The role of choroidal hypoperfusion associated with photodynamic therapy in neovascular age-related macular degeneration and the consequences for combination strategies

The clinical benefits of verteporfin therapy have been documented in a wide variety of patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD), and there is encouraging evidence of improved outcomes when this angioocclusive modality is combined with antiangiogenic agents. Although the clinical benefits of verteporfin mono- and combination therapy are well established, there has been concern that treatment with verteporfin results in hypoperfusion in the treated area and that concomitant use of antiangiogenic agents could prolong this effect. However, despite well-documented occurrences of hypoperfusion on fluorescein and indocyanine green angiography, there is little evidence of associations with functional impairment or other adverse effects. It has also been suggested that hypoperfusion might actually help to reduce recanalization of CNV and permit neuronal recovery by decreasing exposure to oxygen and oxidative radicals. The reduced need for frequent retreatments clearly has a major appeal due to the lower costs associated with fewer interventions and reduced burden of clinical monitoring and diagnostic reevaluations. Ongoing evaluation in randomized clinical trials will provide further clarification on the effect of verteporfin plus ranibizumab compared with ranibizumab monotherapy in terms of visual acuity, anatomical outcomes, treatment frequency, and health economics. The results of these large-scale clinical trials will provide a strong basis for determining the benefits and risks of combination therapy.     

Development and Characterization of Active Gelatin Films Loaded with Rapeseed Meal Extracts

The use of industrial waste as a material for the development of natural innovative and active packaging is economically and environmentally appealing. The aim of this study was to develop and characterize active gelatin films incorporating rapeseed oil industry waste. Water (RM-WE) and methanolic (RM-MWE) extracts of rapeseed meal (RM) were used as active agents in film formulations. The active films were produced by a casting technique. The physicochemical, mechanical, optical, morphological, radical scavenging, and antibacterial properties of the films were analyzed. The addition of RM-WE and RM-MWE in the concentrations range between 4 and 12% promoted an increase of Young’s modulus (YM) and radical scavenging properties of films investigated by the direct QUick, Easy, New, CHEap and Reproducible procedure using 2,2-diphenyl-1-picrylhydrazyl (QUENCHER_DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (QUENCHER_ABTS) radicals. The antibacterial properties of films were examined against five bacterial strains: E. coli, S. enterica, M. luteus, L. monocytogenes, and S. aureus. Additionally, color and opacity of the control and fortified films differed significantly. The gelatin films with RM extracts are resistant to the microbial spoilage and could be used to produce active packaging for food that is vulnerable to rancidity effects.     

Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.     

Effectiveness of antiplatelet therapy in atherosclerotic disease: comparing the ASA low-response prevalence in CVD,CAD and PAD

Although acetylsalicylic acid (ASA, aspirin) reduces the risk of ischemic events in patients with atherosclerosis, a substantial number of incidents continue to occur. As only limited data exist we evaluated the antiplatelet effectiveness of ASA in patients with different manifestations of atherosclerosis as in cerebrovascular, coronary artery and peripheral arterial disease (CVD, CAD, PAD). For the evaluation of the antiplatelet effectiveness of ASA we used whole blood aggregometry (Chrono-log Model 590). The patients in the different subgroups received ASA 100, 200 or 500 mg daily. We analysed 737 consecutive patients: 47.5 % with CVD, 33.6 % with CAD, and 18.9 % with PAD. We identified 28.0 % of the CVD, 18.1 % of the CAD and 21.6 % of the PAD patients to be ASA low-responder (ALR). Comparing subgroups treated with 100 mg ASA, 36.4 % were ALR in the CVD group as were 13.1 % of the CAD and 21.6 % of the PAD patients. Multivariate regression analysis revealed an odds ratio for being ALR of 4.50 (95 % confidence interval (CI) 1.70–11.9) when 100 mg and of 2.97 (95 % CI 1.58–5.60) when 200 mg ASA was taken compared to a dose of 500 mg. Despite the proven benefits of antiplatelet therapy in the secondary prevention of atherosclerotic disease, current antiplatelet management is suboptimal as up to 36 % of patients failed to achieve an adequate platelet inhibitory effect. Our findings may explain, at least in part, the high rates of cardiovascular events observed in the course of atherothrombotic disease and support the need to improve antiplatelet therapy.     

Commentary: Dermal penetration of bisphenol A—Consequences for risk assessment

With this comment we would raise awareness for applying appropriate procedures in route-to-route extrapolation. The paper of Demierre et al. (2012) prompted us to comment on the simple approach for route-to-route extrapolation and to explain some short comings. For the risk assessment of exposures resulting from a non-oral route, route-to-route extrapolation is often done by correcting the non-oral route exposure by the route specific absorption into the systemic circulation and comparing the result with the (oral) threshold value. Making use of this procedure means that an internal dose obtained from the non-oral route is compared with an external dose of the oral route. This procedure would be appropriate only if the absorption on the oral route is 100%. If the absorption on the oral route is less than 100% the procedure may underestimate the risk of the exposure of the non-oral route. For some chemicals with a high first pass metabolism in the liver, e.g. BPA, the situation is even more complex and in addition, the target organ for toxicity has to be taken into consideration.