Comparison of a Drug-Free Early Programmed Dismantling PDLLA Bioresorbable Scaffold and a Metallic Stent in a Porcine Coronary Artery Model at 3-Year Follow-Up.

BACKGROUND: Arterial Remodeling Technologies bioresorbable scaffold (ART-BRS), composed of l- and d-lactyl units without drug, has shown its safety in a porcine coronary model at 6 months. However, long-term performance remains unknown. The aim of this study was to evaluate the ART-BRS compared to a bare metal stent (BMS) in a healthy porcine coronary model for up to 3 years. METHODS AND RESULTS: Eighty-two ART-BRS and 66 BMS were implanted in 64 Yucatan swine, and animals were euthanatized at intervals of 1, 3, 6, 9, 12, 18, 24, and 36 months to determine the vascular response using quantitative coronary angiography, optical coherence tomography, light and scanning electron microscopy, and molecular weight analysis. Lumen enlargement was observed in ART-BRS as early as 3 months, which progressively increased up to 18 months, whereas BMS showed no significant difference over time. Percentage area stenosis by optical coherence tomography was greater in ART-BRS than in BMS at 1 and 3 months, but this relationship reversed beyond 3 months. Inflammation peaked at 6 months and thereafter continued to decrease up to 36 months. Complete re-endothelialization was observed at 1 month following implantation in both ART-BRS and BMS. Scaffold dismantling started at 3 months, which allowed early vessel enlargement, and bioresorption was complete by 24 months. CONCLUSIONS: ART-BRS has the unique quality of early programmed dismantling accompanied by vessel lumen enlargement with mild to moderate inflammation. The main distinguishing feature of the ART-BRS from other scaffolds made from poly-l-lactic acid may result in early and long-term vascular restoration.

Comparison of Particulate Embolization after Femoral Artery Treatment with IN.PACT Admiral versus Lutonix 035 Paclitaxel-Coated Balloons in Healthy Swine.

PURPOSE: Different carrier excipients unique to individual drug-coated balloons (DCBs) may influence embolic safety characteristics in peripheral vascular territories through embolization of released particulates. A comparator study of IN.PACT Admiral vs Lutonix 035 balloons in healthy swine was therefore performed to assess which balloon produces more downstream emboli. MATERIALS AND METHODS: Single or overlapping 80-mm IN.PACT and Lutonix 035 DCBs were assessed in the femoral arteries of 21 swine with 28- and 90-day follow-up, with standard balloon angioplasty as a control. Histologic analysis of arterial wall and downstream skeletal muscle and coronary band was performed. This analysis was supported by an analytic measurement of paclitaxel levels. RESULTS: IN.PACT DCBs demonstrated a more pronounced change in medial wall composition, characterized by a paclitaxel-induced loss of medial smooth muscle cells accompanied by increased proteoglycans. The percentage of sections with arterioles exhibiting paclitaxel-associated fibrinoid necrosis in downstream tissues was higher at 90 days with overlapping IN.PACT DBCs compared with Lutonix 035 DCBs (46.2% [interquartile range, 19.2-57.7] vs 0.0% [0.0-11.5]; P = .01), with similar trends noted for 28-day single and overlapping DCBs. Drug analysis in parallel tissues further confirmed higher paclitaxel concentrations in nontarget tissues for IN.PACT than Lutonix 035 balloons for single and overlapping configurations at both time points. Rare embolic crystalline material was observed in downstream tissues, but only for IN.PACT balloons. CONCLUSIONS: There was more fibrinoid necrosis in tissues treated with IN.PACT DCBs compared with Lutonix DCBs, suggesting increased emboli debris with higher paclitaxel levels.

Preclinical evaluation of a novel polyphosphazene surface modified stent.

BACKGROUND: Treatment options for patients with coronary artery disease at high risk for bleeding complications are limited. The aim of the current preclinical study was to evaluate neointimal coverage, endothelial recovery, inflammation and thrombogenicity in a novel thin-strut (71µm thickness) Cobalt Chromium (CoCr) stent modified with a nano-thin Polyzene®-F (PzF) surface coating. METHODS AND RESULTS: Twenty-eight single PzF nano-coated stents and 20 bare metal control stents (BMS) were implanted in the coronary arteries of 24 pigs, with scheduled 5- (n=5), 28- (n=13), and 90-day (n=6) follow-up in addition to overlapping configuration (n=6 each), examined at 28-days. Histomorphometric analysis showed significantly lower neointimal thickness in PzF nano-coated stents than BMS controls at both 28- and 90-days (p=0.023 and 0.005) and reduced inflammation (p=0.06 and 0.13). Endothelial coverage over luminal surfaces at all time points was similar between nano-coated stents and BMS controls. We conducted supplementary in-vitro experiments using human monocytes and an ex-vivo swine carotid-jugular arterio-venous shunt model to better understand the healing properties afforded by the PzF nano-coating. Overall, the PzF-nano-coating showed reduced monocyte adhesion and thrombus formation compared to the un-coated controls. CONCLUSIONS: Stents modified with a nano-thin PzF-coating implanted in healthy swine indicate favorable vascular healing properties shown by reduced neointimal hyperplasia and inflammation, along with resistance to thrombus formation in an ex-vivo shunt model over unmodified stents.

Controle alternativo de Planococcus citri (Risso, 1813) com extratos aquosos de pinhão-manso / Alternative control Planococcus citri (Risso, 1813) with aqueous extracts of Jatropha

A cochonilha-da-roseta, Planococcus citri (Risso, 1813) (Hemiptera: Pseudococcidae), constitui um problema fitossanitário na cultura do café. O controle mais usual dessa praga é o químico, o que pode acarretar, além de problemas socioambientais, a seleção de indivíduos resistentes. Com isso, torna-se necessário o controle alternativo. Dessa forma, o objetivo deste trabalho foi estudar, em condições de laboratório, o potencial inseticida de diferentes partes da planta de Jatropha curcas , em variadas concentrações, sobre P. citri . Discos de folhas de café conilon com 10 cochonilhas (ninfas e adultos) foram pulverizados direta e indiretamente com auxílio da torre de Potter, com pressão de 15 Lb/pol2, aplicando 6 mL de solução por repetição. Testaram-se sete concentrações do óleo e de extratos, tanto na aplicação direta quanto na indireta, com 10 repetições por tratamento, sendo avaliada a mortalidade em função do tempo. Todas as estruturas de pinhão-manso, em ambas as vias de aplicação, apresentaram índices de mortalidade satisfatórios de P. citri , alcançando 91,6% de mortalidade nas concentrações de 1,5, 2,0 e 3,0% do óleo na aplicação direta.(AU)

The Planococcus citri (Risso, 1813) (Hemiptera: Pseudococcidae) is a phytosanitary problem in the coffee's cultivation. The most used type of control for this pest is the chemical one, which leads to the selection of resistant individuals, as well as social and environmental problems. Therefore, it is necessary to control the alternative. Thus, this paper had the aim of studying the potential insecticide in different parts of the plant Jatropha curcas , in some concentrations, over the P. citri . Dices of leaf containing 10 P. citri (nymphs and adults) were directly and indirectly sprayed with the Potter Tower's assistance, on the pressure at 15 Lb/pol2, applying 6 mL of solution per repetition. Seven concentrations of oil and extracts were tested, and the mortality was evaluated in function of time. All physic nut's structures in both routes of administration showed satisfactory mortality P. citri , reaching 91.6% mortality at the concentrations of 1.5, 2.0 e 3.0% oil in the direct application.(AU)

Long-term safety of an everolimus-eluting bioresorbable vascular scaffold and the cobalt-chromium XIENCE V stent in a porcine coronary artery model.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb) has shown promising clinical results; however, only limited preclinical data have been published. We sought to investigate detailed pathological responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with duration of implant extending from 1 to 42 months. METHODS AND RESULTS: A total of 335 devices (263 Absorb and 72 XV) were implanted in 2 or 3 main coronary arteries of 136 nonatherosclerotic swine and examined by light microscopy, scanning electron microscopy, pharmacokinetics, and gel permeation chromatography analyses at various time points. Vascular responses to Absorb and XV were largely comparable at all time points, with struts being sequestered within the neointima. Inflammation was mild to moderate (with absence of inflammation at 1 month) for both devices, although the scores were greater in Absorb at 6 to 36 months. Percent area stenosis was significantly greater in Absorb than XV at all time points except at 3 months. The extent of fibrin deposition was similar between Absorb and XV, which peaked at 1 month and decreased rapidly thereafter. Histomorphometry showed expansile remodeling of Absorb-implanted arteries starting after 12 months, and lumen area was significantly greater in Absorb than XV at 36 and 42 months. These changes correlated with dismantling of Absorb seen after 12 months. Gel permeation chromatography analysis confirmed that degradation of Absorb was complete by 36 months. CONCLUSIONS: Absorb demonstrates comparable long-term safety to XV in porcine coronary arteries with mild to moderate inflammation. Although Absorb was associated with greater percent stenosis relative to XV, expansile remodeling was observed after 12 months in Absorb with significantly greater lumen area at ≥ 36 months. Resorption is considered complete at 36 months.

Lumen gain and restoration of pulsatility after implantation of a bioresorbable vascular scaffold in porcine coronary arteries.

OBJECTIVES: Using intravascular ultrasound (IVUS) and histomorphometry, this study sought to evaluate the potential of nonatherosclerotic porcine coronary arteries to undergo progressive lumen gain and a return of pulsatility after implantation with an everolimus-eluting bioresorbable vascular scaffold (BVS). BACKGROUND: Unique benefits such as lumen gain and restored vasomotion have been demonstrated clinically after treatment with BVS; however, a more rigorous demonstration of these benefits with a randomized clinical trial has not yet been conducted. METHODS: Seventy nonatherosclerotic swine received 109 everolimus-eluting BVS and 70 everolimus-eluting metal stents randomized among the main coronary arteries. Arteries were evaluated in vivo by angiography and IVUS and post-mortem by histomorphometry at time points from 1 to 42 months. RESULTS: From 1 to 6 months, both BVS- and everolimus-eluting metal stent-implanted arteries demonstrated stable lumen areas (LAs). From 12 months to 42 months, there was a progressive increase in the LA of arteries implanted with a BVS as assessed by histomorphometry and IVUS. This lumen gain in the implanted segment corresponded to an increase in the reference vessel LA. Normalization in the in-segment LA (LA:reference vessel LA) was observed qualitatively by angiography and quantitatively by IVUS. Additionally, BVS-implanted arteries demonstrated restored in-segment pulsatility on the basis of IVUS assessment of the differences in the mid-scaffold area between end-diastole to end-systole. CONCLUSIONS: Starting at 12 months, BVS-implanted porcine coronary arteries underwent progressive lumen gain and showed restored pulsatility. These benefits demonstrated preclinically may translate into improvements in long-term clinical outcomes for patients treated with BVS compared with conventional drug-eluting stents.

Vascular, downstream, and pharmacokinetic responses to treatment with a low dose drug-coated balloon in a swine femoral artery model.

OBJECTIVES: This study was designed to evaluate the safety of a novel drug-coated balloon (DCB) with 2 µg/mm(2) paclitaxel and a carrier comprised of polysorbate and sorbitol in a swine femoral artery model. BACKGROUND: DCB have emerged as a therapeutic alternative in the treatment of peripheral vascular disease. METHODS: The femoral arteries of 45 swine were treated with low pressure balloon inflation either 1× clinical dose (single inflation, 2 µg/mm(2) paclitaxel) or 4× dose (2 DCBs, each with 4 µg/mm(2) paclitaxel) or control (uncoated) balloons. The treated arteries, downstream vascular beds, and organs were assessed histologically at 28, 90, and 180-days. Twenty-four swine were treated with 1× dose for pharmacokinetic analysis through 30 days. RESULTS: Arterial tissue paclitaxel concentration was 58.8 ± 54.2 ng/mg at 1-hr and 0.3 ± 0.4 ng/mg at 30 days, whereas plasma paclitaxel could no longer be detected after 1 day. The treated arteries displayed minimal endothelial loss, fibrin deposition, and inflammation with long-term dose-dependent drug effect (medial smooth muscle cell loss) peaking at 90 days for both 1× (1.1 ± 1.4 vs. 0.0 ± 0.0, P = 0.008) and 4× dose (2.0 ± 1.5 vs. 0.0 ± 0.0, P < 0.001). In parallel, healing of the treated arteries was evident by significantly greater medial proteoglycan and collagen deposition at 180 days. No evidence of ischemia from downstream emboli or systemic toxicity was observed even for 4× DCB groups. CONCLUSIONS: The findings indicate desired pharmacologic levels with biologic effects at early and healing at late time points in the treated arteries, without evidence of significant downstream emboli or systemic toxicity, consistent with safety of the Lutonix DCB.

Clima organizacional e estresse em equipes de trabalho / Organizational climate and stress in work teams

A influência do clima da organização sobre comportamentos e desempenhos dos trabalhadores tem sido constante objeto de estudo de pesquisadores da área. Entretanto, o seu impacto sobre o estresse investigado enquanto manifestação coletiva de equipes não está claramente estabelecido. Assim, a presente pesquisa teve como objetivo verificar o impacto do clima sobre o estresse relatado em equipes de trabalho. Os dados foram levantados de uma amostra composta por 2.071 unidades de desempenho, totalizando 48.538 pessoas. O clima foi mensurado por escala composta de quatro fatores que focaram em aspectos como promoção, recompensa e benefícios; relacionamento com os pares; características da tarefa; e relacionamento com a chefia. O estresse foi mensurado por escala unifatorial. O modelo preditivo explicou 21,1% do estresse relatado pelas equipes. A análise detalhada revelou que o fator denominado Promoção, recompensa e benefícios exerce um efeito mais intenso que os outros fatores da escala, de sorte que quanto melhor o clima percebido nesse aspecto, menor estresse é relatado pela equipe. Assim, os resultados encontrados contribuem para a compreensão dos efeitos diferenciados dos fatores do clima sobre estresse, permitindo desenhar intervenções focadas na especificidade de cada elemento preditor.(AU)

The effect of an organization's climate on the behavior and performance of their its employees has been a constant object of study of for researchers in organizational psychology. However, the impact of the organization's climate on the amount of stress levels as a collective manifestation of teams has not been clearly established. Thus, the present study's had as objective was to verify the impact of organizational climate on the reported amount of stress in work teams. Data were analyzed of from 2,071 performance units, containing 48,538 persons overall. Organizational climate was measured by on a scale composed of four factors focusing on aspects like such as: promotion, rewards, and benefits; relationship with colleagues; task characteristics; and relationship with the directionmanagement. Stress was measured by on a unidimensional scale. The predictive model explained 21.1% of the teams' reported stress. Detailed analysis revealed that, of the four climate factors, the promotion, rewards, and benefits factor had the biggest strongest effect. This effect was negative, so higher values of the promotion factor were related to less reported stress by the work team. The results of this study will hopefully contribute to a better understanding of how the differing impacts different factors of organizational climate factors impact on work related stress, and facilitatebeing able the to planning of specific interventions to reduce this type of stress.(AU)

Clima organizacional e estresse em equipes de trabalho / Organizational climate and stress in work teams

A influência do clima da organização sobre comportamentos e desempenhos dos trabalhadores tem sido constante objeto de estudo de pesquisadores da área. Entretanto, o seu impacto sobre o estresse investigado enquanto manifestação coletiva de equipes não está claramente estabelecido. Assim, a presente pesquisa teve como objetivo verificar o impacto do clima sobre o estresse relatado em equipes de trabalho. Os dados foram levantados de uma amostra composta por 2.071 unidades de desempenho, totalizando 48.538 pessoas. O clima foi mensurado por escala composta de quatro fatores que focaram em aspectos como promoção, recompensa e benefícios; relacionamento com os pares; características da tarefa; e relacionamento com a chefia. O estresse foi mensurado por escala unifatorial. O modelo preditivo explicou 21,1% do estresse relatado pelas equipes. A análise detalhada revelou que o fator denominado Promoção, recompensa e benefícios exerce um efeito mais intenso que os outros fatores da escala, de sorte que quanto melhor o clima percebido nesse aspecto, menor estresse é relatado pela equipe. Assim, os resultados encontrados contribuem para a compreensão dos efeitos diferenciados dos fatores do clima sobre estresse, permitindo desenhar intervenções focadas na especificidade de cada elemento preditor.

The effect of an organization's climate on the behavior and performance of their its employees has been a constant object of study of for researchers in organizational psychology. However, the impact of the organization's climate on the amount of stress levels as a collective manifestation of teams has not been clearly established. Thus, the present study's had as objective was to verify the impact of organizational climate on the reported amount of stress in work teams. Data were analyzed of from 2,071 performance units, containing 48,538 persons overall. Organizational climate was measured by on a scale composed of four factors focusing on aspects like such as: promotion, rewards, and benefits; relationship with colleagues; task characteristics; and relationship with the directionmanagement. Stress was measured by on a unidimensional scale. The predictive model explained 21.1% of the teams' reported stress. Detailed analysis revealed that, of the four climate factors, the promotion, rewards, and benefits factor had the biggest strongest effect. This effect was negative, so higher values of the promotion factor were related to less reported stress by the work team. The results of this study will hopefully contribute to a better understanding of how the differing impacts different factors of organizational climate factors impact on work related stress, and facilitatebeing able the to planning of specific interventions to reduce this type of stress.

In vitro and in vivo characterization of novel biodegradable polymers for application as drug-eluting stent coatings.

We have used a series of in vitro and in vivo tests to assess the suitability of two new degradable polymers for application as coatings for drug-eluting stents. The first is a family of urethane-linked multi-block copolymers (MBCP) that comprise blocks of lactide, glycolide, epsilon-caprolactone and/or poly(ethylene glycol) chain-extended with 1,4-butanediisocyanate (SynBiosys polymers). The second is a family of maltodextrin (MD) modified with fatty acid sidechains to yield a hydrophobic polymer (Eureka() SOLO polymers). We coated stainless-steel stents with two representative urethane-linked MBCPs and one hydrophobic MD polymer alone or in combination with the anti-restenotic drug sirolimus. Urethane-linked MBCPs formed uniform coatings on the stent substrates, withstood crimping and expansion on balloon catheters, completely released sirolimus from the coating within 30 days, and degraded within 30-60 days in PBS. The hydrophobic MD polymer formed uniform coatings, exhibited somewhat slower release of sirolimus (approx. 85% within 30 days), degraded within 60 days in PBS when sirolimus was incorporated in the coating, but showed very slow degradation in the absence of drug. We implanted stents coated with urethane-linked MBCPs or hydrophobic MD polymers in a porcine coronary artery model and used histological analysis at 28- and 90-day end-points to assess the biological response to the materials. Measures of stenosis and inflammation for urethane-linked MBCP and hydrophobic MD polymer coatings were not statistically different from bare metal controls at 28 and 90 days, suggesting that the polymers show good vascular biocompatibility. Endothelialization was nearly complete at 28 days and complete at 90 days for all formulations. Urethane-linked MBCP polymer-only and drug-eluting coatings and hydrophobic MD drug-eluting coatings were nearly completely degraded within 90 days in vivo whereas roughly half of hydrophobic MD polymer-only coatings remained after 90 days. Taken together, our in vitro and in vivo results suggest that SynBiosys urethane-linked MBCP and Eureka SOLO hydrophobic MD polymer families possess the physical and chemical properties and vascular biocompatibility necessary for further investigation for use in the next generation of drug-eluting stents.

Late stent expansion and neointimal proliferation of oversized Nitinol stents in peripheral arteries.

For peripheral endovascular intervention, self-expanding (SE) stents are commonly oversized in relation to target arteries to assure optimal wall apposition and prevent migration. However, the consequences of oversizing have not been well studied. The purpose of this study was to examine the effects of SE stent oversizing (OS) with respect to the kinetics of late stent expansion and the long-term histological effects of OS. Pairs of overlapped 8 x 28-mm Nitinol SE stents were implanted into the iliofemoral arteries of 14 Yucatan swine. Due to variations in target artery size, the stent-to-artery ratio ranged from 1.2:1 to 1.9:1. Lumen and stent diameters were assessed by quantitative angiography at the time of implantation. Following angiographic assessment at 6 months, stented arteries were perfusion-fixed, sectioned, and stained for histological analysis. Immediately following implantation, the stents were found to be expanded to a range of 4.7-7.1 mm, largely conforming to the diameter of the recipient target artery. The stents continued to expand over time, however, and all stents had enlarged to nearly their 8-mm nominal diameter by 6 months. The histological effects of OS were profound, with marked increases in injury and luminal area stenosis, including a statistically significant linear correlation between stent-to-artery ratio and area stenosis. In this experimental model of peripheral endovascular intervention, oversized Nitinol SE stents are constrained by their target artery diameter upon implantation but expand to their nominal diameter within 6 months. Severe OS (stent-to-artery ratio >1.4:1) results in a profound long-term histological response including exuberant neointimal proliferation and luminal stenosis.

Thin-walled microvessels in human coronary atherosclerotic plaques show incomplete endothelial junctions relevance of compromised structural integrity for intraplaque microvascular leakage.

OBJECTIVES: This study sought to examine the ultrastructure of microvessels in normal and atherosclerotic coronary arteries and its association with plaque phenotype. BACKGROUND: Microvessels in atherosclerotic plaques are an entry point for inflammatory and red blood cells; yet, there are limited data on the ultrastructural integrity of microvessels in human atherosclerosis. METHODS: Microvessel density (MVD) and ultrastructural morphology were determined in the adventitia, intima-media border, and atherosclerotic plaque of 28 coronary arteries using immunohistochemistry for endothelial cells (Ulex europeaus, CD31/CD34), basement membrane (laminin, collagen IV), and mural cells (desmin, alpha-smooth muscle [SM] actin, smoothelin, SM1, SM2, SMemb). Ultrastructural characterization of microvessel morphology was performed by electron microscopy. RESULTS: The MVD was increased in advanced plaques compared with early plaques, which correlated with lesion morphology. Adventitial MVD was higher than intraplaque MVD in normal arteries and early plaques, but adventitial and intraplaque MVD were similar in advanced plaques. Although microvessel basement membranes were intact, the percentage of thin-walled microvessels was similarly low in normal and atherosclerotic adventitia, in the adventitia and the plaque, and in all plaque types. Intraplaque microvascular endothelial cells (ECs) were abnormal, with membrane blebs, intracytoplasmic vacuoles, open EC-EC junctions, and basement membrane detachment. Leukocyte infiltration was frequently observed by electron microscopy, and confirmed by CD45RO and CD68 immunohistochemistry. CONCLUSIONS: The MVD was associated with coronary plaque progression and morphology. Microvessels were thin-walled in normal and atherosclerotic arteries, and the compromised structural integrity of microvascular endothelium may explain the microvascular leakage responsible for intraplaque hemorrhage in advanced human coronary atherosclerosis.