Strategies to Reverse Endothelial Progenitor Cell Dysfunction in Diabetes

Bone-marrow-derived cells-mediated postnatal vasculogenesis has been reported as the main responsible for the regulation of vascular homeostasis in adults. Since their discovery, endothelial progenitor cells have been depicted as mediators of postnatal vasculogenesis for their peculiar phenotype (partially staminal and partially endothelial), their ability to differentiate in endothelial cell line and to be incorporated into the vessels wall during ischemia/damage. Diabetes mellitus, a condition characterized by cardiovascular disease, nephropathy, and micro- and macroangiopathy, showed a dysfunction of endothelial progenitor cells. Herein, we review the mechanisms involved in diabetes-related dysfunction of endothelial progenitor cells, highlighting how hyperglycemia affects the different steps of endothelial progenitor cells lifetime (i.e., bone marrow mobilization, trafficking into the bloodstream, differentiation in endothelial cells, and homing in damaged tissues/organs). Finally, we review preclinical and clinical strategies that aim to revert diabetes-induced dysfunction of endothelial progenitor cells as a means of finding new strategies to prevent diabetic complications

Rendimiento de achicoria ‘Folha larga’ y ‘Pão de açúcar’ en función de la densidad de plantación

1 recurso en línea (páginas 322-328) : ilustraciones color.La densidad de planta influye directamente en el potencial productivo de los cultivos y la mejor puede no ser la misma para todos. Debido a la falta de investigación en esta línea con achicoria, con el objetivo de estudiar el efecto de la densidad de plantas sobre el rendimiento de los dos cultivares de achicoria, de Folha Larga y Pão de Açúcar. Se evaluaron siete densidades de plantas (444.444, 370.370, 333.333, 277.778, 266.667, 222.222 y 185.185 plantas/ha), en un diseño de bloques al azar con cuatro repeticiones. Se evaluaron el peso fresco, altura de planta, número de hojas y la rendimiento. A pesar de la densidad no influyó en altura de la planta, había una disminución en el peso fresco y el número de hojas por planta y hubo un aumento de la rendimiento de los dos cultivares de mayor densidad.Plant density directly influences the productive potential of crops, and the best density is not the same for all cultivars. Because of a lack of research in this area with chicory, this study aimed to evaluate the effect of plant density on the production of two chicory cultivares, Folha Larga and Pão de Açúcar. Seven planting densities were evaluated (444,444; 370,370; 333,333; 277,778; 266,667; 222,222 and 185,185 plants/ha); the experiment design used a randomized block design with four replications. The fresh weight, plant height, leaf number and yield were evaluated. Despite the fact that density did not influence plant height, mass reduction was observed in the fresh weight and number of leaves per plant and there was an increase in yield of both cultivars with the higher density.Bibliografía: páginas 327-328

Evoluzione chimico-fisica, sensoriale e della texture di un formaggio fresco pecorino confezionato in atmosfera modificata durante la shelf-life

This paper reports the results obtained from the analysis of a fresh ewe’s cheese packed under different modified atmospheres during the shelf- life. Cheese stored in 80% N2/20% CO2, at the end of the shelf-life was better than cheese packed with a 10% CO2, both for sensory characteristics and for rheological parameters, specially for the puncture force and hardness and chewiness obtained from the TPA assay. The colour was slightly more yellow than the cheese stored with 10% CO2. Il presente lavoro riporta i risultati ottenuti dall’analisi di un formaggio pecorino fresco conservato in atmosfera modificata mediante due differenti condizioni e prodotto ad una settimana di distanza uno dall’altro. L’analisi dei cambiamenti fisico-chimici, di texture e sensoriali durante la shelf-life, ha evidenziato che il campione conservato in atmosfera modificata con una percentuale di N2/CO2 pari a 80/20 si è rivelato qualitativamente superiore rispetto a quello conservato con una percentuale di N2/CO2pari a 90/10, sia per quanto concerne le caratteristiche sensoriali sia per i parametri di texture, in particolar modo per la forza alla rottura in compressione e per la durezza e masticabilità all’analisi TPA, anche se ha mostrato un ingiallimento del colore leggermente superiore rispetto alla prova conservata in miscela di gas 90/10

Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans.

Objective: In this study we examined the effect of rapamycin (RAPA), a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function in vivo. Methods and results: Diabetic C57BL/6 or BALB/C recipient mice were transplanted with 350 syngeneic islets through the portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose concentrations and glucose tolerance were observed between RAPA-and vehicle-treated mice. The impact of RAPA on human islet engraftment was assessed in 10 patients with type 1 diabetes treated with 0.1 mg/kg/day rapamycin before islet transplantation. Compared to non pre-treated islet transplant recipents (n = 12), RAPA pre-treated patients had increased blood RAPA concentrations (p = 0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post-transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2 and CCL3 concentrations pre-transplant (p < 0.01), and a dampened chemokine response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the secretion of CCL2 and CCL3 by monocytes. Conclusion: Rapamycin does not adversely affect intrahepatic islet engraftment in the mouse, and potentially improves islet engraftment in humans by an anti-inflammatory mechanism

Mendelian breeding units <i>versus</i> standard sampling strategies: mitochondrial DNA variation in southwest Sardinia

We report a sampling strategy based on Mendelian Breeding Units (MBUs), representing an interbreeding group of individuals sharing a common gene pool. The identification of MBUs is crucial for case-control experimental design in association studies. The aim of this work was to evaluate the possible existence of bias in terms of genetic variability and haplogroup frequencies in the MBU sample, due to severe sample selection. In order to reach this goal, the MBU sampling strategy was compared to a standard selection of individuals according to their surname and place of birth. We analysed mitochondrial DNA variation (first hypervariable segment and coding region) in unrelated healthy subjects from two different areas of Sardinia: the area around the town of Cabras and the western Campidano area. No statistically significant differences were observed when the two sampling methods were compared, indicating that the stringent sample selection needed to establish a MBU does not alter original genetic variability and haplogroup distribution. Therefore, the MBU sampling strategy can be considered a useful tool in association studies of complex traits

Cabbage production in function of castor bean cake doses in top dressing

The researches with organic fertilization in top dressing in production of vegetables are rare, thereby, the objective of this study was to evaluate castor bean cake doses in top dressing in cabbage production. Seven treatments, six castor bean cake doses in top dressing (0; 50; 100; 150; 200 and 250 g m-2) and an inorganic control with ammonium sulphate (11.5 g m-2 of N) and potassium chloride (5.4 g m-2 of K2O) in top dressing were evaluated, in randomized blocks experimental design, with five replicates. Before planting it was made fertilization with organic compost (20 t ha-1) and inorganic NPK fertilizer (4-14-8) (1 t ha-1), only in inorganic control. The characteristics evaluated were: cabbage head diameter, height, number of leaves, fresh and dry weight of cabbage. The application of castor bean cake in top dressing increased the diameter, height, number of leaves, fresh and dry weight of cabbage, with maximum values of 164 mm, 109 mm, 30 leaves, 1470 g and 103 g, respectively. The average fresh and dry weight obtained in the two highest doses of castor bean cake did not differ from the inorganic control, proving the technical viability of its using. Therefore, it can be recommended application of at least 200 g m-2 of castor bean cake in top dressing for cabbage production.The researches with organic fertilization in top dressing in production of vegetables are rare, thereby, the objective of this study was to evaluate castor bean cake doses in top dressing in cabbage production. Seven treatments, six castor bean cake doses in top dressing (0; 50; 100; 150; 200 and 250 g m-2) and an inorganic control with ammonium sulphate (11.5 g m-2 of N) and potassium chloride (5.4 g m-2 of K2O) in top dressing were evaluated, in randomized blocks experimental design, with five replicates. Before planting it was made fertilization with organic compost (20 t ha-1) and inorganic NPK fertilizer (4-14-8) (1 t ha-1), only in inorganic control. The characteristics evaluated were: cabbage head diameter, height, number of leaves, fresh and dry weight of cabbage. The application of castor bean cake in top dressing increased the diameter, height, number of leaves, fresh and dry weight of cabbage, with maximum values of 164 mm, 109 mm, 30 leaves, 1470 g and 103 g, respectively. The average fresh and dry weight obtained in the two highest doses of castor bean cake did not differ from the inorganic control, proving the technical viability of its using. Therefore, it can be recommended application of at least 200 g m-2 of castor bean cake in top dressing for cabbage production

Human pancreatic islet preparations release HMGB1: (ir)relevance for graft engraftment.

High levels of donor-derived high-mobility group box 1 (HMGB1) protein have been associated with poor islet graft outcome in mouse models. The aim of our work was to determine whether HMGB1 released by human islets had independent proinflammatory effects that influence engraftment in humans. Human islet preparations contained and released HMGB1 in different amounts, as determined by Western blot and ELISA (median 17 pg/ml/IEQ/24 h; min–max 0–211, n = 74). HMGB1 release directly correlated with brain death, donor hyperamilasemia, and factors related to the pancreas digestion procedure (collagenase and digestion time). HMGB1 release was significantly positively associated with the release of other cytokines/chemokines, particularly with the highly released "proinflammatory" CXCL8/IL-8, CXCL1/GRO-α, and the IFN-γ-inducible chemokines CXCL10/IP-10 and CXCL9/MIG. HMGB1 release was not modulated by Toll-like receptor 2, 3, 4, 5, and 9 agonists or by exposure to IL-1β. When evaluated after islet transplantation, pretransplant HMGB1 release was weakly associated with the activation of the coagulation cascade (evaluated as serum cross-linked fibrin products), but not with the immediate posttransplant inflammatory response. Concordantly, HMGB1 did not affect short-term human islet function. Our data show that human islet HMGB1 release is a sign of "damaged" islets, although without any independent direct role in graft failure