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Adriana Raffin Pohlmann - One of the best experts on this subject based on the ideXlab platform.

  • healing of dermal wounds property of caryocar brasiliense oil loaded polymeric Lipid Core nanocapsules formulation and in vivo evaluation
    European Journal of Pharmaceutical Sciences, 2020
    Co-Authors: Jader Pires, Simone Tasca Cargnin, Suellen Alves Costa, Valeria Dornelles Gindri Sinhorin, Amilcar Sabino Damazo, Adilson Paulo Sinhorin, Rogerio De Campos Bicudo, Larissa Cavalheiro, Denia Mendes De Souza Valladao, Adriana Raffin Pohlmann
    Abstract:

    ABSTRACT Cutaneous lesions lead to complications in patients, since they may be recurrent and also represent risk of progression to infection and/or amputation. Therefore, effective, protective, and topical treatments of easy application and removal need to be developed to provide effective alternatives to patients. The Caryocar brasiliense Cambess (CBC) presents important pharmacological activities and proved in the healing process. This paper reports the improvement of the CBC nanostructured (LNCCBC and LNCCBC+) activity in dermal wounds in vivo. The oil was physico-chemically characterized and used in the development of Lipid-Core nanocapsules (LNCs), coated (LNCCBC+) or without chitosan (LNCCBC), in concentration of 1.0 mg mL−1. Hydrogel (HG) was tested in vivo on lesions in the back of male Wistar rats for 14 days. The oil presented appropriate physico-chemical characteristics for its use, such as moisture 0.76 %, acidity 0.85 % and oleic acid 25.90 %. The LNCs showed nanometric size (around 200 nm), monomodal distribution, slight acid pH and zeta potential of + 22.1 mV in accordance with the composition. The nanostructured oil induced dermal healing in vivo showing significantly better improvement than free oil. LNCCBC+ showed best results showing the higher increase of the production of type 1 collagen, an important protein to the healing repair. These results suggest that development of formulations LNCCBC and LNCCBC+ are promising and important alternative for the treatment of dermal wounds, avoiding complications related to cutaneous lesions.

  • chemical stability mass loss and hydrolysis mechanism of sterile and non sterile Lipid Core nanocapsules the influence of the molar mass of the polymer wall
    Reactive & Functional Polymers, 2018
    Co-Authors: Selma Calgaroto, Silvia Stanisçuaski Guterres, Lucas E Fauri, Luiza Abrahao Frank, Karina Paese, Adriana Raffin Pohlmann
    Abstract:

    Abstract The purpose of this study was to investigate the chemical stability and the mechanism of hydrolysis of the polyester wall of Lipid-Core nanocapsules (LNC) dispersed in water comparing sterile and non-sterile formulations. Sterile or non-sterile LNC formulations (LNCS and LNC, respectively) were prepared using poly(e-caprolactone) (PCL) with different molar masses (Mn 10 kg mol−1, Mn 80 kg mol−1 and a mixture (1:9, w/w) of both PCL). All formulations presented unimodal size distribution profile without significant changes (p > .05) after 60 days. Molar weight changes, fraction of chain scissions and hydrolysis mechanism of LNC under storage (60 days; 5 °C) were determined by size exclusion chromatography (SEC). The highest PCL weight loss was observed for the non-sterile formulations (LNC 1–45%; LNC 2–32%; LNC 3–27%). In turn, the sterile formulations showed a lower weight loss, proving that biotic hydrolysis was responsible for accelerating hydrolysis of the LNC even when stored at low temperature (5 °C). In conclusion, the predominant hydrolysis mechanism was of the non-catalyzed type.

  • Lipid Core nanocapsules act as a drug shuttle through the blood brain barrier and reduce glioblastoma after intravenous or oral administration
    Journal of Biomedical Nanotechnology, 2016
    Co-Authors: Stephen F Rodrigues, Adriana Raffin Pohlmann, Silvia Stanisçuaski Guterres, Luana Almeida Fiel, Ana Lucia Borges Shimada, Natalia Rubio Claret Pereira, Sandra Helena Poliselli Farsky
    Abstract:

    Lipid-Core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  • methotrexate loaded Lipid Core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model
    International Journal of Nanomedicine, 2015
    Co-Authors: Antonio Luiz Boechat, Silvia Stanisçuaski Guterres, Catiuscia P De Oliveira, Andrea Monteiro Tarrago, Allyson Guimaraes Costa, Adriana Malheiro, Adriana Raffin Pohlmann
    Abstract:

    Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, Lipid-Core nanocapsules.The aim of the investigation reported here was to evaluate if methotrexate-loaded Lipid-Core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments.Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX.The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

  • methotrexate loaded Lipid Core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model
    International Journal of Nanomedicine, 2015
    Co-Authors: Antonio Luiz Boechat, Silvia Stanisçuaski Guterres, Catiuscia P De Oliveira, Andrea Monteiro Tarrago, Allyson Guimaraes Costa, Adriana Malheiro, Adriana Raffin Pohlmann
    Abstract:

    Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, Lipid-Core nanocapsules.The aim of the investigation reported here was to evaluate if methotrexate-loaded Lipid-Core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments.Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX.The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

Silvia Stanisçuaski Guterres - One of the best experts on this subject based on the ideXlab platform.

  • chemical stability mass loss and hydrolysis mechanism of sterile and non sterile Lipid Core nanocapsules the influence of the molar mass of the polymer wall
    Reactive & Functional Polymers, 2018
    Co-Authors: Selma Calgaroto, Silvia Stanisçuaski Guterres, Lucas E Fauri, Luiza Abrahao Frank, Karina Paese, Adriana Raffin Pohlmann
    Abstract:

    Abstract The purpose of this study was to investigate the chemical stability and the mechanism of hydrolysis of the polyester wall of Lipid-Core nanocapsules (LNC) dispersed in water comparing sterile and non-sterile formulations. Sterile or non-sterile LNC formulations (LNCS and LNC, respectively) were prepared using poly(e-caprolactone) (PCL) with different molar masses (Mn 10 kg mol−1, Mn 80 kg mol−1 and a mixture (1:9, w/w) of both PCL). All formulations presented unimodal size distribution profile without significant changes (p > .05) after 60 days. Molar weight changes, fraction of chain scissions and hydrolysis mechanism of LNC under storage (60 days; 5 °C) were determined by size exclusion chromatography (SEC). The highest PCL weight loss was observed for the non-sterile formulations (LNC 1–45%; LNC 2–32%; LNC 3–27%). In turn, the sterile formulations showed a lower weight loss, proving that biotic hydrolysis was responsible for accelerating hydrolysis of the LNC even when stored at low temperature (5 °C). In conclusion, the predominant hydrolysis mechanism was of the non-catalyzed type.

  • Lipid Core nanocapsules act as a drug shuttle through the blood brain barrier and reduce glioblastoma after intravenous or oral administration
    Journal of Biomedical Nanotechnology, 2016
    Co-Authors: Stephen F Rodrigues, Adriana Raffin Pohlmann, Silvia Stanisçuaski Guterres, Luana Almeida Fiel, Ana Lucia Borges Shimada, Natalia Rubio Claret Pereira, Sandra Helena Poliselli Farsky
    Abstract:

    Lipid-Core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  • methotrexate loaded Lipid Core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model
    International Journal of Nanomedicine, 2015
    Co-Authors: Antonio Luiz Boechat, Silvia Stanisçuaski Guterres, Catiuscia P De Oliveira, Andrea Monteiro Tarrago, Allyson Guimaraes Costa, Adriana Malheiro, Adriana Raffin Pohlmann
    Abstract:

    Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, Lipid-Core nanocapsules.The aim of the investigation reported here was to evaluate if methotrexate-loaded Lipid-Core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments.Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX.The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

  • methotrexate loaded Lipid Core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model
    International Journal of Nanomedicine, 2015
    Co-Authors: Antonio Luiz Boechat, Silvia Stanisçuaski Guterres, Catiuscia P De Oliveira, Andrea Monteiro Tarrago, Allyson Guimaraes Costa, Adriana Malheiro, Adriana Raffin Pohlmann
    Abstract:

    Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, Lipid-Core nanocapsules.The aim of the investigation reported here was to evaluate if methotrexate-loaded Lipid-Core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution.Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments.Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX.The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.

  • how sorbitan monostearate can increase drug loading capacity of Lipid Core polymeric nanocapsules
    Journal of Nanoscience and Nanotechnology, 2015
    Co-Authors: Fernanda Poletto, Heberto Wende, D Rege, Una Donida, Artira Rossibergma, Silvia Stanisçuaski Guterres, Adriana Raffi Pohlma
    Abstract:

    Abstract Lipid-Core polymeric nanocapsules are innovative devices that present distinguished characteristics due to the presence of sorbitan monostearate into the oily-Core. This component acted as low-molecular-mass organic gelator for the oil (medium chain triglycerides). The organogel-structured Core influenced the polymeric wall characteristics disfavoring the formation of more stable polymer crystallites. This probably occurred due to interpenetration of these pseudo-phases. Sorbitan monostearate dispersed in the oily-Core was also able to interact by non-covalent bonding with the drugs increasing the drug loading capacity more than 40 times compared to conventional nanocapsules. We demonstrated that the drug-models quercetin and quercetin pentaacetate stabilized the organogel network probably due to interactions of the drug molecules with the sorbitan monostearate headgroups by hydrogen bonding.

Renu Virmani - One of the best experts on this subject based on the ideXlab platform.

  • increased thin cap neoatheroma and periprocedural myocardial infarction in drug eluting stent restenosis multimodality intravascular imaging of drug eluting and bare metal stents
    Circulation-cardiovascular Interventions, 2013
    Co-Authors: Ziad A Ali, Tomasz Roleder, Gary S Mintz, Jagat Narula, Bibhu D Mohanty, Usman Baber, Jason C Kovacic, Fumiyuki Otsuka, Stephen Pan, Renu Virmani
    Abstract:

    Background—Re-endothelialization is delayed after drug-eluting stent (DES) implantation. In this setting, neointima is more prone to become Lipid laden and develop neoatherosclerosis (NA), potentially increasing plaque vulnerability. Methods and Results—Optical coherence tomography and near-infrared spectroscopy with intravascular ultrasound were used to characterize NA in 65 (51 DES and 14 bare-metal stents) consecutive symptomatic patients with in-stent restenosis. Median duration poststent implantation was 33 months. Optical coherence tomography–verified NA was observed in 40 stents with in-stent restenosis (62%), was more prevalent in DES than bare-metal stents (68% versus 36%; P=0.02), and demonstrated significantly higher prevalence of thin-cap neoatheroma (47% versus 7%; P=0.01) in DES. Near-infrared spectroscopy assessment demonstrated that the total Lipid Core burden index (34 [interquartile range, 12–92] versus 9 [interquartile range, 0–32]; P<0.001) and the density of Lipid Core burden index (l...

  • a case of Lipid Core plaque progression and rupture at the edge of a coronary stent elucidating the mechanisms of drug eluting stent failure
    Circulation-cardiovascular Interventions, 2010
    Co-Authors: Sergio Waxman, Renu Virmani, Mark I Freilich, Melissa J Suter, Milen Shishkov, Seth D Bilazarian, Brett E Bouma, Gary J Tearney
    Abstract:

    Received October 20, 2009; accepted January 20, 2010. Understanding the mechanisms of coronary drug-eluting stent (DES) failure remains relevant in light of concerns brought on by clinical reports of life-threatening late and very late stent thrombosis and by autopsy studies showing delayed and incomplete healing inside the stents, which may be related to underlying necrotic Lipid Core.1 Frequency-domain optical coherence tomography, also known as optical frequency-domain imaging (OFDI), is a new intracoronary imaging technology that enables 3-dimensional visualization of coronary structure in vivo at a resolution (≈6 μm) sufficient to identify many microscopic features of the coronary wall and stents.2 Here, we present a case of late DES failure that was imaged by OFDI at the time of stent implantation and 15 months later on presentation with unstable angina. The patient was a 52-year-old man with hypertension, dysLipidemia, a family history of coronary artery disease, and prior myocardial infarction in 1998. The patient presented again to the Lahey Clinic in 2007 (baseline), complaining of rest and exertional chest pain and with a positive stress test.2 Angiography revealed a 99% stenosis in the right coronary artery near the bifurcation of the posterior descending artery (Figure 1A). Deployment of a 3×18-mm sirolimus DES (Cypher Cordis, Miami, Fla) was performed with a good result (Figure 1B and 1C). The operators were blinded to the results of OFDI imaging. The patient was maintained on dual antiplatelet therapy (aspirin and clopidogrel) and a statin. The patient returned 15 months later with symptoms of unstable angina. Diagnostic angiography was performed, followed by OFDI of the right coronary artery. The angiogram revealed a 95% right …

  • detection of Lipid Core coronary plaques in autopsy specimens with a novel catheter based near infrared spectroscopy system
    Jacc-cardiovascular Imaging, 2008
    Co-Authors: Craig M Gardner, Allen P Burke, Renu Virmani, Edward L Hull, Jennifer B Lisauskas, Thomas M Meese, Chunsheng Jiang, Sean P Madden, Jay Caplan, James A Goldstein
    Abstract:

    Objectives This study sought to assess agreement between an intravascular near-infrared spectroscopy (NIRS) system and histology in coronary autopsy specimens. Background Lipid Core plaques cannot be detected by conventional tests, yet are suspected to be the cause of most acute coronary syndromes. Near-infrared spectroscopy is widely used to determine the chemical content of substances. A NIRS system has been developed and used successfully in 99 patients. Methods Scanning NIRS was performed through blood in 212 coronary segments from 84 autopsy hearts. One histologic section was analyzed for every 2 mm of artery. Lipid Core plaque of interest (LCP) was defined as a Lipid Core >60° in circumferential extent, >200-μm thick, with a mean fibrous cap thickness Results The LCPs were present in 115 of 2,649 (4.3%) sections from the 51 validation hearts. The algorithm prospectively identified LCP with a receiver-operator characteristic area of 0.80 (95% confidence interval [CI]: 0.76 to 0.85). The Lipid Core burden index detected the presence or absence of any fibroatheroma with an area under the curve of 0.86 (95% CI: 0.81 to 0.91). A retrospective analysis of Lipid Core burden index conducted in extreme artery segments with either no or extensive fibroatheroma yielded an area under the curve of 0.96 (95% CI: 0.92 to 1.00), confirming the accuracy of spectroscopy in identifying plaques with markedly different Lipid content under ideal circumstances. Conclusions This novel catheter-based NIRS system accurately identified Lipid Core plaques through blood in a prospective study in coronary autopsy specimens. It is expected that this novel capability will be of assistance in the management of patients with coronary artery disease.

  • coronary plaque erosion without rupture into a Lipid Core a frequent cause of coronary thrombosis in sudden coronary death
    Circulation, 1996
    Co-Authors: Andrew Farb, Allen P Burke, Anita L Tang, Youhui Liang, Poonam Mannan, John E Smialek, Renu Virmani
    Abstract:

    Background Coronary thrombosis has been reported to occur most frequently in Lipid-rich plaques with rupture of a thin fibrous cap and contact of the thrombus with a pool of extracellular Lipid. However, the frequency of coronary artery thrombosis with or without fibrous cap rupture in sudden coronary death is unknown. In this study, we compared the incidence and morphological characteristics of coronary thrombosis associated with plaque rupture versus thrombosis in eroded plaques without rupture. Methods and results Fifty consecutive cases of sudden death due to coronary artery thrombosis were studied by histology and immunohistochemistry. Plaque rupture of a fibrous cap with communication of the thrombus with a Lipid pool was identified in 28 cases. Thrombi without rupture were present in 22 cases, all of which had superficial erosion of a proteoglycan-rich plaque. The mean age at death was 53 +/- 10 years in plaque rupture cases versus 44 +/- 7 years in eroded plaques without rupture (P Conclusions Erosion of proteoglycan-rich and smooth muscle cell-rich plaques lacking a superficial Lipid Core or plaque rupture is a frequent finding in sudden death due to coronary thrombosis, comprising 44% of cases in the present study. These lesions are more often seen in younger individuals and women, have less luminal narrowing and less calcification, and less often have foci of macrophages and T cells compared with plaque ruptures.

  • coronary plaque erosion without rupture into a Lipid Core a frequent cause of coronary thrombosis in sudden coronary death
    Circulation, 1996
    Co-Authors: Andrew Farb, Allen P Burke, Anita L Tang, Youhui Liang, Poonam Mannan, John E Smialek, Renu Virmani
    Abstract:

    Background Coronary thrombosis has been reported to occur most frequently in Lipid-rich plaques with rupture of a thin fibrous cap and contact of the thrombus with a pool of extracellular Lipid. However, the frequency of coronary artery thrombosis with or without fibrous cap rupture in sudden coronary death is unknown. In this study, we compared the incidence and morphological characteristics of coronary thrombosis associated with plaque rupture versus thrombosis in eroded plaques without rupture. Methods and results Fifty consecutive cases of sudden death due to coronary artery thrombosis were studied by histology and immunohistochemistry. Plaque rupture of a fibrous cap with communication of the thrombus with a Lipid pool was identified in 28 cases. Thrombi without rupture were present in 22 cases, all of which had superficial erosion of a proteoglycan-rich plaque. The mean age at death was 53 +/- 10 years in plaque rupture cases versus 44 +/- 7 years in eroded plaques without rupture (P Conclusions Erosion of proteoglycan-rich and smooth muscle cell-rich plaques lacking a superficial Lipid Core or plaque rupture is a frequent finding in sudden death due to coronary thrombosis, comprising 44% of cases in the present study. These lesions are more often seen in younger individuals and women, have less luminal narrowing and less calcification, and less often have foci of macrophages and T cells compared with plaque ruptures.

Evelyn Regar - One of the best experts on this subject based on the ideXlab platform.

  • near infrared spectroscopy derived Lipid Core burden index predicts adverse cardiovascular outcome in patients with coronary artery disease during long term follow up
    European Heart Journal, 2018
    Co-Authors: Annesophie Schuurman, Hector M Garciagarcia, Evelyn Regar, Maxime M Vroegindewey, Isabella Kardys, Rohit M Oemrawsingh, Jin M Cheng, Sanneke P M De Boer, Robertjan Van Geuns
    Abstract:

    Aims: Near-infrared spectroscopy (NIRS) is able to quantify cholesterol within coronary arteries by the Lipid Core burden index (LCBI). We studied the prognostic value of NIRS-derived LCBI in patients with coronary artery disease (CAD) for adverse cardiac outcome during long-term follow-up. Methods and results: During 2009-2013, NIRS was performed in a non-culprit artery of 275 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. LCBI was quantified by an independent Corelab for the region of interest (LCBIROI) and the 4 and 10 mm long segment with the maximum LCBI (MaxLCBI4mm and MaxLCBI10mm). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, non-fatal ACS, or unplanned revascularization. Hazard ratios (HR) were adjusted for age, gender, clinical risk factors, and segment plaque burden based on intravascular ultrasound. During a median follow-up of 4.1 years, 79 patients (28.7%) had MACE. There was a statistically significant and independent continuous relationship between higher MaxLCBI4mm values and a higher risk of MACE. Each 100 units increase of MaxLCBI4mm was associated with a 19% increase in MACE [hazard ratios (HR) 1.19, 95% confidence intervals (95% CI): 1.07-1.32, P = 0.001]. Continuous MaxLCBI4mm remained independently associated with MACE after exclusion of target lesion-related events (HR 1.21, 95% CI: 1.08-1.35), as well as after exclusion of adverse events related to the NIRS-imaged coronary segment (HR 1.19, 95% CI: 1.06-1.34). Results for MaxLCBI10mm were comparable. Conclusion: NIRS-derived LCBI is associated with adverse cardiac outcome in CAD patients during long-term follow-up independent of clinical risk factors and plaque burden.

  • in vivo 3d distribution of Lipid Core plaque in human coronary artery as assessed by fusion of near infrared spectroscopy intravascular ultrasound and multislice computed tomography scan
    Circulation-cardiovascular Imaging, 2010
    Co-Authors: Jolanda J Wentzel, Patrick W Serruys, Alina G Van Der Giessen, Scot Garg, Carl Schultz, Frits Mastik, Frank J H Gijsen, Antonius F W Van Der Steen, Evelyn Regar
    Abstract:

    There is ample evidence that the development of acute coronary syndrome is linked to the presence of Lipid-Core, necrotic plaque. However, there is little information on the natural history of Lipid-Core plaques in humans. A close link between structural changes of atherosclerotic plaques over time to the local shear stress conditions in the arterial system has been reported.1 Although low shear stress is recognized for its proatherogenic impact on the endothelium,1 its role in plaque composition, destabilization, and rupture is less clear. The current paradigm postulates that low shear stress is a necessary condition for plaque accumulation. However, once lumen narrowing occurs because of plaque, local shear stress increases.2 We describe an approach that allows studying the interaction of Lipid-Core plaque accumulation and local shear stress in a correct anatomic 3D reconstruction of coronary arteries in living patients. A 61-year-old man with a history of myocardial infarction and stenting of the right coronary …

  • cardiovascular images in vivo 3d distribution of Lipid Core plaque in human coronary artery as assessed by fusion of near infrared spectroscopy intravascular ultrasound and multislice computed tomography scan
    2010
    Co-Authors: Jolanda J Wentzel, Patrick W Serruys, Alina G Van Der Giessen, Scot Garg, Carl Schultz, Frits Mastik, Evelyn Regar
    Abstract:

    There is ample evidence that the development of acute coronary syndrome is linked to the presence of LipidCore, necrotic plaque. However, there is little information on the natural history of Lipid-Core plaques in humans. A close link between structural changes of atherosclerotic plaques over time to the local shear stress conditions in the arterial system has been reported. 1 Although low shear stress is recognized for its proatherogenic impact on the endothelium, 1 its role in plaque composition, destabilization, and rupture is less clear. The current paradigm postulates that low shear stress is a necessary condition for plaque accumulation. However, once lumen narrowing occurs because of plaque, local shear stress increases.2 We describe an approach that allows studying the interaction of Lipid-Core plaque accumulation and local shear stress in a correct anatomic 3D reconstruction of coronary arteries in living patients. A 61-year-old man with a history of myocardial infarction and stenting of the right coronary artery underwent coronary catheterization for recurrent angina. A prior 128-slice dualsource computed tomography scan (MSCT, Somaton Definition Flash, Siemens, Germany) had suggested a lumen narrowing in the anterior descending artery (Figure, A) that was subsequently proven to be physiologically significant by pressure wire studies. To identify the presence of Lipid-Core plaque, a pullback with a recently developed combination catheter with intravascular ultrasound (IVUS) and near infrared spectroscopy (NIR) (InfraReDx, Burlington, Mass) was performed (pullback speed, 0.5 mm/s; acquiring 16 frames per second). NIR data were displayed as color maps indicating the probability of the presence of Lipid Core by NIR as described previously.3 Although the combination catheter allows simultaneous display of the IVUS-derived 2D geometry and presence of Lipid-Core plaque in vivo (Figure, B), it was until now not feasible to visualize that information in anatomically correct 3D space, which is crucial to understand the relationship with other pathophysiologic parameters, such as shear stress. Recently, we developed a technique to produce 3D coronary reconstructions by fusion of MSCT and IVUS information.4 We adapted this approach for the combined NIR-IVUS data to reconstruct the Lipid-Core plaque distribution in 3 dimensions. Moreover, in the lumen of this 3D reconstruction, the local shear stress was assessed by computational fluid dynamics.2 In our patient, a complex plaque and shear stress distribution pattern is visible (Figure, C and D). Confluent Lipid-Core plaques are exclusively located on the inner curvature of the artery toward the myocardium (Figure, C), which is generally considered a low shear-stress region. In the region of maximum Lipid-Core plaque accumulation, Lipid-Core plaque extends over roughly 75% of the artery’s circumference (Figure, asterisk). At this site and at some other locations, the local shear stress as computed is relatively high (Figure, D). This can be explained by the fact that there is advanced disease with marked thickening of the vessel wall, which resulted in lumen narrowing. Our observation illustrates that the combination of NIR, IVUS, and MSCT data can be used to study the relationship between shear stress and Lipid-Core distribution in the arteries of patients undergoing catheterization, which is of high potential for longitudinal studies on plaque modulation. Moreover, hypotheses on plaque progression and destabilization can be tested in patients in vivo.

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  • Lipid Core peptide targeting the cathepsin d hemoglobinase of schistosoma mansoni as a component of a schistosomiasis vaccine
    Human Vaccines & Immunotherapeutics, 2014
    Co-Authors: Annette M Dougall, Istvan Toth, Mariusz Skwarczynski, Makan Khoshnejad, Saranya Chandrudu, Norelle L Daly, Alex Loukas
    Abstract:

    The self-adjuvanting Lipid Core peptide (LCP) system offers a safe alternative vaccine delivery strategy, eliminating the need for additional adjuvants such as CpG Alum. In this study, we adopted the LCP as a scaffold for an epitope located on the surface of the cathepsin D hemoglobinase (Sm-CatD) of the human blood fluke Schistosoma mansoni. Sm-CatD plays a pivotal role in digestion of the fluke’s bloodmeal and has been shown to be efficacious as a subunit vaccine in a murine model of human schistosomiasis. Using molecular modeling we showed that S. mansoni cathepsin D possesses a predicted surface exposed α-helix (A263K) that corresponds to an immunodominant helix and target of enzyme–neutralizing antibodies against Necator americanus APR-1 (Na-APR-1), the orthologous protease and vaccine antigen from blood-feeding hookworms. The A263K epitope was engineered as two peptide variants, one of which was flanked at both termini with a coil maintaining sequence, thereby promoting the helical characteristics o...

  • Lipid Core peptide system for self adjuvanting synthetic vaccine delivery
    Methods of Molecular Biology, 2011
    Co-Authors: Mariusz Skwarczynski, Istvan Toth
    Abstract:

    Disadvantages of classical vaccines, such as the risk of an autoimmune reaction, might be overcome by using a subunit vaccine containing the minimal microbial components necessary to stimulate appropriate immune responses. However, vaccines based on minimal epitopes suffer from poor immunogenicity and require the use of an additional immunostimulant (adjuvant). Only a few adjuvants have been permitted for use with vaccines intended for human administration. We have developed several vaccine candidates based on a Lipid-Core-peptide (LCP) system. This system has self-adjuvanting properties, and it can be used for the delivery of a variety of epitopes to produce vaccine candidates against a targeted disease. The LCP system is easily assembled by simple stepwise Boc solid-phase peptide synthesis.

  • Lipid Core peptide system for gene drug and vaccine delivery
    Australian Journal of Chemistry, 2009
    Co-Authors: Wei Zhong, Mariusz Skwarczynski, Istvan Toth
    Abstract:

    A vast number of biologically active compounds await efficient delivery to become therapeutic agents. Lipidation has been demonstrated to be a convenient and useful approach to improve the stability and transport across biological membranes of potential drug molecules. The Lipid Core peptide (LCP) system has emerged as a promising Lipidation tool because of its versatile features. This review discusses the progress in the development of the LCP system to improve cell permeability of nucleotides, physicochemical properties of potential drugs, and vaccine immunogenicity. Emphasis was put on the application of the LCP system to deliver antigens for the prevention of group A streptococcus infection, novel techniques of conjugation of target molecules to the LCP, and new alterations of the LCP system itself.

  • a technique for the synthesis of highly pure mono epitopic multi valent Lipid Core peptide vaccines
    Tetrahedron Letters, 2007
    Co-Authors: Peter M Moyle, Colleen Olive, Michael F Good, Yashmeeta Hari, Ning Huang, Istvan Toth
    Abstract:

    The synthesis of Lipid Core peptide (LCP) vaccines using stepwise solid-phase peptide synthesis commonly results in products which are difficult to purify to homogeneity. A new technique for synthesizing highly-pure, mono-epitopic, multi-valent LCP-systems using native chemical ligation is presented. Various conditions were assessed for ligating four copies of a thioester-modified 88/30 serotype group A streptococcal peptide antigen onto an LCP-system featuring four cysteine residues. Overall, the vaccine was synthesized in high purity (>99%), and high yield (90%) when the ligation reaction was performed in the presence of 1% sodium dodecyl sulfate and at elevated temperatures (37 degrees C). (C) 2007 Elsevier Ltd. All rights reserved.

  • enhanced protection against streptococcus pyogenes infection by intranasal vaccination with a dual antigen component m protein sfbi Lipid Core peptide vaccine formulation
    Vaccine, 2007
    Co-Authors: Colleen Olive, Istvan Toth, Kai Schulze, Thomas Ebensen, A Horvath, Carlos A Guzman
    Abstract:

    We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine targeting two virulence factors using the Lipid Core Peptide (LCP) delivery system. BALB/c mice were immunised intranasally with LCPs containing peptides encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a combination formulation containing peptides representing both antigens. LCPs were co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and cellular immune responses stimulated at systemic and mucosal levels were strongest in mice immunised with the dual antigen formulation. Mice were completely protected following a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report demonstrating the elicitation of better protective immunity by a dual antigen component S. pyogenes vaccine.