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Zapata-Morales J.R.,Autonomous University of San Luis Potosi | Galicia-Cruz O.G.,Autonomous University of San Luis Potosi | Franco M.,Instituto Nacional Of Cardiologia Dr Ignacio Chavez | Morales F.M.,Autonomous University of San Luis Potosi
Journal of Biological Chemistry | Year: 2014

In this work, we demonstrated the regulation of glucose transporters by hypoxia inducible factor-1α (HIF-1α) activation in renal epithelial cells. LLC-PK1 monolayers were incubated for 1, 3, 6, or 12 h with 0% or 5% O2 or 300 μm cobalt (CoCl2). We evaluated the effects of hypoxia on the mRNA and protein expression of HIF-1α and of the glucose transporters SGLT1, SGLT2, and GLUT1. The data showed an increase in HIF-1α mRNA and protein expression under the three evaluated conditions (p < 0.05 versus t = 0). An increase in GLUT1 mRNA (12 h) and protein expression (at 3, 6, and 12 h) was observed (p < 0.05 versus t = 0). SGLT1 and SGLT2 mRNA and protein expression decreased under the three evaluated conditions (p < 0.05 versus t = 0). In conclusion, our results suggest a clear decrease in the expression of the glucose transporters SGLT1 and SGLT2 under hypoxic conditions which implies a possible correlation with increased expression of HIF-1α. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


Vanrenterghem Y.,University Hospital Leuven | Bresnahan B.,Medical College of Wisconsin | Campistol J.,University of Barcelona | Durrbach A.,University Paris - Sud | And 11 more authors.
Transplantation | Year: 2011

Background: Cardiovascular disease, the most common cause of death with a functioning graft among kidney transplant recipients, can be exacerbated by immunosuppressive drugs, particularly the calcineurin inhibitors. Belatacept, a selective co-stimulation blocker, may provide a better cardiovascular/metabolic risk profile than current immunosuppressants. Methods: Cardiovascular and metabolic endpoints from two Phase III studies (BENEFIT and BENEFIT-EXT) of belatacept-based regimens in kidney transplant recipients were assessed at month 12. Each study assessed belatacept in more intensive (MI) and less intensive (LI) regimens versus cyclosporine A (CsA). These secondary endpoints included changes in blood pressure, changes in serum lipids, and the incidence of new-onset diabetes after transplant (NODAT). RESULTS.: A total of 1209 patients were randomized and transplanted across the two studies. Mean systolic blood pressure was 6 to 9 mm Hg lower and mean diastolic blood pressure was 3 to 4 mm Hg lower in the MI and LI groups versus CsA (P≤0.002) across both studies at month 12. Non-HDL cholesterol was lower in the belatacept groups versus CsA (P<0.01 MI or LI vs. CsA in each study). Serum triglycerides were lower in the belatacept groups versus CsA (P<0.02 MI or LI vs. CsA in each study). NODAT occurred less often in the belatacept groups versus CsA in a prespecified pooled analysis (P<0.05 MI or LI vs. CsA). CONCLUSIONS.: At month 12, belatacept regimens were associated with better cardiovascular and metabolic risk profiles, with lower blood pressure and serum lipids and less NODAT versus CsA. The overall profile of belatacept will continue to be assessed over the 3-year trials. © 2011 by Lippincott Williams & Wilkins.


Mejia Dominguez A.M.,Instituto Nacional Of Cardiologia Dr Ignacio Chavez
Gaceta Medica de Mexico | Year: 2013

Transfusion-related acute lung injury (TRALI) is a syndrome characterized by acute respiratory distress following the transfusion of blood components. The pathophysiological hallmark of TRALI is increased pulmonary microvascular permeability. Several reports demonstrate that the majority of TRALI cases are precipitated by transfusion of donor antibodies directed against HLA (human leukocyte antigens) or HNA (human neutrophil antigens) expressed on the neutrophils' surface of the recipient. This antibody-antigen interaction is thought to directly cause neutrophils activation and release of cytotoxic agents, with subsequent endothelial damage and capillary leak. Following plasma transfusion is an important and underreported adverse event. Some blood centers have limited the collection of plasma from female donors due to their propensity for developing anti HLA antibodies after pregnancy.


Vincenti F.,University of California at San Francisco | Larsen C.P.,Emory University | Alberu J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran | Bresnahan B.,Medical College of Wisconsin | And 14 more authors.
American Journal of Transplantation | Year: 2012

The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years. BENEFIT is a randomized 3 year, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor. Patients were randomized to a more (MI) or less intensive (LI) regimen of belatacept, or cyclosporine. 471/666 patients completed ≥3 years of therapy. A total of 92% (MI), 92% (LI), and 89% (cyclosporine) of patients survived with a functioning graft. The mean calculated GFR (cGFR) was ∼21 mL/min/1.73 m 2 higher in the belatacept groups versus cyclosporine at year 3. From month 3 to month 36, the mean cGFR increased in the belatacept groups by +1.0 mL/min/1.73 m 2/year (MI) and +1.2 mL/min/1.73 m 2/year (LI) versus a decline of -2.0 mL/min/1.73 m 2/year (cyclosporine). One cyclosporine-treated patient experienced acute rejection between year 2 and year 3. There were no new safety signals and no new posttransplant lymphoproliferative disorder (PTLD) cases after month 18. Belatacept-treated patients maintained a high rate of patient and graft survival that was comparable to cyclosporine-treated patients, despite an early increased occurrence of acute rejection and PTLD. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Gonzalez-Villalva A.,National Autonomous University of Mexico | Pinon-Zarate G.,National Autonomous University of Mexico | De la Pena Diaz A.,National Autonomous University of Mexico | De la Pena Diaz A.,Instituto Nacional Of Cardiologia Dr Ignacio Chavez | And 5 more authors.
Environmental Toxicology and Pharmacology | Year: 2011

Vanadium pentoxide (V 2O 5) inhalation effect on platelet function in mice was explored, as well as the in vitro effect on human platelets. Mouse blood samples were collected and processed for aggregometry and flow cytometry to assess the presence of P-selectin and monocyte-platelet conjugates. Simultaneously, human platelets were processed for aggregometry . The mouse results showed platelet aggregation inhibition in platelet-rich-plasma (PRP) at four-week exposure time, and normality returned at eight weeks of exposure, remaining unchanged after the exposure was discontinued after four weeks. This platelet aggregation inhibition effect was reinforced with the in vitro assay. In addition, P-selectin preserved their values during the exposure, until the exposure was discontinued during four weeks, when this activation marker increased. We conclude that vanadium affects platelet function, but further studies are required to evaluate its effect on other components of the hemostatic system. © 2011 Elsevier B.V.

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