Full Correction of Posttransplant Anemia Is Associated With Stabilized Cardiac Dimensions Among Kidney Transplant Recipients: A Prospective Randomized Controlled Trial.

OBJECTIVES: Posttransplant anemia might be associated with cardiovascular morbidity and increased mortality. To our knowledge, the debate on anemia correction has neither been revisited nor decided definitively. We aimed to assess the effects of full correction of posttransplant anemia on the cardiovascular system and quality of life among renal transplant recipients with stable graft function who were using erythropoietin-stimulating agents. MATERIALS AND METHODS: We enrolled 247 kidney recipients with stable graft function to be assessed for anemia. Eligible patients were randomized to achieve targeted hemoglobin of 11 to 12 g/dL (group 1, n = 183) or of 13 to 15 g/dL (group 2, n = 64) with the use of erythropoietin-stimulating agents. Patients underwent monthly clinical and laboratory evaluations of kidney graft function. Quality of life and echocardiography were assessed at study start and at 12 months. RESULTS: The 2 groups were comparable regarding pretransplant characteristics. In group 2, we observed comparable posttransplant complications (P > .05) but better graft function at 6 months and better cardiac indexes at 1 year of the study (P < .05). At 12 months, quality of life had improved after full correction of posttransplant anemia in the renal transplant recipients who received erythropoietinstimulating agents. CONCLUSIONS: Full correction of posttransplant anemia in renal transplant recipients was associated with improved quality of life and cardiac indexes without an effect on cardiovascular comorbidity.

Management of Chronic Active Antibody-Mediated Rejection in Renal Transplant Recipients: Single-Center Experience.

OBJECTIVES: Data on the management of chronic antibody-mediated rejection after kidney transplantation are limited. We aimed to assess the impact of treatment of biopsy-proven chronic active antibodymediated rejection with combined plasma exchange, intravenous immunoglobulin, and rituximab treatment versus intravenous immunoglobulin alone or conservative management on the evolution of renal function in renal transplant recipients. MATERIALS AND METHODS: In this retrospective study, we compared patients diagnosed with chronic active antibody-mediated rejection who were treated with standard of care steroids, intravenous immunoglobulin, plasma exchange, and rituximab (n = 40) at our center versus those who received intravenous immunoglobulin only or just intensified maintenance immunosuppression (n = 28). All patients were followed for 12 months clinically and by laboratory tests for graft and patient outcomes. RESULTS: The two groups were matched regarding mean recipient age (41.9 ± 15.4 vs 37.8 ± 15.5 y in patients with conservative versus combined treatment), recipient sex, mean body weight, and the cause of end-stage kidney disease. Most patients and their donors were males. Glomerulonephritis represented the most common cause of end-stage kidney disease in both groups followed by diabetic nephropathy. The type of induction and pretransplant comorbidities were not different between groups (P > .05) except for the significantly higher number of chronic hepatitis C infections in patients who received conservative treatment (P = .007). Mean serum creatinine values before and after treatment of chronic active antibodymediated rejection were comparable between groups (P > .05). Active treatment with heavier immunosuppression (rituximab and plasma exchange) was associated with posttreatment viral (cytomegalovirus and BK virus) and bacterial infections that necessitated more hospitalization (P > .05). However, graft and patient outcomes were significantly better in the active treatment group than in patients with conservative treatment (P = .002 and .028, respectively). CONCLUSIONS: Combined treatment of chronic active antibody-mediated rejection with plasma exchange, intravenous immunoglobulin, and rituximab can significantly improve outcomes after renal transplant.

Diurnal-activity Patterns of the Small Bee-eater (Merops orientalis) in Southern India.

The diurnal time-activity patterns of the Small Bee-eater (Merops orientalis) were studied between 2005 and 2006 in the Nagapattinam District of Southern India. Bee-eaters were observed to spend an average of 52.5% of their day time scanning, 21.3% feeding, 13.3% flying, 8.8% resting and 4.1% engaging in preening activities. The time spent on scanning varied among seasons in 2005 (p<0.05) and among time blocks (p<0.05), but it did not vary among years or habitats (p>0.05). The feeding patterns differed among years, seasons within years, time blocks and habitats (p<0.05). The flying habits varied among years, time blocks and habitats (p<0.05) but did not change between seasons within years (p>0.05). The resting habits differed among years and habitats (p<0.05) but did not differ among seasons within years or time blocks (p>0.05). Preening differed among years and time blocks (p<0.05) but did not vary among seasons within years or habitats (p>0.05). We conclude that several factors, such as food availability, environmental factors and predation threats, may affect the diurnal activity patterns of Bee-eaters between habitats and seasons; a further study could clarify this conclusion.

Modeling in vitro inhibition of butyrylcholinesterase using molecular docking, multi-linear regression and artificial neural network approaches.

Butyrylcholinesterase (BChE) has been an important protein used for development of anti-cocaine medication. Through computational design, BChE mutants with ∼2000-fold improved catalytic efficiency against cocaine have been discovered in our lab. To study drug-enzyme interaction it is important to build mathematical model to predict molecular inhibitory activity against BChE. This report presents a neural network (NN) QSAR study, compared with multi-linear regression (MLR) and molecular docking, on a set of 93 small molecules that act as inhibitors of BChE by use of the inhibitory activities (pIC50 values) of the molecules as target values. The statistical results for the linear model built from docking generated energy descriptors were: r(2)=0.67, rmsd=0.87, q(2)=0.65 and loormsd=0.90; the statistical results for the ligand-based MLR model were: r(2)=0.89, rmsd=0.51, q(2)=0.85 and loormsd=0.58; the statistical results for the ligand-based NN model were the best: r(2)=0.95, rmsd=0.33, q(2)=0.90 and loormsd=0.48, demonstrating that the NN is powerful in analysis of a set of complicated data. As BChE is also an established drug target to develop new treatment for Alzheimer's disease (AD). The developed QSAR models provide tools for rationalizing identification of potential BChE inhibitors or selection of compounds for synthesis in the discovery of novel effective inhibitors of BChE in the future.

Molecular basis of the selectivity of the immunoproteasome catalytic subunit LMP2-specific inhibitor revealed by molecular modeling and dynamics simulations.

Given that immunoproteasome inhibitors are currently being developed for a variety of potent therapeutic purposes, the unique specificity of an α',ß'-epoxyketone peptide (UK101) toward the LMP2 subunit of the immunoproteasome (analogous to ß5 subunit of the constitutive proteasome) has been investigated in this study for the first time by employing homology modeling, molecular docking, molecular dynamics simulation, and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations. On the basis of the simulated binding structures, the calculated binding free energies are in qualitative agreement with the corresponding experimental data, and the selectivity of UK101 is explained reasonably. The observed selectivity of UK101 for the LMP2 subunit is rationalized by the requirement for both a linear hydrocarbon chain at the N terminus and a bulky group at the C terminus of the inhibitor, because the LMP2 subunit has a much more favorable hydrophobic pocket interacting with the linear hydrocarbon chain, and the bulky group at the C terminus has a steric clash with the Tyr 169 in ß5 subunit. Finally, our results help to clarify why UK101 is specific to the LMP2 subunit of immunoproteasome, and this investigation should be valuable for rational design of more potent LMP2-specific inhibitors.