RESUMO
BACKGROUND AND AIMS: The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA. METHODS: Colonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively. RESULTS: Biopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p<0.001) and lower EPA (p<0.010) contents and a higher AA:EPA ratio (p<0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p<0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations). CONCLUSIONS: Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.
Assuntos
Colite Ulcerativa/metabolismo , Colo/metabolismo , Ácidos Graxos Ômega-3/farmacocinética , Ácidos Graxos Ômega-6/farmacocinética , Mucosa Intestinal/metabolismo , Adulto , Disponibilidade Biológica , Estudos de Casos e Controles , Colite Ulcerativa/patologia , Colo/patologia , Dieta , Esterificação , Ácidos Graxos Ômega-3/química , Ácidos Graxos Ômega-6/química , Feminino , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFß and other cytokines and characterised by neutrophil infiltration and tissue destruction. AIM: To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls. METHODS: Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age-sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFß and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann-Whitney U test and Spearman's correlation. RESULTS: 69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFß was measured compared with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001); IL-8 was positively correlated (rs=0.481, p<0.01) and TGFß inversely correlated (rs=0.462; p<0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002). CONCLUSION: Our findings suggest that IL-8 is elevated and TGFß is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFß mediated tissue healing.
Assuntos
Colite Ulcerativa/metabolismo , Citocinas/metabolismo , Mucosa Intestinal/metabolismo , Adulto , Biópsia , Estudos de Casos e Controles , Colite Ulcerativa/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Feminino , Glucocorticoides/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
Our objectives were to develop catalytic atom-economic processes accessing and/or incorporating versatile functionality using aryl/heteroaryl acetonitriles as substrates. We report essentially solvent-free [Cp*IrCl2]2 catalyzed redox neutral processes whereby substituted acetonitriles react with primary alcohols to deliver monosubstituted aryl/heteroaryl acetonitriles in excellent yield. We further demonstrate that such processes can be achieved by conventional or microwave heating and that bis- and tris-primary alcohols are also processed efficiently.