Pig-to-Nonhuman Primates Pancreatic Islet Xenotransplantation: An Overview

The therapy of type 1 diabetes is an open challenging problem. The restoration of normoglycemia and insulin independence in immunosuppressed type 1 diabetic recipients of islet allotransplantation has shown the potential of a cell-based diabetes therapy. Even if successful, this approach poses a problem of scarce tissue supply. Xenotransplantation can be the answer to this limited donor availability and, among possible candidate tissues for xenotransplantation, porcine islets are the closest to a future clinical application. Xenotransplantation, with pigs as donors, offers the possibility of using healthy, living, and genetically modified islets from pathogen-free animals available in unlimited number of islets. Several studies in the pig-to-nonhuman primate model demonstrated the feasibility of successful preclinical islet xenotransplantation and have provided insights into the critical events and possible mechanisms of immune recognition and rejection of xenogeneic islet grafts. Particularly promising results in the achievement of prolonged insulin independence were obtained with newly developed, genetically modified pigs islets able to produce immunoregulatory products, using different implantation sites, and new immunotherapeutic strategies. Nonetheless, further efforts are needed to generate additional safety and efficacy data in nonhuman primate models to safely translate these findings into the clinic

Shape description and matching using integral invariants on eccentricity transformed images

Matching occluded and noisy shapes is a problem frequently encountered in medical image analysis and more generally in computer vision. To keep track of changes inside the breast, for example, it is important for a computer aided detection system to establish correspondences between regions of interest. Shape transformations, computed both with integral invariants (II) and with geodesic distance, yield signatures that are invariant to isometric deformations, such as bending and articulations. Integral invariants describe the boundaries of planar shapes. However, they provide no information about where a particular feature lies on the boundary with regard to the overall shape structure. Conversely, eccentricity transforms (Ecc) can match shapes by signatures of geodesic distance histograms based on information from inside the shape; but they ignore the boundary information. We describe a method that combines the boundary signature of a shape obtained from II and structural information from the Ecc to yield results that improve on them separately

A new immunodeficient hyperglycaemic mouse model based on the Ins2Akita mutation for analyses of human islet and beta stem and progenitor cell function.

AIMS/HYPOTHESIS: To develop and validate a new immunodeficient mouse strain that spontaneously develops a non-autoimmune hyperglycaemia to serve as a diabetic host for human islets and human beta stem and progenitor cells without the need for induction of hyperglycaemia by toxic chemicals with their associated side effects. METHODS: We generated and characterised a new strain of immunodeficient spontaneously hyperglycaemic mice, the NOD-Rag1null Prf1null Ins2Akita strain and compared this strain with the NOD-scid Il2rgammanull (also known as Il2rg) immunodeficient strain rendered hyperglycaemic by administration of a single dose of streptozotocin. Hyperglycaemic mice were transplanted with human islets ranging from 1,000 to 4,000 islet equivalents (IEQ) and were monitored for normalisation of blood glucose levels. RESULTS: NOD-Rag1null Prf1null Ins2Akita mice developed spontaneous hyperglycaemia, similar to Ins2Akita-harbouring strains of immunocompetent mice. Histological examination of islets in the host pancreas validated the spontaneous loss of beta cell mass in the absence of mononuclear cell infiltration. Human islets transplanted into spontaneously diabetic NOD-Rag1null Prf1null Ins2Akita and chemically diabetic NOD-scid Il2rgammanull mice resulted in a return to euglycaemia that occurred with transplantation of similar beta cell masses. CONCLUSIONS/INTERPRETATION: The NOD-Rag1null Prf1null Ins2Akita mouse is the first immunodeficient, spontaneously hyperglycaemic mouse strain described that is based on the Ins2Akita mutation. This strain is suitable as hosts for human islet and human beta stem and progenitor cell transplantation in the absence of the need for pharmacological induction of diabetes. This strain of mice also has low levels of innate immunity and can be engrafted with a human immune system for the study of human islet allograft rejection

Are Retinal Vessels Calibers Influenced by Blood Pressure Measured at the Time of Retinography Acquisition?

Retinal arterial narrowing is associated with higher office blood pressure (BP) and ambulatory blood pressure monitoring, and increased incidence of cardiovascular disease, but it is still unknown if the vessel caliber is associated with BP measured at the time of retinography acquisition.Retinal arteriolar and venular calibers were measured by the microdensitometric method in 448 patients with hypertension. Participants underwent 24-hours ambulatory blood pressure (24-h ABP) monitoring simultaneously with the retinography acquisition. Association between arteriolar and venular calibers with increase of 10 mmHg in the mean 24-hours, daily, and nightly BP, and with BP measured at the time of retinography, was evaluated by ANOVA and multivariate analyses.Mean 24-hours, daytime and nighttime systolic and diastolic BP were inversely associated with the arteriolar caliber, but not with the venular caliber. Arteriolar caliber decreased -0.8 (95% CI -1.4 to -0.2) μm per 10-mmHg increase in 24-hours mean systolic BP, adjusted for age, gender, fellow vessel, and duration of hypertension (P = 0.01). The corresponding decreasing in arteriolar caliber by 10 mmHg of increasing in mean diastolic BP was -1.1 μm (-2.0 to -0.2, P = 0.02). The decrease of arteriolar caliber by the same increasing of BP measured at the time of retinography was lower and not statistically significant, particularly for mean diastolic BP and outer arterioles calibers: -1.0 (-1.8 to -0.2) μm in the daytime BP average versus -0.3 (-0.9 to 0.3) at the moment of retinography acquisition.These findings suggest that the caliber of arteriolar retinal vessels in patients with uncontrolled hypertension are not significantly influenced by blood pressure measured at the time of retinography acquisition