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Aims To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress. Methods Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored. Results PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0–9.6) µg/ml, vs. complication-free patients [5.3 (4.7–6.0) µg/ml, P < 0.001] and control subjects [5.3 (4.6–6.1) µg/ml, P < 0.001;anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients ( P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure ( r = 0.317), pulse pressure ( r = 0.337), small artery elasticity ( r = –0.269), glycated haemoglobin ( r = 0.245), body mass index ( r = 0.362), renal dysfunction [including serum creatinine ( r = 0.491), cystatin C ( r = 0.500)], triglycerides ( r = 0.367), and inflammation [including logeC-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 ( r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and logeCRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age ( r2 = 0.427). Conclusions In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation. [ABSTRACT FROM AUTHOR]

The difficulties involved in quantitating passive cutaneous anaphylaxis led us to examine the rat paw as a site for passive anaphylaxis and to define optimum conditions for passive paw anaphylaxis. Generation of homocytotropic antibodies in a number of different rat strains revealed that female Brown Norway rats were excellent producers of high titre antisera after only a single injection of antigen and Bordetella pertussis. Injection of ratpaws with diluted antisera followed by short (1-2 h) or long (72 h or more) sensitization periods showed that maximum paw swelling occurred 15 min after antigen challenge. Retention of tissue sensitizing capacity in the paw for greater than 35 days but loss of this capacity following heating of antiserum at 56 degrees C, indicated that the rat homocytotropic antibodies involved in passive paw anaphylaxis belong to the IgE class. Experiments using mepyramine, methysergide and diethylcarbamazine showed that 5-hydroxytryptamine is the most important mediator of passive paw anaphylaxis after both a short (2 h) and a long (72 h) sensitization procedure. Passive paw anaphylaxis in the rat is at least as easy to perform as passive cutaneous anaphylaxis, results can be obtained more rapidly and accurate measurement of paw thickness is not difficult. The procedure is a viable alternative to passive cutaneous anaphylaxis and may offer advantages over the latter method especially in the search for, and rapid assessment of, anti-allergic compounds.