adiposo , Adulto , Peso Corporal , Densidade Óssea , Estudos de Casos e Controles , Doença Celíaca/complicações , Dieta Livre de Glúten/efeitos adversos , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Ingestão de Energia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Valores de Referência , Adulto Jovem
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