Toxicological profile of PM from different sources in the bronchial epithelial cell line BEAS-2B

The toxicity of particulate matter (PM) is strictly associated with its physical-chemical characteristics, such as size or chemical composition. While these properties depend on the origin of the particles, the study of the toxicological profile of PM from single sources has rarely been highlighted. Hence, the focus of this research was to investigate the biological effects of PM from five relevant sources of atmospheric PM: diesel exhaust particles, coke dust, pellet ashes, incinerator ashes, and brake dust. Cytotoxicity, genotoxicity, oxidative, and inflammatory response were assessed in a bronchial cell line (BEAS-2B). BEAS-2B cells were exposed to different concentrations (25, 50, 100, and 150 g/mL medium) of particles suspended in water. The exposure lasted 24 h for all the assays performed, except for reactive oxygen species, which were evaluated after 30 min, 1 h, and 4 h of treatment. The results showed a different action of the five types of PM. All the tested samples showed a genotoxic action on BEAS-2B, even in the absence of oxidative stress induction. Pellet ashes seemed to be the only ones able to induce oxidative stress by boosting the formation of reactive oxygen species, while brake dust resulted in the most cytotoxic. In conclusion, the study elucidated the differential response of bronchial cells to PM samples generated by different sources. The comparison could be a starting point for a regulatory intervention since it highlighted the toxic potential of each type of PM tested

Risk Characterization of Botanical Extracts Containing Hydroxyanthracenes as Determined by a Validated Micronucleus In Vitro Assay

Extracts of Rheum palmatum L., Rhamnus purshiana DC., Rhamnus frangula L., and Cassia senna L. are used in traditional medicine thanks to their beneficial properties. These species contain hydroxyanthracene derivatives, considered genotoxic and possibly related to colorectal cancer development. This research aimed to study, using a micronucleus assay in vitro, the genotoxic potential of Rheum palmatum L., Rhamnus purshiana DC., Rhamnus frangula L. (bark), and Cassia senna L. (leaves and fruits) extracts. The extracts were evaluated at different concentrations: from 0 to 2000 µg/mL for Rhamnus purshiana DC, from 0 to 2500 µg/mL for Rheum palmatum L. and Rhamnus frangula L., and from 0 to 5000 µg/mL for Cassia senna L. The cytokinesis-block proliferation index was calculated to analyse if the used concentrations showed cytotoxicity. The hydroxyanthracene content varied between 0.06% and 0.23% for aloe-emodin, and between 0.07% and 0.16% for emodin and rhein. No cytotoxic effect was detected at any of these concentrations. Micronucleus analyses showed a lack of genotoxicity for all the extracts tested. These results show that Rheum palmatum L., Rhamnus purshiana DC, Rhamnus frangula L., and Cassia senna L. extracts do not induce genotoxicity since no increase in micronuclei formation in human lymphocytes in vitro was detected

Lack of in vivo genotoxic effect of dried whole Aloe ferox juice

<p>Aloe ferox Mill is widely used as a traditional herbal medicine for the treatment of a broad spectrum of illnesses given its laxative, anti-inflammatory, bitter tonic, anti-oxidant, antimicrobial and anti-cancer properties. Using the in vivo alkaline comet assay in animals (OECD 489), this study investigated the potential in vivo genotoxicity of dried Aloe ferox juice at dose levels of 500, 1000, and 2000 mg/kg/day in mice. Aloe ferox showed no genotoxic activity in preparations of single cells from the colon of the treated Hsd:ICR (CD-1) male mice. No statistically significant increase in DNA migration over the negative control was observed by analysis of variance for both comet parameters, tail moment and tail intensity, apart from the positive control ethyl methanesulphonate that induced clear and statistically significant increases in DNA migration parameters over the concurrent controls. The new reported scientific evidence unequivocally demonstrates that dried Aloe ferox juice containing hydroxyanthracene derivatives does not induce DNA damage in preparations of single cells from colon in in vivo comet genotoxicity studies. This suggests that the hyperplastic changes and mucosal hyperplasia observed after long-term administration of Aloe vera non-decolourised whole leaf extract may be attributed to an epigenetic effect of the material under investigation.</p&gt

Lack of genotoxicity of rhubarb (rhizome) in the Ames and micronucleus in vitro tests

<p>Aloe ferox Mill is widely used as a traditional herbal medicine for the treatment of a broad spectrum of illnesses given its laxative, anti-inflammatory, bitter tonic, anti-oxidant, antimicrobial and anti-cancer properties. Using the in vivo alkaline comet assay in animals (OECD 489), this study investigated the potential in vivo genotoxicity of dried Aloe ferox juice at dose levels of 500, 1000, and 2000 mg/kg/day in mice. Aloe ferox showed no genotoxic activity in preparations of single cells from the colon of the treated Hsd:ICR (CD-1) male mice. No statistically significant increase in DNA migration over the negative control was observed by analysis of variance for both comet parameters, tail moment and tail intensity, apart from the positive control ethyl methanesulphonate that induced clear and statistically significant increases in DNA migration parameters over the concurrent controls. The new reported scientific evidence unequivocally demonstrates that dried Aloe ferox juice containing hydroxyanthracene derivatives does not induce DNA damage in preparations of single cells from colon in in vivo comet genotoxicity studies. This suggests that the hyperplastic changes and mucosal hyperplasia observed after long-term administration of Aloe vera non-decolourised whole leaf extract may be attributed to an epigenetic effect of the material under investigation.</p&gt

Rhus coriaria L. Fruit Extract Prevents UV-A-Induced Genotoxicity and Oxidative Injury in Human Microvascular Endothelial Cells

Rhus coriaria L. (sumac) is a small plant widely diffused in the Mediterranean region. Its fruit are often consumed as a spice but are also present in traditional medicine of several countries. Recently, interest in this plant has increased and many scientific works reported its beneficial effects including antioxidant and anti-inflammatory properties. Plant extracts can be successfully used against ultraviolet rays, which are able to reach and damage the human skin; however, sumac extracts were never applied to this usage. Thus, in this study, we used a macerated ethanol extract of Rhus coriaria L. dried fruit (mERC) to demonstrate its preventive role against the damage induced by ultraviolet-A rays (UV-A) on microvascular endothelial cells (HMEC-1). In vitro effects of the extract pre-treatment and UV-A exposure were evaluated in detail. The antioxidant capacity was assessed by reactive oxygen species (ROS) formation and cellular antioxidant activity measurement. Genoprotective effects of mERC were investigated as well. Our findings indicate that the extract acts as a cell cycle inhibitor or apoptosis inducer, according to the level of damage. The present work provides new insights into the usage of Rhus coriaria extracts against skin injuries

A novel approach to chronic total occlusions: The CROSSER System

Objectives: To evaluate safety and efficacy of the GROSSER CTO Recanalization System (GROSSER). Background: The GROSSER, a novel device dedicated to recanalization of chronic total occlusions (CTO), relies on a monorail catheter delivering vibrational energy to facilitate the crossing of occluded coronary arteries. Methods: We included de novo or restenotic occlusions in native coronary arteries with typically unfavorable characteristics and a prior failed guidewire attempt either performed in a previous procedure or just before the usage of the GROSSER. The end points analyzed were technical success (ability to cross or facilitate a guidewire crossing into the true lumen), angiographic success ( 20 mm in 76.6%. The median age of the CTO was 9 months (range 3-60 months). Technical success was obtained in 19 (63%) occlusions and angiographic success in 16 (53%): 26.3% in lesions with prior procedural failure and 73.7% when GROSSER was attempted after initial guidewire failure. Complications were: one guidewire perforation without consequences and one peri-procedural myocardial infarction (MI). No events occurred within 30-day follow-up after discharge. Conclusions: In our experience, the GROSSER System is safe and increases the success of opening CTO refractory to guidewires. This novel device may represent an useful adjunct to the armamentarium of the interventional cardiologist

Repeated drug-eluting stent implantation for drug-eluting stent restenosis: The same or a different stent

Background Currently, little data are available on the management of drug-eluting stent (DES) restenosis. Drug resistance may play a role in its etiology. Methods We identified all cases of either sirolimus-eluting or paclitaxel-eluting stent restenosis treated with repeated DES implantation. The lesions were divided into those receiving the same DES as the one that restenosed and those treated with the alternative DES. The end points analyzed were target lesion revascularization (TLR) and angiographic restenosis. Results We included 201 lesions (174 patients); the same DES was implanted in 107 lesions an a different DES in 94 lesions. Angiographic follow-up of the retreatment was available in 69.7% of the lesions. Angiographic restenosis occurred in 26.4% (19) of cases treated with the same DES and 25.8% (17) of those treated with a different DES (P = 1.0). Target lesion revascularization occurred in 15.9% (17) and 16% (15) of lesions, respectively (P = 1.0). A multivariate analysis confirmed the lack of association between the treatment selected and TLR (OR 0.7, 95% CIs [0.29-1.67]; P =.42). A nonfocal pattern of restenosis remained associated with TLR and restenosis (OR 2.99, 95% CIs [1.24-7.241; P = .015 and OR 3.6, 95% CIs [1.5-8.8]; P = .004, respectively). Conclusions Repeated DES implantation for DES restenosis is feasible and safe. The TLR rate is acceptable, with no differences between implantation of the same or a different DES. The pattern of restenosis treated is an important predictor of outcomes

Late Restenosis Following Sirolimus-Eluting Stent Implantation

Despite encouraging results from randomized trials, concerns exist about long-term results of sirolimus-eluting stent implantation. We sought to determine whether in-stent restenosis occurring >1 year ("late") after sirolimus-eluting stent implantation is a real clinical entity. We analyzed data on all sirolimus-eluting stents implanted in our institution before March 2003. During the study period 928 lesions in 433 patients were treated. Angiographic follow-up was performed in 306 patients (70.6%) with 679 lesions (73.2%). Angiography after 1 year was performed only in symptomatic patients. We considered restenosis "early" if it occurred during the first year and late if after 1 year. Late restenosis required demonstration of a widely patent stent at 6 to 9 months, with repeat angiography after 1 year demonstrating restenosis. Restenosis occurred in 160 lesions overall (23.5%). Of the 31 (4.6%) that were documented after 1 year, 13 were excluded from analysis due to absence of 6- to 9-month angiography; the remaining 18 (2.6%, 1.7 to 4.2) fulfilled our criteria for late restenosis (median time of documentation 607 days, interquartile range 511 to 923). In conclusion, late restenosis is an infrequent but real entity; its existence implies we should not discount the possibility of restenosis as the cause of symptoms that develop >1 year after sirolimus-eluting stent implantation. © 2007 Elsevier Inc. All rights reserved

Angiographic analysis of pattern of late luminal loss in sirolimus- and paclitaxel-eluting stents

Late loss is becoming an important end point to compare drug-eluting stents; however, little is known about its pattern of distribution. We analyzed the pattern of late loss distribution in sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) in a consecutive cohort of patients. From a cohort of 529 patients treated with drug-eluting stents in 1 year, we selected all patients who underwent angiographic follow-up. Three hundred fifty-nine patients with 592 de novo lesions received SESs (286 lesions) or PESs (306 lesions). Late loss and binary angiographic restenosis were analyzed. Binary restenosis occurred in 56 lesions (19.6%) treated with SESs compared with 53 (17.3%) treated with PESs (p = 0.48). The 2 late loss distributions were skewed to the right and were not normally distributed (p < 0.001 for SES, p = 0.003 for PES). Late loss was significantly lower in the SES group (p = 0.03), with a median value of 0.29 mm. (interquartile range -0.09 to 0.66) versus 0.41 mm (-0.02 to 0.85) in the PES group. When analyzing only restenotic lesions, late loss had a normal distribution in the SES and PES groups (p = 0.96 and 0.44, respectively) and was similar in the 2 groups (1.75 +/- 0.51 vs 1.82 +/- 0.62, p = 0.48). When evaluating nonrestenotic lesions, late loss was also normally distributed in the 2 groups (p = 0.75 for SES, p = 0.73 for PES) but was significantly lower (p = 0.002) after SES implantation (0.14 +/- 0.39) than after PES implantation (0.27 +/- 0.44). In conclusion, SESs and PESs have a bimodal pattern of late loss distribution. The observed difference in late loss between SES and PES seems to be partly explained by the decrease in late, loss after SES implantation in nonrestenotic lesions (where SES approaches "zero late loss"). Thus, late loss may not be a reliable marker of the true efficacy of these devices due to its complex and nongaussian distribution. (c) 2007 Elsevier Inc. All rights reserved

<i>Vitis vinifera</i> L. Leaf Extract Inhibits In Vitro Mediators of Inflammation and Oxidative Stress Involved in Inflammatory-Based Skin Diseases

Psoriasis is a chronic cutaneous condition characterized by the release of pro-inflammatory mediators and oxidative stress. The reduction of these factors is currently the most effective strategy to inhibit the symptoms of pathology. Antioxidants from natural sources are increasingly used to improve skin conditions. Dried red leaves from grapevine (Vitis vinifera L., cv Teinturiers) showed anti-inflammatory and anti-bacterial activities, but their possible effects on keratinocytes have not been previously investigated. In this study we tested the ability of a water extract from grapevine leaves (VVWE) to inhibit inflammatory conditions in human keratinocytes (HaCaT cells), challenged with proinflammatory (tumor necrosis factor-&#945; (TNF-&#945;) or lipopolysaccharide (LPS)) or prooxidant (ultraviolet B radiation (UVB) or H2O2) mediators. VVWE inhibited interleukin-8 (IL-8) secretion induced by proinflammatory stimuli, acting on the IL-8 promoter activity, but the effect was lower when prooxidant mediators were used. The effect was partly explained by the reduction of nuclear factor-&#954;B (NF-&#954;B)-driven transcription and nuclear translocation. Furthermore, vascular endothelial growth factor (VEGF) secretion, a regulator of angiogenesis, was inhibited by VVWE, but not matrix metalloproteinase-9 (MMP-9), a protease involved in matrix remodeling. VVWE, assayed on Franz diffusion cell system, showed a marked reduction of High Performance Liquid Chromatography (HPLC)-identified compounds. Pure molecules individually failed to reduce TNF-&#945;-induced IL-8 release, suggesting synergistic effects or the presence of other bioactive compounds still unknown