Effect of Different Rituximab Doses on B Cell Count,Anti-A/B Antibody Titer,Graft Function,and Infectious Complications in ABO-Incompatible Renal Transplantation: A Prospective Study

BackgroundABO-incompatible kidney transplantation (ABOiKT) has been accepted as a viable and cost-effective modality with outcomes comparable to ABO-compatible transplants, but there is a concern regarding higher infectious complications in ABOiKT because of the heightened immunosuppression.The desensitization protocol normally includes antibody removal, B cell depletion by rituximab (RTX), and immunomodulation with intravenous immunoglobulin. Efforts have been made over the years to decrease the dose of RTX in an effort to decrease the infective complications. There is limited literature about the minimum effective dose of RTX, which can cause an effective B cell depletion. This prospective study was designed to correlate the RTX dose with peripheral absolute B cell count, graft function, graft and patient survival, and infective complications.MethodsThis study included 52 adult ABOiKT recipients with anti-A/B antibody titer up to a maximum of 1:512. The participants were divided into 2 groups of 26 each according to the RTX dosage used: Group A received 100 mg/patient, and Group B received 200 mg/patient. RTX was given 14 days prior to transplant after B cell measurement by flow cytometry. The outcomes were compared after 1 year of follow-up.ResultsBoth the dosages effectively depleted the absolute B cell count. Although patient survivals, graft survival, graft function, acute rejection episodes, and post-transplant hospital stay were similar in both groups, infective complications were significantly higher in group B.ConclusionA low dose (100 mg/patient) of RTX produces effective depletion of B cells while lowering the infective complications in ABOiKT.     

Comparison between clinical and audiological results of tympanoplasty with double layer graft (modified sandwich fascia) technique and single layer graft (underlay fascia and underlay cartilage) technique

Introduction

Surgical repair of the tympanic membrane, termed a type one tympanoplasty is a tried and tested treatment modality. Overlay or underlay technique of tympanoplasty is common. Sandwich Tympanoplasty is the combined overlay and underlay grafting of tympanic membrane.

3D-QSAR and docking studies of benzoyl urea derivatives as tubulin-binding agents for antiproliferative activity

Tubulins, an αβ heterodimers, the major component of microtubules, are important molecular target of numerous small molecule ligands for anticancer therapy. In this study, the molecular modeling studies were performed to develop predictive 3D-QSAR models using set of 32 compounds of benzoyl urea derivatives as tubulin-binding agents for antiproliferative activity. A five-point common pharmacophore hypotheses with one hydrogen bond acceptor (A), two hydrogen bond donors (D), one hydrophobic (H), and one ring (R) vector features were selected for alignment of all compounds. The 3D-QSAR models generated using training set of 21 compounds and test set of 11 compounds showed good partial least squares statistical results. The developed CPHs and 3D-QSAR models were validated further externally by predicting the activity of database of compounds from literature and comparing it with actual activity. Docking studies were also carried out for all compounds on colchicine-binding site of β-tubulin for studying of binding affinity of compounds for antiproliferative activity. The results of these molecular modeling studies are helpful to refine the pharmacophore for design of new potential compounds for antiproliferative activity.     

The N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated endothelium via P-selectin in vivo

P-selectin glycoprotein ligand-1 (PSGL-1) is present on leukocytes and is the major ligand for endothelial expressed P-selectin. A variety of studies strongly suggests that the N-terminal region of PSGL-1 contains the binding site for P-selectin. We hypothesized that this relatively small N-terminal peptide of PSGL-1 is sufficient to support adhesion to P-selectin in vivo. To test this hypothesis, we coated 2 microm-diameter microspheres with a recombinant PSGL-1 construct, termed 19.ek.Fc. The 19.ek.Fc construct consists of the first 19 N-terminal amino acids of mature PSGL-1 linked to an enterokinase cleavage site that, in turn, is linked to human immunoglobulin G Fc. The 19.ek.Fc-coated microspheres were injected into the jugular vein of mice. Intravital microscopy of postcapillary venules within the cremaster muscle of mice revealed that a significantly greater number of 19.ek.Fc microspheres rolled compared with control microspheres. The number of rolling 19.ek.Fc microspheres was significantly diminished by pretreatment of the mice with a monoclonal antibody to P-selectin or by pretreatment of the 19.ek.Fc microspheres with a monoclonal antibody to PSGL-1. Combined, the results indicate that the N-terminal peptide of PSGL-1 can mediate adhesion to trauma-activated microvascular endothelium via P-selectin in vivo.     

Muscular Basis of Whisker Torsion in Mice and Rats

Whisking mammals move their whiskers in the rostrocaudal and dorsoventral directions with simultaneous rolling about their long axes (torsion). Whereas muscular control of the first two types of whisker movement was already established, the anatomic muscular substrate of the whisker torsion remains unclear. Specifically, it was not clear whether torsion is induced by asymmetrical operation of known muscles or by other largely unknown muscles. Here, we report that mystacial pads of newborn and adult rats and mice contain oblique intrinsic muscles (OMs) that connect diagonally adjacent vibrissa follicles. Each of the OMs is supplied by a cluster of motor end plates. In rows A and B, OMs connect the ventral part of the rostral follicle with the dorsal part of the caudal follicle. In rows C–E, in contrast, OMs connect the dorsal part of the rostral follicle to the ventral part of the caudal follicle. This inverse architecture is consistent with previous behavioral observations [Knutsen et al.: Neuron 59 (2008) 35–42]. In newborn mice, torsion occurred in irregular single twitches. In adult anesthetized rats, microelectrode mediated electrical stimulation of an individual OM that is coupled with two adjacent whiskers was sufficient to induce a unidirectional torsion of both whiskers. Torsional movement was associated with protracting movement, indicating that in the vibrissal system, like in the ocular system, torsional movement is mechanically coupled to horizontal and vertical movements. This study shows that torsional whisker rotation is mediated by specific OMs whose morphology and attachment sites determine rotation direction and mechanical coupling, and motor innervation determines rotation dynamics. Anat Rec, 300:1643–1653, 2017. © 2017 Wiley Periodicals, Inc.