Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model

The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7–14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization.     

In vitro assessment of an antibacterial quaternary ammonium-based polymer loaded with chlorhexidine for the coating of polypropylene prosthetic meshes

Purpose

This study assesses the use of an absorbable polymer loaded with chlorhexidine (CHX) as an antibacterial coating for polypropylene (PP) meshes employed in hernia repair.

Methods

The polymer N,N-dimethyl-N-benzyl-N-(2-methacryloyloxyethyl) ammonium bromide was loaded with CHX (1 % w/w). Fragments (1 cm²) of Optilene^® Mesh Elastic were coated either with the unloaded (POL) or CHX-loaded polymer (POL–CHX). Uncoated fragments (PP) served as controls. The release kinetics of the POL–CHX coating was monitored by HPLC. Sterile fragments were placed on agar plates previously contaminated with 10⁶ CFU of Staphylococcus aureus (Sa) ATCC25923, Staphylococcus epidermidis (Se) ATCC12228, or Escherichia coli (Ec) ATCC25922 and incubated at 37 °C for 1/2/7 days. At each time point, inhibition halos were measured and bacterial adhesion to the meshes quantified by sonication and scanning electron microscopy. Coating cytotoxic effects were examined on cultured fibroblasts.

Results

The polymer coating gradually released CHX over 3 days. Inhibition halos were produced only around the POL–CHX-coated meshes and these were significantly smaller for Ec than Sa or Se (p < 0.01). While POL–CHX prevented bacterial adhesion to the mesh, the reduced bacterial yields over time were observed for the POL-coated versus control PP meshes (p < 0.001). By day 7, only Ec remained attached to the surface of control meshes. The POL coating was not cytotoxic, yet POL–CHX reduced the viability of cultured fibroblasts.

Conclusions

When loaded with the antiseptic CHX, this quaternary ammonium-based polymer coating released its contents in a controlled manner indicating its potential prophylactic use to reduce the risk of infection following PP mesh implantation.

     

Polymorphisms in CYP2D6 have a Greater Effect on Variability of Risperidone Pharmacokinetics than Gender

Within‐subject coefficient of variation (CV_w) plays a decisive role in the determination of sample size in bioequivalence clinical trials. Highly variable drugs may require the participation of a large number of subjects. The aim of this study was to investigate whether gender and polymorphisms in CYP2D6 affect the CV_w of risperidone. Two single‐dose, two‐period crossover studies of risperidone (n = 70) were reanalysed to calculate CV_w for AUC_t and C_max. Subjects were classified into four different CYP2D6 phenotype groups [poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM)]. The effect of gender was evaluated in EM and IM. CV_w was lower in PM (13.3% for AUC_t and 10.9% for C_max) and UM (17.4% and 8.7%) than in EM (28.7% and 34.7%) and IM (33.2% and 27.3%). Variability was slightly lower in women (27.9% for AUC_t and 25.7% for C_max) than in men (33.3% and 37.2%, respectively). Genetic polymorphisms affect within‐subject variability more than gender and could considerably affect sample size calculation. Therefore, subjects participating in bioequivalence trials should be genotyped.     

Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain.This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.