Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most imp...Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor γ (PPARγ), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPAR7 agonists are therapeutic agents used in the treatment of type 2 diabetes. This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARγ in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARγ modulators.展开更多
AIM: To determine the diagnostic accuracy of a new point-of-care assay detecting anti-deamidated gliadin peptides in celiac disease(CD) patients.METHODS: One-hundred-and-twelve patients(age range: 1.8-79.2 years old) ...AIM: To determine the diagnostic accuracy of a new point-of-care assay detecting anti-deamidated gliadin peptides in celiac disease(CD) patients.METHODS: One-hundred-and-twelve patients(age range: 1.8-79.2 years old) with clinical symptoms suggestive of CD and/or first-degree relatives(FDR) of CD patients(n = 66),and confirmed CD on a gluten-free diet(GFD)(n = 46),were prospectively enrolled in the study at Gastroenterology outpatient clinics for adult patients and from the Gastroenterology Consultation Ward at the Pediatric Department of the University Hospital of Geneva.Written informed consent was obtained from all subjects enrolled.The study received approval from the local ethics committee.The original CD diagnosis had been based on serum-positive IgA anti-tissue transglutaminase enzyme-linked immunosorbent assay(ELISA)(QuantaLite,Inova Diagnostics,San Diego,CA,United States) and on biopsy results.Serum samples from all study participants were tested by the new CD lateral flow immunochromatographic assay(CD-LFIA) device,Simtomax Blood Drop(Augurix SA,BioArk,Monthey,Switzerland) to detect immunoglobulin(Ig)A and IgG antibodies against deamidated gliadin peptides.The diagnostic performance was evaluated using receiver operating characteristic curves with 95%CIs.A cut-off of 2 on the Rann colorimetric scale was used to calculate the device's sensitivity and specificity.RESULTS: CD-LFIA was highly accurate in detecting untreated celiac patients.In the group of patients with CD symptoms and/or FDR,eight new cases of CD were detected by ELISA and biopsy.All of these new cases were also correctly identified by CD-LFIA.The test yielded four false positive and four false negative results.The false positive results were all within the groups with clinical symptoms suggestive of CD and/or FDR,whereas the false negative results were all within the GFD group.The test yeld a sensitivity of 78.9%(95%CI: 54.4-93.9) and specificity of 95.7%(95%CI: 89.4-98.8),and the area under the curve reached 0.893(95%CI: 0.798-0.988).The Kappa coefficient,calculated according to the values obtained by two readers from the same device,was of 0.96(SE: 0.06).When the GFD patients were excluded from the analysis,the area under the curve reached 0.989(95%CI: 0.971-1.000) and the Kappa coefficient,calculated according to the values obtained by two readers from the same device,became 0.96(SE: 0.07).Furthermore,using the Rann scale cut-off of 2 without the GFD patients,sensitivity was 100% and specificity was 93.1%(95%CI: 83.3-98.1).CONCLUSION: The new CD-LFIA rapid screening test shows good diagnostic accuracy,sensitivity and specificity,and may rule out CD in patients with CD-related symptoms.展开更多
基金supported by the Etat de Vaud and the Swiss National Science Foundation.
文摘Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferatoractivated receptor γ (PPARγ), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPAR7 agonists are therapeutic agents used in the treatment of type 2 diabetes. This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARγ in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARγ modulators.
基金Supported by the Swiss Celiac Association,Association Romande de Coeliakie,No.ME 8309 awarded to Sch ppi MG
文摘AIM: To determine the diagnostic accuracy of a new point-of-care assay detecting anti-deamidated gliadin peptides in celiac disease(CD) patients.METHODS: One-hundred-and-twelve patients(age range: 1.8-79.2 years old) with clinical symptoms suggestive of CD and/or first-degree relatives(FDR) of CD patients(n = 66),and confirmed CD on a gluten-free diet(GFD)(n = 46),were prospectively enrolled in the study at Gastroenterology outpatient clinics for adult patients and from the Gastroenterology Consultation Ward at the Pediatric Department of the University Hospital of Geneva.Written informed consent was obtained from all subjects enrolled.The study received approval from the local ethics committee.The original CD diagnosis had been based on serum-positive IgA anti-tissue transglutaminase enzyme-linked immunosorbent assay(ELISA)(QuantaLite,Inova Diagnostics,San Diego,CA,United States) and on biopsy results.Serum samples from all study participants were tested by the new CD lateral flow immunochromatographic assay(CD-LFIA) device,Simtomax Blood Drop(Augurix SA,BioArk,Monthey,Switzerland) to detect immunoglobulin(Ig)A and IgG antibodies against deamidated gliadin peptides.The diagnostic performance was evaluated using receiver operating characteristic curves with 95%CIs.A cut-off of 2 on the Rann colorimetric scale was used to calculate the device's sensitivity and specificity.RESULTS: CD-LFIA was highly accurate in detecting untreated celiac patients.In the group of patients with CD symptoms and/or FDR,eight new cases of CD were detected by ELISA and biopsy.All of these new cases were also correctly identified by CD-LFIA.The test yielded four false positive and four false negative results.The false positive results were all within the groups with clinical symptoms suggestive of CD and/or FDR,whereas the false negative results were all within the GFD group.The test yeld a sensitivity of 78.9%(95%CI: 54.4-93.9) and specificity of 95.7%(95%CI: 89.4-98.8),and the area under the curve reached 0.893(95%CI: 0.798-0.988).The Kappa coefficient,calculated according to the values obtained by two readers from the same device,was of 0.96(SE: 0.06).When the GFD patients were excluded from the analysis,the area under the curve reached 0.989(95%CI: 0.971-1.000) and the Kappa coefficient,calculated according to the values obtained by two readers from the same device,became 0.96(SE: 0.07).Furthermore,using the Rann scale cut-off of 2 without the GFD patients,sensitivity was 100% and specificity was 93.1%(95%CI: 83.3-98.1).CONCLUSION: The new CD-LFIA rapid screening test shows good diagnostic accuracy,sensitivity and specificity,and may rule out CD in patients with CD-related symptoms.