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Sample records for arterial intimal hyperplasia

  1. Intimal hyperplasia in autogenous veins used for arterial replacement.

    PubMed

    Gunstensen, J; Smith, R C; El-Maraghi, N; Julian, J; Belbeck, L

    1982-03-01

    This study compares the effects on intimal hyperplasia of different methods of manipulating a vein graft before using it as an arterial substitute. Grafts that were denuded of endothelium showed the most intimal hyperplasia, while those that were washed with saline, dilated with saline or crushed did not differ appreciably from each other with respect to the degree of intimal hyperplasia. The hyperplasia was well developed and stabilized at 3 weeks, which coincided with restoration of the endothelial surface. The similarity between the last three methods of graft manipulation suggests that minor endothelial disruption produced at the time of harvesting the vein is equalized after insertion of the vein into the arterial circulation.

  2. BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries.

    PubMed

    Wang, Bowen; Zhang, Mengxue; Takayama, Toshio; Shi, Xudong; Roenneburg, Drew Alan; Craig Kent, K; Guo, Lian-Wang

    2015-11-01

    Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic "readers" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known. We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model. While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(-), substantially down-regulated PDGF receptor-α which, in JQ1(+)-treated arteries versus vehicle control, was also reduced. Blocking BET bromodomains mitigates neointima formation, suggesting an epigenetic approach for effective prevention of intimal hyperplasia and associated vascular diseases. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  3. BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries.

    PubMed

    Wang, Bowen; Zhang, Mengxue; Takayama, Toshio; Shi, Xudong; Roenneburg, Drew Alan; Kent, K Craig; Guo, Lian-Wang

    2015-11-01

    Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic "readers" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known. We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model. While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(-), substantially down-regulated PDGF receptor-α which, in JQ1(+)-treated arteries versus vehicle control, was also reduced. Blocking BET bromodomains mitigates neointima formation, suggesting an epigenetic approach for effective prevention of intimal hyperplasia and associated vascular diseases.

  4. Adjunctive arterial injury and photodynamic therapy with aluminium disulphonated phthalocyanine inhibits intimal hyperplasia

    NASA Astrophysics Data System (ADS)

    Nyamekye, Isaac; McEwan, Jean R.; MacRobert, Alexander J.; Bishop, Christopher C. R.; Bown, Stephen G.

    1994-12-01

    Photodynamic therapy (PDT) of proliferative vascular smooth muscle cells (SMC) reduces intimal hyperplasia (FCIH). We assess the effects of adjunctive balloon injury and immediate PDT on contractile SMC, using aluminum disulphonated phthalocyanine (AlS2Pc) sensitization, on intimal hyperplasia. Groups of 5 Wistar rats underwent tail vein injection with 2.5 mg/kg of aluminum disulphonated phthalocyanine (AlS2Pc). Standard carotid artery balloon injury was performed with a 2FG Fogarty embolectomy catheter and the artery irradiated with 50 J/cm2. Control groups were also studied. Rats were killed at 2 and 4 weeks after treatment and perfusion fixed H&E stained cross-sections assessed by computerized morphometric measurements. Three sections per rat were analyzed. PDT treated arteries were free of FCIH formation in all cases. Laser alone (and to a lesser extent sensitizer alone) produced some reduction in the levels of FCIH compared to untreated but balloon injured vessels. The ratio of the area of intimal hyperplasia in treated vessels to the area of intimal hyperplasia in untreated (balloon only) rats were sensitizer only 98%, laser only 68% and PDT 0% at 4 weeks. PDT given at the time of angioplasty may be affective in the management of restenosis.

  5. Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats.

    PubMed

    Sun, Qiang; Kawamura, Tomohiro; Masutani, Kosuke; Peng, Ximei; Sun, Qing; Stolz, Donna B; Pribis, John P; Billiar, Timothy R; Sun, Xuejun; Bermudez, Christian A; Toyoda, Yoshiya; Nakao, Atsunori

    2012-04-01

    Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H(2)O → Mg (OH)(2) + H(2)). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life.

  6. Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats

    PubMed Central

    Sun, Qiang; Kawamura, Tomohiro; Masutani, Kosuke; Peng, Ximei; Sun, Qing; Stolz, Donna B.; Pribis, John P.; Billiar, Timothy R.; Sun, Xuejun; Bermudez, Christian A.; Toyoda, Yoshiya; Nakao, Atsunori

    2012-01-01

    Aims Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia. Methods and results The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H2O → Mg (OH)2 + H2). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration. Conclusion Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life. PMID:22287575

  7. Boundary layer infusion of basic fibroblast growth factor accelerates intimal hyperplasia in endarterectomized canine artery.

    PubMed

    Chen, C; Li, J; Mattar, S G; Pierce, G F; Aukerman, L; Hanson, S R; Lumsden, A B

    1997-05-01

    We examined the effects of human recombinant basic fibroblast growth factor (bFGF) on the proliferation and migration of cultured dog smooth muscle cells (SMCs) and endothelial cells (ECs) and the effect of continuous local boundary layer infusion of bFGF on intimal hyperplasia in endarterectomized dog artery. In vitro proliferation and migration of dog SMCs or ECs were performed using direct counting and Boyden's chamber, respectively. At a dose of 10 ng/mL, bFGF significantly promoted both SMC and EC proliferation (7- and 4-fold, respectively) and migration (2.3- and 1.9-fold, respectively). Six dogs underwent bilateral carotid endarterectomies. A newly designed local infusion device with an osmotic pump continuously delivered bFGF to one artery or vehicle solution to the contralateral artery for 14 days. The intimal thickness and area in the bFGF-treated vessels were increased by 72 and 81%, respectively, compared with control arteries (P < 0.05). As assessed by the bromodeoxyuridine index, the proliferative activity was increased by 73% in bFGF-treated arteries (P = 0.03). Furthermore, cell proliferation at the distal anastomoses of local infusion device was significantly increased in the bFGF-infused grafts compared with distal anastomoses in the control grafts (13.24 +/- 1.24% versus 5.24 +/- 1.01%, P < 0.01). These data demonstrate that human recombinant bFGF has a potent effect on dog SMC and EC proliferation and migration, and that local infusion of exogenous bFGF significantly enhances the intimal hyperplasia formation and cell proliferation to vascular injury. We conclude that the bFGF pathway may contribute to the development of intimal hyperplastic lesions.

  8. Intimal hyperplasia: slow but deadly.

    PubMed

    Mills, B; Robb, T; Larson, D F

    2012-11-01

    Intimal hyperplasia is the leading cause of long-term failure in coronary artery bypass vein grafting, coronary artery stenting, angioplasty, arteriovenous fistula for dialysis, and allograft transplantation. Intimal hyperplasia is a product of vascular smooth muscle cell proliferation, migration through the internal elastic lamina, and deposition of extracellular matrix proteins driven by growth factors in the vasculature. This vascular pathology results in a progressive diminution of the vessel lumen and serves as a site for thrombosis and atherosclerotic lesions. A key cell type in the initiation of intimal hyperplasia is the vascular endothelial cell, which appears to have down-stream effects on the vascular smooth muscle proliferation and migration. Currently, the only means available for prevention of intimal hyperplasia is through inhibition of mammalian target of rapamycin (mTOR) with the immunosuppressant rapamycin. mTOR integrates up-stream signals from growth factors such as IL-2 and senses the cellular nutrient and energy levels and redox status. This presentation will discuss the potential means of preserving the vascular endothelial cell and, thereby, reducing the development of intimal hyperplasia in our open-heart surgical patients.

  9. Local CXCR4 Upregulation in the Injured Arterial Wall Contributes to Intimal Hyperplasia.

    PubMed

    Shi, Xudong; Guo, Lian-Wang; Seedial, Stephen; Takayama, Toshio; Wang, Bowen; Zhang, Mengxue; Franco, Sarah R; Si, Yi; Chaudhary, Mirnal A; Liu, Bo; Kent, K Craig

    2016-11-01

    CXCR4 is a stem/progenitor cell surface receptor specific for the cytokine stromal cell-derived factor-1 (SDF-1α). There is evidence that bone marrow-derived CXCR4-expressing cells contribute to intimal hyperplasia (IH) by homing to the arterial subintima which is enriched with SDF-1α. We have previously found that transforming growth factor-β (TGFβ) and its signaling protein Smad3 are both upregulated following arterial injury and that TGFβ/Smad3 enhances the expression of CXCR4 in vascular smooth muscle cells (SMCs). It remains unknown, however, whether locally induced CXCR4 expression in SM22 expressing vascular SMCs plays a role in neointima formation. Here, we investigated whether elevated TGFβ/Smad3 signaling leads to the induction of CXCR4 expression locally in the injured arterial wall, thereby contributing to IH. We found prominent CXCR4 upregulation (mRNA, 60-fold; protein, 4-fold) in TGFβ-treated, Smad3-expressing SMCs. Chromatin immunoprecipitation assays revealed a specific association of the transcription factor Smad3 with the CXCR4 promoter. TGFβ/Smad3 treatment also markedly enhanced SDF-1α-induced ERK1/2 phosphorylation as well as SMC migration in a CXCR4-dependent manner. Adenoviral expression of Smad3 in balloon-injured rat carotid arteries increased local CXCR4 levels and enhanced IH, whereas SMC-specific depletion of CXCR4 in the wire-injured mouse femoral arterial wall produced a 60% reduction in IH. Our results provide the first evidence that upregulation of TGFβ/Smad3 in injured arteries induces local SMC CXCR4 expression and cell migration, and consequently IH. The Smad3/CXCR4 pathway may provide a potential target for therapeutic interventions to prevent restenosis. Stem Cells 2016;34:2744-2757. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  10. Local CXCR4 Upregulation in the Injured Arterial Wall Contributes to Intimal Hyperplasia

    PubMed Central

    Seedial, Stephen; Takayama, Toshio; Wang, Bowen; Zhang, Mengxue; Franco, Sarah R.; Si, Yi; Chaudhary, Mirnal A; Liu, Bo

    2016-01-01

    Abstract CXCR4 is a stem/progenitor cell surface receptor specific for the cytokine stromal cell‐derived factor‐1 (SDF‐1α). There is evidence that bone marrow‐derived CXCR4‐expressing cells contribute to intimal hyperplasia (IH) by homing to the arterial subintima which is enriched with SDF‐1α. We have previously found that transforming growth factor‐β (TGFβ) and its signaling protein Smad3 are both upregulated following arterial injury and that TGFβ/Smad3 enhances the expression of CXCR4 in vascular smooth muscle cells (SMCs). It remains unknown, however, whether locally induced CXCR4 expression in SM22 expressing vascular SMCs plays a role in neointima formation. Here, we investigated whether elevated TGFβ/Smad3 signaling leads to the induction of CXCR4 expression locally in the injured arterial wall, thereby contributing to IH. We found prominent CXCR4 upregulation (mRNA, 60‐fold; protein, 4‐fold) in TGFβ‐treated, Smad3‐expressing SMCs. Chromatin immunoprecipitation assays revealed a specific association of the transcription factor Smad3 with the CXCR4 promoter. TGFβ/Smad3 treatment also markedly enhanced SDF‐1α‐induced ERK1/2 phosphorylation as well as SMC migration in a CXCR4‐dependent manner. Adenoviral expression of Smad3 in balloon‐injured rat carotid arteries increased local CXCR4 levels and enhanced IH, whereas SMC‐specific depletion of CXCR4 in the wire‐injured mouse femoral arterial wall produced a 60% reduction in IH. Our results provide the first evidence that upregulation of TGFβ/Smad3 in injured arteries induces local SMC CXCR4 expression and cell migration, and consequently IH. The Smad3/CXCR4 pathway may provide a potential target for therapeutic interventions to prevent restenosis. Stem Cells 2016;34:2744–2757 PMID:27340942

  11. Arterial Levels of Oxygen Stimulate Intimal Hyperplasia in Human Saphenous Veins via a ROS-Dependent Mechanism

    PubMed Central

    Joddar, Binata; Firstenberg, Michael S.; Reen, Rashmeet K.; Varadharaj, Saradhadevi; Khan, Mahmood; Childers, Rachel C.; Zweier, Jay L.; Gooch, Keith J.

    2015-01-01

    Saphenous veins used as arterial grafts are exposed to arterial levels of oxygen partial pressure (pO2), which are much greater than what they experience in their native environment. The object of this study is to determine the impact of exposing human saphenous veins to arterial pO2. Saphenous veins and left internal mammary arteries from consenting patients undergoing coronary artery bypass grafting were cultured ex vivo for 2 weeks in the presence of arterial or venous pO2 using an established organ culture model. Saphenous veins cultured with arterial pO2 developed intimal hyperplasia as evidenced by 2.8-fold greater intimal area and 5.8-fold increase in cell proliferation compared to those freshly isolated. Saphenous veins cultured at venous pO2 or internal mammary arteries cultured at arterial pO2 did not develop intimal hyperplasia. Intimal hyperplasia was accompanied by two markers of elevated reactive oxygen species (ROS): increased dihydroethidium associated fluorescence (4-fold, p<0.05) and increased levels of the lipid peroxidation product, 4-hydroxynonenal (10-fold, p<0.05). A functional role of the increased ROS saphenous veins exposed to arterial pO2 is suggested by the observation that chronic exposure to tiron, a ROS scavenger, during the two-week culture period, blocked intimal hyperplasia. Electron paramagnetic resonance based oximetry revealed that the pO2 in the wall of the vessel tracked that of the atmosphere with a ~30 mmHg offset, thus the cells in the vessel wall were directly exposed to variations in pO2. Monolayer cultures of smooth muscle cells isolated from saphenous veins exhibited increased proliferation when exposed to arterial pO2 relative to those cultured at venous pO2. This increased proliferation was blocked by tiron. Taken together, these data suggest that exposure of human SV to arterial pO2 stimulates IH via a ROS-dependent pathway. PMID:25799140

  12. Ex vivo carbon monoxide delivery inhibits intimal hyperplasia in arterialized vein grafts

    PubMed Central

    Nakao, Atsunori; Huang, Chien-Sheng; Stolz, Donna B.; Wang, Yinna; Franks, Jonathan M.; Tochigi, Naobumi; Billiar, Timothy R.; Toyoda, Yoshiya; Tzeng, Edith; McCurry, Kenneth R.

    2011-01-01

    Aims Veins are still the best conduits available for arterial bypass surgery. When these arterialized vein grafts fail, it is often due to the development of intimal hyperplasia (IH). We investigated the feasibility and efficacy of the ex vivo pre-treatment of vein grafts with soluble carbon monoxide (CO) in the inhibition of IH. Methods and results The inferior vena cava was excised from donor rats and placed as an interposition graft into the abdominal aorta of syngeneic rats. Prior to implantation, vein grafts were stored in cold Lactated Ringer (LR) solution with or without CO saturation (bubbling of 100% CO) for 2 h. Three and 6 weeks following grafting, vein grafts treated with cold LR for 2 h developed IH, whereas grafts implanted immediately after harvest demonstrated significantly less IH. Treatment in CO-saturated LR significantly inhibited IH and reduced vascular endothelial cell (VEC) apoptosis. Electron microscopy revealed improved VEC integrity with less platelet/white blood cell aggregation in CO-treated grafts. The effects of CO in preventing IH were associated with activation of hypoxia inducible factor-1α (HIF-1α) and an increase in vascular endothelial growth factor (VEGF) expression at 3–6 h after grafting. Treatment with a HIF-1α inhibitor completely abrogated the induction of VEGF by CO and reversed the protective effects of CO on prevention of IH. Conclusion Ex vivo treatment of vein grafts in CO-saturated LR preserved VEC integrity perioperatively and significantly reduced neointima formation. These effects appear to be mediated through the activation of the HIF1α/VEGF pathway. PMID:20851811

  13. Interference of IP-10 expression inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in carotid artery: a new insight in the prevention of restenosis.

    PubMed

    Zuojun, Hu; Lingyu, Hu; Wei, He; Henghui, Yin; Chonggang, Zhang; Jingsong, Wang; Mian, Wang; Yong, Liu; Shenming, Wang

    2012-01-01

    After vascular angioplasty, vascular smooth muscle cell (VSMC) proliferation causes atherosclerosis and intimal hyperplasia leading to restenosis. Interferon-γ-inducible protein (IP)-10 plays a role in atherogenesis, but the mechanism remains unclear. We evaluated the role of IP-10 in intimal hyperplasia and restenosis. IP-10 expression was determined in arterial specimens from 20 arteriosclerotic obliteration patients and 6 healthy individuals. VSMCs were stimulated in vitro with IFN-γ and transfected with IP-10 siRNA. Silencing was verified with RT-PCR/Western blot; cell proliferation rate was detected by methyl-thiazol-tetrazolium. The carotid artery model of atherosclerosis injury was established with IP-10 siRNA. IP-10 expression was detected at 1 and 4 weeks using RT-PCR and immunohistochemistry. Artery morphology was assessed with hematoxylin-and-eosin staining, and intimal hyperplasia was evaluated by electron microscopy. IP-10 was overexpressed in arteriosclerotic obliteration group compared with control group (P < 0.05). IP-10 expression in transfected group was significantly lower than in untransfected group. The intima-to-media ratio of transfected group at 4 weeks was lower than that of untransfected group (P < 0.01). The transfected group exhibited more regular intimal structure and less hyperplasia under electron microscopy. We, therefore, concluded that IP-10 played an important role in intimal hyperplasia as siRNA-mediated IP-10 silencing inhibited aberrant VSMCs hyperplasia and reduced restenosis.

  14. HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4

    PubMed Central

    Cai, Jingjing; Yuan, Hong; Wang, Qingde; Yang, Huan; Al-Abed, Yousef; Hua, Zhong; Wang, Jiemei; Chen, Dandan; Wu, Jinze; Lu, Ben; Pribis, John P.; Jiang, Weihong; Yang, Kan; Hackam, David J.; Tracey, Kevin J.; Billiar, Timothy R.; Chen, Alex F.

    2016-01-01

    Objective Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall. The aim of this study is to investigate whether approaches that reduce the levels of HMGB1 or inhibit its activity suppresses IH after arterial injury. Approach and Results Here, we show that HMGB1 regulates IH in a mouse carotid wire injury model. Induced genetic deletion or neutralization of HMGB1 prevents IH, monocyte recruitment, and smooth muscle cell growth factor production after endoluminal carotid artery injury. A specific inhibitor of HMGB1 myeloid differentiation factor 2–toll-like receptor 4 (TLR4) interaction, P5779, also significantly inhibits IH. HMGB1 deletion is mimicked in this model by global deletion of TLR4 and partially replicated by myeloid-specific deletion of TLR4 but not TLR2 or receptor for advanced glycation endproducts deletion. The specific HMGB1 isoform known to activate TLR4 signaling (disulfide HMGB1) stimulates smooth muscle cell to migrate and produce monocyte chemotactic protein 1/CCL2) via TLR4. Macrophages produce smooth muscle cell mitogens in response to disulfide HMGB1 also in a TLR4/myeloid differentiation primary response gene (88)/Trif-dependent manner. Conclusions These findings place HMGB1 and its receptor, TLR4 as critical regulators of the events that drive the inflammation leading to IH after endoluminal arterial injury and identify this pathway as a possible therapeutic target to limit IH to attenuate damage-associated molecular pattern molecule–mediated vascular inflammatory responses. PMID:26515416

  15. Reduction of Intimal Hyperplasia in Injured Rat Arteries Promoted by Catheter Balloons Coated with Polyelectrolyte Multilayers that Contain Plasmid DNA Encoding PKCδ

    PubMed Central

    Bechler, Shane L.; Si, Yi; Yu, Yan; Ren, Jun; Liu, Bo; Lynn, David M.

    2012-01-01

    New therapeutic approaches that eliminate or reduce the occurrence of intimal hyperplasia following balloon angioplasty could improve the efficacy of vascular interventions and improve the quality of life of patients suffering from vascular diseases. Here, we report that treatment of arteries using catheter balloons coated with thin polyelectrolyte-based films (‘polyelectrolyte multilayers’, PEMs) can substantially reduce intimal hyperplasia in an in vivo rat model of vascular injury. We used a layer-by-layer (LbL) process to coat the surfaces of inflatable catheter balloons with PEMs composed of nanolayers of a cationic poly(β-amino ester) (polymer 1) and plasmid DNA (pPKCδ) encoding the δ isoform of protein kinase C (PKCδ), a regulator of apoptosis and other cell processes that has been demonstrated to reduce intimal hyperplasia in injured arterial tissue when administered via perfusion using viral vectors. Insertion of balloons coated with polymer 1/pPKCδ multilayers into injured arteries for 20 min resulted in local transfer of DNA and elevated levels of PKCδ expression in the media of treated tissue 3 days after delivery. IFC and IHC analysis revealed these levels of expression to promote downstream cellular processes associated with up-regulation of apoptosis. Analysis of arterial tissue 14 days after treatment revealed polymer 1/pPKCδ-coated balloons to reduce the occurrence of intimal hyperplasia by ~60% compared to balloons coated with films containing empty plasmid vectors. Our results demonstrate the potential therapeutic value of this nanotechnology-based approach to local gene delivery in the clinically important context of balloon-mediated vascular interventions. These PEM-based methods could also prove useful for other in vivo applications that require short-term, surface-mediated transfer of plasmid DNA. PMID:23069712

  16. Reduction of intimal hyperplasia in injured rat arteries promoted by catheter balloons coated with polyelectrolyte multilayers that contain plasmid DNA encoding PKCδ.

    PubMed

    Bechler, Shane L; Si, Yi; Yu, Yan; Ren, Jun; Liu, Bo; Lynn, David M

    2013-01-01

    New therapeutic approaches that eliminate or reduce the occurrence of intimal hyperplasia following balloon angioplasty could improve the efficacy of vascular interventions and improve the quality of life of patients suffering from vascular diseases. Here, we report that treatment of arteries using catheter balloons coated with thin polyelectrolyte-based films ('polyelectrolyte multilayers', PEMs) can substantially reduce intimal hyperplasia in an in vivo rat model of vascular injury. We used a layer-by-layer (LbL) process to coat the surfaces of inflatable catheter balloons with PEMs composed of nanolayers of a cationic poly(β-amino ester) (polymer 1) and plasmid DNA (pPKCδ) encoding the δ isoform of protein kinase C (PKCδ), a regulator of apoptosis and other cell processes that has been demonstrated to reduce intimal hyperplasia in injured arterial tissue when administered via perfusion using viral vectors. Insertion of balloons coated with polymer 1/pPKCδ multilayers into injured arteries for 20 min resulted in local transfer of DNA and elevated levels of PKCδ expression in the media of treated tissue three days after delivery. IFC and IHC analysis revealed these levels of expression to promote downstream cellular processes associated with up-regulation of apoptosis. Analysis of arterial tissue 14 days after treatment revealed polymer 1/pPKCδ-coated balloons to reduce the occurrence of intimal hyperplasia by ~60% compared to balloons coated with films containing empty plasmid vectors. Our results demonstrate the potential therapeutic value of this nanotechnology-based approach to local gene delivery in the clinically important context of balloon-mediated vascular interventions. These PEM-based methods could also prove useful for other in vivo applications that require short-term, surface-mediated transfer of plasmid DNA.

  17. Local association between endothelial dysfunction and intimal hyperplasia: relevance in peripheral artery disease.

    PubMed

    Heinen, Yvonne; Stegemann, Emilia; Sansone, Roberto; Benedens, Kolja; Wagstaff, Rabea; Balzer, Jan; Rassaf, Tienush; Lauer, Thomas; Kelm, Malte; Heiss, Christian

    2015-02-03

    Endothelial dysfunction is a key factor in the development of atherosclerosis. Commonly, endothelial function is determined in the brachial artery, whereas patients with peripheral artery disease (PAD) present with lower limb atherosclerosis. We hypothesized that in PAD, a segmental or local association exists between endothelial dysfunction and atherosclerotic structural changes. We used ultrasound to study endothelial function as flow-mediated vasodilation, intima media thickness, and local stiffness of the superficial femoral artery (SFA) and brachial artery (BA). PAD patients with symptomatic SFA or below-the-knee disease were compared with age-matched patients without PAD and young healthy controls. PAD patients with SFA or below-the-knee disease exhibited endothelial dysfunction of the proximal SFA (flow-mediated vasodilation: 3.9±0.6%, 3.7±0.6%) compared with healthy controls (7.4±1.0%) and patients without PAD (5.4±0.6%). Brachial artery flow-mediated vasodilation values were not different in PAD patients with SFA or below-the-knee disease compared with patients without PAD, but they were significantly lower than those of healthy controls. Endothelial dysfunction correlated with increased intima media thickness or plaque thickness at the site of flow-mediated vasodilation measurement across vascular sites. In PAD patients with SFA disease, SFA flow-mediated vasodilation was further impaired within and distal to stenosis (prestenosis 3.9±0.6%, intrastenosis 2.3±0.7%, poststenosis 2.5±0.6%) and recovered within 24 hours after SFA balloon angioplasty to prestenotic values but not to the brachial artery or SFA values in patients without PAD or controls. A close association exists between local endothelial function and atherosclerotic structural remodeling, suggesting that in PAD, local and segmental factors-in addition to systemic factors-influence local endothelial function. Our data point toward a pathophysiological role for lower extremity endothelial

  18. Effect on Intimal Hyperplasia of Dexamethasone Released from Coated Metal Stents Compared with Non-Coated Stents in Canine Femoral Arteries

    SciTech Connect

    Strecker, Ernst-Peter; Gabelmann, Andreas; Boos, Irene; Lucas, Christopher; Xu, Zhongying; Haberstroh, Joerg; Freudenberg, Nicolaus; Stricker, Helmut; Langer, Mathias; Betz, Eberhard

    1998-11-15

    Purpose: Polymer-coated, dexamethasone (DXM)-releasing stents were tested in order to assess the efficacy of DXM released locally for the prevention of stent restenosis due to intimal hyperplasia. Methods: Strecker stents coated with a biodegradable membrane containing DXM were implanted percutaneously into the femoral artery in 14 dogs. The contralateral artery received a conventional non-coated stent serving as control. The drugs are eluted by degradation of the carrier membrane. Follow-up intraarterial digital subtraction angiography (DSA) was obtained at 3, 6, 9, 12, and 24 weeks with subsequent autopsy. Specimens for gross and microscopic pathology were obtained and histomorphometry was performed. Results: Four of 14 DXM-coated stents showed thrombotic occlusion within the first 3 weeks; ten DXM-coated stents remained patent. At follow-up DSA, DXM-coated stents showed a significantly wider lumen than the non-coated stents. At morphometry there was less intimal hyperplasia over DXM-coated stents than over non-coated stents (p < 0.05). Conclusion: DXM-coated stents reduce neointimal hyperplasia in dogs when compared with non-coated stents.

  19. Endothelin-1 promotes vascular smooth muscle cell migration across the artery wall: a mechanism contributing to vascular remodelling and intimal hyperplasia in giant-cell arteritis.

    PubMed

    Planas-Rigol, Ester; Terrades-Garcia, Nekane; Corbera-Bellalta, Marc; Lozano, Ester; Alba, Marco A; Segarra, Marta; Espígol-Frigolé, Georgina; Prieto-González, Sergio; Hernández-Rodríguez, José; Preciado, Sara; Lavilla, Rodolfo; Cid, Maria C

    2017-09-01

    Giant-cell arteritis (GCA) is an inflammatory disease of large/medium-sized arteries, frequently involving the temporal arteries (TA). Inflammation-induced vascular remodelling leads to vaso-occlusive events. Circulating endothelin-1 (ET-1) is increased in patients with GCA with ischaemic complications suggesting a role for ET-1 in vascular occlusion beyond its vasoactive function. To investigate whether ET-1 induces a migratory myofibroblastic phenotype in human TA-derived vascular smooth muscle cells (VSMC) leading to intimal hyperplasia and vascular occlusion in GCA. Immunofluorescence/confocal microscopy showed increased ET-1 expression in GCA lesions compared with control arteries. In inflamed arteries, ET-1 was predominantly expressed by infiltrating mononuclear cells whereas ET receptors, particularly ET-1 receptor B (ETBR), were expressed by both mononuclear cells and VSMC. ET-1 increased TA-derived VSMC migration in vitro and α-smooth muscle actin (αSMA) expression and migration from the media to the intima in cultured TA explants. ET-1 promoted VSMC motility by increasing activation of focal adhesion kinase (FAK), a crucial molecule in the turnover of focal adhesions during cell migration. FAK activation resulted in Y397 autophosphorylation creating binding sites for Src kinases and the p85 subunit of PI3kinases which, upon ET-1 exposure, colocalised with FAK at the focal adhesions of migrating VSMC. Accordingly, FAK or PI3K inhibition abrogated ET-1-induced migration in vitro. Consistently, ET-1 receptor A and ETBR antagonists reduced αSMA expression and delayed VSMC outgrowth from cultured GCA-involved artery explants. ET-1 is upregulated in GCA lesions and, by promoting VSMC migration towards the intimal layer, may contribute to intimal hyperplasia and vascular occlusion in GCA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  20. The ratio of diameters between the target artery and the bypass modifies hemodynamic parameters related to intimal hyperplasia in the distal end-to-side anastomosis.

    PubMed

    Grus, T; Lambert, L; Matěcha, J; Grusová, G; Špaček, M; Mlček, M

    2016-12-13

    Hemodynamics in the distal end-to-side anastomosis is related to early development of intimal hyperplasia and bypass failure. In this study we investigated the effect of diameter ratios between the target artery and the bypass at three different angles of the connection. The pulsatile flow field was visualized using particle image velocimetry in transparent models with three different angles of the connection (25°, 45°, 60°) and the diameter ratio between the bypass and the target artery was 4.6 mm : 6 mm, 6 mm : 6 mm, and 7.5 mm : 6 mm. Six parameters including location and oscillation of the stagnation point, local energy dissipation, wall shear stress (WSS), oscillatory shear index, spatial and temporal gradient of WSS and their distribution in the target artery were calculated from the flow field. In the wider bypass, the stagnation point oscillated in a greater range and was located more proximal to the anastomosis. Energy dissipation was minimal in a wider bypass with a more acute angle. The maximum WSS values were tree times greater in a narrow bypass and concentrated in a smaller circular region at the floor of the anastomosis. The oscillatory shear index increased with wider bypass and more acute angle. The maximum of spatial gradient of WSS concentrated around the floor and toe of the anastomosis and decreased with more acute angle and wider bypass, the temporal gradient of WSS was stretched more towards the side wall. Greater bypass to target vessel ratio and more acute anastomosis angle promote hemodynamics known to reduce formation of intimal hyperplasia.

  1. Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow†

    PubMed Central

    Caro, Colin Gerald; Seneviratne, Anusha; Heraty, Kevin B.; Monaco, Claudia; Burke, Martin G.; Krams, Rob; Chang, Carlos C.; Coppola, Gianfilippo; Gilson, Paul

    2013-01-01

    Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels. PMID:24132200

  2. [Pulmonary artery intimal sarcoma].

    PubMed

    Bourry, N; Chabrot, P; Jeannin, G; Filaire, M; Charpy, C; Bay, J O; Kemeny, J L; Caillaud, D; Escande, G; Boyer, L

    2008-02-01

    Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.

  3. Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.

    PubMed

    Li, Yonghong; Cai, Shanglang; Wang, Qixin; Zhou, Jingwei; Hou, Bo; Yu, Haichu; Ge, Zhiming; Guan, Renyan; Liu, Xu

    2016-05-15

    The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1-7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Altered catecholamine receptor affinity in rabbit aortic intimal hyperplasia

    SciTech Connect

    O'Malley, M.K.; Cotecchia, S.; Hagen, P.O. )

    1991-08-01

    Intimal thickening is a universal response to endothelial denudation and is also thought to be a precursor of atherosclerosis. The authors have demonstrated selective supersensitivity in arterial intimal hyperplasia to norepinephrine and they now report a possible mechanism for this. Binding studies in rabbit aorta with the selective alpha 1-adrenergic radioligand 125I-HEAT demonstrated that there was no change in receptor density (20 {plus minus} 4 fmole/10(6) cells) in intact vascular smooth muscle cells at either 5 or 14 days after denudation. However, competition studies showed a 2.6-fold increase in alpha 1-adrenergic receptor affinity for norepinephrine in intimal hyperplastic tissue (P less than 0.05). This increased affinity for norepinephrine was associated with a greater increase in 32P-labeled phosphatidylinositol (148% intimal thickening versus 76% control) and phosphatidic acid (151% intimal thickening versus 56% control) following norepinephrine stimulation of free floating rings of intimal hyperplastic aorta. These data suggest that the catecholamine supersensitivity in rabbit aortic intimal hyperplasia is receptor mediated and may be linked to the phosphatidylinositol cycle.

  5. Topical application of {beta}-radiation to reduce intimal hyperplasia after carotid artery balloon injury in rabbit A possible application for brachytherapy in vascular surgery

    SciTech Connect

    Rosenthal, David; Stevens, Scott L.; Skillern, C.S.; Wellons, Eric D.; Robinson, Keith; Matsuura, John H.; Gannon, Brian J

    2002-03-01

    Purpose: Endovascular brachytherapy for the prevention of intimal hyperplasia (IH) and restenosis after balloon/stent angioplasty has proven effective both in animal preparations and clinical trials. A variety of {beta}-emitting isotopes and catheter-based devices have been developed for the delivery of low-dose radiation in clinical coronary and peripheral trials. No platform, however, has yet been developed for brachytherapy in concert with vascular surgical operations. The purpose of this study was to evaluate the vascular histopathologic response following balloon injury to rabbit carotid arteries with and without topically applied low-dose {beta}-radiation. Methods: The {beta}-emitting isotope strontium-90 (Sr-90) was conjugated onto the matrix of polypropylene (PLYP) mesh. Rabbit carotid arteries were balloon-injured with a no. 2 embolectomy catheter. Six carotid arteries were wrapped with nonradioactive PLYP mesh (controls) and Sr-90 ({approx}90 {mu}Ci) PLYP mesh in order to deliver low-dose radiation to the vessel wall from the external (adventitial) surface. Tissue was harvested at 6 weeks and processed for histologic examination. Results: There was consistent blockade of fibrocellular neointima formation with virtually no neointima present in all treated segments, compared to moderate neointima formation in controls. Medial thinning and smooth muscle cell (SMC) necrosis were also associated with topical brachytherapy. Conclusion: {beta}-Radiation applied by an externally wrapped PLYP mesh labeled with Sr-90 markedly suppressed neointima formation in an animal vascular surgical injury model. Further studies, however, are necessary to determine a suitable isotope and dosage for clinical application.

  6. Inhibition of neo-intimal hyperplasia in porcine coronary arteries utilizing a novel paclitaxel-coated scoring balloon catheter.

    PubMed

    Cremers, Bodo; Schmitmeier, Stephanie; Clever, Yvonne P; Gershony, Gary; Speck, Ulrich; Scheller, Bruno

    2014-12-01

    Scoring balloons are particularly useful in the acute treatment of fibro-calcific, bifurcation and in-stent restenosis lesions but have not been shown to affect the restenosis rate. Conventional balloons coated with paclitaxel have recently been shown to reduce restenosis rates in certain lesion subsets, but are associated with suboptimal acute results. A novel paclitaxel-coated scoring balloon was developed to overcome these limitations. AngioSculpt(®) scoring balloons (SB) were coated with paclitaxel admixed with a specific excipient. Four in vitro and in vivo studies were performed: (a) loss of the drug during passage to the lesion, (b) transfer of the drug to the vessel wall; (c) inhibition of neo-intimal proliferation in porcine coronary arteries as compared to uncoated SB and the Paccocath™, and (d) evaluation of the dose-response to 1.5-12 μg of paclitaxel/mm(2) . Drug loss during delivery to the lesion was 17% ± 8%, and transfer to the vessel wall was 9% ± 4% of dose on unused balloons. The paclitaxel-coated SB resulted in a lower late lumen loss of 0.27 ± 0.24 mm compared to 1.4 ± 0.7 mm with the uncoated SB (P = 0.001). Histomorphometry revealed larger luminal areas of 6.8 ± 1.6 mm(2) (paclitaxel-coated SB) and 5.8 ± 1.7 mm(2) (Paccocath) as compared to the uncoated SB (2.3 ± 1.5 mm(2) ; P = 0.001). No coating related adverse effects were observed on follow-up angiography or histologic examination at the treatment site or downstream myocardium. A novel paclitaxel-coated SB leads to a significant inhibition of neointimal proliferation in the porcine coronary model. © 2013 Wiley Periodicals, Inc.

  7. A simplified murine intimal hyperplasia model founded on a focal carotid stenosis.

    PubMed

    Tao, Ming; Mauro, Christine R; Yu, Peng; Favreau, John T; Nguyen, Binh; Gaudette, Glenn R; Ozaki, C Keith

    2013-01-01

    Murine models offer a powerful tool for unraveling the mechanisms of intimal hyperplasia and vascular remodeling, although their technical complexity increases experimental variability and limits widespread application. We describe a simple and clinically relevant mouse model of arterial intimal hyperplasia and remodeling. Focal left carotid artery (LCA) stenosis was created by placing 9-0 nylon suture around the artery using an external 35-gauge mandrel needle (middle or distal location), which was then removed. The effect of adjunctive diet-induced obesity was defined. Flowmetry, wall strain analyses, biomicroscopy, and histology were completed. LCA blood flow sharply decreased by ∼85%, followed by a responsive right carotid artery increase of ∼71%. Circumferential strain decreased by ∼2.1% proximal to the stenosis in both dietary groups. At 28 days, morphologic adaptations included proximal LCA intimal hyperplasia, which was exacerbated by diet-induced obesity. The proximal and distal LCA underwent outward and negative inward remodeling, respectively, in the mid-focal stenosis (remodeling indexes, 1.10 and 0.53). A simple, defined common carotid focal stenosis yields reproducible murine intimal hyperplasia and substantial differentials in arterial wall adaptations. This model offers a tool for investigating mechanisms of hemodynamically driven intimal hyperplasia and arterial wall remodeling.

  8. Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia.

    PubMed

    Longchamp, Alban; Allagnat, Florent; Alonso, Florian; Kuppler, Christopher; Dubuis, Céline; Ozaki, Charles-Keith; Mitchell, James R; Berceli, Scott; Corpataux, Jean-Marc; Déglise, Sébastien; Haefliger, Jacques-Antoine

    2015-01-01

    Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment.

  9. Connexin43 Inhibition Prevents Human Vein Grafts Intimal Hyperplasia

    PubMed Central

    Longchamp, Alban; Allagnat, Florent; Alonso, Florian; Kuppler, Christopher; Dubuis, Céline; Ozaki, Charles-Keith; Mitchell, James R.; Berceli, Scott; Corpataux, Jean-Marc

    2015-01-01

    Venous bypass grafts often fail following arterial implantation due to excessive smooth muscle cells (VSMC) proliferation and consequent intimal hyperplasia (IH). Intercellular communication mediated by Connexins (Cx) regulates differentiation, growth and proliferation in various cell types. Microarray analysis of vein grafts in a model of bilateral rabbit jugular vein graft revealed Cx43 as an early upregulated gene. Additional experiments conducted using an ex-vivo human saphenous veins perfusion system (EVPS) confirmed that Cx43 was rapidly increased in human veins subjected ex-vivo to arterial hemodynamics. Cx43 knock-down by RNA interference, or adenoviral-mediated overexpression, respectively inhibited or stimulated the proliferation of primary human VSMC in vitro. Furthermore, Cx blockade with carbenoxolone or the specific Cx43 inhibitory peptide 43gap26 prevented the burst in myointimal proliferation and IH formation in human saphenous veins. Our data demonstrated that Cx43 controls proliferation and the formation of IH after arterial engraftment. PMID:26398895

  10. Unusually aggressive immature neo-intimal hyperplasia causing in-stent restenosis.

    PubMed

    McCutcheon, Keir; Triantafyllis, Andreas S; Bennett, Johan; Adriaenssens, Tom

    2017-10-10

    This image illustrates a very unusual pattern of early and aggressive immature neo-intimal hyperplasia in a 52-year-old man with unstable angina, two months after deployment of a drug-eluting stent in the proximal left anterior descending artery.

  11. Neo-intimal hyperplasia, diabetes and endovascular injury.

    PubMed

    Kruger, Deirdre

    2012-10-01

    Diabetes is a significant major risk factor for peripheral arterial disease (PAD) and critical limb ischaemia (CLI), the latter which is also the most common cause of amputation in these patients. Revascularisation of the lower extremities of such patients is imperative for limb salvage and has become First-line therapy. However, the incidence of restenosis following endovascular stenting is very high and is largely due to neo-intimal hyperplasia (NIH), the regulation of which is for the greater part not understood. This article therefore reviews our understanding on the regulation of NIH following stent-induced vascular injury, and highlights the importance of future studies to investigate whether the profile of vascular progenitor cell differentiation, neo-intimal growth factors and lumen diameters predict the severity of post-stent NIH in the peripheral arteries. Results from future studies will (1) better our understanding of the regulation of NIH in general, (2) determine whether combinations of any of the vascular factors discussed are predictive of the extent of NIH postoperatively, and (3) potentially facilitate future therapeutic targets and/or change preventive strategies.

  12. Inhibitory Effect of TLR4 Gene Silencing on Intimal Hyperplasia of Vein Grafting.

    PubMed

    Zhu, Zhicheng; Xu, Rihao; Zheng, Xiaomei; Wang, Tiance; Li, Dan; Wang, Yong; Liu, Kexiang

    2016-10-01

    The present study aimed to explore the regulating effect of Toll-like receptor 4 (TLR4) on intimal hyperplasia in rat vein grafts. Rat models of external jugular vein carotid artery bypass grafting were established. Afterward, TLR4 small interfering RNA (siRNA) recombinant plasmids were constructed, which were transfected into rat vein graft bypass to study the effect of TLR4 silencing on intimal hyperplasia and to explore the underlying mechanisms. Real-time polymerase chain reaction and Western blot were used to detect the expression levels of TLR4 and inflammatory factors in TLR4 siRNA-transfected vein graft bypass. The intimal thickness was evaluated using hematoxylin-eosin staining. Compared with the scramble siRNA group, the intimal thickness of vein grafting was decreased significantly, while the inflammatory factors including interleukin (IL) 1β, IL-6, and tumor necrosis factor α in grafted vein were dramatically downregulated in the TLR4 siRNA group. These results showed that local silencing of TLR4 in the vein grafts could inhibit intimal hyperplasia by downregulating the expression of inflammatory factors in the vein grafts, suggesting that TLR4 can be used as a new target for therapy of vascular intimal hyperplasia. © The Author(s) 2016.

  13. Nicorandil attenuates carotid intimal hyperplasia after balloon catheter injury in diabetic rats.

    PubMed

    Zhang, Ying Qian; Tian, Feng; Zhou, Ying; Chen, Yun Dai; Li, Bo; Ma, Qiang; Zhang, Ying

    2016-04-08

    Diabetic patients suffer from undesired intimal hyperplasia after angioplasty. Nicorandil has a trend to reduce the rate of target lesion revascularization. However, whether nicorandil inhibits intimal hyperplasia and the possible mechanisms underlying it remain to be determined. We aimed at assessing the effect of nicorandil on intimal hyperplasia in diabetic rats. After intraperitoneal injection of streptozotocin (STZ, 50 mg/kg), balloon injury model was established in carotid arteries of diabetic rats. Rats were randomized to vehicle, nicorandil (15 mg/kg/day) or 5-hydroxydecanoate (5-HD, 10 mg/kg/day), a mitochondrial ATP-sensitive potassium channel (mitoKATP channel)-selective antagonist. Perivascular delivery of εPKC siRNA was conducted to determine the role of εPKC pathway in intimal hyperplasia. In hyperglycemia environment (25 mM glucose), primary culture of vascular smooth muscle cells (VSMCs) were treated with nicorandil or 5-HD. Cell proliferation and cell migration were analyzed. Intimal hyperplasia significantly increased 14 days after balloon injury in diabetic rats (p < 0.01). Nicorandil inhibited intima development, reduced inflammation and prevented cell proliferation in balloon-injured arteries (p < 0.01). The protective effects of nicorandil were reversed by 5-HD (p < 0.05). εPKC was activated in balloon-injured arteries (p < 0.01). Nicorandil inhibited εPKC activation by opening mitoKATP channel. Perivascular delivery of εPKC siRNA inhibited intimal hyperplasia, inflammation and cell proliferation (p < 0.01). High glucose-induced VSMCs proliferation and migration were inhibited by nicorandil. εPKC activation induced by high glucose was also inhibited by nicorandil and that is partially reversed by 5-HD. εPKC knockdown prevented VSMCs proliferation and migration (p < 0.01). Our study demonstrates that nicorandil inhibits intimal hyperplasia in balloon-injured arteries in diabetic rats. Nicorandil also prevents VSMCs proliferation and

  14. Cigarette smoke increases intimal hyperplasia and homocysteine in a rat carotid endarterectomy.

    PubMed

    Davis, Joseph A; Brown, Aliza T; Chen, Hongjiang; Wang, Yunfang; Poirier, Lionel A; Eidt, John F; Cruz, Carlos P; Moursi, Mohammed M

    2004-09-01

    Homocysteine and smoking are independent risks for CVD; however their importance in post-CEA intimal hyperplasia is unclear. We performed a CEA in rats exposed to cigarette smoke with the hypothesis that smoking would increase intimal hyperplasia that may be associated with an elevated serum homocysteine. Folic acid (FA) and the homocysteine metabolic enzymes MTHFR and CBS were used to test for the significance of homocysteine elevation. Rats underwent an open CEA. N = 13 rats received smoke exposure 2 weeks prior, and 2 weeks post-CEA and N = 12 received no smoke. Each group was divided into either control or an FA-added diet resulting in four groups. Rats were sacrificed at 2 weeks post-CEA; liver, urine, blood, and carotid arteries samples were obtained. Smoked rats had increased urinary peak and trough cotinine levels versus non-smoke rats, which decreased with FA. Smoke exposure increased intimal hyperplasia versus non-smoke controls by nearly 120% (57.8 +/- 6.2 versus 26.8 +/- 5.4% luminal stenosis, P = 0.005). Smoke-exposed rats had an increased serum homocysteine versus non-smoke controls (8.3 +/- 0.8 versus 5.7 +/- 0.8 microm, P = 0.014). Smoked rats given FA had decreased serum homocysteine compared to the smoke group. Along with reductions in homocysteine, FA eliminated the increase in intimal hyperplasia seen with smoke exposure (33.5 +/- 6.1 versus 57.8 +/- 6.2% luminal stenosis, P = 0.03). CBS activity decreased in smoked rats by nearly 20% versus non-smoke rats. FA supplementation in smoked rats both (1) increased CBS activity and (2) decreased MTHFR compared to control non-smoke-exposure levels. Smoking increases plasma homocysteine and post-CEA intimal hyperplasia. This suggests homocysteine has an etiological role in the intimal hyperplasia increase observed with smoking, since both were negated with FA.

  15. A Gbetagamma inhibitor reduces intimal hyperplasia in aortocoronary saphenous vein grafts.

    PubMed

    Petrofski, Jason A; Hata, Jonathan A; Williams, Matthew L; Parsa, Cyrus J; Thompson, Richard B; Hanish, Steven I; Gehrig, Thomas R; Koch, Walter J; Milano, Carmelo A

    2005-12-01

    Approximately 50% of aortocoronary saphenous vein grafts are occluded 10 years after coronary revascularization surgery. Intimal hyperplasia, a critical component in saphenous vein graft failure, is defined by vascular smooth muscle cell proliferation, which is mediated in part by betagamma subunits of heterotrimeric G proteins (G(betagamma)) and downstream effectors such as mitogen-activated protein kinases. A peptide consisting of the carboxyl-terminus of the beta-adrenergic receptor kinase (betaARKct) binds G(betagamma), thereby inhibiting G(betagamma) signaling. Utilizing a recombinant adenovirus containing the coding sequence for the betaARKct peptide (AdbetaARKct), this study investigates whether treatment of the vein graft with AdbetaARKct reduces intimal hyperplasia in a large animal model of aortocoronary saphenous vein graft intimal hyperplasia. Twenty-seven dogs (27-32 kg) underwent aortocoronary bypass grafting to the left anterior descending artery using autologous saphenous vein. Vein grafts were treated with saline (n = 8), an empty adenovirus (n = 8), or AdbetaARKct (n = 8). A subset of dogs (n = 3) were sacrificed on postoperative day 7 and betaARKct expression confirmed by Northern blotting. Arteriograms performed on postoperative day 90 confirmed that saphenous vein grafts were patent. At postoperative day 90, AdbetaARKct-treated grafts demonstrated reduced intimal area compared to empty virus and saline treated animals (P < .05). Additionally, AdbetaARKct treatment of isolated vascular smooth muscle cells in vitro inhibited mitogen-activated protein kinase activation and decreased overall vascular smooth muscle cell proliferation. This study demonstrates that betaARKct expression in aortocoronary saphenous vein grafts reduces intimal hyperplasia and decreases vascular smooth muscle cell proliferation in vitro via inhibition of G(betagamma)-mediated mitogen-activated protein kinase activation. Modulation of G(betagamma) via betaARKct may

  16. A successful experimental model for intimal hyperplasia prevention using a resveratrol-delivering balloon.

    PubMed

    Tolva, Valerio; Mazzola, Silvia; Zerbi, Pietro; Casana, Renato; Albertini, Mariangela; Calvillo, Laura; Selmin, Francesca; Cilurzo, Francesco

    2016-03-01

    Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound. A 140 μg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drug-delivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period. The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies. RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  17. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia.

    PubMed Central

    Law, R E; Meehan, W P; Xi, X P; Graf, K; Wuthrich, D A; Coats, W; Faxon, D; Hsueh, W A

    1996-01-01

    Vascular smooth muscle cell (VSMC) proliferation and migration are responses to arterial injury that are highly important to the processes of restenosis and atherosclerosis. In the arterial balloon injury model in the rat, platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are induced in the vessel wall and regulate these VSMC activities. Novel insulin sensitizing agents, thiazolidinediones, have been demonstrated to inhibit insulin and epidermal growth factor-induced growth of VSMCs. We hypothesized that these agents might also inhibit the effect of PDGF and bFGF on cultured VSMCs and intimal hyperplasia in vivo. Troglitazone (1 microM), a member of the thiazolidinedione class, produced a near complete inhibition of both bFGF-induced DNA synthesis as measured by bromodeoxyuridine incorporation (6.5+/-3.9 vs. 17.6+/-4.3% cells labeled, P < 0.05) and c-fos induction. This effect was associated with an inhibition (by 73+/-4%, P < 0.01) by troglitazone of the transactivation of the serum response element, which regulates c-fos expression. Inhibition of c-fos induction by troglitazone appeared to occur via a blockade of the MAP kinase pathway at a point downstream of MAP kinase activation by MAP kinase kinase. At this dose, troglitazone also inhibited PDGF-BB-directed migration of VSMC (by 70+/-6%, P < 0.01). These in vitro effects were operative in vivo. Quantitative image analysis revealed that troglitazone-treated rats had 62% (P < 0.001) less neointima/media area ratio 14 d after balloon injury of the aorta compared with injured rats that received no troglitazone. These results suggest troglitazone is a potent inhibitor of VSMC proliferation and migration and, thus, may be a useful agent to prevent restenosis and possibly atherosclerosis. PMID:8878442

  18. Kindlin-2 siRNA inhibits vascular smooth muscle cell proliferation, migration and intimal hyperplasia via Wnt signaling.

    PubMed

    Wu, Xiaolin; Liu, Wenwei; Jiang, Hong; Chen, Jing; Wang, Jichun; Zhu, Rui; Li, Bin

    2016-02-01

    It is known that vascular smooth muscle cell (VSMC) proliferation and migration leads to intimal hyperplasia in cases of atherosclerosis and restenosis. In the present study, we investigated the effects of kindlin-2 on VSMC proliferation, migration and intimal hyperplasia, and the underlying mechanisms. The left common carotid artery of Sprague‑Dawley rats were subjected to balloon injury in order to induce intimal hyperplasia, and then transfected with kindlin-2 small interfering RNA (siRNA) lentivirus or negative control siRNA lentivirus. We noted that the degree of intimal hyperplasia 4 weeks after balloon injury was significantly reduced in arteries transfected with kindlin-2 siRNA lentivirus (P<0.05). In vitro, kindlin-2 siRNA suppressed VSMC proliferation and migration induced by Wnt3a (100 ng/ml). Western blot analyses and RT-qPCR revealed that kindlin-2 regulated Wnt/β-catenin signaling and thereby modulated the expression of β-catenin target genes, including c-myc and cyclin D1. This study demonstrated that kindlin-2 plays a critical role in VSMC proliferation, migration and intimal hyperplasia via Wnt signaling. Therefore, blocking the activity of kindlin-2 represents a novel therapeutic strategy for vascular injury.

  19. Leoligin, the major lignan from Edelweiss, inhibits intimal hyperplasia of venous bypass grafts

    PubMed Central

    Reisinger, Ute; Schwaiger, Stefan; Zeller, Iris; Messner, Barbara; Stigler, Robert; Wiedemann, Dominik; Mayr, Tobias; Seger, Christoph; Schachner, Thomas; Dirsch, Verena M.; Vollmar, Angelika M.; Bonatti, Johannes O.; Stuppner, Hermann; Laufer, Günther; Bernhard, David

    2009-01-01

    Aims Despite the lower patency of venous compared with arterial coronary artery bypass grafts, ∼50% of grafts used are saphenous vein conduits because of their easier accessibility. In a search for ways to increase venous graft patency, we applied the results of a previous pharmacological study screening for non-toxic compounds that inhibit intimal hyperplasia of saphenous vein conduits in organ cultures. Here we analyse the effects and mechanism of action of leoligin [(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl (2Z)-2-methylbut-2-enoat, the major lignan from Edelweiss (Leontopodium alpinum Cass.). Methods and results We found that leoligin potently inhibits vascular smooth muscle cell (SMC) proliferation by inducing cell cycle arrest in the G1-phase. Leoligin induced cell death neither in SMCs nor, more importantly, in endothelial cells. In a human saphenous vein organ culture model for graft disease, leoligin potently inhibited intimal hyperplasia, and even reversed graft disease in pre-damaged vessels. Furthermore, in an in vivo mouse model for venous bypass graft disease, leoligin potently inhibited intimal hyperplasia. Conclusion Our data suggest that leoligin might represent a novel non-toxic, non-thrombogenic, endothelial integrity preserving candidate drug for the treatment of vein graft disease. PMID:19228707

  20. Pulmonary Artery Intimal Sarcoma: A Case Report.

    PubMed

    Kriz, Joseph P; Munfakh, Nabil A; King, Gregory S; Carden, Juan O

    2016-01-01

    Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung.

  1. Pulmonary Artery Intimal Sarcoma: A Case Report

    PubMed Central

    Kriz, Joseph P.; Munfakh, Nabil A.; King, Gregory S.; Carden, Juan O.

    2016-01-01

    Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung. PMID:27239183

  2. Reduced Intimal Hyperplasia in Rabbits via Medical Therapy after Carotid Venous Bypass

    PubMed Central

    Yucel, Semih; Bahcivan, Muzaffer; Gol, Mehmet Kamil; Erenler, Behice H.; Kolbakir, Fersat; Keceligil, Hasan T.

    2009-01-01

    Intimal hyperplasia is a major cause of restenosis after the interventional or surgical treatment of occlusive arterial disease. We investigated the effects of clopidogrel, calcium dobesilate, nebivolol, and atorvastatin on the development of intimal hyperplasia in rabbits after carotid venous bypass surgery. We divided 40 male New Zealand rabbits into 4 study groups and 1 control group. After occluding the carotid arteries of the rabbits, we constructed jugular venous grafts between the proximal and the distal segments of the occluded artery. Thereafter, group 1 (control) received no medication. We administered daily oral doses of clopidogrel to group 2, calcium dobesilate to group 3, nebivolol to group 4, and atorvastatin to group 5. The rabbits were killed 28 days postoperatively. The arterialized jugular venous grafts were extracted for histopathologic examination. Intimal thicknesses were 42.87 ± 6.95 μm (group 2), 46.5 ± 9.02 μm (group 3), 34.12 ± 5.64 μm (group 4), and 48.37 ± 6.16 μm (group 5), all significantly less than the 95.12 ± 9.93 μm in group 1 (all P < 0.001). Medial thicknesses were 94 ± 6 μm (group 2), 101.5 ± 13.52 μm (group 3), 90.5 ± 9.69 μm (group 4), and 101.37 ± 7.99 μm (group 5), all significantly thinner than the 126.62 ± 13.53 μm in group 1 (all P < 0.001). In our experimental model of carotid venous bypass grafting in rabbits, clopidogrel, calcium dobesilate, nebivolol, and atorvastatin each effectively reduced the development of intimal hyperplasia. Herein, we discuss our findings and review the medical literature. PMID:19876413

  3. Reduced intimal hyperplasia in rabbits via medical therapy after carotid venous bypass.

    PubMed

    Yucel, Semih; Bahcivan, Muzaffer; Gol, Mehmet Kamil; Erenler, Behice H; Kolbakir, Fersat; Keceligil, Hasan T

    2009-01-01

    Intimal hyperplasia is a major cause of restenosis after the interventional or surgical treatment of occlusive arterial disease. We investigated the effects of clopidogrel, calcium dobesilate, nebivolol, and atorvastatin on the development of intimal hyperplasia in rabbits after carotid venous bypass surgery. We divided 40 male New Zealand rabbits into 4 study groups and 1 control group. After occluding the carotid arteries of the rabbits, we constructed jugular venous grafts between the proximal and the distal segments of the occluded artery. Thereafter, group 1 (control) received no medication. We administered daily oral doses of clopidogrel to group 2, calcium dobesilate to group 3, nebivolol to group 4, and atorvastatin to group 5. The rabbits were killed 28 days postoperatively. The arterialized jugular venous grafts were extracted for histopathologic examination. Intimal thicknesses were 42.87 +/- 6.95 microm (group 2), 46.5 +/- 9.02 microm (group 3), 34.12 +/- 5.64 microm (group 4), and 48.37 +/- 6.16 microm (group 5), all significantly less than the 95.12 +/- 9.93 microm in group 1 (all P < 0.001). Medial thicknesses were 94 +/- 6 microm (group 2), 101.5 +/- 13.52 microm (group 3), 90.5 +/- 9.69 microm (group 4), and 101.37 +/- 7.99 microm (group 5), all significantly thinner than the 126.62 +/- 13.53 microm in group 1 (all P < 0.001). In our experimental model of carotid venous bypass grafting in rabbits, clopidogrel, calcium dobesilate, nebivolol, and atorvastatin each effectively reduced the development of intimal hyperplasia. Herein, we discuss our findings and review the medical literature.

  4. Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia

    PubMed Central

    Wang, Li; Yu, Tianzheng; Lee, Hakjoo; O'Brien, Dawn K.; Sesaki, Hiromi; Yoon, Yisang

    2015-01-01

    Aims Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process in the development of intimal hyperplasia. Cell migration is an energy-demanding process that is predicted to require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, the role of mitochondrial morphology in VSMC migration is not well understood. The aim of the study is to understand how mitochondrial fission contributes to VSMC migration and provides its in vivo relevance in the mouse model of intimal hyperplasia. Methods and results In primary mouse VSMCs, the chemoattractant PDGF induced mitochondrial shortening through the mitochondrial fission protein dynamin-like protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF-induced lamellipodia formation and VSMC migration, indicating that mitochondrial fission is an important process in VSMC migration. PDGF induced an augmentation of mitochondrial energetics as well as ROS production, both of which were found to be necessary for VSMC migration. Mechanistically, the inhibition of mitochondrial fission induced an increase of mitochondrial inner membrane proton leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing DLP1-K38A displayed markedly reduced ROS levels and neointima formation in response to femoral artery wire injury. Conclusions Mitochondrial fission is an integral process in cell migration, and controlling mitochondrial fission can limit VSMC migration and the pathological intimal hyperplasia by altering mitochondrial energetics and ROS levels. PMID:25587046

  5. Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia.

    PubMed

    Wang, Li; Yu, Tianzheng; Lee, Hakjoo; O'Brien, Dawn K; Sesaki, Hiromi; Yoon, Yisang

    2015-05-01

    Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process in the development of intimal hyperplasia. Cell migration is an energy-demanding process that is predicted to require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, the role of mitochondrial morphology in VSMC migration is not well understood. The aim of the study is to understand how mitochondrial fission contributes to VSMC migration and provides its in vivo relevance in the mouse model of intimal hyperplasia. In primary mouse VSMCs, the chemoattractant PDGF induced mitochondrial shortening through the mitochondrial fission protein dynamin-like protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF-induced lamellipodia formation and VSMC migration, indicating that mitochondrial fission is an important process in VSMC migration. PDGF induced an augmentation of mitochondrial energetics as well as ROS production, both of which were found to be necessary for VSMC migration. Mechanistically, the inhibition of mitochondrial fission induced an increase of mitochondrial inner membrane proton leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing DLP1-K38A displayed markedly reduced ROS levels and neointima formation in response to femoral artery wire injury. Mitochondrial fission is an integral process in cell migration, and controlling mitochondrial fission can limit VSMC migration and the pathological intimal hyperplasia by altering mitochondrial energetics and ROS levels. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  6. A Rapamycin-Releasing Perivascular Polymeric Sheath Produces Highly Effective Inhibition of Intimal Hyperplasia

    PubMed Central

    Yu, Xaohua; Takayama, Toshio; Goel, Shakti A.; Shi, Xudong; Zhou, Yifan; Kent, K. Craig; Murphy, William L.; Guo, Lian-Wang

    2014-01-01

    Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50 days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90 days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel’s anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery. PMID:24852098

  7. A rapamycin-releasing perivascular polymeric sheath produces highly effective inhibition of intimal hyperplasia.

    PubMed

    Yu, Xiaohua; Takayama, Toshio; Goel, Shakti A; Shi, Xudong; Zhou, Yifan; Kent, K Craig; Murphy, William L; Guo, Lian-Wang

    2014-10-10

    Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel's anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

  8. Effect of clopidogrel on platelet aggregation and intimal hyperplasia following carotid endarterectomy in the rat.

    PubMed

    Bledsoe, Shelly L; Brown, Aliza T; Davis, Joseph A; Chen, Hongjiang; Eidt, John F; Moursi, Mohammed M

    2005-01-01

    Intimal hyperplasia results in significant morbidity and mortality following vascular intervention. Both platelets and elevated homocysteine have been implicated in the development of intimal hyperplasia. We previously demonstrated that a locally applied antiplatelet agent decreases the development of intimal hyperplasia. We were therefore interested in a systemic antiplatelet agent, clopidogrel. We hypothesized that clopidogrel would decrease platelet aggregation and activity and intimal hyperplasia. Male Sprague-Dawley rats underwent carotid endarterectomy (CEA) and treatment with either placebo or varying regimens of clopidogrel, including chronic, pre-CEA bolus, chronic plus pre-CEA bolus, and chronic plus post-CEA bolus; a homocystine diet was used to elevate both plasma homocysteine and the degree of intimal hyperplasia. Platelet aggregation, platelet activity, and intimal hyperplasia were then assessed. Platelet aggregation was not decreased with chronic clopidogrel; however, it was decreased with pre-CEA bolus clopidogrel. Similarly, platelet activity was not inhibited by chronic clopidogrel but was inhibited by pre-CEA and chronic plus pre-CEA bolus clopidogrel. Neither chronic, pre-CEA bolus, chronic plus pre-CEA bolus, nor chronic plus post-CEA bolus clopidogrel resulted in a decrease in intimal hyperplasia. Although pre-CEA bolus clopidogrel resulted in a decrease in both platelet aggregation and activity, it was unable to decrease the development of intimal hyperplasia at any dose. Additional factors must therefore contribute to the pathologic development of intimal hyperplasia.

  9. Prevention of intimal hyperplasia using short-period vascular heating without surrounding tissue injury: in vitro/in vivo experiments and thermal conduction calculation

    NASA Astrophysics Data System (ADS)

    Suga, Eriko; Kaneko, Kenji; Futami, Hikaru; Yamashita, Erika; Arai, Tsunenori

    2005-04-01

    We have been proposed novel short-term (<10s) heating balloon using the combination of light-heat conversion mechanism and heated contrast medium irrigation in the balloon to improve dilatation characteristics of balloon angioplasty. Our new balloon angioplasty had suppressed intimal hyperplasia in rabbit model. We designed following experiments to understand the mechanism of suppression of intimal hyperplasia in our new thermal balloon angioplasty. We also aimed to obtain the suitable heating condition in our angioplasty to suppress intimal hyperplasia. We studied influence of the short-term heating on smooth muscle cells (SMCs) lethality in vitro. We investigated number of SMCs reduction in media in order to prevent intimal hyperplasia. We applied to our heating balloon dilatation to chronic rabbit model using normal iliac artery to study relation between heating condition and hyperplasia suppression. We estimated temperature history of the rabbit vascular wall by thermal conduction calculation. We related the estimated temperature history to the hyperplasia suppression effect in the chronic rabbit model. Finally, we obtained the relation between number of SMCs decreases and intimal hyperplasia suppression. We obtained that the short-term heating with 10s laser irradiation corresponding to estimated temperature of 50°C in the media and prevented intimal hyperplasia in the rabbit chronic model. In this case, we estimated about 30 percents of SMCs cellular lethality in media.

  10. Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.

    PubMed

    Ohkawara, Nana; Ueda, Hiroki; Shinozaki, Shohei; Kitajima, Takashi; Ito, Yoshihiro; Asaoka, Hiroshi; Kawakami, Akio; Kaneko, Eiji; Shimokado, Kentaro

    2007-08-01

    Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half-life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery. The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed. The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF -treated rats. Neointimal formation was significantly more pronounced in the CBD-HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met). CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries.

  11. Cerebral Arteriovenous Malformation Flow Is Associated With Venous Intimal Hyperplasia.

    PubMed

    Shakur, Sophia F; Hussein, Ahmed E; Amin-Hanjani, Sepideh; Valyi-Nagy, Tibor; Charbel, Fady T; Alaraj, Ali

    2017-04-01

    The pathogenesis of venous intimal hyperplasia and venous outflow stenosis associated with cerebral arteriovenous malformation (AVM) draining veins is poorly understood. We sought to determine the relationship between maximum vein wall thickness and AVM flow. Patients who underwent AVM surgical resection and had flow measured before treatment using quantitative magnetic resonance angiography were retrospectively reviewed. Specimens were mounted on slides and stained with elastin special stain. Perinidal veins were identified, and maximum wall thickness was measured from digitized images. Relationship between maximum vein wall thickness and AVM flow was assessed. Twenty-eight patients were included. Spearman correlation revealed a statistically significant relationship between maximum vein wall thickness and total AVM flow (ρ=+0.51; P=0.006), AVM flow per draining vein (ρ=+0.41; P=0.03), and mean intranidal vessel diameter (ρ=+0.39; P=0.04). Maximum vein wall thickness increases with higher total AVM flow and AVM flow per draining vein. This finding implicates chronically high AVM inflow in venous intimal hyperplasia. © 2017 American Heart Association, Inc.

  12. Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia in aortocoronary saphenous vein grafts.

    PubMed

    Hata, Jonathan A; Petrofski, Jason A; Schroder, Jacob N; Williams, Matthew L; Timberlake, Sarah H; Pippen, Anne; Corwin, Michael T; Solan, Amy K; Jakoi, Andre; Gehrig, Thomas R; Kontos, Christopher D; Milano, Carmelo A

    2005-06-01

    Fifty percent of human aortocoronary saphenous vein grafts are occluded after 10 years. Intimal hyperplasia is an initial step in graft occlusion and consists of vascular smooth muscle cell proliferation. Phosphatidylinositol 3-kinase and its downstream regulator, the inositol 3-phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), are important regulators of vascular smooth muscle cell proliferation, migration, and cell death. This study tests whether overexpression of PTEN in aortocoronary saphenous vein grafts can reduce intimal hyperplasia. Adult dogs underwent aortocoronary bypass grafting to the left anterior descending artery by using the autologous saphenous vein. Saphenous vein grafts were treated with phosphate-buffered saline (n = 9), empty adenovirus (n = 8), or adenovirus encoding for PTEN (n = 8). Arteriography at 30 and 90 days assessed saphenous vein graft patency. A subset received saphenous vein grafts treated with a marker transgene (beta-galactosidase, n = 3), empty adenovirus (n = 4), or adenovirus encoding for PTEN (n = 4) and were killed on postoperative day 3 to confirm expression. Vascular smooth muscle cells were isolated from canine saphenous vein infected with adenovirus encoding for PTEN, and immunoblotting and proliferation assays were performed. Saphenous vein graft transgene expression was confirmed by means of immunohistochemistry, immunoblotting, and polymerase chain reaction. Arteriograms revealed all saphenous vein grafts to be patent. Saphenous vein grafts treated with adenovirus encoding for PTEN demonstrated reduced intimal area compared with those treated with empty adenovirus and phosphate-buffered saline (1.39 +/- 0.11 vs 2.35 +/- 0.3 and 2.57 +/- 0.4 mm 2 , P < .05), and the intima/media ratio was lower in saphenous vein grafts treated with adenovirus encoding for PTEN (0.50 +/- 0.05 vs 1.43 +/- 0.18 and 1.11 +/- 0.14, P < .005). PTEN overexpression in vascular smooth muscle cells inhibited platelet

  13. Oral mycophenolate mofetil prevents in-stent intimal hyperplasia without edge effect.

    PubMed

    Ilkay, Erdogan; Tirikli, Latif; Ozercan, Ibrahim; Yavuzkir, Mustafa; Karaca, Ilgin; Rahman, Ali; Arslan, Nadi

    2006-01-01

    Neointimal hyperplasia is in the forefront in in-stent restenosis. Prevention of in-stent restenosis is possible by reducing and inhibiting the hyperplasia of smooth muscle cells. The authors planned this study to test the hypothesis that when administered orally, mycophenolate mofetil (MMF) could inhibit in-stent neointimal hyperplasia. The study included 14 New Zealand rabbits. The rabbits were allocated to 2 different groups: Group 1 included 7 rabbits that were given MMF, 40 mg/kg/day by oral route. Group 2 included 7 rabbits that were not given MMF after the stenting. Sampling materials were taken before and after stenting by incising the artery so as to cover a 5-mm area. The samples taken from the edge of the stent in Group 1 showed focal neointimal cell proliferation, but it was less than that from the control group. Neointimal thickness was 0.048 +/-0.009 mm and neointimal area was 0.0925 +/-0.019 mm(2). Apparent neointimal cell proliferation and thickening of the intimal layer were observed in Group 2. Neointimal thickness at the stent edge was 0.147 +/-0.051 mm and the neointimal area was 0.154 +/-0.023 mm(2). The differences between groups in terms of neointimal thickness and neointimal area were statistically significant (p=0.001 for thickness and p=0.001 for area). In-stent artery samples of Group 1 showed that some subjects had no neointimal cell proliferation, while others had very limited focal intimal thickening. Neointimal thickening was 0.071 +/-0.003 mm and neointimal area was 0.073 +/-0.003 mm(2). In Group 2 apparent, and mostly focal, neointimal cell proliferation and formation of intimal layer were observed in the stent. Neointimal thickening was 0.154 +/-0.069 mm and neointimal area was 0.279 +/-0.059 mm(2). The comparison between groups showed significant differences (p=0.011 for thickness and p=0.001 for area). It was established in the third month that endothelialization was completed in both groups. Oral MMF decreased in-stent intimal

  14. Induction or prevention of intimal hyperplasia by photodynamic therapy in a porcine model

    NASA Astrophysics Data System (ADS)

    Sobeh, Mohammed S.; Greenwald, Stephen E.; Ham, Robert J.; Phypers, Barrie J.; Cross, Frank W.; Hsiang, York N.

    1995-05-01

    Photodynamic therapy (PDT) has been proposed as a treatment for intimal hyperplasia (IH). We studied the effect of PDT on the development of IH following endothelial injury, using the photosensitizer Metatetrahydroxyphenyl-chlorin (m-THPC) and 652 nm illumination. 9 mini- pigs were used in 3 groups of 3. Pigs in the first group (balloon alone; BA) were anaesthetized and the lower 4 cm of abdominal aorta was denuded using a balloon catheter through the right femoral artery. In the second group (light alone; LA) the procedure was repeated, followed by illumination of the denuded area at an energy density of 20 Jcm-2 using a transparent PDT catheter. In the third group pigs were sensitized and an intravenous injection of 0.3 mg/kg of m-THPC 4 hours prior to balloon injury and illumination (PDT Group). Animals were allowed to recover for 8 weeks before being killed and perfusion fixed with 10% formal saline. 5 sections were cut from the treated segments and stained for elastin. Specimens were measured by a computerized morphometry system and the areas of the lumen (L), intima (I) and media (M) were measured. The degree of intimal hyperplasia was expressed as (a) I/M; (b) I/(I+M) and (c) I/(I+L) to take account of changes that could have occurred to the media and the overall diameter of the vessel. We found that when compared to BA controls, the lumenal area was decreased by 46% in LA group and increased by 44% in PDT group. The changes in the medical areas were minimal. These results show that both light alone and PDT produced more intimal hyperplasia than balloon injury alone (P < 0.002 for both groups, Student's t test). When allowance is made for the large increase in lumenal area associated with PDT the degree of intimal hyperplasia I/(I+L) was significantly reduced in PDT treated vessels when compared to those treated with light and balloon alone in spite of the greater absolute area of the intima in the PDT group. We conclude that PDT under the above conditions

  15. Saratin (an inhibitor of platelet-collagen interaction) decreases platelet aggregation and homocysteine-mediated postcarotid endarterectomy intimal hyperplasia in a dose-dependent manner.

    PubMed

    Davis, Joseph A; Brown, Aliza T; Alshafie, Tarek; Poirier, Lionel A; Cruz, Carlos P; Wang, Yunfang; Eidt, John F; Moursi, Mohammed M

    2004-12-01

    This study investigated Saratin's (Merck KGaA, Darmstadt, Germany) prevention of platelet adhesion and intimal hyperplasia at different doses and in the hyperhomocystinemia rat carotid endarterectomy (CEA) model. Rats were divided into two groups: (1) platelet adhesion or (2) luminal stenosis because of intimal hyperplasia. At CEA, rats received 0, 0.5, 5.0, 10.0, or 20.0 microg Saratin on the artery. Post-CEA platelet aggregation was evaluated by standard error of the mean. Intimal hyperplasia group received either (1) control or (2) 4.5 g/kg DL-homocystine diets for two weeks followed by CEA and treated with diluent or 5.0 microg Saratin. Endpoints included platelet adhesion, intimal hyperplasia, plasma homocysteine (HCys), and its metabolic enzymes cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR). Platelet adhesion: post-CEA, platelet adhesion was reduced by 63%, 67%, and 67% in Saratin doses > or =5.0 microg. Intimal hyperplasia: 5.0 microg Saratin in the HCys group decreased intimal hyperplasia by 45% compared with the non-Saratin-treated HCys group. Plasma HCys levels were not altered with Saratin treatment in the HCys groups nor were CBS or MTHFR. Saratin significantly inhibited platelet adhesion at > or =5.0 microg, and Saratin at 5.0 microg attenuated luminal stenosis in a hyperhomocysteinemic rat CEA model.

  16. Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft.

    PubMed

    Kodama, Akio; Itoh, Takeo; Komori, Kimihiro

    2014-02-01

    For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency.

  17. Pulmonary artery intimal sarcoma: case report.

    PubMed

    Hou, Yulong; Shen, Zhenya; Gao, Wei; Ye, Wenxue

    2010-01-01

    A 72-year-old woman with pulmonary artery intimal sarcoma was successfully treated with surgery. With heightened clinical awareness and technological advancement, more and more cases were diagnosed definitely before operation. Computed tomography of the chest showed a mass in right ventricular extending to pulmonary trunk and the left pulmonary artery. The patient underwent complete surgical resection and repair of the pulmonary artery with no evidence of recurrence during the 12-month follow-up, suggesting that early identification and aggressive surgical intervention would improve survival.

  18. Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia.

    PubMed

    Osgood, Michael J; Sexton, Kevin; Voskresensky, Igor; Hocking, Kyle; Song, Jun; Komalavilas, Padmini; Brophy, Colleen; Cheung-Flynn, Joyce

    2016-08-01

    Intimal hyperplasia remains the primary cause of vein graft failure for the 1 million yearly bypass procedures performed using human saphenous vein (HSV) grafts. This response to injury is caused in part by the harvest and preparation of the conduit. The use of Brilliant Blue FCF (FCF) restores injury-induced loss of function in vascular tissues possibly via inhibition of purinergic receptor signaling. This study investigated whether pretreatment of the vein graft with FCF prevents intimal hyperplasia. Cultured rat aortic smooth muscle cells (A7r5) were used to determine the effect of FCF on platelet-derived growth factor-mediated migration and proliferation, cellular processes that contribute to intimal hyperplasia. The effectiveness of FCF treatment during the time of explantation on preventing intimal hyperplasia was evaluated in a rabbit jugular-carotid interposition model and in an organ culture model using HSV. FCF inhibited platelet-derived growth factor-induced migration and proliferation of A7r5 cells. Treatment with FCF at the time of vein graft explantation inhibited the subsequent development of intimal thickening in the rabbit model. Pretreatment with FCF also prevented intimal thickening of HSV in organ culture. Incorporation of FCF as a component of vein graft preparation at the time of explantation represents a potential therapeutic approach to mitigate intimal hyperplasia, reduce vein graft failure, and improve outcome of the autologous transplantation of HSV. Copyright © 2016. Published by Elsevier Inc.

  19. Use of Brilliant Blue FCF during vein graft preparation inhibits intimal hyperplasia

    PubMed Central

    Osgood, Michael J.; Sexton, Kevin; Voskresensky, Igor; Hocking, Kyle; Song, Jun; Komalavilas, Padmini; Brophy, Colleen; Cheung-Flynn, Joyce

    2017-01-01

    Background Intimal hyperplasia remains the primary cause of vein graft failure for the 1 million yearly bypass procedures performed using human saphenous vein (HSV) grafts. This response to injury is caused in part by the harvest and preparation of the conduit. The use of Brilliant Blue FCF (FCF) restores injury-induced loss of function in vascular tissues possibly via inhibition of purinergic receptor signaling. This study investigated whether pretreatment of the vein graft with FCF prevents intimal hyperplasia. Methods Cultured rat aortic smooth muscle cells (A7r5) were used to determine the effect of FCF on platelet-derived growth factor-mediated migration and proliferation, cellular processes that contribute to intimal hyperplasia. The effectiveness of FCF treatment during the time of explantation on preventing intimal hyperplasia was evaluated in a rabbit jugular-carotid interposition model and in an organ culture model using HSV. Results FCF inhibited platelet-derived growth factor-induced migration and proliferation of A7r5 cells. Treatment with FCF at the time of vein graft explantation inhibited the subsequent development of intimal thickening in the rabbit model. Pretreatment with FCF also prevented intimal thickening of HSV in organ culture. Conclusions Incorporation of FCF as a component of vein graft preparation at the time of explantation represents a potential therapeutic approach to mitigate intimal hyperplasia, reduce vein graft failure, and improve outcome of the autologous transplantation of HSV. PMID:27763268

  20. An arteriovenous fistula model of intimal hyperplasia for evaluation of a nitinol U-Clip anastomosis.

    PubMed

    Varcoe, R L; Teo, A B P; Pelletier, M H; Yu, Y; Yang, J-L; Crowe, P J; Walsh, W R

    2012-02-01

    The aim of this study was to create an ovine arteriovenous fistula (AVF) model which would closely replicate a human forearm fistula and use this to quantify the degree of intimal hyperplasia in those created with the U-Clip compared to a conventional sutured anastomosis. Twenty AVFs were created in 10 Border Leicester-Merino sheep between the superficial femoral artery and vein of each hind limb. On one side the U-Clip and on the other a continuous polypropylene suture was used to perform the anastomosis. The animals were sacrificed at 2 (n = 3), 4 (n = 4), 6 (n = 3) weeks and histological slices were taken of each AVF in cross section to determine the intimal media area per unit length (IMA/L). Intimal hyperplasia (IH) was observed at all time points with one AVF found occluded with thrombus at the time of harvest. The IMA/L was significantly lower in the U-Clip groups by 24% at 2 weeks, 32% at 4 weeks and 23% at 6 weeks (Two-way ANOVA, p = 0.019, observed power = 0.825, time or side p ≥ 0.766, type p = 0.001; Paired t-test, p < 0.001 between matched anastomotic types). Time taken to perform the anastomosis was similar between the two anastomotic techniques (Polypropylene 14(8-18) vs. U-Clip 15.3(11-23) min; p = 0.47). This ovine AVF model results in IH similar to that seen in a human AVF. The IH that occurs with the U-Clip is less than that of continuous polypropylene suture. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  1. Photochemotherapy of intimal hyperplasia using psoralen activated by uv light in porcine model

    NASA Astrophysics Data System (ADS)

    Buckley, Lisa A.; Gregory, Kenton W.; Bahlman, Deborah T.; Shangguan, HanQun; Fahrenbach, Henner; Rosenthal, Eli; Block, Peter C.

    1996-05-01

    Psoralen activated by UVA light (PUVA) was investigated as a means of inhibiting smooth muscle cell proliferation resulting from balloon injury. Twenty kilogram domestic swine were anesthetized and underwent balloon angioplasty to create a 133% overstretch injury. Assignments of treatment and control were randomized between the left anterior descending (LAD) and circumflex (LCX) coronaries arteries. The animals were given with 5 mg/kg of 8- methoxypsoralen eternally. Treatment vessels received 600 mJ/cm2 of 364 nm light during balloon inflation to activate the psoralen. Control vessels received drug and balloon injury only. Serum was obtained during the light delivery to assess psoralen levels. At 30 days, animals were sacrificed and the coronary arteries perfusion fixed. Five sections per vessel were analyzed morphometrically to determine percent intimal area and extent of injury. The restenosis injury index was 0.21 plus or minus .02 in treatment vessels and 0.14 plus or minus .01 in the controls with a p-value less than .02. In this large animal model of balloon angioplasty injury, psoralen activated by ultraviolet light increased intimal hyperplasia.

  2. Intimal hyperplasia in rats after subcutaneous injection of a somatostatin analog.

    PubMed

    Wells, Monique Y; Voute, Hélène; Lonchampt, Marie-Odile; Fisch, Cécile; Boulifard, Virginie; Picaut, Philippe

    2009-02-01

    The somatostatin analog octreotide was administered to male and female Sprague-Dawley rats by subcutaneous injection for thirteen weeks at 0 (saline control), 0 (placebo control [mannitol and lactic acid; pH 4.2]), 1.25 mg/kg/day and 2.5 mg/kg/day to explore its potential effect on cutaneous vascular morphology. The placebo caused an increase in the incidence of intimal hyperplasia compared to saline controls in female rats; octreotide increased the incidence and severity of intimal hyperplasia in males and females. Intimal hyperplasia consisted of increased numbers of cells located between the endothelial cell layer and the internal elastic lamina. Severity was based on the degree of compromise of the vascular lumen (regardless of vessel size and number), with severely affected vessels having no visible lumen. Intimal hyperplasia in rats treated with octreotide was considered to be an unexpected and adverse finding, given that this compound and other somatostatin analogs have been investigated as reducers of intimal proliferation or restenosis after angioplasty in humans and that no such lesion has been reported in the literature for this class of compound to date. The induction of intimal hyperplasia by the placebo is also a notable finding; this may be because of the low pH of the formulation.

  3. Inhibition of vein graft intimal hyperplasia by periadventitial application of hyaluronic acid-carboxymethyl cellulose: an experimental study.

    PubMed

    Bahcivan, Muzaffer; Yucel, Semih; Kefeli, Mehmet; Gol, M Kamil; Can, Bilge; Keceligil, Hasan Tahsin

    2008-04-01

    Placement of an external support has been reported to prevent intimal hyperplasia of vein grafts. In this study, we investigated the effect of HA/CMC on intimal hyperplasia in a rabbit model. Right jugular vein to common carotid artery bypass grafting was performed in 24 female New Zealand white rabbits (2.5-3.0 kg). Animals were divided into two groups: control group (n=12) and HA/CMC group (n=12). Absorbable membrane barrier was wrapped around vein grafts in HA/CMC group. In control group, no material was applied following venous graft bypass. At 1 month, in the vein grafts supported with the HA/CMC membrane neointimal thickening was significantly less (109 microm [IQR, 78-166]) compared to the unsupported control grafts (220 microm [IQR; 101-312]; p<0.001). Medial thickening in the HA/CMC group (128 microm [IQR, 101-181]) compared to unsheathed control grafts (182 microm [IQR, 131-255] p<0.001) was also significantly less. Periadventitial placement of HA/CMC as an absorbable membrane inhibits intimal hyperplasia of vein bypass grafts in a rabbit model.

  4. Muscle-derived stem cells promote angiogenesis and attenuate intimal hyperplasia in different murine vascular disease models.

    PubMed

    Park, Hyung Sub; Hahn, Soli; Choi, Geum Hee; Yoo, Young Sun; Lee, Ji Youl; Lee, Taeseung

    2013-03-15

    Muscle-derived stem cells (MDSCs) are known to promote angiogenesis, but have never been studied in vascular diseases. We differentiated MDSCs into endothelial lineage cells in vitro by stimulation with shear stress and vascular endothelial growth factor. Such differentiated MDSCs (diff-MDSC) showed strong angiogenic potential in vitro. When tested in ischemic hindlimbs of mice, diff-MDSCs increased perfusion and decreased necrosis of the ischemic limbs, by promoting new vessel formation and by upregulating genes involved in endothelial expression. Such effects were not observed with native MDSCs (without endothelial stimulation in vitro). Diff-MDSCs were also injected into carotid arteries of rats after balloon denudation of the intima layer to induce intimal hyperplasia. The cell-treated group had significantly reduced intima-to-media thickness ratio compared to control, thus attenuating intimal hyperplasia by early re-endothelialization of the intima layer. Our findings suggest that MDSCs are a potential source of stem cell therapy for treatment of various vascular diseases, by inducing angiogenesis to improve perfusion in sites of ischemia, and by preventing intimal hyperplasia in sites of vessel injury.

  5. Nanoparticle-Mediated Local Delivery of an Antisense TGF-β1 Construct Inhibits Intimal Hyperplasia in Autogenous Vein Grafts in Rats

    PubMed Central

    Sun, Da-Xin; Liu, Zhen; Tan, Xiao-Dong; Cui, Dong-Xu; Wang, Bao-Sheng; Dai, Xian-Wei

    2012-01-01

    Background Intimal hyperplasia is one of the most important causes of vascular graft failure. Numerous studies have correlated transforming growth factor-β1 (TGF-β1) with extracellular matrix (ECM) deposition, a hallmark of intimal thickening. Principal Findings In the present study, we performed immunohistochemistry, RT-PCR, and Western blot to examine the dynamic expression of TGF-β1, TGF-β1 receptor type I (TGF-β RI), matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) during intimal hyperplasia in grafted veins of a rat model generated by grafting a portion of the right internal jugular vein to the ipisiliary caroid artery. Additionally, we determined whether nanoparticle-mediated delivery of a TGF-β1 antisense-expressing construct prevented TGF-β1 expression and intimal hyperplasia in grafted veins. In grafted veins, the expression of TGF-β1 significantly increased on day 3 after transplantation, peaked on day 7, slightly decreased on day 14, and returned to baseline levels on day 28. The positive expression of TGF-β RI in grafted veins remarkably increased on day 7, peaked on day 14, and decreased thereafter. MMP-1 expression decreased significantly, while TIMP-1 expression increased, significantly on days 14 and 28. Nanoparticle-mediated delivery of a TGF-β1 antisense-expressing construct down-regulated TGF-β1 expression and inhibited intimal hyperplasia in grafted veins. Conclusions Our findings provide further evidence that TGF-β1 plays an integral role in the development of intimal hyperplasia after vascular injury. Nanoparticle-mediated delivery of a TGF-β1 antisense-expressing construct is a feasible strategy to target TGF-β1-induced intimal thickening. PMID:22860019

  6. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes.

    PubMed

    Qi, Weier; Li, Qian; Liew, Chong Wee; Rask-Madsen, Christian; Lockhart, Samuel M; Rasmussen, Lars Melholt; Xia, Yu; Wang, Xuanchun; Khamaisi, Mogher; Croce, Kevin; King, George L

    2017-03-01

    Accelerated migration and proliferation of vascular smooth muscle cells (VSMCs) enhances arterial restenosis after angioplasty in insulin resistance and diabetes. Elevation of Src homology 2-containing protein tyrosine phosphatase 1 (SHP-1) induces apoptosis in the microvasculature. However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1 expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known as Map2k1) and increased DNA methylation of the Shp-1 promoter. VSMCs from Shp-1-Tg mice exhibited impaired platelet-derived growth factor (PDGF)-stimulated tyrosine phosphorylation with a concomitant decrease in PDGF-stimulated VSMC proliferation and migration. Similarly, HFD-fed Shp-1-Tg mice and mice treated with the SHP-1 inducer, Icariside II, were protected from the development of intimal hyperplasia following wire injury. Suppression of SHP-1 by oxidised lipids may contribute to the excessive VSMC proliferation, inflammatory cytokine production and intimal hyperplasia observed in arteries from diabetes and insulin resistance. Augmenting SHP-1 levels is a potential therapeutic strategy to maintain stent patency in patients with insulin resistance and diabetes.

  7. Intimal sarcoma of the pulmonary artery--diagnostic challenge.

    PubMed

    Fukuda, Wakako; Morohashi, Satoko; Fukuda, Ikuo

    2011-08-01

    Pulmonary artery intimal sarcoma is a rare tumour and the diagnosis is often delayed. We report the case of a woman with a primary pulmonary artery intimal sarcoma who presented with massive pulmonary embolism. The definitive diagnosis was elucidated after the patient's death by autopsy specimen. We discuss the diagnosis and lessons learned from this case.

  8. Preoperative Venous Intimal Hyperplasia, Postoperative Arteriovenous Fistula Stenosis, and Clinical Fistula Outcomes

    PubMed Central

    Robbin, Michelle L.; Young, Carlton J.; Deierhoi, Mark H.; Goodman, Jeremy; Hanaway, Michael; Lockhart, Mark E.; Litovsky, Silvio

    2013-01-01

    Summary Background and objectives Arteriovenous fistulas often fail to mature, and nonmaturation has been attributed to postoperative stenosis caused by aggressive neointimal hyperplasia. Preexisting intimal hyperplasia in the native veins of uremic patients may predispose to postoperative arteriovenous fistula stenosis and arteriovenous fistula nonmaturation. Design, setting, participants, & measurements This work explored the relationship between preexisting venous intimal hyperplasia, postoperative arteriovenous fistula stenosis, and clinical arteriovenous fistula outcomes in 145 patients. Venous specimens obtained during arteriovenous fistula creation were quantified for maximal intimal thickness (median thickness=22.3 μm). Postoperative ultrasounds at 4–6 weeks were evaluated for arteriovenous fistula stenosis. Arteriovenous fistula maturation within 6 months of creation was determined clinically. Results Postoperative arteriovenous fistula stenosis was equally frequent in patients with preexisting venous intimal hyperplasia (thickness>22.3 μm) and patients without hyperplasia (46% versus 53%; P=0.49). Arteriovenous fistula nonmaturation occurred in 30% of patients with postoperative stenosis versus 7% of those patients without stenosis (hazard ratio, 4.33; 95% confidence interval, 1.55 to 12.06; P=0.001). The annual frequency of interventions to maintain arteriovenous fistula patency for dialysis after maturation was higher in patients with postoperative stenosis than patients without stenosis (0.83 [95% confidence interval, 0.58 to 1.14] versus 0.42 [95% confidence interval, 0.28 to 0.62]; P=0.008). Conclusions Preexisting venous intimal hyperplasia does not predispose to postoperative arteriovenous fistula stenosis. Postoperative arteriovenous fistula stenosis is associated with a higher arteriovenous fistula nonmaturation rate. Arteriovenous fistulas with hemodynamically significant stenosis frequently mature without an intervention. Postoperative

  9. Exovascular application of epigallocatechin-3-O-gallate-releasing electrospun poly(L-lactide glycolic acid) fiber sheets to reduce intimal hyperplasia in injured abdominal aorta.

    PubMed

    Lee, Mi Hee; Kwon, Byeong-ju; Koo, Min-Ah; Jang, Eui Hwa; Seon, Gyeung Mi; Park, Jong-Chul

    2015-09-21

    Intimal hyperplasia is an excessive ingrowth of tissue resulting in chronic structural lesions commonly found at sites of atherosclerotic lesions, arterial angioplasty, vascular graft anastomoses, and other vascular abnormalities. Epigallocatechin-3-O-gallate (EGCG) was shown to elicit antioxidant, anti-proliferative, and anti-thrombogenic effects. In this study, we used an electrospinning technique to synthesize EGCG-eluting biodegradable poly(L-lactide glycolic acid) (PLGA) fiber sheets for local delivery of EGCG and investigated the effect of their exovascular application on intimal hyperplasia following balloon-induced abdominal aorta injury in a rabbit experimental model. The morphology of the composite sheets was characterized using scanning electron microscopy and Fourier transform-infrared spectroscopy. EGCG was loaded and dispersed into the PLGA-based electrospun fibers. The EGCG-loaded PLGA sheets exhibited sustained EGCG release following the initial 24 h of burst release in phosphate-buffered saline. In vivo studies demonstrated significant inhibition of intimal hyperplasia following the application of the EGCG-eluting electrospun PLGA fiber sheets, compared with vehicle PLGA controls. In conclusion, our results show that exovascular application of EGCG-eluting PLGA electrospun fiber sheets may provide a useful system for the effective local delivery of drugs for the prevention of intimal hyperplasia.

  10. Neointimal hyperplasia and calcification in medium sized arteries in adult patients with chronic kidney disease.

    PubMed

    Chitalia, Nihil; Ross, Louise; Krishnamoorthy, Mahesh; Kapustin, Alexander; Shanahan, Catherine M; Kaski, Juan Carlos; Roy-Chaudhury, Prabir; Chemla, Eric; Banerjee, Debasish

    2015-01-01

    The nature of arterial changes resulting in cardiovascular events and dialysis vascular access failures in adult predialysis patients is not well known. This study examined intimal changes, calcium deposition, and consequent stiffness in brachial and radial arteries of adult CKD patients. Ten brachial-artery and seven radial-artery specimens were obtained during fistula creation from nine predialysis and eight dialysis-dependent, nondiabetic patients; and age-gender matched controls undergoing coronary bypass grafts (6 radial) or kidney donation (6 renal). Arterial stiffness was measured at baseline. Vessel histology, morphometric analysis of intima-media, and direct quantification of calcium load was performed using standard techniques. Both predialysis and dialysis patients demonstrated significant arterial intimal hyperplasia with intima:media ratio higher than controls (0.13 ± 0.12 vs. 0.02 ± 0.05, p = 0.01). Calcium deposition was demonstrated on histology and the calcium content in patients was higher than controls (34.68 ± 26.86 vs. 10.95 ± 9.18 μg/μg, p = 0.003). The blood vessel calcium content correlated with arterial stiffness (r = 0.64, p = 0.018). This study for the first time describes, and suggests mechanistic linkage between, intimal hyperplasia, pathological calcium deposition, and increased functional arterial stiffness in dialysis and predialysis patients. Our research could serve as a unique window into the in vivo status of the uremic vasculature impacting fistula maturation and cardiovascular disease.

  11. Modulating vascular intimal hyperplasia using HSV-1 mutant requires activated MEK.

    PubMed

    Skelly, C L; He, Q; Spiguel, L; McCormick, S; Weichselbaum, R

    2013-02-01

    Outcomes of cardiovascular procedures, such as angioplasty and stent or bypass grafting are limited by failure, predominantly caused by pathological smooth muscle cell (SMC) proliferation, known as intimal hyperplasia. Local delivery of a genetically engineered herpes simplex virus (HSV) is known to block vascular SMC proliferation while allowing for re-endothelialization. However, the mechanism this mutant virus uses to prevent SMC hyperplasia is unknown. The Ras signaling cascade is activated in SMCs undergoing hyperplasia leading to phosphorylation of the mitogen-activated protein kinase (MAPK). In this study we tested the hypothesis that MAPK kinase (MEK) activity is the molecular basis by which SMCs are susceptible to mutant HSV. We show that genetically engineered herpes simplex-1 viruses (HSV-1) can target proliferating SMCs. We demonstrate that the molecular basis of this HSV-1 anti-proliferative effect is MEK activation in SMCs. We demonstrate efficacy and practicality of the MEK-dependent HSV-1 for the treatment of intimal hyperplasia in a clinically relevant in vivo model. Important to this strategy is the ability to modulate the effects by controlling viral dose. These results propel genetically engineered HSV-1 therapy towards clinical evaluation in treatment of intimal hyperplasia.

  12. Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries

    PubMed Central

    Shimizu, Takuya; De Wispelaere, Allison; Winkler, Martin; D’Souza, Travis; Caylor, Jacob; Chen, Lihua; Dastvan, Frank; Deou, Jessie; Cho, Aesim; Larena-Avellaneda, Axel; Reidy, Michael; Daum, Guenter

    2012-01-01

    Objective The objective of this study is to define a role for S1PR3 in intimal hyperplasia. Methods and Results A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 is higher in these arteries when compared to carotid arteries. At 28 days after surgery, wild-type arteries form significantly larger lesions than S1PR3-null arteries. BrdU labeling experiments demonstrate that upon injury, wild-type arteries exhibit higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro is low, we expressed S1PR3 in S1PR3-null SMCs using retroviral-mediated gene transfer to study S1PR3 effects on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, respond to S1P stimulation with activation of Rac, Erk and Akt. SMCs expressing S1PR3 also grow migrate more. Conclusion In humans and mice, S1PR3 expression is higher in iliac-femoral arteries compared to carotid arteries. S1PR3 promotes neointimal hyperplasia upon denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt and Rac. PMID:22308044

  13. Inhibition of intimal hyperplasia after stenting by over-expression of p15: a member of the INK4 family of cyclin-dependent kinase inhibitors.

    PubMed

    Segev, Amit; Nili, Nafiseh; Qiang, Beiping; Osherov, Azriel B; Giordano, Frank J; Jaffe, Ronen; Gauldie, Jack; Sparkes, John D; Fraser, Ashley R; Ladouceur-Wodzak, Michelle; Butany, Jagdish; Strauss, Bradley H

    2011-03-01

    We evaluated the role of p15(Ink4), a member of the INK4 family of CDK inhibitors on vascular smooth muscle cells (VSMCs) proliferation, cell cycle progression and intimal hyperplasia after stenting. Aortic VSMCs transduced with either adenovirus encoding for p15(Ink4) or β-galactosidase were assessed for DNA synthesis, cell cycle progression, and pRb phosphorylation. Rabbit carotid arteries were stented and treated with peri-adventitial delivery of saline or adenovirus encoding for p15(Ink4) or β-galactosidase. p15(Ink4) transgene and protein expression were evaluated at 24 h and 72 h, respectively. In-stent cell proliferation was evaluated by BrdU at day 7. Histomorphometric analysis of in-stent intimal hyperplasia was performed at 10 weeks. Human p15(Ink4) DNA was detected in transduced VSMCs at 24h. p15(Ink4) over-expression reduced VSMCs DNA synthesis by 60%. Cell cycle progression was inhibited, with a 30% increase in G1 population accompanied by inhibition of pRb phosphorylation. Human p15(Ink4) transgene was identified in transduced stented arteries but not in control arteries. p15(Ink4) immunostaining was increased and cell proliferation significantly reduced by 50% in p15(Ink4) transduced arteries. Intimal cross-sectional area (CSA) of p15(Ink4)-treated group was significantly lower than the β-gal treated and non-transduced groups (p=0.008). There were no differences in the intimal or medial inflammatory response between groups. p15(Ink4) over-expression blocks cell cycle progression leading to inhibition of VSMCs proliferation. Peri-adventitial delivery of p15(Ink4) significantly inhibits in-stent intimal hyperplasia.

  14. Intimal sarcoma of the superficial femoral artery with osteosarcomatous differentiation.

    PubMed

    Ebaugh, James L; Yuan, Minsheng; Hu, Jeffery; Chen, Ahchean; Raffetto, Joseph D

    2011-05-01

    Sarcomas of the large vessels usually present centrally in the aorta, pulmonary artery, and inferior vena cava. Peripheral arterial sarcomas are exceptionally rare. They have been reported in the iliac and common or profunda femoral arteries, and are frequently undifferentiated. In this study, we describe a differentiated intimal sarcoma of the superficial femoral artery with abundant osteosarcoma within the specimen. Before knowing the diagnosis, treatment was for a presumed pseudoaneurysm using excision and bypass. Postoperatively, the patient received palliative radiation therapy. The tumor's location and histopathology are unique. A differentiated intimal sarcoma has never been reported in the superficial femoral artery, and it represents the second peripheral arterial intimal sarcoma reported with osteosarcomatous differentiation.

  15. Roles of oral bacteria in cardiovascular diseases--from molecular mechanisms to clinical cases: Porphyromonas gingivalis is the important role of intimal hyperplasia in the aorta.

    PubMed

    Hokamura, Kazuya; Umemura, Kazuo

    2010-01-01

    It has been reported that DNA of oral bacterial species, such as Porphyromonas gingivalis and Streptococcus mutans, was detected frequently in specimens of arteriosclerotic vessels. However, the source of DNA, whether from live intact bacteria or a part of the bacteria, has not been identified yet. Moreover, there was no precise evidence concerning involvement of oral bacteria in the progression of arteriosclerosis. We tried to clarify the involvement of P. gingivalis on the mechanisms of development of aortic intimal hyperplasia. Intravenous administration of P. gingivalis dramatically induced intimal hyperplasia in the mouse model with photochemical impairment of the femoral artery. However there were no changes identified in the mice without aortic impairment, even with the P. gingivalis infection. Concomitantly, S100 calcium-binding protein A9 (S100A9) and the embryonic isoform of myosin heavy chain (SMemb), a proliferative phenotypic marker of smooth muscle cells, were significantly overexpressed on the surfaces of smooth muscle cells present in the injured blood vessels. Similarly, increased expressions of S100A9 and SMemb proteins were observed in aneurismal specimens obtained from P. gingivalis-infected patients. We found that bacteremia induced by P. gingivalis leads to intimal hyperplasia associated with overexpressions of S100A9 and SMemb. Our results strongly suggest that oral-hematogenous spreading of P. gingivalis is a causative event in the development of aortic hyperplasia in periodontitis patients.

  16. Intimal Sarcoma of the Pulmonary Artery Treated with Pazopanib.

    PubMed

    Funatsu, Yohei; Hirayama, Miwa; Shiraishi, Junichi; Asakura, Takanori; Wakaki, Misa; Yamada, Erina; Fujimoto, Kazuyuki; Satomi, Ryosuke; Inaki, Shunsuke; Murata, Yuya; Oyamada, Yoshitaka

    2016-01-01

    Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.

  17. Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population.

    PubMed

    Weissman, N J; Wilensky, R L; Tanguay, J F; Bartorelli, A L; Moses, J; Williams, D O; Bailey, S; Martin, J L; Canos, M R; Rudra, H; Popma, J J; Leon, M B; Kaplan, A V; Mintz, G S

    2001-08-01

    Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 +/- 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 +/- 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 +/- 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.

  18. MK2 inhibitory peptide delivered in nanopolyplexes prevents vascular graft intimal hyperplasia

    PubMed Central

    Evans, Brian C.; Hocking, Kyle M.; Osgood, Michael J.; Voskresensky, Igor; Dmowska, Julia; Kilchrist, Kameron V.; Brophy, Colleen M.; Duvall, Craig L.

    2017-01-01

    Autologous vein grafts are commonly used for coronary and peripheral artery bypass but have a high incidence of intimal hyperplasia (IH) and failure. We present a nanopolyplex (NP) approach that efficiently delivers a mitogen-activated protein kinase (MAPK)–activated protein (MAPKAP) kinase 2 inhibitory peptide (MK2i) to graft tissue to improve long-term patency by inhibiting pathways that initiate IH. In vitro testing in human vascular smooth muscle cells revealed that formulation into MK2i-NPs increased cell internalization, endosomal escape, and intracellular half-life of MK2i. This efficient delivery mechanism enabled MK2i-NPs to sustain potent inhibition of inflammatory cytokine production and migration in vascular cells. In intact human saphenous vein, MK2i-NPs blocked inflammatory and migratory signaling, as confirmed by reduced phosphorylation of the posttranscriptional gene regulator heterogeneous nuclear ribonucleoprotein A0, the transcription factor cAMP (adenosine 3′,5′-monophosphate) element–binding protein, and the chaperone heat shock protein 27. The molecular effects of MK2i-NPs caused functional inhibition of IH in human saphenous vein cultured ex vivo. In a rabbit vein transplant model, a 30-min intraoperative graft treatment with MK2i-NPs significantly reduced in vivo IH 28 days posttransplant compared with untreated or free MK2i–treated grafts. The decrease in IH in MK2i-NP–treated grafts in the rabbit model also corresponded with decreased cellular proliferation and maintenance of the vascular wall smooth muscle cells in a more contractile phenotype. These data indicate that nanoformulated MK2 inhibitors are a promising strategy for preventing graft failure. PMID:26062847

  19. Surgical vein graft preparation promotes cellular dysfunction, oxidative stress, and intimal hyperplasia in human saphenous vein

    PubMed Central

    Osgood, Michael J.; Hocking, Kyle M.; Voskresensky, Igor V.; Li, Fan Dong; Komalavilas, Padmini; Cheung-Flynn, Joyce; Brophy, Colleen M.

    2014-01-01

    Introduction Human saphenous vein (HSV) is the most widely used bypass conduit for peripheral and coronary vascular reconstructions. However, outcomes are limited by a high rate of intimal hyperplasia (IH). HSV undergoes a series of ex vivo surgical manipulations prior to implantation, including hydrostatic distension, marking, and warm ischemia in solution. We investigated the impact of surgical preparation on HSV cellular function and development of IH in organ culture. We hypothesized that oxidative stress is a mediator of HSV dysfunction. Methods HSV was collected from patients undergoing vascular bypass before and after surgical preparation. Smooth muscle and endothelial function were measured using a muscle bath. Endothelial preservation was assessed with immunohistochemical staining. An organ culture model was used to investigate the influence of surgical preparation injury on the development of IH. Superoxide levels were measured using a high-performance liquid chromatography-based assay. The influence of oxidative stress on HSV physiologic responses was investigated by exposing HSV to hydrogen peroxide (H2O2). Results Surgical vein graft preparation resulted in smooth muscle and endothelial dysfunction, endothelial denudation, diminished endothelial nitric oxide synthase staining, development of increased IH, and increased levels of reactive oxygen species. Experimental induction of oxidative stress in unmanipulated HSV by treatment with H2O2 promoted endothelial dysfunction. Duration of storage time in solution did not contribute to smooth muscle or endothelial dysfunction. Conclusions Surgical vein graft preparation causes dysfunction of the smooth muscle and endothelium, endothelial denudation, reduced endothelial nitric oxide synthase expression, and promotes IH in organ culture. Moreover, increased levels of reactive oxygen species are produced and may promote further vein graft dysfunction. These results argue for less injurious means of preparing

  20. Surgical vein graft preparation promotes cellular dysfunction, oxidative stress, and intimal hyperplasia in human saphenous vein.

    PubMed

    Osgood, Michael J; Hocking, Kyle M; Voskresensky, Igor V; Li, Fan Dong; Komalavilas, Padmini; Cheung-Flynn, Joyce; Brophy, Colleen M

    2014-07-01

    Human saphenous vein (HSV) is the most widely used bypass conduit for peripheral and coronary vascular reconstructions. However, outcomes are limited by a high rate of intimal hyperplasia (IH). HSV undergoes a series of ex vivo surgical manipulations prior to implantation, including hydrostatic distension, marking, and warm ischemia in solution. We investigated the impact of surgical preparation on HSV cellular function and development of IH in organ culture. We hypothesized that oxidative stress is a mediator of HSV dysfunction. HSV was collected from patients undergoing vascular bypass before and after surgical preparation. Smooth muscle and endothelial function were measured using a muscle bath. Endothelial preservation was assessed with immunohistochemical staining. An organ culture model was used to investigate the influence of surgical preparation injury on the development of IH. Superoxide levels were measured using a high-performance liquid chromatography-based assay. The influence of oxidative stress on HSV physiologic responses was investigated by exposing HSV to hydrogen peroxide (H2O2). Surgical vein graft preparation resulted in smooth muscle and endothelial dysfunction, endothelial denudation, diminished endothelial nitric oxide synthase staining, development of increased IH, and increased levels of reactive oxygen species. Experimental induction of oxidative stress in unmanipulated HSV by treatment with H2O2 promoted endothelial dysfunction. Duration of storage time in solution did not contribute to smooth muscle or endothelial dysfunction. Surgical vein graft preparation causes dysfunction of the smooth muscle and endothelium, endothelial denudation, reduced endothelial nitric oxide synthase expression, and promotes IH in organ culture. Moreover, increased levels of reactive oxygen species are produced and may promote further vein graft dysfunction. These results argue for less injurious means of preparing HSV prior to autologous transplantation

  1. Fluvastatin inhibits intimal hyperplasia in wild-type but not Thbs1-null mice.

    PubMed

    Desai, Pratik; Helkin, Alex; Odugbesi, Adeola; Stein, Jeff; Bruch, David; Lawler, Jack; Maier, Kristopher G; Gahtan, Vivian

    2017-04-01

    Thrombospondin-1 (TSP-1) is functionally important to intimal hyperplasia (IH) development. Statin drugs have beneficial pleiotropic effects, including reduced IH; however, the effect of statins on IH in a TSP-1-independent setting is unknown. Statins will be less effective in attenuating IH after vascular injury in TSP-1-null (Thbs1(-/-)) mice compared with wild-type (WT) mice. Carotid artery ligation was performed on WT and Thbs1(-/-) mice. Each strain was divided into two groups: no statin control or standard chow containing fluvastatin (10 or 40 mg/kg/d). After 28 d, analysis included morphometric analysis and real-time quantitative reverse transcription polymerase chain reaction on the arteries and enzyme-linked immunosorbent assay on plasma (TSP-1 WT, TSP-2 WT, and Thbs1(-/-)). Comparisons were made by analysis of variance, with P < 0.05 considered significant. In no statin controls, WT mice had more IH than Thbs1(-/-) mice (0.46 ± 0.09 versus 0.15 ± 0.04). Fluvastatin reduced IH in the WT (0.46 ± 0.09 versus 0.23 ± 0.06), but not in Thbs1(-/-) groups (0.15 ± 0.04 versus 0.22 ± 0.07). No difference in IH existed between Thbs1(-/-) no statin controls and fluvastatin WT and Thbs1(-/-) groups. Statin dose did not affect IH. TSP-1 plasma levels were increased in fluvastatin WT. TSP-2 levels were decreased in fluvastatin WT and elevated in fluvastatin Thbs1(-/-). Fluvastatin had no effect on tissue Thbs1 or Thbs2 gene expression. TSP-1 is necessary for robust IH after arterial injury. Because fluvastatin had no effect on IH in Thbs1(-/-), the data suggest that the statin effect on IH may be largely TSP-1 dependent. Both statins and the presence of TSP-1 affect TSP-1 and TSP-2 plasma levels. Published by Elsevier Inc.

  2. Effect of isoflavone on balloon catheter-induced neointimal hyperplasia in ovariectomised rabbit carotid artery.

    PubMed

    Zhang, Gai-Ying; Qiu, Ren-Feng; Sun, Ying-Chun; Wang, Le-Xin

    2013-02-01

    This study was designed to investigate the effects of phytoestrogen isoflavone on balloon catheter-induced hyperplasia of carotid artery. Forty-eight female New Zealand rabbits were randomly divided into four groups: control (balloon-induced carotid artery injury only); ovariectomy control (ovariectomy and carotid artery injury), oestrogen (ovariectomy, carotid artery injury and nilestriol, 5mg/kg daily for 28 days), and isoflavone (ovariectomy, carotid artery injury and isoflavone 120 mg/kg daily for 28 days). The arterial wall thickness was assessed by coloured ultrasonography, and the oestrogen-α and oestrogen-β receptors in the abdominal aorta were measured by Western blotting. The medial layer thickness in the isoflavone group was less than in the ovariectomy control group (0.28±0.03 vs. 0.35±0.04 mm, p<0.01), and the intimal/medial layer (I/M) ratio is the isoflavone group was also less than in the ovariectomy control group (16.85±3.79 vs. 48.94±8.92, p<0.01). There was no statistically significant difference in the medial layer thickness or I/M ratio between the isoflavone and the oestrogen groups. The optical density of the oestrogen-α receptors in the isoflavone group (0.317±0.002) was less than in the oestrogen (0.633±0.002) or ovariectomy control group (0.590±0.001, p<0.01). The optical density of the oestrogen-β receptors in the isoflavone group (1.350±0.002) and the ovariectomy control group (1.2033±0.002) was less than in the oestrogen group (1.7699±0.003, p<0.01). Isoflavone therapy in the ovariectomised rabbit model attenuated balloon catheter-induced intimal and medial layer hyperplasia in the carotid arteries. Down-regulation of the oestrogen-α receptors may be involved in the hyperplasia-preventative effect. Copyright © 2012. Published by Elsevier B.V.

  3. Pulmonary embolism caused by intimal sarcoma of the pulmonary artery.

    PubMed

    Yamamoto, Kei; Nozue, Tsuyoshi; Tsuchida, Masayuki; Iwaki, Taku; Nagamine, Hiroshi; Yasuda, Tamotsu; Kawase, Hiroshi; Matsushita, Kazuhiko; Michishita, Ichiro

    2012-01-01

    We herein report the case of a 39-year-old woman with a pulmonary embolism caused by intimal sarcoma of the pulmonary artery. She presented with shortness of breath and leg edema. Computed tomography showed a low density area that extended from the main pulmonary artery to the bilateral pulmonary arteries. We diagnosed her to have a pulmonary thromboembolism. The thrombosis did not decrease after the administration of anti-coagulant therapy, and she underwent resection of the thrombotic tissue. Histopathologically, the surgical specimen was not found to be thrombotic tissue but rather an intimal sarcoma of the pulmonary artery. After undergoing surgery, she received radiation therapy and chemotherapy; however, she died 31 months after being diagnosed.

  4. [An intimal sarcoma of the pulmonary artery. An immunohistochemical study].

    PubMed

    Pérez del Río, M J; Molina Suárez, R; Fresno Forcelledo, M F; Veiga González, M; Madrigal Rubiales, B; González González, M; Herrero Zapatero, A

    1998-10-01

    Pulmonary artery intimal sarcomas tend to be presented with symptoms of pulmonary thromboembolism and grow regionally, with little capacity to metastasize. They probably originate from subendothelial cells, that become myofibroblasts. Knowledge of it is important to establish a presurgery diagnosis, with the possibility of a total resection, the only useful treatment until now. We report a case of a pulmonary artery primary sarcoma, in a 73 year old woman, admitted with hemoptysis and pleuritic chest pain, who died ten days after. Autopsy revealed an intraluminal mass at the pulmonary artery trunk, without regional nor distance involvement. Microscopic study showed a pleomorphic tumor with spindle and epithelioid cells, positive for actin, desmin and vimentin. All these data support the diagnosis of primary intimal sarcoma of the pulmonary artery. We want to emphasize the myogenic differentiation of the tumor, uncommon in previously reported cases.

  5. Increasing levels of dietary homocystine with carotid endarterectomy produced proportionate increases in plasma homocysteine and intimal hyperplasia.

    PubMed

    Southern, F; Eidt, J; Drouilhet, J; Mukunyadzi, P; Williams, D K; Cruz, C; Wang, Y F; Poirier, L A; Brown, A T; Moursi, M M

    2001-09-01

    The role that homocysteine may play in post-carotid endarterectomy (CEA) restenosis due to intimal hyperplasia is not well understood. This study was designed to investigate the effects of different levels of dietary homocystine on: (1) plasma homocysteine; (2) post-CEA intimal hyperplasia; and (3) levels of the methyl donor S-adenosylmethionine (SAM) and its counterpart S-adenosylhomocysteine (SAH) in the homocysteine pathway. Male rats were fed specialized diets for 2 weeks pre- and post-CEA. Groups included control (0 homocystine added, n=9), 1.5 (1.5 g/kg homocystine added, n=10), 3.0 (3.0 g/kg homocystine added, n=9), and 4.5 (4.5 g/kg homocystine added, n=11). The rats underwent a surgical carotid endarterectomy. Endpoints included; plasma homocysteine, intimal hyperplasia, replicative index using with alpha-SM actin and BrdU, hepatic SAM levels, SAH levels, and the hepatic activities of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS). Increasing dietary homocystine produced a proportionate increase in plasma homocysteine and an increase in intimal hyperplasia. Regression analysis of plasma homocysteine levels and intimal hyperplasia showed a significant correlation (r=0.71,P=0.003). Plasma homocysteine levels above 15 microM were associated with significant increases in intimal hyperplasia above 6.5% (P=0.04). Elevation of plasma homocysteine levels to moderate levels (5-25 microM) resulted in significant post-CEA intimal hyperplasia. Cellular analysis of the area of intimal hyperplasia in all diet groups showed comparable amounts of cells positive for alpha-SM actin. However, with increasing levels of dietary homocystine and plasma homocysteine there was an increase in replicative index (P<0.001) as determined by BrdU staining. Increasing dietary homocystine increased plasma homocysteine and was followed by increases in the replicative index thus producing increased intimal hyperplasia and lumenal stenosis. In hepatic

  6. Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

    PubMed Central

    Murthy, SN; Fonseca, VA; McNamara, DB

    2005-01-01

    The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28

  7. Prostate Artery Embolization for Benign Prostatic Hyperplasia: Current Status.

    PubMed

    Mirakhur, Anirudh; McWilliams, Justin P

    2017-02-01

    Prostate artery embolization has garnered much attention as a promising treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. We aim to provide an up-to-date review of this minimally invasive technique, including discussion of potential benefits and technical challenges. Current evidence suggests it is a safe and effective option for patients with medication-refractory urinary obstructive symptoms who are poor surgical candidates or refuse surgical therapy. Larger, randomized studies with long-term follow-up data are needed for this technique to be formally established in the treatment paradigm for benign prostatic hyperplasia. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  8. Novel short-duration heating balloon dilatation with uniform temperature distribution: the heating conditions to suppress neo-intimal hyperplasia.

    PubMed

    Kunio, M; Shimazaki, N; Arai, T; Sakurada, M

    2011-01-01

    We investigate the relation between the influences on smooth muscle cells and the chronic performances of our novel short-duration heating balloon dilatation to reveal the heating conditions which can suppress the neo-intimal hyperplasia after our heating dilatations. The temperature of prototype balloon catheter surface was measured during short-duration heating balloon dilatation ex vivo. There existed 2 °C temperature variations in the long direction of prototype balloon catheter at a maximum. The neo-intimal hyperplasia occupancy rate after our short-duration heating dilatations were measured in vivo porcine study. The neo-intimal hyperplasia was suppressed most at 75 °C in balloon peak temperature in vivo. The estimated dead rate of smooth muscle cells at this condition was about 13% by the Arrhenius equation. We think that the suppression of neo-intimal hyperplasia was obtained after our short-duration heating dilatation due to the proper decrease of smooth muscle cells by heating and no thermal damages to the adventitia and surrounding tissues.

  9. Hyperplasia

    MedlinePlus

    Hyperplasia is increased cell production in a normal tissue or organ. Hyperplasia may be a sign of abnormal or precancerous changes. This is called pathologic hyperplasia. It can also be due to the growth ...

  10. Laser-induced fluorescence identification of intimal hyperplasia after intravascular stent implantation

    NASA Astrophysics Data System (ADS)

    Lucas, Alexandra; Perk, Masis; Wen, Yue; Tio, Fermin O.; Schneider, Wolfgang

    1992-08-01

    Laser-induced fluorescence spectroscopy has been developed as a guidance system for laser angioplasty. We have investigated fluorescence spectroscopic detection of neo-intimal formation from the endoluminal surface of stent implanted arteries. Nine White Leghorn roosters had Palmaz-Schatz intra-abdominal aortic stent implantation, nine had aortic balloon angioplasty. Five roosters with stent implantation and four roosters with balloon angioplasty were on a high cholesterol diet and the remainder were on a normal diet. Roosters were sacrificed at intervals of 1, 2, 4, 8, and 12 weeks after intervention. Fluorescence emission spectra were recorded from aortic segments during excimer laser excitation at 308 nm (XeCl, 1.5 - 2.0 mJ/pulse, 5 Hertz). Spectra were then correlated with histology. Fluorescence emission intensity recorded from abdominal aortic segments with stent implantation was higher than that of adjacent segments (p < 0.002 at 440 - 460 nm). Abdominal aortic segments of roosters on normal diets with stent implantation and balloon angioplasty were similar (p equals NS). With cholesterol feeding, aortic spectra from roosters with stent implant had higher intensity at 440 - 460 nm than spectra from aortic segments with balloon angioplasty (p < 0.004). Morphometric analysis demonstrated a twofold increase in intimal thickness in stent segments from cholesterol fed roosters when compared to similar segments of roosters on normal diets (p < 0.005). Our conclusion is: (1) Fluorescence emission spectra can be used to detect native artery fluorescence in stent implant areas. (2) Neo-intimal thickening at the stet implant site can be distinguished from adjacent areas by fluorescence emission spectra. (3) Cholesterol feeding increased neo-intimal thickening.

  11. A novel biodegradable external mesh stent improved long-term patency of vein grafts by inhibiting intimal-medial hyperplasia in an experimental canine model.

    PubMed

    Sato, Atsuhiko; Kawamoto, Shunsuke; Watanabe, Mika; Suzuki, Yusuke; Takahashi, Goro; Masaki, Naoki; Kumagai, Kiichiro; Saijo, Yoshifumi; Tabayashi, Koichi; Saiki, Yoshikatsu

    2016-01-01

    Increased hemodynamic stress on vein grafts used in the arterial system is associated with vein graft disease. We determined whether a novel biodegradable external mesh stent could inhibit medial-intimal hyperplasia by suppressing hemodynamic stress on vein grafts and improve long-term patency. Twenty-four beagles underwent bilateral femoral interposition grafting using reversed femoral veins. Vein grafts were externally supported by a novel poly L-lactide-ε-caprolactone copolymer (P(LA/CL)) biodegradable mesh stent or a nonabsorbable mesh stent. Vein grafts with no reinforcement were used as controls. The grafts were harvested 6 and 12 months after implantation for morphometric and immunohistochemical assessment. The endoluminal circumferential vein graft length was smaller in the P(LA/CL) and nonabsorbable groups (17.2 ± 2.9 and 19.0 ± 0.3 mm, respectively), than that in the control group (25.0 ± 2.6 mm, P < 0.01) at 12 months. The mean intimal-medial thickness was thinner in P(LA/CL) and nonabsorbable stent groups (0.18 ± 0.05 and 0.16 ± 0.05 mm, respectively), than that in the control group (0.30 ± 0.08 mm, P < 0.01). Differences in the intimal-medial thickness among the groups were associated with the magnitude of cellular proliferating activity. The graft patency ratio (100 %) was higher in the P(LA/CL) group than that in the nonabsorbable and control groups (72.2 and 63.6%, respectively, P < 0.05). The biodegradable P(LA/CL) external mesh stent improved vein graft patency for 12 months and prevented vein graft dilatation and intimal hyperplasia associated with suppressed neointimal layer cellular proliferating activity.

  12. Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation.

    PubMed

    Yu, Dan; Makkar, George; Strickland, Dudley K; Blanpied, Thomas A; Stumpo, Deborah J; Blackshear, Perry J; Sarkar, Rajabrata; Monahan, Thomas S

    2015-10-08

    Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo. MARCKS knockdown blocked platelet-derived growth factor (PDGF)-induced translocation of cortactin to the cell cortex, impaired both lamellipodia and filopodia formation, and attenuated motility of human coronary artery smooth muscle cells (CASMCs). Activation of the small GTPases, Rac1 and Cdc42, was prevented by MARCKS knockdown. Phosphorylation of MARCKS resulted in a transient shift of MARCKS from the plasma membrane to the cytosol. MARCKS knockdown significantly decreased membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Cotransfection with an intact, unphosphorylated MARCKS, which has a high binding affinity for PIP2, restored membrane-associated PIP2 levels and was indispensable for activation of Rac1 and Cdc42 and, ultimately, VSMC migration. Overexpression of MARCKS in differentiated VSMCs increased membrane PIP2 abundance, Rac1 and Cdc42 activity, and cell motility. MARCKS protein was upregulated early in the development of intimal hyperplasia in the murine carotid ligation model. Decreased MARKCS expression, but not total knockdown, attenuated intimal hyperplasia formation. MARCKS upregulation increases VSMC motility by activation of Rac1 and Cdc42. These effects are mediated by MARCKS sequestering PIP2 at the plasma membrane. This study delineates a novel mechanism for MARCKS-mediated VSMC migration and supports the rational for MARCKS knockdown to prevent intimal hyperplasia. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  13. Establishment of a rat and guinea pig aortic interposition graft model reveals model-specific patterns of intimal hyperplasia.

    PubMed

    Gregory, Elaine K; Vercammen, Janet M; Flynn, Megan E; Kibbe, Melina R

    2016-12-01

    Although the aortic interposition bypass model has been widely used to evaluate biomaterials for bypass grafting, there is no comprehensive description of the procedure or of the distribution of intimal hyperplasia that results. The objectives of this study were to (1) review and summarize approaches of aortic interposition grafting in animal models, (2) determine the pertinent anatomy for this procedure, (3) validate this model in the rat and guinea pig, and (4) compare the distribution of intimal hyperplasia that develops in each species. A literature search was performed in PubMed from 1980 to the present to analyze the use of anesthesia, anticoagulation, antiplatelet agents, graft material, suture, and anastomotic techniques. Using 10-week-old male Sprague-Dawley rats and Hartley guinea pigs, we established pertinent aortic anatomy, developed comparable models, and assessed complications for each model. At 30 days, the graft and associated aorta were explanted, intimal formation was assessed morphometrically, and cellularity was assessed via nuclear counting. We reviewed 30 articles and summarized the pertinent procedural findings. Upon establishing both animal models, key anatomic differences between the species that affect this model were noted. Guinea pigs have a much larger cecum, increased retroperitoneal fat, and lack the iliolumbar vessels compared with the rat. Surgical outcomes for the rat model included a 53% technical success rate and a 32% technical error rate. Surgical outcomes for the guinea pig model included a 69% technical success rate and a 31% technical error rate. These two species demonstrated unique distribution of intimal hyperplasia at 30 days. Intimal hyperplasia in the rat model was greatest at two areas, the proximal graft (5400 μm(2); P < .001) and distal graft (2800 μm(2); P < .04), whereas the guinea pig model developed similar intimal hyperplasia throughout the graft (4500-5100 μm(2); P < .01). In this report, we summarize

  14. Leukotriene B4 signaling through NF-κB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia

    PubMed Central

    Bäck, Magnus; Bu, De-xiu; Bränström, Robert; Sheikine, Yuri; Yan, Zhong-Qun; Hansson, Göran K.

    2005-01-01

    Leukotriene B4 (LTB4), a potent leukocyte chemoattractant derived from the 5-lipoxygenase metabolism of arachidonic acid, exerts its action by means of specific cell surface receptors, denoted BLT1 and BLT2. In this study, BLT1 receptor proteins were detected in human carotid artery atherosclerotic plaques, colocalizing with markers for macrophages, endothelial cells, and vascular smooth muscle cells (SMC). Challenge of human coronary artery SMC with either LTB4 or U75302, a partial agonist that is selective for the BLT1 receptor, induced an ≈4-fold increase of whole-cell currents by using the patch-clamp technique, indicating that these cells express functional BLT1 receptors. LTB4 induced migration and proliferation of SMC in vitro, and treatment with the BLT receptor antagonist BIIL 284 (10 mg/kg, once daily) for 14 days after carotid artery balloon injury in vivo inhibited intimal hyperplasia in rats. In the latter model, SMC derived from the intima exhibited increased levels of BLT1 receptor mRNA compared with medial SMC. BLT receptor up-regulation in the intima in vivo, as well as that induced by IL-1β in vitro, were prevented by transfection with a dominant-negative form of Iκ kinase β carried by adenovirus, indicating that BLT1 receptor expression depends on NF-κΒ. These results show that LTB4 activates functional BLT1 receptors on vascular SMC, inducing chemotaxis and proliferation, and that BLT1 receptors were up-regulated through an Iκ kinase β/NF-κB-dependent pathway. Inhibition of LTB4/BLT1 signaling during the response to vascular injury reduced intimal hyperplasia, suggesting this pathway as a possible target for therapy. PMID:16293697

  15. FGF-1 affixation stimulates ePTFE endothelialization without intimal hyperplasia.

    PubMed

    Gray, J L; Kang, S S; Zenni, G C; Kim, D U; Kim, P I; Burgess, W H; Drohan, W; Winkles, J A; Haudenschild, C C; Greisler, H P

    1994-11-01

    The affixation of FGF-1 to porous vascular grafts has been reported to stimulate capillary ingrowth and surface endothelialization. The current study further characterizes responses to fibroblast growth factor (FGF)-1 affixation to 30-cm-long grafts followed 140 days. ePTFE grafts (30 cm x 8 mm i.d.), 60 microns internodal distance, were impregnated with fibrin glue (FG) suspensions containing FGF-1 and heparin. Two negative control groups were treated either with FG with heparin alone or left untreated. Grafts were explanted from the canine thoracoabdominal aortic position after 10, 30, or 140 days (n = 3/time/group) 10 hr after im injection of tritiated thymidine (0.5 muCi/kg). Specimens were studied by light and electron microscopy, immunohistochemistry, morphometric analyses, and cross-sectional autoradiography. RNA preparations from inner capsule tissues were used for reverse transcription-polymerase chain reaction (RT-PCR) analyses of FGF-1, FGF-2, transforming growth factor-beta 1, (TGF-beta 1) and FGF receptor mRNA species. Inner capsule collagen was quantitated by hydroxyproline colorimetry. Histologic analyses of perianastomotic regions were performed for comparison purposes. All explants were patent and without intimal hyperplasia. Progressive capillarization of the internodal spaces occurred over time and was significantly more extensive in the FGF-1-treated group. Endothelialization of the luminal surface increased with time, at 140 days covering 86.7 +/- 11.6% of the FGF-1 explants vs 46.1 +/- 7.5% and 48.1 +/- 13.3% in the other groups, P < 0.007 and P < 0.04, respectively. Inner capsule thickness at 140 days differed significantly (P < 0.05) between the FGF-1 group (138.8 microns) vs either control group (93 and 67 microns, respectively), which did not significantly differ from each other. Cross-sectional autoradiography demonstrated an FGF-1-induced mitotic index increase at 30 days, 9.6 +/- 4.4% compared to 2.5 +/- 1.0 and 0 +/- 0%, respectively

  16. Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression.

    PubMed

    Hlawaty, Hanna; Suffee, Nadine; Sutton, Angela; Oudar, Olivier; Haddad, Oualid; Ollivier, Veronique; Laguillier-Morizot, Christelle; Gattegno, Liliane; Letourneur, Didier; Charnaux, Nathalie

    2011-01-15

    The therapeutic potential of low molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed was investigated on vascular smooth muscle cell (VSMC) and human vascular endothelial cell (HUV-EC-C) proliferation and migration in vitro and in a rat model of intimal hyperplasia. Sprague-Dawley rats were subjected to balloon injury in the thoracic aorta followed by two weeks' treatment with either LMWF (5mg/kg/day) or vehicle. Morphological analysis and proliferating cell nuclear antigen immunostaining at day 14 indicated that LMWF prevented intimal hyperplasia in rat thoracic aorta as compared with vehicle (neo-intima area, 3±0.50mm(2) versus 5±0.30mm(2), P<0.01). In situ zymography showed that LMWF significantly decreased the activity of matrix metalloproteinase (MMP)-2 in the neo-intima compared to vehicle. The in vitro study demonstrated that 10μg/ml LMWF increased HUV-EC-C migration by 45±5% but reduced VSMC migration by 40±3%. LMWF also increased MMP-2 mRNA expression in HUV-EC-Cs and reduced it in VSMCs. MMP-2 level in the conditioned medium from cells incubated with 10μg/ml LMWF was 5.4-fold higher in HUV-EC-Cs, but 6-fold lower in VSMCs than in untreated control cells. Furthermore, decreasing MMP-2 expression in HUV-EC-Cs or VSMCs by RNA interference resulted in reduced LMWF-induced effects on cell migration. In conclusion, LMWF increased HUV-EC-C migration and decreased VSMC migration in vitro. In vivo, this natural compound reduced the intimal hyperplasia in the rat aortic wall after balloon injury. Therefore, LMWF could be of interest for the prevention of intimal hyperplasia.

  17. Role of the Renin–Angiotensin System in the Pathogenesis of Intimal Hyperplasia: Therapeutic Potential for Prevention of Vein Graft Failure?

    PubMed Central

    Osgood, Michael J.; Harrison, David G.; Sexton, Kevin W.; Hocking, Kyle M.; Voskresensky, Igor V.; Komalavilas, Padmini; Cheung-Flynn, Joyce; Guzman, Raul J.; Brophy, Colleen M.

    2014-01-01

    The saphenous vein remains the most widely used conduit for peripheral and coronary revascularization despite a high rate of vein graft failure. The most common cause of vein graft failure is intimal hyperplasia. No agents have been proven to be successful for the prevention of intimal hyperplasia in human subjects. The rennin–angiotensin system is essential in the regulation of vascular tone and blood pressure in physiologic conditions. However, this system mediates cardiovascular remodeling in pathophysiologic states. Angiotensin II is becoming increasingly recognized as a potential mediator of intimal hyperplasia. Drugs modulating the renin–angiotensin system include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These drugs are powerful inhibitors of atherosclerosis and cardiovascular remodeling, and they are first-line agents for management of several medical conditions based on class I evidence that they delay progression of cardiovascular disease and improve survival. Several experimental models have demonstrated that these agents are capable of inhibiting intimal hyperplasia. However, there are no data supporting their role in prevention of intimal hyperplasia in patients with vein grafts. This review summarizes the physiology of the rennin–angiotensin system, the role of angiotensin II in the pathogenesis of cardiovascular remodeling, the medical indications for these agents, and the experimental data supporting an important role of the rennin–angiotensin system in the pathogenesis of intimal hyperplasia. PMID:22445245

  18. Dialysis Arteriovenous Fistula Failure and Angioplasty: Intimal Hyperplasia and Other Causes of Access Failure.

    PubMed

    Duque, Juan C; Tabbara, Marwan; Martinez, Laisel; Cardona, Jose; Vazquez-Padron, Roberto I; Salman, Loay H

    2017-01-01

    The arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients' morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty continues to be the gold-standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a 2-stage brachiobasilic AVF that was complicated by failure 4 months after creation. An angiogram showed multiple juxta-anastomotic and midfistula stenotic lesions. Percutaneous transluminal angioplasty was successful in assisting maturation and subsequently cannulating the AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis because biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH and highlights the need for more therapeutic options to reduce AVF failure rate. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Pulmonary arterial intimal sarcoma with retrograde extension: report of a case and review of literature.

    PubMed

    Vaideeswar, Pradeep; Pillai, Raji

    2013-01-01

    Most of the pulmonary arterial sarcomas arise from multi-potential mesenchymal intimal cells and are designated as intimal sarcomas. These tumors grow in the direction of blood flow into peripheral arteries producing clinical features mimicking pulmonary thromboembolism. Retrograde extension is rare. We report one such case of intimal sarcoma that had a retrograde extension into the right ventricular outflow tract, and review such a presentation in the last ten years.

  20. Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress.

    PubMed

    Chen, Henry Y; Sinha, Anjan K; Choy, Jenny S; Zheng, Hai; Sturek, Michael; Bigelow, Brian; Bhatt, Deepak L; Kassab, Ghassan S

    2011-12-01

    Stent can cause flow disturbances on the endothelium and compliance mismatch and increased stress on the vessel wall. These effects can cause low wall shear stress (WSS), high wall shear stress gradient (WSSG), oscillatory shear index (OSI), and circumferential wall stress (CWS), which may promote neointimal hyperplasia (IH). The hypothesis is that stent-induced abnormal fluid and solid mechanics contribute to IH. To vary the range of WSS, WSSG, OSI, and CWS, we intentionally mismatched the size of stents to that of the vessel lumen. Stents were implanted in coronary arteries of 10 swine. Intravascular ultrasound (IVUS) was used to size the coronary arteries and stents. After 4 wk of stent implantation, IVUS was performed again to determine the extent of IH. In conjunction, computational models of actual stents, the artery, and non-Newtonian blood were created in a computer simulation to yield the distribution of WSS, WSSG, OSI, and CWS in the stented vessel wall. An inverse relation (R(2) = 0.59, P < 0.005) between WSS and IH was found based on a linear regression analysis. Linear relations between WSSG, OSI, and IH were observed (R(2) = 0.48 and 0.50, respectively, P < 0.005). A linear relation (R(2) = 0.58, P < 0.005) between CWS and IH was also found. More statistically significant linear relations between the ratio of CWS to WSS (CWS/WSS), the products CWS × WSSG and CWS × OSI, and IH were observed (R(2) = 0.67, 0.54, and 0.56, respectively, P < 0.005), suggesting that both fluid and solid mechanics influence the extent of IH. Stents create endothelial flow disturbances and intramural wall stress concentrations, which correlate with the extent of IH formation, and these effects were exaggerated with mismatch of stent/vessel size. These findings reveal the importance of reliable vessel and stent sizing to improve the mechanics on the vessel wall and minimize IH.

  1. Pulmonary artery intimal sarcoma: a brief case series.

    PubMed

    Austin, Bethany A; Griffin, Brian P

    2008-08-01

    Primary pulmonary artery intimal sarcomas are often diagnosed only at the time of surgery or autopsy as a result of few specific findings both clinically and on imaging studies. We report two cases of this rare and lethal malignancy, both of which were initially thought to be manifestations of thromboembolic disease. In the case of one man, the diagnosis was delayed several months, at which point attempted surgical resection was not feasible. In the second case the echocardiographic and computed tomographic results generated further evaluation. This led to a more prompt diagnosis and treatment extending the patient's survival. In addition, we describe the echocardiographic findings that lent support to the need for surgical intervention and histologic diagnosis.

  2. Downstream anastomotic hyperplasia. A mechanism of failure in Dacron arterial grafts.

    PubMed Central

    LoGerfo, F W; Quist, W C; Nowak, M D; Crawshaw, H M; Haudenschild, C C

    1983-01-01

    The precise location and progression of anastomotic hyperplasia and its possible relationship to flow disturbances was investigated in femoro-femoral Dacron grafts in 28 dogs. In 13 grafts, the outflow from the end-to-side downstream anastomosis was bidirectional (BDO), and in 15 it was unidirectional (UDO) (distally). Grafts were electively removed at intervals of two to 196 days or at the time of thrombosis. Each anastomosis and adjacent artery was perfusion-fixed and sectioned sagittally. The mean sagittal section was projected onto a digitized pad, and the total area of hyperplasia internal to the arterial internal elastic lamina and within the adjacent graft was integrated by computer. The location of the hyperplasia was compared with previously established sites of flow separation and stagnation. The observation was made that hyperplasia is significantly greater at the downstream, as compared with the upstream, anastomosis in both groups (BDO = p less than 0.001 and UDO = p less than 0.001) (analysis of variance for independent groups). Furthermore, this downstream hyperplasia was progressive with time (BDO p less than 0.01) (UDO p less than 0.01); Spearman Rank Correlation. There was no significant increase in the extent of downstream hyperplasia where flow separation was known to be greater (BDO). Five grafts failed (three BDO, two UDO), as a result of complete occlusion of the downstream anastomosis by fibrous hyperplasia. Transmission electron microscopy showed the hyperplasia to consist of collagen-producing smooth muscle cells. Anastomotic hyperplasia is significantly greater at the downstream anastomosis, is progressive with time, and is the primary cause of failure of Dacron arterial grafts in this model. Quantitative analysis of downstream anastomotic hyperplasia may be a valuable measure of the biocompatibility of Dacron grafts. Images Fig. 2. Fig. 3. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:6219641

  3. Testosterone replacement attenuates intimal hyperplasia development in an androgen deficient model of vascular injury.

    PubMed

    Freeman, Brian M; Univers, Junior; Fisher, Richard K; Kirkpatrick, Stacy S; Klein, Frederick A; Freeman, Michael B; Mountain, Deidra J H; Grandas, Oscar H

    2017-01-01

    Androgen deficiency (AD) is associated with increased risk of vascular disease. Dysfunctional remodeling of the vessel wall and atypical proliferative potential of vascular smooth muscle cells (VSMCs) are fundamental processes in the development of intimal hyperplasia (IH). We have demonstrated an inverse relationship between dihydrotestosterone (DHT) levels, matrix metalloproteinase activity, and VSMC migration and proliferation in vitro. Here, we investigated the role of AD and testosterone (TST) replacement in IH development in an animal model of vascular injury to elucidate mechanisms modulated by AD that could be playing a role in the development of vascular pathogenesis. Aged orchiectomized male rats underwent TST supplementation via controlled release pellet (0.5-35 mg). Young adult and middle-age adult intact (MI) and orchiectomized placebo (Plac) groups served as controls. All groups underwent balloon angioplasty of the left common carotid at a 14-d post-TST. Carotid tissue was collected at a 14-d post-balloon angioplasty and subjected to morphologic and immunohistochemical analyses. Human male VSMCs were treated with DHT (0-3000 nM) for 24 h then subjected to quantitative PCR for gene expression analyses and costained for F-actin and G-actin for visualization of cytoskeletal organization. I:M ratio was increased in Plac, subphysiological, low-physiological, and high pharmacologic level TST animals compared with MI controls but was decreased with high-physiological TST supplementation. Injury-induced expression of previously defined matrix metalloproteinase remodeling enzymes was not significantly affected by TST status. Urotensin (UTS) receptor (UTSR) staining was low in injured vessels of all young adult intact, MI, and Plac controls but was significantly upregulated in all groups receiving exogenous TST supplementation, irrespective of dose. In vitro DHT exposure increased the expression of UTSR in VSMCs in a dose-dependent manner. However, this did

  4. Inhibition of cell surface expression of endothelial adhesion molecules by ursolic acid prevents intimal hyperplasia of venous bypass grafts in rats

    PubMed Central

    Zeller, Iris; Wiedemann, Dominik; Schwaiger, Stefan; Stelzmüller, Marlies; Kreutmayer, Simone; Leberfing, Oliver; Stuppner, Hermann; Bernhard, David

    2012-01-01

    OBJECTIVES Despite rapid progress in surgical techniques, there is still a significant lack of surgery-supportive pharmacological treatments. The aim of this study was to test the hypothesis that ursolic acid (UA) may prevent intimal hyperplasia of venous bypass grafts. METHODS The hypothesis was tested by means of primary cell isolation and culture followed by real-time polymerase chain reaction, western blotting, fluorescence microscopy and fluorescence-activated cell sorting analyses, as well as an in vivo rat model for intimal hyperplasia of venous bypass grafts and immunohistochemistry and histochemistry. RESULTS The local application of UA significantly inhibited intimal hyperplasia in vivo (intimal thickness control: 25 μm, UA group: 18 μM–8 weeks after surgery). The UA treatment of grafts significantly resulted in reduced endothelial vascular cell adhesion molecule-1 (VCAM-1) expression, reduced infiltration of the grafts vessel wall by CD45-positive cells and increased smooth muscle cell (SMC) death. In in vitro condition, it could be shown that UA inhibits VCAM-1 expression downstream of NFκB and is likely to interfere with VCAM-1 protein synthesis in endothelial cells. Quantification of cell death in vascular smooth muscle cells treated with UA indicated that UA is a potent inducer of SMC apoptosis. CONCLUSIONS Our results suggest that UA-mediated inhibition of endothelial VCAM-1 expression reduces the infiltration of venous bypass grafts by CD45-positive cells and inhibits intimal hyperplasia. Apoptosis induction in SMCs may be another method in which UA reduces intimal thickening. UA may constitute a surgery-supportive pharmacon that reduces intimal hyperplasia of vein grafts. PMID:22551965

  5. [An unusual primary vascular tumor: intimal sarcoma of the pulmonary artery].

    PubMed

    Brochériou, I; Quillard, A; Gatecel, C; Wassef, M

    2000-01-01

    Primary sarcomas of great vessels are rare and involve the aorta, pulmonary artery and inferior vena cava. The pathologic classification of these tumors can be made on the location of the sarcoma in relation to the vessel wall, luminal or mural. Luminal sarcomas are usually intimal sarcoma and mural sarcoma are most frequently leiomyosarcoma. The myofibroblastic or endothelial differentiation of these tumors is still debated. We report a case of intimal sarcoma of the pulmonary artery.

  6. Intimal sarcoma of the pulmonary artery: a differential diagnosis of chronic pulmonary thromboembolism.

    PubMed

    Dornas, Ana Paula Alves Valle; Campos, Frederico Thadeu Assis Figueiredo; Rezende, Cláudia Juliana; Ribeiro, Carlos Alberto; Amaral, Nilson Figueiredo; Corrêa, Ricardo de Amorim

    2009-08-01

    Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor, the diagnosis of which is difficult and therefore frequently delayed. The clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary thromboembolism (CPTE). We report the case of a 45-year-old male under treatment for CPTE associated with pulmonary arterial hypertension and chronic cor pulmonale. There was no response to treatment with anticoagulants and sildenafil. We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary artery, the need to investigate this neoplasm in the differential diagnosis of CPTE and the systematic use of criteria for the appropriate prescription of new medications for pulmonary artery hypertension.

  7. [A case of primary pulmonary intimal sarcoma of the pulmonary artery].

    PubMed

    Araki, Y; Tajima, K; Yoshikawa, M; Abe, T; Suenaga, Y

    1997-07-01

    We report the pulmonary intimal sarcoma of the pulmonary artery which is encountered infrequently. The patient, a 67-year-old man, was admitted with right heart failure. Diagnosis was not established completely by computed tomography of the thorax, pulmonary angiogram and pulmonary scintigram, therefore chronic pulmonary thromboembolism was suspected. Palliative resection was performed with cardiopulmonary bypass and total circulatory arrest. Pathologic examination of the resected tumor revealed pulmonary intimal sarcoma, which originated from the pulmonary artery. The patient died four months postoperatively. The cause of death was determined by autopsy to be recurrent pulmonary intimal sarcoma invading the left atrium and multiple metastasis of the brain, pancreas, adrenal glands and right lung.

  8. Regulation of cellular proliferation and intimal formation following balloon injury in atherosclerotic rabbit arteries.

    PubMed Central

    Simari, R D; San, H; Rekhter, M; Ohno, T; Gordon, D; Nabel, G J; Nabel, E G

    1996-01-01

    Injury to atherosclerotic arteries induces the expression of growth regulatory genes that stimulate cellular proliferation and intimal formation. Intimal expansion has been reduced in vivo in nonatherosclerotic balloon-injured arteries by transfer of genes that inhibit cell proliferation. It is not known, however, whether vascular cell proliferation can be inhibited after injury in more extensively diseased atherosclerotic arteries. Accordingly, the purpose of this study was to investigate whether expression of recombinant genes in atherosclerotic arteries after balloon injury could inhibit intimal cell proliferation. To test this hypothesis, we examined the response to balloon injury in atherosclerotic rabbit arteries after gene transfer of herpesvirus thymidine kinase gene (tk) and administration of ganciclovir. Smooth muscle cells from hyperlipidemic rabbit arteries infected with adenoviral vectors encoding tk were sensitive to ganciclovir, and bystander killing was observed in vitro. In atherosclerotic arteries, a human placental alkaline phosphatase reporter gene was expressed in intimal and medial smooth muscle cells and macrophages, identifying these cells as targets for gene transfer. Expression of tk in balloon-injured hyperlipidemic rabbit arteries followed by ganciclovir treatment resulted in a 64% reduction in intimal cell proliferation 7 d after gene transfer (P = 0.004), and a 35-49% reduction in internal area 21 d after gene transfer, compared with five different control groups (P < 0.05). Replication of smooth muscle cells and macrophages was inhibited by tk expression and ganciclovir treatment. These findings indicate that transfer of a gene that inhibits cellular proliferation limits the intimal area in balloon-injured atherosclerotic arteries. Molecular approaches to the inhibition of cell proliferation in atherosclerotic arteries constitute a possible treatment for vascular proliferative diseases. PMID:8690797

  9. The laser driven short-term heating balloon catheter: Relation between the chronic neointimal hyperplasia formation and thermal damage to arterial smooth muscle cells.

    PubMed

    Shimazaki, Natsumi; Hayashi, Tomoaki; Kunio, Mie; Igami, Yuka; Arai, Tsunenori; Sakurada, Masami

    2010-01-01

    We proposed a novel laser-driven short-term heating angioplasty to realize restenosis-suppressive angioplasty for peripheral artery disease. In this study, we investigated the chronic intimal hyperplasia formation after the short-term heating dilatation in vivo, as well as the thermal damage calculation on arterial smooth muscle cells (SMCs). The prototype short-term heating balloon catheter with 5.0, 5.5, 6.0 mm φ in balloon diameter and 25 mm in balloon length were employed. The short-term heating dilatation was performed in porcine iliac arteries with dilatation conditions of 75°C (N=4) and 65°C (N=5) as peak balloon temperature, 18 ± 4s as heating duration, 3.5 atm as balloon dilatation pressure. Four weeks after the balloon dilatation, the balloon-dilated artery segments were extracted and were stained with HE and picrosirius red for histological observation. In the case of 75°C as the peak balloon temperature, neointimal hyperplasia formation was significantly reduced. In this case, the SMCs density in the artery media measured from the HE-stained specimen was 20% lower than that in the reference artery. According to the thermal damage calculation, it was estimated that the SMCs lethality in artery media after the short-term heating angioplasty was 20% in the case of 75°C as the peak balloon temperature. We demonstrated that the short-term heating dilatation reduced the number of SMCs in artery media. We think this SMCs reduction might contribute to the suppression of chronic neointimal hyperplasia.

  10. Transcatheter Arterial Embolization as a Safe and Effective Treatment for Focal Nodular Hyperplasia of the Liver

    SciTech Connect

    Terkivatan, Tuerkan; Hussain, Shahid M.; Lameris, Johan S.; Ijzermans, Jan N.M.

    2002-10-15

    When surgical treatment is being considered for focal nodular hyperplasia, the risk of liver surgery must be carefully balanced against the benefit of resection, especially in the case of a large or centrally located lesion. However, when resection is contraindicated or even impossible, transcatheter arterial embolization should be considered as a safe and less invasive alternative treatment.We describe two cases of young women who presented with abdominal pain and a hypervascular enhancing mass with the radiologic features of focal nodular hyperplasia. Arterial embolization was the therapy selected due to the risk of surgery. In both cases the procedure was successful, and the lesion showed shrinkage during follow-up.

  11. Pipoxolan Ameliorates Cerebral Ischemia via Inhibition of Neuronal Apoptosis and Intimal Hyperplasia through Attenuation of VSMC Migration and Modulation of Matrix Metalloproteinase-2/9 and Ras/MEK/ERK Signaling Pathways

    PubMed Central

    Chen, Yuh-Fung; Tsai, Huei-Yann; Wu, Kuo-Jen; Siao, Lian-Ru; Wood, W. Gibson

    2013-01-01

    Pipoxolan (PIPO) has anti-spasmodic effects, and it is used clinically to relieve smooth muscle spasms. Cerebrovascular disease is one of the leading causes of disability and death worldwide. The main aim of this study was to investigate the effects of PIPO on cerebral ischemia and vascular smooth muscle cell (VSMC) migration in vivo and in vitro. Cerebral infarction area, ratio of intima to media area (I/M ratio) and PCNA antibody staining of the carotid artery in vivo were measured. Cell viability of A7r5 cells, PDGF-BB-stimulated cell migration, and potential mechanisms of PIPO were evaluated by wound healing, transwell and Western blotting. PIPO (10 and 30 mg/kg p.o.) reduced: the cerebral infarction area; neurological deficit; TUNEL-positive cells; cleaved caspase 3-positive cells; intimal hyperplasia; and inhibited proliferating cell nuclear antigen (PCNA)-positive cells in rodents. PIPO (5, 10 and 15 µM) significantly inhibited PDGF-BB-stimulated VSMC migration and reduced Ras, MEK, and p-ERK levels. Moreover, PIPO decreased levels of matrix metalloproteinases -2 and -9 in PDGF-BB-stimulated A7r5 cells. In summary, PIPO is protective in models of ischemia/reperfusion-induced cerebral infarction, carotid artery ligation-induced intimal hyperplasia and VSMC migration both in vivo and in vitro. PIPO could be potentially efficacious in preventing cerebrovascular and vascular diseases. PMID:24086601

  12. Pipoxolan ameliorates cerebral ischemia via inhibition of neuronal apoptosis and intimal hyperplasia through attenuation of VSMC migration and modulation of matrix metalloproteinase-2/9 and Ras/MEK/ERK signaling pathways.

    PubMed

    Chen, Yuh-Fung; Tsai, Huei-Yann; Wu, Kuo-Jen; Siao, Lian-Ru; Wood, W Gibson

    2013-01-01

    Pipoxolan (PIPO) has anti-spasmodic effects, and it is used clinically to relieve smooth muscle spasms. Cerebrovascular disease is one of the leading causes of disability and death worldwide. The main aim of this study was to investigate the effects of PIPO on cerebral ischemia and vascular smooth muscle cell (VSMC) migration in vivo and in vitro. Cerebral infarction area, ratio of intima to media area (I/M ratio) and PCNA antibody staining of the carotid artery in vivo were measured. Cell viability of A7r5 cells, PDGF-BB-stimulated cell migration, and potential mechanisms of PIPO were evaluated by wound healing, transwell and Western blotting. PIPO (10 and 30 mg/kg p.o.) reduced: the cerebral infarction area; neurological deficit; TUNEL-positive cells; cleaved caspase 3-positive cells; intimal hyperplasia; and inhibited proliferating cell nuclear antigen (PCNA)-positive cells in rodents. PIPO (5, 10 and 15 µM) significantly inhibited PDGF-BB-stimulated VSMC migration and reduced Ras, MEK, and p-ERK levels. Moreover, PIPO decreased levels of matrix metalloproteinases -2 and -9 in PDGF-BB-stimulated A7r5 cells. In summary, PIPO is protective in models of ischemia/reperfusion-induced cerebral infarction, carotid artery ligation-induced intimal hyperplasia and VSMC migration both in vivo and in vitro. PIPO could be potentially efficacious in preventing cerebrovascular and vascular diseases.

  13. Intimal sarcoma of the pulmonary artery with retrograde extension into the pulmonic valve and right ventricle.

    PubMed

    Ozbek, Cengiz; Emrecan, Bilgin; Calli, Aylin Orgen; Gurbuz, Ali

    2007-01-01

    We describe the case of a 42-year-old man who presented with dyspnea on exertion and a history of anticoagulation therapy for what was thought to be pulmonary arterial thromboembolism. He underwent surgery for obstruction of the right ventricular outflow tract. This is a very rare case of an intimal sarcoma of the pulmonary artery, which we confirmed by pathologic studies.

  14. A case of pulmonary artery intimal sarcoma diagnosed with multislice CT scan with 3D reconstruction.

    PubMed

    Choi, Eui-Young; Yoon, Young-Won; Kwon, Hyuck Moon; Kim, Dongsoo; Park, Byung-Eun; Hong, Yoo-Sun; Koo, Ja-Seung; Kim, Tae-Hoon; Kim, Hyun-Seung

    2004-06-30

    Pulmonary artery intimal sarcoma is a rare highly lethal disease, with additional retrograde extension to pulmonic valve and right ventricle being an extremely rare condition. It is frequently mistaken for pulmonary thromboembolism. We report a case of 64-year-old woman with progressive dyspnea initially suspected and treated for pulmonary thromboembolism. Her helical chest CT scan with 3 dimensional (3D) reconstruction combined with echocardiography revealed a compacting main pulmonary artery mass extending to the right ventricular outflow tract and the right pulmonary artery. After excision of the mass, the patient's condition improved dramatically, and the pathologic findings revealed pulmonary intimal sarcoma. This report emphasizes that helical chest CT with 3D reconstruction can be an important tool to differentiate the characteristics of pulmonary artery lesions, such as intimal sarcoma and thromboembolism.

  15. Effect of atorvastatin on postcardiac transplant increase in low-density lipoprotein cholesterol reduces development of intimal hyperplasia and progression of endothelial dysfunction.

    PubMed

    See, Vincent Y; DeNofrio, David; Goldberg, Lee; Chang, Gene; Sasseen, Brett; Kolansky, Daniel M; Pickering, Faith; Kao, Andrew; Loh, Evan; Wilensky, Robert L

    2003-07-01

    Following cardiac transplantation, accelerated coronary disease limits long-term survival. Because statins may reduce the progression of the disease in part by their anti-inflammatory effects, this study was designed to assess if atorvastatin prevented neointimal hyperplasia and endothelial dysfunction independently of baseline cholesterol levels. Patients were randomized to usual therapy (n = 13) or to 10 to 20 mg of atorvastatin (n = 12). Control subjects received niacin when their low-density lipoprotein (LDL) cholesterol levels were >130 mg/dl (n = 4). Neointimal hyperplasia by intracoronary ultrasonography, endothelial dependent vascular reactivity, and coronary flow reserve were measured at baseline and 1 year. Control group total cholesterol (203 +/- 11 to 200 +/- 13 mg/dl) and LDL (116 +/- 10 to 119 +/- 11 mg/dl) remained stable, whereas there was a nonsignificant reduction at 12 months in the atorvastatin group (total cholesterol 216 +/- 28 to 178 +/- 21 mg/dl; LDL 126 +/- 17 to 100 +/- 18 mg/dl). At 2 to 3 months there was a significant increase in total cholesterol and LDL cholesterol that was reduced with atorvastatin. At 1 year, patients taking atorvastatin showed a decrease in new or progressing lesions (2.5 +/- 1.7 vs 4.2 +/- 1.8 lesions/patient, p = 0.02), progression of maximal intimal thickness (0.12 +/- 0.07 vs 0.52 +/- 0.17 mm, p = 0.04), and percent area stenosis (5.9 +/- 2.2% vs 19.0 +/- 5.5%, p = 0.04). Atorvastatin ameliorated progressive endothelial dysfunction, whereas coronary flow reserve was unchanged in both groups. Atorvastatin administered to patients with normal or mild hypercholesterolemia in the initial year after transplant reduced the initial increase in LDL cholesterol, and, by doing so, prevented the development and progression of coronary artery lesions and endothelial dysfunction with only mild long-term decreases in cholesterol levels.

  16. A case of intimal sarcoma of the pulmonary artery treated with chemoradiotherapy.

    PubMed

    Hirose, Takashi; Ishikawa, Noboru; Hamada, Kenji; Inagaki, Tomoko; Kusumoto, Sojiro; Shirai, Takao; Okuda, Kentaro; Ohnishi, Tsukasa; Kadokura, Mitsutaka; Adachi, Mitsuru

    2009-01-01

    We report on a 45-year-old woman with intimal sarcoma of the pulmonary artery. She presented with a chief complaint of shortness of breath. Computed tomography (CT) of the chest showed an intraluminal hypoattenuated area extending from the main pulmonary artery into the right main pulmonary artery and bilateral lobar pulmonary arteries. She underwent resection of the lobulated mass from the pulmonary artery. The tumor was diagnosed as an intimal sarcoma. Although she received chemotherapy with amrubicin and carboplatin when the tumor recurred, the tumor enlarged. After radiotherapy was performed, CT of the chest showed shrinkage of the tumor and the regression of consolidation and ground-glass opacity. Radiotherapy and chemotherapy are treatment option for patients with pulmonary artery sarcoma.

  17. Promoting Vasa Vasorum Neovascularization of Vein Grafts Extenuates Hypoxia of the Wall and Its Subsequent Influence on Intimal Hyperplasia

    PubMed Central

    Zou, Rong-Jiang; Wang, Zheng-Hua; Wang, Chen-Xi; Xue, Song

    2017-01-01

    .04 for adventitia) and Group 3 (HIF-1α: 33 ± 4% vs. 7 ± 2%, P = 0.04 for media; 13 ± 3% vs. 3 ± 1%, P = 0.02 for adventitia; HIF-2α: 27 ± 4% vs. 12 ± 3%, P = 0.02 for media; 19 ± 2% vs. 6 ± 1%, P = 0.02 for adventitia). There were no differences in mean thickness of intima, media, and adventitia between bilateral vein grafts at 2, 6, and 12 weeks postoperatively. Conclusions: This study indicated that promoting vasa vasorum neovascularization of vein grafts extenuated hypoxia, but did not influence the intimal hyperplasia of the wall. PMID:28524833

  18. Pulmonary artery intimal sarcoma: poor 18F-fluorodeoxyglucose uptake in positron emission computed tomography.

    PubMed

    Lee, Dong-Hyup; Jung, Tae-Eun; Lee, Jang-Hoon; Shin, Dong-Gu; Park, Won-Jong; Choi, Jun-Hyuk

    2013-03-07

    Intimal sarcoma of the pulmonary artery is a rare malignant tumor that may be misdiagnosed as chronic pulmonary thromboembolism, even if various imaging techniques are used. We report a case of a 58-year-old man with pulmonary artery intimal sarcoma.18F-fleuorodeoxyglucose (FDG) uptake was poor in the mass of the pulmonary artery, and no other hypermetabolic lesions were noted elsewhere. Our presumptive diagnosis was a massive mural thrombus and a concomitant chronic thromboembolism. Intravenous heparin and recombinant human tissue-type plasminogen activator was subsequently administered. However, the patient needed an emergency operation for sudden aggravation of the vital signs, and the tissue diagnosis was intimal sarcoma with poor clinical outcomes.

  19. [Intimal sarcoma of the pulmonary artery: a rare cause of pulmonary hypertension].

    PubMed

    Furest, I; Marín, M; Escribano, P; Gómez, M A; Cortinac, J; Blanquer, R

    2006-03-01

    Intimal sarcoma of the pulmonary artery is a rare tumor that is usually diagnosed during surgery or autopsy. Such tumors are characterized by local growth, with only slight ability to metastasize. Diagnosis is difficult and often delayed owing to the nonspecific nature of the symptoms. Since intimal sarcoma of the pulmonary artery is so rare and insidious it is often confused with pulmonary thromboembolism and is therefore treated inappropriately with prolonged anticoagulation or thrombolysis. With a mean survival of 12 months from the onset of symptoms, the prognosis is poor. We present the case of a woman who was preoperatively diagnosed with intimal sarcoma of the pulmonary artery and who underwent surgical resection with no apparent recurrence at long term follow-up. A review of the literature is also included.

  20. c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins.

    PubMed

    Ni, Jun; Waldman, Alla; Khachigian, Levon M

    2010-02-05

    Coronary artery bypass graft failure represents an unsolved problem in interventional cardiology and heart surgery. Late occlusion of autologous saphenous vein bypass grafts is a consequence of neointima formation underpinned by smooth muscle cell (SMC) migration and proliferation. Poor long term patency and the lack of pharmacologic agents that prevent graft failure necessitate effective alternative therapies. Our objective here was to evaluate the effect of targeted inhibition of the bZIP transcription factor c-Jun on intimal hyperplasia in human saphenous veins and vein graft stenosis after autologous end-to-side transplantation. DNAzymes targeting c-Jun attenuated intimal hyperplasia in human saphenous vein explants. Adenovirus-forced c-Jun expression stimulated SMC proliferation, proliferating cell nuclear antigen, and MMP-2 expression. c-Jun DNAzymes abrogated Adeno-c-Jun-inducible SMC growth and wound repair and reduced intimal thickening in jugular veins of New Zealand white rabbits 4 weeks after autologous end-to-side transplantation to carotid arteries. Conversely, in a DNAzyme-free setting, Adeno-c-Jun potentiated neointima formation in the veins compared with Adeno-LacZ. Inducible c-Jun expression is ERK1/2- and JNK-dependent but p38-independent. Injury- and shear-inducible c-Jun controls early growth response-1. These data demonstrate that strategies targeting c-Jun may be useful for the prevention of vein graft stenosis. Control of one important shear-responsive transcription factor by another indicates the existence of transcriptional amplification mechanisms that magnify the vascular response to cell injury or stress through inducible transcriptional networks.

  1. c-Jun Regulates Shear- and Injury-inducible Egr-1 Expression, Vein Graft Stenosis after Autologous End-to-Side Transplantation in Rabbits, and Intimal Hyperplasia in Human Saphenous Veins*

    PubMed Central

    Ni, Jun; Waldman, Alla; Khachigian, Levon M.

    2010-01-01

    Coronary artery bypass graft failure represents an unsolved problem in interventional cardiology and heart surgery. Late occlusion of autologous saphenous vein bypass grafts is a consequence of neointima formation underpinned by smooth muscle cell (SMC) migration and proliferation. Poor long term patency and the lack of pharmacologic agents that prevent graft failure necessitate effective alternative therapies. Our objective here was to evaluate the effect of targeted inhibition of the bZIP transcription factor c-Jun on intimal hyperplasia in human saphenous veins and vein graft stenosis after autologous end-to-side transplantation. DNAzymes targeting c-Jun attenuated intimal hyperplasia in human saphenous vein explants. Adenovirus-forced c-Jun expression stimulated SMC proliferation, proliferating cell nuclear antigen, and MMP-2 expression. c-Jun DNAzymes abrogated Adeno-c-Jun-inducible SMC growth and wound repair and reduced intimal thickening in jugular veins of New Zealand white rabbits 4 weeks after autologous end-to-side transplantation to carotid arteries. Conversely, in a DNAzyme-free setting, Adeno-c-Jun potentiated neointima formation in the veins compared with Adeno-LacZ. Inducible c-Jun expression is ERK1/2- and JNK-dependent but p38-independent. Injury- and shear-inducible c-Jun controls early growth response-1. These data demonstrate that strategies targeting c-Jun may be useful for the prevention of vein graft stenosis. Control of one important shear-responsive transcription factor by another indicates the existence of transcriptional amplification mechanisms that magnify the vascular response to cell injury or stress through inducible transcriptional networks. PMID:19940138

  2. Vanin-1 pantetheinase drives smooth muscle cell activation in post-arterial injury neointimal hyperplasia.

    PubMed

    Dammanahalli, K Jagadeesha; Stevens, Stephanie; Terkeltaub, Robert

    2012-01-01

    The pantetheinase vanin-1 generates cysteamine, which inhibits reduced glutathione (GSH) synthesis. Vanin-1 promotes inflammation and tissue injury partly by inducing oxidative stress, and partly by peroxisome proliferator-activated receptor gamma (PPARγ) expression. Vascular smooth muscle cells (SMCs) contribute to neointimal hyperplasia in response to injury, by multiple mechanisms including modulation of oxidative stress and PPARγ. Therefore, we tested the hypothesis that vanin-1 drives SMC activation and neointimal hyperplasia. We studied reactive oxygen species (ROS) generation and functional responses to platelet-derived growth factor (PDGF) and the pro-oxidant diamide in cultured mouse aortic SMCs, and also assessed neointima formation after carotid artery ligation in vanin-1 deficiency. Vnn1(-/-) SMCs demonstrated decreased oxidative stress, proliferation, migration, and matrix metalloproteinase 9 (MMP-9) activity in response to PDGF and/or diamide, with the effects on proliferation linked, in these studies, to both increased GSH levels and PPARγ expression. Vnn1(-/-) mice displayed markedly decreased neointima formation in response to carotid artery ligation, including decreased intima:media ratio and cross-sectional area of the neointima. We conclude that vanin-1, via dual modulation of GSH and PPARγ, critically regulates the activation of cultured SMCs and development of neointimal hyperplasia in response to carotid artery ligation. Vanin-1 is a novel potential therapeutic target for neointimal hyperplasia following revascularization.

  3. Pleomorphic intimal sarcoma of pulmonary artery. A case report.

    PubMed

    Pandit, S P; Chitale, A R; Shah, V K

    1990-12-01

    A rare case of pleomorphic intimal sarcoma of pulmonary trunk is reported. The patient presented with symptoms of right ventricular out flow tract (RVOT) obstruction. Metastatic deposits were seen in lungs, diaphragm and thyroid. Bronchial mucosal involvement was also seen. The tumour showed multicentric origin and on electron microscopic examination in a particular cell line was seen.

  4. Presentation of pulmonary artery intimal sarcoma in an infant with a history of neonatal valvular pulmonic stenosis.

    PubMed

    Chappell, Tresa; Creech, C Buddy; Parra, David; Strauss, Arnold; Scholl, Frank; Whitney, Gina

    2008-03-01

    Intimal sarcoma of the pulmonary artery is rare in the adult population. It is usually diagnosed postmortem in patients thought to have pulmonary emboli. We present a case of intimal sarcoma of the pulmonary artery in an infant with a history of neonatal pulmonic stenosis.

  5. Systemic delivery of proresolving lipid mediators resolvin D2 and maresin 1 attenuates intimal hyperplasia in mice.

    PubMed

    Akagi, Daisuke; Chen, Mian; Toy, Robert; Chatterjee, Anuran; Conte, Michael S

    2015-06-01

    Vascular injury induces a potent inflammatory response that influences vessel remodeling and patency, limiting long-term benefits of cardiovascular interventions such as angioplasty. Specialized proresolving lipid mediators (SPMs) derived from ω-3 polyunsaturated fatty acids [eicosapentaenoic acid and docosahexaenoic acid (DHA)] orchestrate resolution in diverse settings of acute inflammation. We hypothesized that systemic administration of DHA-derived SPMs [resolvin D2 (RvD2) and maresin 1 (MaR1)] would influence vessel remodeling in a mouse model of arterial neointima formation (carotid ligation). In vitro, SPM treatment inhibited mouse aortic smooth muscle cell migration (IC₅₀ ≅ 1 nM) to a PDGF gradient and reduced TNF-α-stimulated p65 translocation, superoxide production, and proinflammatory gene expression (MCP-1). In vivo, adult FVB mice underwent unilateral carotid artery ligation with administration of RvD2, MaR1, or vehicle (100 ng by intraperitoneal injection at 0, 1, 3, 5, and 7 d after ligation). In ligated carotid arteries at 4 d, SPM treatment was associated with reduced cell proliferation and neutrophil and macrophage recruitment and increased polarization of M2 macrophages in the arterial wall. Neointimal hyperplasia (at 14 d) was notably attenuated in RvD2 (62%)- and MaR1 (67%)-treated mice, respectively. Modulation of resolution pathways may offer new opportunities to regulate the vascular injury response and promote vascular homeostasis.

  6. Intimal sarcoma of the pulmonary artery: a report of two cases.

    PubMed

    Timmers, Liesbeth; Bové, Thierry; De Pauw, Michel

    2009-10-01

    Intimal sarcoma of the pulmonary artery (PAS) is a rare but potentially lethal tumour, frequently misdiagnosed as chronic thrombo-embolic pulmonary artery disease. Despite the availability of advanced imaging technologies, its preoperative diagnosis remains difficult. We report on two patients with clinical features mimicking chronic pulmonary thrombo-embolism. Further discussion will focus on the differential diagnosis with more classical causes of obstructive pulmonary vascular disease.

  7. Traumatic Intimal Tear of the Renal Artery Treated by Insertion of a Palmaz Stent

    SciTech Connect

    Goodman, Daniel N.F.; Saibil, Eric A.; Kodama, Ronald T.

    1998-01-15

    A renal artery intimal injury induced by blunt trauma in a 23-year-old man was treated by percutaneous placement of a Palmaz endovascular stent. The patient was placed on anticoagulation for 2 months following stent insertion. Nuclide renal scans demonstrated recovery of normal renal function on the affected side at 9 months postprocedure.

  8. Intimal sarcoma of the left pulmonary artery: diagnosis, treatment and survival.

    PubMed

    Gosalbez, F; Gudin, C; Miralles, M; Naya, J; Valle, J M

    1993-08-01

    A rare case of intimal sarcoma of the left pulmonary artery, diagnosed by fine needle aspiration biopsy and treated by pneumonectomy, is presented. Survival was nearly 4 years and the patient died as the result of attempted resection of a local recurrence. The literature is reviewed.

  9. Intra-Arterial Angiolymphoid Hyperplasia with Eosinophilia: A Rare Case Report of Peripheral Medium Sized Muscular Artery Involvement.

    PubMed

    Amin, Ashima; Umashankar, T; Dsouza, Chryselle Olive

    2015-08-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon benign vasoproliferative disease with distinct clinical and histopathological features. The most common clinical presentation is dermal and subcutaneous painless nodules in the head and neck region. The involvement of medium sized peripheral muscular artery is uncommon. It predominantly affects Caucasian adults during the third and fourth decades, but is also known to occur in Asians and it very rarely occurs in children. We here by present a case of intravascular ALHE in a 46-year-old female presenting with subcutaneous forearm nodule clinically diagnosed as ulnar artery thrombosis.

  10. Roscovitine attenuates intimal hyperplasia via inhibiting NF-κB and STAT3 activation induced by TNF-α in vascular smooth muscle cells.

    PubMed

    He, Ming; Wang, Chao; Sun, Jia-Huan; Liu, Yu; Wang, Hong; Zhao, Jing-Shan; Li, Yun-Feng; Chang, Hong; Hou, Jian-Ming; Song, Jun-Na; Li, Ai-Ying; Ji, En-Sheng

    2017-08-01

    Roscovitine is a selective CDK inhibitor originally designed as anti-cancer agent, which has also been shown to inhibit proliferation in vascular smooth muscle cells (VSMCs). However, its effect on vascular remodeling and its mechanism of action remain unknown. In our study, we created a new intimal hyperplasia model in male Sprague-Dawley rats by trypsin digestion method, which cause to vascular injury as well as the model of rat carotid balloon angioplasty. Roscovitine administration led to a significant reduction in neointimal formation and VSMCs proliferation after injury in rats. Western blot analysis revealed that, in response to vascular injury, TNF-α stimulation induced p65 and STAT3 phosphorylation and promoted translocation of these molecules into the nucleus. p65 can physically associate with STAT3 and bind to TNF-α-regulated target promoters, such as MCP-1 and ICAM-1, to initiate gene transcription. Roscovitine can interrupt activation of NF-κB and reduce expression of TNF-α-induced proinflammatory gene, thus inhibiting intimal hyperplasia. These findings provide a novel mechanism to explain the roscovitine-mediated inhibition of intimal hyperplasia induced by proinflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The Effect of Short-term Intra-arterial Delivery of Paclitaxel on Neointimal Hyperplasia and the Local Thrombotic Environment after Angioplasty

    SciTech Connect

    Yajun, E; He Nengshu Fan Hailun

    2013-08-01

    PurposeTo evaluate the effects of short-term intra-arterial delivery of paclitaxel on neointimal hyperplasia and the local thrombotic environment after angioplasty.MethodsAn experimental common carotid artery injury model was established in 60 rats, which were divided into experimental groups (40 rats) and controls (20 rats). Local intra-arterial administration of paclitaxel was applied at 2 doses (90 and 180 {mu}g/30 {mu}l), and the effects of short-term delivery of paclitaxel on neointimal hyperplasia and the expression of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated at days 15 and 30 by hematoxylin and eosin staining and immunohistochemistry.ResultsAt 15 and 30 days after injury, neointimal thickness and area, the ratio of intimal area to medial area and the stenotic rate were all significantly decreased in the group provided the high concentrations (180 {mu}g/30 {mu}l) of paclitaxel for 2 min or 10 min and in the group provided the low concentration (90 {mu}g/30 {mu}l) of paclitaxel for 10 min (p < 0.05). At 30 days after injury, there were no significant changes in TF expression among all experimental groups. PAI-1 expression increased in the neointima of the high concentration 10 min group (p < 0.05), while t-PA expression decreased in the neointima of the high concentration 2 min group (p < 0.05).ConclusionIn the rat common carotid artery injury model, the short-term delivery of paclitaxel could effectively inhibit neointimal hyperplasia in the long term, with very little influence on the local expression of TF and PAI-1.

  12. Protandim attenuates intimal hyperplasia in human saphenous veins cultured ex vivo via a catalase-dependent pathway.

    PubMed

    Joddar, Binata; Reen, Rashmeet K; Firstenberg, Michael S; Varadharaj, Saradhadevi; McCord, Joe M; Zweier, Jay L; Gooch, Keith J

    2011-03-15

    Human saphenous veins (HSVs) are widely used for bypass grafts despite their relatively low long-term patency. To evaluate the role of reactive oxygen species (ROS) signaling in intima hyperplasia (IH), an early stage pathology of vein-graft disease, and to explore the potential therapeutic effects of up-regulating endogenous antioxidant enzymes, we studied segments of HSV cultured ex vivo in an established ex vivo model of HSV IH. Results showed that HSV cultured ex vivo exhibit an ~3-fold increase in proliferation and ~3.6-fold increase in intimal area relative to freshly isolated HSV. Treatment of HSV during culture with Protandim, a nutritional supplement known to activate Nrf2 and increase the expression of antioxidant enzymes in several in vitro and in vivo models, blocks IH and reduces cellular proliferation to that of freshly isolated HSV. Protandim treatment increased the activity of SOD, HO-1, and catalase 3-, 7-, and 12-fold, respectively, and decreased the levels of superoxide (O(2)(•-)) and the lipid peroxidation product 4-HNE. Blocking catalase activity by cotreating with 3-amino-1,2,4-triazole abrogated the protective effect of Protandim on IH and proliferation. In conclusion, these results suggest that ROS-sensitive signaling mediates the observed IH in cultured HSV and that up-regulation of endogenous antioxidant enzymes can have a protective effect. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Correlation of permeability with the structure of the endothelial layer of pulmonary artery intimal explants

    SciTech Connect

    Meyrick, B.; Perkett, E.A.; Harris, T.R.; Brigham, K.L.

    1987-06-01

    Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows the authors to dissect the mechanisms responsible for endothelial damage. They have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilations and an increased rate of equilibration of tritiated water and (/sup 14/C)sucrose across the intimal explant. Exposure to endotoxin also causes interendothial dilations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Migration toward lymphocyte-conditioned medium does result in increased equilibration of (/sup 14/C)sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.

  14. Andrographolide inhibits NF-kappaBeta activation and attenuates neointimal hyperplasia in arterial restenosis.

    PubMed

    Wang, Yu-Jiu; Wang, Jin-Tao; Fan, Quan-Xin; Geng, Jian-Guo

    2007-11-01

    The NF-kappaBeta transcription factors modulate the expression of tissue factor (TF), E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1), which are essential for thrombosis and inflammation. We have previously shown that andrographolide (Andro) covalently modifies the reduced cysteine(62) of p50 - a major subunit of NF-kappaBeta transcription factors, thus blocking the binding of NF-kappaBeta transcription factors to the promoters of their target genes, preventing NF-kappaBeta activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro, but not its inactive structural analog 4H-Andro, significantly suppressed the proliferation of arterial neointima ( approximately 60% reduction) in a murine model of arterial restenosis. Consistently, p50(-/-) mice manifested attenuated neointimal hyperplasia upon arterial ligation. Notably, the same dosage of Andro did not further reduce neointimal formation in p50(-/-) mice, which implicates the specificity of Andro on p50 for treating experimental arterial restenosis. The upregulation of NF-kappaBeta target genes, including TF, E-selectin and VCAM-1, and the increased deposition of leukocytes (mainly CD68+ macrophages) were clearly detected within the injured arterial walls, all of which were significantly abolished by treatment with Andro or genetic deletion of p50. The expression of TF, E-selectin and VCAM-1 was also markedly upregulated in the patient sample of thrombotic vasculitis, indicating the clinical relevance of NF-kappaBeta activation in the pathogeneses of occlusive arterial diseases. Our data thus indicate that, by the downregulation of the NF-kappaBeta target genes that are critical in thrombosis and inflammation, specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating thrombotic arterial diseases, including neointimal hyperplasia in arterial restenosis.

  15. Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury.

    PubMed

    Pellet-Many, Caroline; Mehta, Vedanta; Fields, Laura; Mahmoud, Marwa; Lowe, Vanessa; Evans, Ian; Ruivo, Jorge; Zachary, Ian

    2015-11-01

    Neuropilins 1 and 2 (NRP1 and NRP2) play crucial roles in endothelial cell migration contributing to angiogenesis and vascular development. Both NRPs are also expressed by cultured vascular smooth muscle cells (VSMCs) and are implicated in VSMC migration stimulated by PDGF-BB, but it is unknown whether NRPs are relevant for VSMC function in vivo. We investigated the role of NRPs in the rat carotid balloon injury model, in which endothelial denudation and arterial stretch induce neointimal hyperplasia involving VSMC migration and proliferation. NRP1 and NRP2 mRNAs and proteins increased significantly following arterial injury, and immunofluorescent staining revealed neointimal NRP expression. Down-regulation of NRP1 and NRP2 using shRNA significantly reduced neointimal hyperplasia following injury. Furthermore, inhibition of NRP1 by adenovirally overexpressing a loss-of-function NRP1 mutant lacking the cytoplasmic domain (ΔC) reduced neointimal hyperplasia, whereas wild-type (WT) NRP1 had no effect. NRP-targeted shRNAs impaired, while overexpression of NRP1 WT and NRP1 ΔC enhanced, arterial re-endothelialization 14 days after injury. Knockdown of either NRP1 or NRP2 inhibited PDGF-BB-induced rat VSMC migration, whereas knockdown of NRP2, but not NRP1, reduced proliferation of cultured rat VSMC and neointimal VSMC in vivo. NRP knockdown also reduced the phosphorylation of PDGFα and PDGFβ receptors in rat VSMC, which mediate VSMC migration and proliferation. NRP1 and NRP2 play important roles in the regulation of neointimal hyperplasia in vivo by modulating VSMC migration (via NRP1 and NRP2) and proliferation (via NRP2), independently of the role of NRPs in re-endothelialization. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  16. A novel cell permeant peptide inhibitor of MAPKAP kinase II inhibits intimal hyperplasia in a human saphenous vein organ culture model.

    PubMed

    Lopes, Luciana B; Brophy, Colleen M; Flynn, Charles R; Yi, Zhengping; Bowen, Benjamin P; Smoke, Christopher; Seal, Brandon; Panitch, Alyssa; Komalavilas, Padmini

    2010-12-01

    The present study was aimed at developing a new cell-permeant peptide inhibitor (MK2i) of the kinase that phosphorylates and activates heat-shock protein (HSP)27 (MAPKAP kinase II), and evaluating the ability of this peptide to inhibit HSP27 phosphorylation and intimal thickening. The ability of MK2i to reduce HSP27 phosphorylation and cell migration was evaluated in A7R5 cells stimulated with arsenite or lysophosphatidic acid. Stable isotopic labeling using amino acids in cell culture, in combination with liquid chromatography mass spectrometry, was used to characterize the effect of MK2i on global protein expression in fibroblasts. The effect of MK2i on intimal thickening and connective tissue growth factor expression was evaluated in human saphenous vein (HSV) rings maintained with 30% fetal bovine serum for 14 days by light microscopy and immunoblotting. Pretreatment of cells with MK2i (10 μM) prior to arsenite or lysophosphatidic acid stimulation decreased phosphorylation of HSP27 (36% ± 9% and 33% ± 10%, respectively) compared with control (not pretreated) cells. MK2i also inhibited A7R5 migration, and downregulated the transforming growth factor-induced expression of collagen and fibronectin in keloid cells, two major matrix proteins involved in the development of intimal hyperplasia. Treatment of HSV segments with MK2i enhanced relaxation, reduced HSP27 phosphorylation (40% ± 17%), connective tissue growth factor expression (17% ± 5%), and intimal thickness (48.2% ± 10.5%) compared with untreated segments. On the other hand, treatment with a recombinant fusion protein containing a cell-permeant peptide attached to the HSP27 sequence increased intimal thickness of HSV segments by 48% ± 14%. Our results suggest that HSP27 may play a role in the development of processes leading to intimal hyperplasia in HSV, and reduction of HSP27 phosphorylation by MK2i may be a potential strategy to inhibit the development of intimal hyperplasia in HSV to prevent the

  17. A Novel Cell Permeant Peptide Inhibitor of MAPKAP Kinase II Inhibits Intimal Hyperplasia in a Human Saphenous Vein Organ Culture Model

    PubMed Central

    Lopes, Luciana B.; Brophy, Colleen M.; Flynn, Charles R.; Yi, Zhengping; Bowen, Benjamin P.; Smoke, Christopher; Seal, Brandon; Panitch, Alyssa; Komalavilas, Padmini

    2010-01-01

    Objective The present study was aimed at developing a new cell-permeant peptide inhibitor (MK2i) of the kinase that phosphorylates and activates HSP27 (MAPKAP kinase II), and evaluating the ability of this peptide to inhibit HSP27 phosphorylation and intimal thickening. Design of study The ability of MK2i to reduce HSP27 phosphorylation and cell migration was evaluated in A7R5 cells stimulated with arsenite or lysophosphatidic acid. Stable isotopic labeling using amino acids in cell culture (SILAC), in combination with liquid chromatography mass spectrometry was used to characterize the effect of MK2i on global protein expression in fibroblasts. The effect of MK2i on intimal thickening and CTGF expression was evaluated in human saphenous vein (HSV) rings maintained with 30% FBS for 14 days by light microscopy and immunoblotting. Results Pre-treatment of cells with MK2i (10 μM) prior to arsenite or lysophosphatidic acid stimulation decreased phosphorylation of HSP27 (36±9% and 33±10% respectively) compared to control (not pre-treated) cells. MK2i also inhibited A7R5 migration, and downregulated the TGF-induced expression of collagen and fibronectin in keloid cells, two major matrix proteins involved in the development of intimal hyperplasia. Treatment of HSV segments with MK2i enhanced relaxation, reduced HSP27 phosphorylation (40±17%), CTGF expression (17±5%) and intimal thickness (48.2±10.5%) compared to untreated segments. On the other hand, treatment with a recombinant fusion protein containing a cell permeant peptide attached to the HSP27 sequence increased intimal thickness of HSV segments by 48±14%. Conclusion Our results suggest that HSP27 may play a role in the development of processes leading to intimal hyperplasia in HSV, and reduction of HSP27 phosphorylation by MK2i may be a potential strategy to inhibit the development of intimal hyperplasia in HSV to prevent the autologous vascular graft failure. PMID:20864298

  18. Accumulation of intimal platelets in cerebral arteries following experimental subarachnoid hemorrhage in cats

    SciTech Connect

    Haining, J.L.; Clower, B.R.; Honma, Y.; Smith, R.R.

    1988-07-01

    From 2 hours to 23 days following experimental subarachnoid hemorrhage, the accumulation of indium-111-labeled platelets on the intimal surface of the middle cerebral artery was studied in 23 cats. Subarachnoid hemorrhage was produced by transorbital rupture of the right middle cerebral artery. Of the 23 cats, 17 exhibited right middle cerebral artery/left middle cerebral artery radioactivity ratios of greater than 1.25. When these results were compared with those of 12 control cats, 0.001 less than p less than 0.005 (chi2 test). Thus, the results from the control and experimental groups are significantly different and indicate early (after 2 hours) preferential accumulation of intimal platelets in the ruptured right middle cerebral artery compared with the unruptured left middle cerebral artery and new platelet deposition continuing for up to 23 days. However, the experimental group did not reveal a clear pattern for platelet accumulation following subarachnoid hemorrhage. There was no simple correlation between the magnitude of the radioactivity ratios and the time after hemorrhage when the cats were killed although the ratios for 2 hours to 7 days seemed greater than those for 8 to 23 days. Assuming the pivotal role of platelets in the angiopathy of subarachnoid hemorrhage, the administration of antiplatelet agents as soon as possible following its occurrence may be of value.

  19. Posttraumatic innominate artery aneurysm with occlusion of the common carotid artery at its origin by an intimal flap.

    PubMed

    Edwards, J D; Sapienza, P; Lefkowitz, D M; Thorpe, P E; McGregor, P E; Agrawal, D K; Samocha, M S

    1993-07-01

    Blunt trauma involving the innominate and carotid arteries is a rare occurrence that can be lethal or have serious neurologic sequelae. To our knowledge this is the first reported case in the international literature describing the association of posttraumatic innominate artery aneurysm with total occlusion and thrombosis of the common carotid artery at its origin by an intimal flap. The diagnostic problems created by this unusual injury are discussed. In this case the patency of the distal portion of the common and internal carotid arteries was demonstrated by magnetic resonance angiography (MRA), whereas color duplex and digital arteriographic studies were unsuccessful. This demonstration was crucial to patient management. Since no studies are available comparing color duplex imaging, conventional arteriography, and MRA in the evaluation of blunt carotid trauma, this case study is presented to demonstrate the utility of MRA in emergency situations. In addition, we analyze the possible pathogenesis and discuss the surgical treatment.

  20. Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

    PubMed Central

    Vos, Annelotte; Van Hecke, Wim; Vink, Aryan; Bleys, Ronald L. A. W.; Verdoorn, Daphne; Mali, Willem P. Th. M.; Hendrikse, Jeroen; Koek, Huiberdina L.; de Jong, Pim A.; De Vis, Jill B.

    2017-01-01

    Background Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. Methods First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. Results First, CT features of the score were circularity (absent, dot(s), <90°, 90–270° or 270–360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. Conclusions The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification. PMID:28060941

  1. Valsartan prevents neointimal hyperplasia after carotid artery stenting by suppressing endothelial cell injuries.

    PubMed

    Suzuki, Hidenori; Sano, Takanori; Umeda, Yasuyuki; Yamamoto, Akitaka; Toma, Naoki; Sakaida, Hiroshi; Taki, Waro

    2015-01-01

    Restenosis or neointimal hyperplasia remains an important complication after carotid artery stenting (CAS) for carotid artery stenosis. The purpose of this study was to examine if an anti-hypertensive drug, angiotensin receptor blocker (ARB), prevents post-CAS neointimal hyperplasia during the first 1-year period after CAS, and to clarify the possible mechanisms. Hypertension had been treated with a calcium channel blocker (CCB) and/or an ARB, valsartan, by the preference of the neurosurgeon in charge in our department. At admission to perform CAS, patients were assigned to normotensive, valsartan (hypertensive patients treated with valsartan with/without any kind of CCBs), and non-valsartan (hypertensive patients treated with any kind of CCBs without ARBs) groups. Post-CAS neointimal hyperplasia was evaluated by carotid duplex ultrasound imaging in terms of intima-media thickening (IMT), which was performed at pre-CAS and at 90, 180, 270, and 360 days post-CAS. Biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein, tenascin-C) and endothelial cell injury (von Willebrand factor [vWF] antigen) were measured at pre-CAS and at 1, 7, and 180 days post-CAS. The non-valsartan group (n  =  8) had a higher incidence of maximum in-stent IMT ≧ 1.1 mm compared with the normotensive group (n  =  6). Valsartan (n  =  9) significantly suppressed plasma vWF levels at 7 days post-CAS and decreased the incidence of maximum in-stent IMT ≧ 1.1 mm compared with the non-valsartan group, although clinical parameters were similar between the two groups. Other biomarkers were not significantly different among the three groups. These findings suggest that valsartan may prevent post-CAS neointimal hyperplasia possibly by suppressing endothelial cell injury.

  2. Pulmonary artery intimal sarcoma diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration

    PubMed Central

    Caraway, Nancy P.; Salina, Davide; Deavers, Michael T.; Morice, Rodolfo; Landon, Gene

    2015-01-01

    Intimal sarcoma of the pulmonary artery is a rare intraluminal malignant neoplasm that has an aggressive biological behavior, and early diagnosis may improve patient outcome. We describe a case of pulmonary artery intimal sarcoma diagnosed on cytologic material obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy with rapid on-site evaluation (ROSE). The aspirate showed loosely cohesive clusters of pleomorphic malignant spindled and epithelioid cells. An immunostain panel did not demonstrate any definitive mesenchymal or epithelial differentiation. The tumor's intraluminal origin was supported by radiographic imaging studies. Subsequently, the patient received preoperative chemotherapy and underwent tumor resection with reconstruction. This report describes the cytomorphologic features of this rare intravascular tumor and demonstrates how EBUS-TBNA with ROSE was instrumental in obtaining optimal cytologic sampling for ancillary studies, thus expediting the management. PMID:25745502

  3. Pulmonary artery intimal sarcoma diagnosed using endobronchial ultrasound-guided transbronchial needle aspiration.

    PubMed

    Caraway, Nancy P; Salina, Davide; Deavers, Michael T; Morice, Rodolfo; Landon, Gene

    2015-01-01

    Intimal sarcoma of the pulmonary artery is a rare intraluminal malignant neoplasm that has an aggressive biological behavior, and early diagnosis may improve patient outcome. We describe a case of pulmonary artery intimal sarcoma diagnosed on cytologic material obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy with rapid on-site evaluation (ROSE). The aspirate showed loosely cohesive clusters of pleomorphic malignant spindled and epithelioid cells. An immunostain panel did not demonstrate any definitive mesenchymal or epithelial differentiation. The tumor's intraluminal origin was supported by radiographic imaging studies. Subsequently, the patient received preoperative chemotherapy and underwent tumor resection with reconstruction. This report describes the cytomorphologic features of this rare intravascular tumor and demonstrates how EBUS-TBNA with ROSE was instrumental in obtaining optimal cytologic sampling for ancillary studies, thus expediting the management.

  4. Pulmonary intimal sarcoma: a rare differential diagnosis for arterial filling defects on a chest CT

    PubMed Central

    Huber, Adrian; Ott, Daniel; Christe, Andreas

    2014-01-01

    We present a rare case of pulmonary intimal sarcoma mimicking pulmonary embolism in a 40-year-old woman. Although extremely rare, these tumors must be considered in patients who present inappropriate imaging findings that suggest embolism. Chest computed tomography is the modality of choice to determine the extent of the tumor. We present a female patient with suspected embolism that was in fact found to be an endothelial sarcoma of the pulmonary arteries. PMID:24778802

  5. Pulmonary intimal sarcoma: a rare differential diagnosis for arterial filling defects on a chest CT.

    PubMed

    Ebner, Lukas; Huber, Adrian; Ott, Daniel; Christe, Andreas

    2014-02-01

    We present a rare case of pulmonary intimal sarcoma mimicking pulmonary embolism in a 40-year-old woman. Although extremely rare, these tumors must be considered in patients who present inappropriate imaging findings that suggest embolism. Chest computed tomography is the modality of choice to determine the extent of the tumor. We present a female patient with suspected embolism that was in fact found to be an endothelial sarcoma of the pulmonary arteries.

  6. Crucial role of nuclear factor-kappaB in neointimal hyperplasia of the mouse carotid artery after interruption of blood flow.

    PubMed

    Squadrito, Francesco; Deodato, Barbara; Bova, Antonio; Marini, Herbert; Saporito, Francesco; Calò, Margherita; Giacca, Mauro; Minutoli, Letteria; Venuti, Francesco S; Caputi, Achille P; Altavilla, Domenica

    2003-02-01

    We used a molecular genetics approach to investigate the role of nuclear factor-kappaB (NF-kappaB) in neointimal hyperplasia induced by flow interruption of carotid artery in mice. Wild type mice (WT mice) and mice rendered deficient in p105, the precursor of p50, one of the components of the multimeric transcription factor NF-kappaB (NF-kappaB knockout mice; KO mice), were subjected to a complete ligation of the left common carotid artery. Morphometric analysis of the structural alteration caused by the disruption of the arterial blood flow was performed 14 days after surgery. Furthermore the expression of intercellular adhesion molecule-1 (ICAM-1) in injured arteries was evaluated 4 days after artery ligation by the means of reverse transcriptase polymerase chain reaction (RT-PCR) and quantification of the ICAM-1 protein levels. In a separate experiment normal mice were randomly assigned to receive a recombinant adeno-associated virus (rAAV) encoding the gene for the NF-kappaB inhibitory protein IkappaBalpha (rAAV-IkappaBalpha), or the beta-galactosidase gene (rAAV-LacZ), both at a dose of 10(11) copies and 2 weeks later were subjected to the complete ligation of the left carotid artery. NF-kappaB activity (studied by means of electrophoretic mobility shift assay-EMSA), IkappaBalpha expression (evaluated by Western blot analysis) ICAM-1 evaluation (RT-PCR and quantification of the protein levels) and a morphometric analysis were evaluated in the injured arteries. Disruption of the arterial blood flow caused a marked neointimal hyperplasia. The mean intimal area was 0.023+/-0.002 mm(2) in wild type mice compared with 0.002+/-0.001 mm(2) in NF-kappaB knockout mice. ICAM-1 expression was 1.7+/-0.8 relative amount of ICAM-1 mRNA in wild type mice compared with 0.4+/-0.06 relative amount of ICAM-1 mRNA in NF-kappaB knockout mice. ICAM-1 protein levels were also significantly reduced in NF-kappaB knockout mice. Injured arteries treated with rAAV-IkappaBalpha had a

  7. A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia.

    PubMed

    Xu, Rong-Wei; Zhang, Wen-Jian; Zhang, Jian-Bin; Wen, Jian-Yan; Wang, Meng; Liu, Hong-Lin; Pan, Lin; Yu, Chang-An; Lou, Jin-Ning; Liu, Peng

    2015-12-20

    Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells (EPCs) derived from human early fetal aortas in rat injured arteries. The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas (<14 weeks) were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control (P < 0.05) and the residual lumen area was larger (P < 0.05). After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human von Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury.

  8. A Preliminary Study of the Therapeutic Role of Human Early Fetal Aorta-derived Endothelial Progenitor Cells in Inhibiting Carotid Artery Neointimal Hyperplasia

    PubMed Central

    Xu, Rong-Wei; Zhang, Wen-Jian; Zhang, Jian-Bin; Wen, Jian-Yan; Wang, Meng; Liu, Hong-Lin; Pan, Lin; Yu, Chang-An; Lou, Jin-Ning; Liu, Peng

    2015-01-01

    Background: Endothelial cell damage is an important pathophysiological step of restenosis after angioplasty and stenting. Cell transplantation has great therapeutic potential for endothelial recovery. We investigated the effect of transplanting endothelial progenitor cells (EPCs) derived from human early fetal aortas in rat injured arteries. Methods: The carotid arterial endothelium of Sprague-Dawley rats was damaged by dilatation with a 1.5 F balloon catheter, and then EPCs derived from human early fetal aortas (<14 weeks) were injected into the lumen of the injured artery in transplanted rats, with an equal volume of normal saline injected into control rats. Rats were sacrificed at 2 and 4 weeks after treatment and transplanted cells were identified by immunohistochemical staining with anti-human CD31 and anti-human mitochondria antibodies. Arterial cross-sections were analyzed by pathology, immunohistochemistry, and morphometry. Results: Green fluorescence-labeled EPCs could be seen in the endovascular surface of balloon-injured vessels after transplantation. The intimal area and intimal/medial area ratio were significantly smaller in the transplanted group than in the control (P < 0.05) and the residual lumen area was larger (P < 0.05). After EPC transplantation, a complete vascular endothelial layer was formed, which was positive for human von Willebrand factor after immunohistochemical staining, and immunohistochemical staining revealed many CD31- and mitochondria-positive cells in the re-endothelialized endothelium with EPC transplantation but not control treatment. Conclusion: EPCs derived from human early fetal aorta were successfully transplanted into injured vessels and might inhibit neointimal hyperplasia after vascular injury. PMID:26668152

  9. Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

    SciTech Connect

    Carnevale, Francisco C.; Antunes, Alberto A.

    2013-12-15

    Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

  10. Evidence for the Use of Multiple Mechanisms by Herpes Simplex Virus-1 R7020 to Inhibit Intimal Hyperplasia

    PubMed Central

    McCormick, Susan; He, Qi; Stern, Jordan; Khodarev, Nikolai; Weichselbaum, Ralph; Skelly, Christopher L.

    2015-01-01

    Intimal hyperplasia (IH) is the primary cause of vein bypass graft failure. The smooth muscle cell (SMC) is a key element of IH as it phenotypically switches from a contractile to a synthetic state which can become pathological. R7020, which is an engineered strain of Herpes Simplex Virus-1, inhibits IH in animal models. Although it has many characteristics which make it a strong candidate for use as a prophylactic agent how it inhibits IH is not well understood. The objective of this study was to identify modes of action used by R7020 to function in blood vessels that may also contribute to its inhibition of IH. The cytopathic effect of R7020 on SMCs was determined in vitro and in a rabbit IH model. In vitro assays with R7020 infected SMCs were used to quantify the effect of dose on the release kinetics of the virus as well as the effects of R7020 on cell viability and the adhesion of peripheral blood mononuclear cells (PBMCs) to SMCs in the absence and presence of tumor necrosis factor alpha (TNF-α). The observed cytopathic effect, which included R7020 positive filopodia that extend from cell to cell and the formation of syncytia, suggests that R7020 remains cell associated after egress and spreads cell to cell instead of by diffusion through the extracellular fluid. This would allow the virus to rapidly infect vascular cells while evading the immune system. The directionality of the filopodia in vivo suggests that the virus preferentially travels from the media towards the intima targeting SMCs that would lead to IH. The formation of syncytia would inhibit SMC proliferation as incorporated cells are not able to multiply. It was also observed that R7020 induced the fusion of PBMCs with syncytia suggesting the virus may limit the effect of macrophages on IH. Furthermore, R7020 inhibited the proliferative effect of TNF-α, an inflammatory cytokine associated with increased IH. Thus, the results of this study suggest that R7020 inhibits IH through multiple

  11. A nitinol "U-Clip" versus sutured arteriovenous anastomosis: local tissue response and intimal hyperplasia development in a sheep model.

    PubMed

    Varcoe, R L; Teo, A B P; Pelletier, M H; Yu, Y; Yang, J L; Crowe, P J; Walsh, W R

    2015-03-01

    This study sought to compare the local tissue response and subsequent volume of intimal hyperplasia (IH) that develops throughout the maturation of an arteriovenous fistula created using continuous/interrupted polypropylene with that of a novel, metal-alloy, penetrating anastomotic clip device. Forty-six fistulae were created in 23 sheep under a paired design using the nitinol U-Clip (n = 23) in one hind limb and continuous (n = 20) or interrupted (n = 3) polypropylene suture for the other. Animals were killed at 4 (n = 3), 14 (n = 3), 28 (n = 10), 42 (n = 3), and 180 (n = 4) days. Histological sections were evaluated for quantitative histology and immunohistochemistry. Compared with continuous polypropylene, U-Clip specimens demonstrated less intima-media area per unit length (IMA/L), proliferating cells, and tissue necrosis at all time points (MANOVA, F = 9.8-24.1, all p ≤ .005; observed power >82%). Specifically, values of IMA/L were reduced by 5% (p = .97), 37% (p = .02), 33% (p < .01), 9% (p = .42), and 14% (p = .22) at the time points of 4, 14, 28, 42, and 180 days respectively. Proliferating cells were reduced by 75% (p < .01), 72% (p = .03), 76% (p = .03), 27% (p = .31), and 60% (p = .01) and tissue necrosis by 67% (p < .01), 58% (p = .02), 40% (p = .33), 21% (p = .43), 77% (p = .11). In a 28-day comparison between U-Clip and interrupted polypropylene the U-Clip group demonstrated a 4% (p = .65) reduction in IMA/L, 74% (p < .01) in proliferating cells and 49% (p < .05) in tissue necrosis. These results provide evidence of reduced local tissue necrosis, proliferating cells, and IH, favouring arteriovenous fistulae created using the U-Clip anastomotic device over conventional polypropylene suture techniques most evident over the first 4 weeks. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  12. The histology of prostate tissue following prostatic artery embolization for the treatment of benign prostatic hyperplasia.

    PubMed

    Camara-Lopes, George; Mattedi, Romulo; Antunes, Alberto A; Carnevale, Francisco C; Cerri, Giovanni G; Srougi, Miguel; Alves, Venancio A; Leite, Katia R M

    2013-01-01

    Prostatic artery embolization (PAE) for the treatment of patients with symptomatic benign prostatic hyperplasia (BPH) is believed to be a safe procedure with a low risk of adverse side effects. Artery embolization is a viable treatment option in patients who are refractory to the classic noninvasive treatments. Knowledge of the histological characteristics of prostate tissue following the procedure is still limited. In this study, we describe the microscopic aspects of the prostate following PAE for BPH. Two patients underwent transurethral resections of the prostate (TURP) after PAE. Embolizations were performed under local anesthesia with an initial pelvic angiography to evaluate the iliac vessels and the prostate arteries using a 2.8 French microcatheter. The prostate was embolized with 300-500 µm Microspheres (Embosphere ®), using complete blood stasis as the end point. The prostate tissues were analyzed histologically to characterize the effects of the embolization. The embolic material within the prostate tissue was easily identified as homogeneous, bright eosin-red spheroids filling the vessel lumens. Ischemic necrosis surrounded or not by chronic inflammatory reactions containing macrophages were considered as a result of the artery embolization. Also, some aspects related to the healing process were observed being fibrotic nodules surrounded by glands with squamous metaplasia of the epithelial lining the most important. In the remaining sections, due to the precocious surgical intervention, the classic findings of BPH were still present with the glandular and stromal hyperplasia associated with nonspecific chronic prostatitis. This is the first description of prostate histology in BPH patients treated by PAE, a new procedure that is being used increasingly as a therapeutic intervention. The recognition of the changes caused by this new modality of treatment has become a very important differential in a chronic granulomatous reaction of the prostate

  13. Pulmonary artery intimal sarcoma: the role of ¹⁸F-fluorodeoxyglucose positron emission tomography in monitoring response to treatment.

    PubMed

    Ote, Enrique Leonardo P; Oriuchi, Noboru; Miyashita, Go; Paudyal, Bishnuhari; Ishikita, Tomohiro; Arisaka, Yukiko; Higuchi, Tetsuya; Hirato, Junko; Endo, Keigo

    2011-05-01

    We report the case of 58-year-old man with pulmonary artery intimal sarcoma. He initially presented with cough, right-sided chest pain, and shortness of breath. Although the diagnosis of pulmonary embolism had been considered, chest radiograph and pulmonary perfusion scintigraphy showed a mass in the right hilum and no perfusion in the right lung. (18)F-fluorodeoxyglucose positron emission computed tomography (FDGPET) showed increased FDG uptake in the mass obstructing the right pulmonary artery. Fine-needle biopsy revealed a pathological diagnosis of pulmonary artery intimal sarcoma. The patient was successfully treated with radiotherapy and adjuvant chemotherapy. FDG-PET was used for monitoring the response to therapy.

  14. Diarrhea as initial manifestation of pulmonary artery intimal sarcoma: a case report and literature review.

    PubMed

    Xu, Xiaoling; Zhang, Ruifeng; Hu, Huihui; Ye, Wu; Wang, Jin; Chen, Liying; Qiu, Lijun; Ying, Kejing

    2015-01-01

    Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We report a case of a 40-year-old female who presented with diarrhea as the initial symptom, was misdiagnosed and received thrombolytic therapy for presumed pulmonary embolism. Progressive symptoms and subsequent surgery led to the diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as initial manifestation of PAIS has not been described.

  15. Diarrhea as initial manifestation of pulmonary artery intimal sarcoma: a case report and literature review

    PubMed Central

    Xu, Xiaoling; Zhang, Ruifeng; Hu, Huihui; Ye, Wu; Wang, Jin; Chen, Liying; Qiu, Lijun; Ying, Kejing

    2015-01-01

    Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We report a case of a 40-year-old female who presented with diarrhea as the initial symptom, was misdiagnosed and received thrombolytic therapy for presumed pulmonary embolism. Progressive symptoms and subsequent surgery led to the diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as initial manifestation of PAIS has not been described. PMID:26425101

  16. [Resection and reconstruction of intimal sarcoma of the pulmonary artery with autologous pericardial roll].

    PubMed

    Takai, Noriko; Yamamoto, Yoshio; Kitayama, Hitoshi; Nakagawa, Tatsushi

    2010-09-01

    Tumors of the pulmonary artery (PA) are rare and their prognosis is poor. Proper diagnosis is often delayed or made post mortem despite diagnostic advances. Although the only treatment of choice is radical surgical resection, local recurrences are soon recognized after the operation. There is no standard regimen of perioperative additional therapy, and its effectiveness is still unknown. We report a case of an 80-year-old male whose PA was almost completely obstructed by the intimal sarcoma. It was resected and reconstructed with autologous pericardial roll. His postoperative course was uneventful.

  17. Intimal sarcoma of the pulmonary artery: report of an autopsy case.

    PubMed

    Miura, Shiro; Meirmanov, Serik; Nakashima, Masahiro; Hayashi, Tomayoshi; Abe, Kuniko; Tamaru, Naoe; Miyahara, Yoshiyuki; Sekine, Ichiro

    2005-01-01

    Primary pulmonary artery sarcomas (PASs) are rare and lethal tumors. They are easily misdiagnosed as chronic pulmonary embolism, mediastinal mass or tumor emboli, which delay a proper treatment. Although the advanced technologies are now increasingly being used, their diagnosis is usually hard to establish preoperatively at the present time. We report here a case of a 68-year-old female with PAS with lung metastases, who firstly presented with symptoms of common cold and anemia. Although a PAS had been suspected, the final diagnosis of pulmonary intimal sarcoma was made only postoperatively by histological and immunohistochemical examination. The patient died 8 months after the operation because of tumor growth progression, despite adjuvant chemotherapy and radiation therapy. Although pulmonary intimal sarcomas are usually of poorly differentiated mesenchymal malignancy, most reported cases are immunohistochemically positive for vimentin, alpha-smooth muscle actin (SMA), and/or desmin, therefore resembling leiomyosarcomas. However, the diagnosis of leiomyosarcoma should not be made on the basis of immunostains in the absence of typical morphologic features, and PAS, like the present case, should be more appropriately classified as intimal sarcoma according to the new WHO Classification of Tumours of Soft Tissue and Bone published in 2002.

  18. Angiolymphoid Hyperplasia with Eosinophilia Involving the Occipital Artery: Case Report and Review of Literature

    PubMed Central

    Martos-Fernandez, Miriam; Alberola-Ferranti, Margarita; Pablo-Garcia-Cuenca, Alba De; Bescosatin, Coro

    2017-01-01

    Angiolymphoid Hyperplasia with Eosinophilia (ALHE) is an atypical vascular tumour occurring primarily in the head and neck area, which must be distinguished from Kimura’s disease. The lesions can appear as single or multiple grouped intradermal papules or subcutaneous nodules. We report a rare case of ALHE in a 57-year-old female with a large lesion of three nodules involving the right occipital artery which had a long term evolution and we treated it by surgical excision. The definitive histopathological diagnosis was ALHE. Our case report is accompanied by a discussion of clinical, radiological and histological features. Surgical excision with free margins is the treatment of choice but, even though ALHE is considered a benign condition, recurrence is common. PMID:28511526

  19. Vitamin K antagonism aggravates chronic kidney disease-induced neointimal hyperplasia and calcification in arterialized veins: role of vitamin K treatment?

    PubMed

    Zaragatski, Emma; Grommes, Jochen; Schurgers, Leon J; Langer, Stephan; Kennes, Lieven; Tamm, Miriam; Koeppel, Thomas A; Kranz, Jennifer; Hackhofer, Tina; Arakelyan, Karen; Jacobs, Michael J; Kokozidou, Maria

    2016-03-01

    Arteriovenous fistula (AVF) is the common vascular access type for a hemodialysis patient. Its failure is due to neointimal hyperplasia. Vitamin K antagonists are given to lower thrombosis tendency, but have side effects that enhance arterial calcifications. Here, we investigated the effects of vitamin K antagonists and vitamin K2 (K2) treatment on neointimal hyperplasia development and calcification in rats and in arterialized human veins. AVF was generated in female rats while chronic kidney disease (CKD) was induced using an adenine-enriched diet. Arterialization, CKD, and vitamin K antagonists all significantly enhanced venous neointimal hyperplasia. K2 treatment, additional to vitamin K antagonists, significantly reduced neointimal hyperplasia in arterialized veins in healthy rats but not in rats with CKD. Arterialization, CKD, and vitamin K antagonism all significantly increased, whereas K2 supplementation attenuated calcification in healthy rats and rats with CKD. K2 significantly enhanced matrix Gla protein carboxylation in control rats and rats with CKD. Arterialized human vein samples contained inactive matrix Gla protein at calcification and neointimal hyperplasia sites, indicating local vitamin K deficiency. Thus, vitamin K antagonists have detrimental effects on AVF remodeling, whereas K2 reduced neointimal hyperplasia and calcification indicating vasoprotective effects. Hence, K2 administration may be useful to prevent neointimal hyperplasia and calcification in arterialized veins

  20. Prevention of occlusive arterial thrombus formation by a single loading dose of prasugrel suppresses neointimal hyperplasia in mice.

    PubMed

    Ohno, Kousaku; Tomizawa, Atsuyuki; Jakubowski, Joseph A; Mizuno, Makoto; Sugidachi, Atsuhiro

    2015-12-01

    The present study examined the effects of prasugrel in a mouse model of thrombosis-induced neointimal hyperplasia. Following carotid artery injury by application of ferric chloride solution, thrombus formation was assessed on Day 1 and neointimal thickening was assessed on Day 21. Single administrations of prasugrel at 0.3-3mg/kg (p.o.) resulted in a dose-related and sustained inhibition of ADP-induced platelet aggregation through 24h. Single and multiple (1 and 3 weeks) administration of prasugrel (3mg/kg loading and 1mg/kg/day maintenance doses) resulted in a marked inhibition of neointimal thickening in the injured artery. In the dose-response study, a single administration of prasugrel at 0.3-3mg/kg (p.o.) dose-relatedly inhibited thrombus formation and neointimal thickening on Days 1 and 21, respectively. The degree of neointimal hyperplasia in the injured artery correlated significantly with the thrombus indices, time to occlusion and patency rate. To explore possible mechanisms of inhibition of neointimal hyperplasia by prasugrel, mRNA expression levels of inflammatory and fibrosis markers were determined in injured arteries. Prasugrel treatment resulted in reduced MCP-1, ICAM-1 and TGF-β mRNA levels on Day 2 (24h after the injury) and Day 8 (1 week after the injury) in the target arteries. In conclusion, we found that a single oral loading dose of prasugrel markedly prevented neointimal hyperplasia by inhibiting platelet activation and thrombus formation and was associated with inhibition of the expression of inflammatory and fibrosis markers, including MCP-1, ICAM-1 and TGF-β, in the injured arteries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Mechanical Properties of Coronary Arteries and Internal Mammary Arteries Beyond Physiological Deformations

    DTIC Science & Technology

    2007-11-02

    initiate intimal hyperplasia , which could eventually lead to stenosis of the anastomosis. Therefore it is important to know more about the mechanical...the case for the muscular coronary artery. Fig. 3 shows the typical stress-strain relationship in circumferential direction of one coronary artery at...coronary artery is an artery of the muscular type, which means that the media consists mainly of smooth muscle cells. The IMA is an elastic artery

  2. Effect of D-003 on intimal thickening and circulating endothelial cells in rabbit cuffed carotid artery.

    PubMed

    Noa, Miriam; Mendoza, Sarahí; Más, Rosa

    2005-01-01

    D-003 is a mixture of very-high-molecular-weight aliphatic primary acids purified from sugar-cane (Saccharum officinarum L.) wax, in which octacosanoic acid is the most abundant component. Previous experimental studies have shown that D-003 not only shows cholesterol-lowering and anti-platelet effects, but also reduces thromboxane B2 and increases prostacyclin levels. It acts by inhibiting cholesterol biosynthesis. The positioning of a non-occlusive silicone collar around the rabbit carotid artery results in the formation of a neointima. Collars were placed around the left carotid for 15 days. The contralateral artery was sham-operated. We included three experimental groups: A control group received vehicle, and two others received D-003 at 5 and 25 mg/kg until sacrificed. Samples of arteries were examined by light microscopy. To evaluate intimal thickening the cross-sectional areas of intima and media were measured. Neointima was significantly reduced in D-003-treated animals compared with controls. Furthermore, the circulating endothelial cell has been studied in this experimental model with endothelium damage. The results demonstrate the protective effect of D-003 on vascular endothelium of the studied rabbits. It is concluded that the protective effect of D-003 against neointima formation and circulating endothelial cells in this experimental model could represent potential beneficial pleiotropic effects in the anti-atherogenic profile of this substance, beyond its cholesterol-lowering and anti-platelet effects independently demonstrated.

  3. Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients

    SciTech Connect

    Carnevale, Francisco Cesar; Antunes, Alberto Azoubel; Motta Leal Filho, Joaquim Mauricio da; Oliveira Cerri, Luciana Mendes de; Baroni, Ronaldo Hueb; Marcelino, Antonio Sergio Zafred; Freire, Geraldo Campos; Moreira, Airton Mota; Srougi, Miguel; Cerri, Giovanni Guido

    2010-04-15

    Symptomatic benign prostatic hyperplasia (BPH) typically occurs in the sixth and seventh decades, and the most frequent obstructive urinary symptoms are hesitancy, decreased urinary stream, sensation of incomplete emptying, nocturia, frequency, and urgency. Various medications, specifically 5-{alpha}-reductase inhibitors and selective {alpha}-blockers, can decrease the severity of the symptoms secondary to BPH, but prostatectomy is still considered to be the traditional method of management. We report the preliminary results for two patients with acute urinary retention due to BPH, successfully treated by prostate artery embolization (PAE). The patients were investigated using the International Prostate Symptom Score, by digital rectal examination, urodynamic testing, prostate biopsy, transrectal ultrasound (US), and magnetic resonance imaging (MRI). Uroflowmetry and postvoid residual urine volume complemented the investigation at 30, 90, and 180 days after PAE. The procedure was performed under local anesthesia; embolization of the prostate arteries was performed with a microcatheter and 300- to 500-{mu}m microspheres using complete stasis as the end point. One patient was subjected to bilateral PAE and the other to unilateral PAE; they urinated spontaneously after removal of the urethral catheter, 15 and 10 days after the procedure, respectively. At 6-month follow-up, US and MRI revealed a prostate reduction of 39.7% and 47.8%, respectively, for the bilateral PAE and 25.5 and 27.8%, respectively, for the patient submitted to unilateral PAE. The early results, at 6-month follow-up, for the two patients with BPH show a promising potential alternative for treatment with PAE.

  4. Effect of verapamil on intimal thickening and vascular reactivity in the collared carotid artery of the rabbit.

    PubMed Central

    Ustünes, L.; Yasa, M.; Kerry, Z.; Ozdemir, N.; Berkan, T.; Erhan, Y.; Ozer, A.

    1996-01-01

    1. Intimal thickening is a common site for atherosclerosis. Therefore, we investigated whether the calcium entry blocker verapamil (10 mg kg-1 body weight day-1, s.c.) can retard intimal thickening and changes in vascular reactivity induced by a non-occlusive, silicone collar positioned around the left carotid artery of rabbits. The contralateral carotid artery was sham-operated and served as a control. 2. Verapamil and placebo (saline 0.1 ml kg-1, day-1, s.c.) treatments were initiated 7 days before placing the collar and lasted 3 weeks. Thereafter, segments were cut from collared and sham-treated arteries for histology and isometric tension recording. 3. The intima/media (I/M ratio increased after 14 days of collar treatment, but intimal thickening was not inhibited by verapamil (I/M ratio placebo 0.31 +/- 0.07, verapamil 0.32 +/- 0.09). 4. The collar decreased the capacity to develop force, as indicated by the response to a supramaximal concentration of KCl, decreased the sensitivity (pD2) to acetylcholine (ACh) and phenylephrine (Phe), but increased the sensitivity to 5-hydroxytryamine (5-HT). 5. Although verapamil did not affect intimal thickening, it normalized the hypersensitivity to 5-HT in collared arteries. 6. The contraction to the supramaximal concentration of KCl was not affected by verapamil. Verapamil decreased the Emax of ACh, but this was only seen in collar-treated arteries. Verapamil also decreased the sensitivity to ACh and Phe, in both sham- and collar-treated arteries. 7. We conclude that verapamil, without preventing thickening of the intima, can modify collar-induced changes in vascular reactivity. PMID:8842432

  5. Low-dose psoralen and UVA (PUVA) therapy-enhanced arterial shrinkage after balloon angioplasty in rabbits

    NASA Astrophysics Data System (ADS)

    Perree, Jop; van Leeuwen, Ton G. J. M.; Velema, Evelyn; Borst, Cornelius

    1998-07-01

    Restenosis after balloon angioplasty is caused by both intimal hyperplasia and arterial shrinkage (constrictive remodeling). Previous studies have indicated the inhibitory effect of photodynamic therapy on intimal hyperplasia development after angioplasty. The potential of a photoactivation regime (Psoralen + UVA irradiation: PUVA), which does not cause unwanted systemic side effects, for the prevention of both intimal hyperplasia formation and constrictive remodeling following balloon dilation was explored in the present study. In the rabbit iliac artery, balloon dilation followed by PUVA- therapy at a radiant exposure of 1 J/cm2 was performed (n equals 10). Control balloon dilation was performed in the contralateral arteries (n equals 10). After 4 weeks of survival, angiographic lumen renarrowing was determined in terms of intimal hyperplasia and constrictive remodeling. Late loss, but not intimal hyperplasia, was significantly larger in the PUVA group as compared to the control group (p less than 0.05). This difference in angiographic lumen loss can only be attributed to the difference in constrictive remodeling (arterial shrinkage). Thus, PUVA-therapy did not prevent intimal hyperplasia following balloon dilation. PUVA-therapy even enhanced luminal narrowing by augmented constrictive arterial remodeling.

  6. Parathyroid hyperplasia

    MedlinePlus

    Enlarged parathyroid glands; Osteoporosis - parathyroid hyperplasia; Bone thinning - parathyroid hyperplasia; Osteopenia - parathyroid hyperplasia; High calcium level - parathyroid hyperplasia; Chronic kidney disease - parathyroid hyperplasia; ...

  7. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 1, Pathological Background and Clinical Implications

    SciTech Connect

    Sun, Fei Crisóstomo, Verónica Báez-Díaz, Claudia Sánchez, Francisco M.

    2016-01-15

    Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.

  8. Nitric oxide inhibits neointimal hyperplasia following vascular injury via differential, cell-specific modulation of SOD-1 in the arterial wall.

    PubMed

    Bahnson, Edward S M; Koo, Nathaniel; Cantu-Medellin, Nadiezhda; Tsui, Aaron Y; Havelka, George E; Vercammen, Janet M; Jiang, Qun; Kelley, Eric E; Kibbe, Melina R

    2015-01-30

    Superoxide (O2(•-)) promotes neointimal hyperplasia following arterial injury. Conversely, nitric oxide ((•)NO) inhibits neointimal hyperplasia through various cell-specific mechanisms, including redox regulation. What remains unclear is whether (•)NO exerts cell-specific regulation of the vascular redox environment following arterial injury to inhibit neointimal hyperplasia. Therefore, the aim of the present study was to assess whether (•)NO exerts cell-specific, differential modulation of O2(•-) levels throughout the arterial wall, establish the mechanism of such modulation, and determine if it regulates (•)NO-dependent inhibition of neointimal hyperplasia. In vivo, (•)NO increased superoxide dismutase-1 (SOD-1) levels following carotid artery balloon injury in a rat model. In vitro, (•)NO increased SOD-1 levels in vascular smooth muscle cells (VSMC), but had no effect on SOD-1 in endothelial cells or adventitial fibroblasts. This SOD-1 increase was associated with an increase in sod1 gene expression, increase in SOD-1 activity, and decrease in O2(•-) levels. Lastly, to determine the role of SOD-1 in (•)NO-mediated inhibition of neointimal hyperplasia, we performed the femoral artery wire injury model in wild type and SOD-1 knockout (KO) mice, with and without (•)NO. Interestingly, (•)NO inhibited neointimal hyperplasia only in wild type mice, with no effect in SOD-1 KO mice. In conclusion, these data show the cell-specific modulation of O2(•-) by (•)NO through regulation of SOD-1 in the vasculature, highlighting its importance on the inhibition of neointimal hyperplasia. These results also shed light into the mechanism of (•)NO-dependent redox balance, and suggest a novel VSMC redox target to prevent neointimal hyperplasia. Published by Elsevier Inc.

  9. Nitric oxide inhibits neointimal hyperplasia following vascular injury via differential, cell-specific modulation of SOD-1 in the arterial wall

    PubMed Central

    Bahnson, Edward S.M.; Koo, Nathaniel; Cantu-Medellin, Nadiezhda; Tsui, Aaron Y.; Havelka, George E.; Vercammen, Janet M.; Jiang, Qun; Kelley, Eric E.; Kibbe, Melina R.

    2014-01-01

    Superoxide (O2•−) promotes neointimal hyperplasia following arterial injury. Conversely, nitric oxide (•NO) inhibits neointimal hyperplasia through various cell-specific mechanisms, including redox regulation. What remains unclear is whether •NO exerts cell-specific regulation of the vascular redox environment following arterial injury to inhibit neointimal hyperplasia. Therefore, the aim of the present study was to assess whether •NO exerts cell-specific, differential modulation of O2•− levels throughout the arterial wall, establish the mechanism of such modulation, and determine if it regulates •NO-dependent inhibition of neointimal hyperplasia. In vivo, •NO increased superoxide dismutase-1 (SOD-1) levels following carotid artery balloon injury in a rat model. In vitro, •NO increased SOD-1 levels in vascular smooth muscle cells (VSMC), but had no effect on SOD-1 in endothelial cells or adventitial fibroblasts. This SOD-1 increase was associated with an increase in sod1 gene expression, increase in SOD-1 activity, and decrease in O2•− levels. Lastly, to determine the role of SOD-1 in •NO-mediated inhibition of neointimal hyperplasia, we performed the femoral artery wire injury model in wild type and SOD-1 knockout (KO) mice, with and without •NO. Interestingly, •NO inhibited neointimal hyperplasia only in wild type mice, with no effect in SOD-1 KO mice. In conclusion, these data show the cell-specific modulation of O2•− by •NO through regulation of SOD-1 in the vasculature, highlighting its importance on the inhibition of neointimal hyperplasia. These results also shed light into the mechanism of •NO-dependent redox balance, and suggest a novel VSMC redox target to prevent neointimal hyperplasia. PMID:25460325

  10. Robotic-Assisted Versus Manual Prostatic Arterial Embolization for Benign Prostatic Hyperplasia: A Comparative Analysis.

    PubMed

    Bagla, Sandeep; Smirniotopoulos, John; Orlando, Julie C; Piechowiak, Rachel

    2017-03-01

    Prostatic artery embolization (PAE) is a safe and efficacious procedure for benign prostatic hyperplasia (BPH), though is technically challenging. We present our experience of technical and clinical outcomes of robotic and manual PAE in patients with BPH. IRB-approved retrospective study of 40 consecutive patients 49-81 years old with moderate or severe grade BPH from May 2014 to July 2015: 20 robotic-assisted PAE (group 1), 20 manual PAE (group 2). Robotic-assisted PAE was performed using the Magellan Robotic System. American Urological Association (AUA-SI) score, cost, technical and clinical success, radiation dose, fluoroscopy, and procedure time were reviewed. Statistical analysis was performed within and between each group using paired t test and one-way analysis of variance respectively, at 1 and 3 months. No significant baseline differences in age and AUA-SI between groups. Technical success was 100% (group 1) and 95% (group 2). One unsuccessful subject from group 2 returned for a successful embolization using robotic assistance. Fluoroscopy and procedural times were similar between groups, with a non-significant lower patient radiation dose in group 1 (30,632.8 mGy/cm(2) vs 35,890.9, p = 0.269). Disposable cost was significantly different between groups with the robotic-assisted PAE incurring a higher cost (group 1 $4530.2; group 2 $1588.5, p < 0.0001). Clinical improvement was significant in both arms at 3 months: group 1 mean change in AUA-SI of 8.3 (p = 0.006), group 2: 9.6 (p < 0.0001). No minor or major complications occurred. Robotic-assisted PAE offers technical success comparable to manual PAE, with similar clinical improvement with an increased cost.

  11. Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia.

    PubMed Central

    Newman, K D; Dunn, P F; Owens, J W; Schulick, A H; Virmani, R; Sukhova, G; Libby, P; Dichek, D A

    1995-01-01

    Adenovirus vectors are capable of high efficiency in vivo arterial gene transfer, and are currently in use as therapeutic agents in animal models of vascular disease. However, despite substantial data on the ability of viruses to cause vascular inflammation and proliferation, and the presence in current adenovirus vectors of viral open reading frames that are translated in vivo, no study has examined the effect of adenovirus vectors alone on the arterial phenotype. In a rabbit model of gene transfer into a normal artery, we examined potential vascular cell activation, inflammation, and neointimal proliferation resulting from exposure to replication-defective adenovirus. Exposure of normal arteries to adenovirus vectors resulted in: (a) pronounced infiltration of T cells throughout the artery wall; (b) upregulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in arterial smooth muscle cells; (c) neointimal hyperplasia. These findings were present both 10 and 30 d after gene transfer, with no evidence of a decline in severity over time. Adenovirus vectors have pleiotropic effects on the arterial wall and cause significant pathology. Interpretation of experimental protocols that use adenovirus vectors to address either biological or therapeutic issues should take these observations into account. These observations should also prompt the design of more inert gene transfer vectors. Images PMID:8675667

  12. Variation of flow rate and angle of injected venous needle on influencing intimal hyperplasia at the venous anastomosis of the hemodialysis graft.

    PubMed

    Yang, Linqiang; Yin, Aijun; Liu, Wanqian

    2017-03-01

    During hemodialysis, arteriovenous (AV) grafts tends to result in intimal hyperplasia (IH) at the venous anastomosis which leads to graft failure. It is well documented that hemodynamic factors have been implicated in IH, as well as pathogenesis of graft stenosis. In this paper, we investigate the flow rate and angle of injection of a venous needle on damaging the hemodialysis graft. Such damage is mainly caused by hemodynamics rather than the actual physical puncture of the needle. By computational fluid dynamic analysis of flow through the AV grafts, we demonstrate that slower flow rate of the needle preserve a larger region of low wall shear stress (WSS). High needle flow angle and fast flow rate tends to induce high shearing of blood against the graft wall, and therefore resulting in a concentrated region of high WSS. Despite that, the increased flow rate causes more significant change to wall shear stress gradient than the flow angle. Obviously, it is important to optimize the injection rate since a high angle can reduce the size of the injection puncture and have smaller injury for the vessel walls; but a slower injection rate may delay hemodialysis. Therefore, the ideal angle and flow rate of needle is sought in this study.

  13. DNA aptamer raised against advanced glycation end products inhibits neointimal hyperplasia in balloon-injured rat carotid arteries.

    PubMed

    Ojima, Ayako; Oda, Eriko; Higashimoto, Yuichiro; Matsui, Takanori; Yamagishi, Sho-ichi

    2014-02-15

    Advanced glycation end products (AGE) and their receptor (RAGE) interaction elicit inflammatory and proliferative reactions in arteries, thus playing a role in cardiovascular disease. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. However, effects of AGE-aptamer on vascular injury remain unknown. In this study, we examined whether and how AGE-aptamer inhibits neointimal hyperplasia in balloon-injured rat carotid arteries. Male Wistar rats (weighting ca. 400 g at 11 weeks old) were anesthetized with sodium pentobarbital. The left common carotid artery was balloon-injured 3 times with 2F Fogaty catheter inserted through the femoral artery. Then the rats received continuous intraperitoneal infusion (3 μg/day) of either AGE-aptamer or control-aptamer by an osmotic mini pump for 2 weeks. 14 days after the procedure, the left common carotid arteries were excised for morphometric, immunohistochemical and western blot analyses. Compared with control-aptamer, AGE-aptamer significantly suppressed neointima formation after balloon injury and reduced AGE accumulation, oxidative stress generation, proliferation cell nuclear antigen-positive area, macrophage infiltration, RAGE and platelet-derived growth factor-BB (PDGF-BB) expression levels in balloon-injured carotid arteries. The present study suggests that AGE-aptamer could prevent balloon injury-induced neointimal hyperplasia by reducing PDGF-BB and macrophage infiltration via suppression of the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for suppressing neointima formation after balloon angioplasty. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. A case of intimal sarcoma of the pulmonary artery successfully treated with chemotherapy.

    PubMed

    Xu, Yanjie; Wang, Kai; Geng, Yiting; Shao, Yongfeng; Yin, Yongmei

    2012-10-01

    Intimal sarcoma of pulmonary artery (PAIS) is a rare disease with no characteristic symptoms. No standard therapeutic guidelines have been established so far. A 55-year-old woman who underwent pulmonary endarterectomy in 2005 with a pathological and immunohistochemical result of PAIS was re-admitted to our hospital on August 24, 2009, presenting with cough and dyspnea. The thoracic computed tomography (CT) scan revealed a 12.5 cm × 9 cm well-defined mass in the right lobe, considered a local neoplasm recurrence after a 44 month symptom-free period. As surgical resection was not proposed, she received combined chemotherapy consisting of doxorubicin, cisplatin, and ifosfamide for two cycles. Because of intolerable side effects, she received vinorelbine and cisplatin for the next four cycles. CT scans after six cycles showed remarkable regression of the tumor. After that, she began to take oral cyclophosphamide (50 mg t.i.d) everyday as a maintenance therapy. As of the time of writing, 19 months after the onset of the recurrence, she remains stable. Several antineoplastic drugs have been reported to be used in PAIS, with poor effects in most cases. To our knowledge, this is the first case of PAIS that has been successfully treated by a vinorelbine-based regimen used as second-line chemotherapy. Vinorelbine is a promising drug that may be relatively well tolerated in heavily pretreated patients with PAIS.

  15. Inhibition of neointimal hyperplasia after stent placement with rhenium 188-filled balloon dilation in a canine iliac artery model.

    PubMed

    Kim, Tae-Hyung; Shin, Ji Hoon; Oh, Seung-Jun; Park, In Kook; Woo, Chul-Woong; Han, Kyung Hee; Dong, Kyung-Rae

    2010-07-01

    To evaluate the efficacy of beta-irradiation therapy with rhenium 188 ((188)Re) mercaptoacetyltriglycine (MAG3)-filled balloon dilation to prevent neointimal hyperplasia after stent placement in a canine iliac artery model. A total of 15 stents were implanted into the iliac arteries of eight dogs (one or two stents in each dog). Rhenium 188 MAG3-filled balloon dilation was performed immediately after placement of 10 bare stents-20 Gy in group II (n = 5) and 40 Gy in group III (n = 5)-and conventional balloon dilation was performed immediately after placement of the remaining five bare stents (group I). A follow-up angiogram was obtained 8 weeks after the procedure, and percentage of luminal stenosis was calculated for the proximal and distal ends of each stent. Neointimal thickening (expressed as the neointimal area divided by the sum of neointimal area and media area) was assessed for microscopic examination. All eight dogs survived until they were euthanized 8 weeks after the procedures. The mean luminal stenosis measurements at 8-week follow-up angiography in groups I, II, and III were 26.63%, -0.44%, and 10.53%, respectively. The mean neointimal thickening measurements in groups I, II, and III were 0.77, 0.21, and 0.34, respectively. The mean percentage of luminal stenosis and neointimal thickening differed significantly among the three groups (P < .05). beta-Irradiation with (188)Re-MAG3-filled balloon dilation has the potential to reduce neointimal hyperplasia secondary to stent placement in a canine iliac artery model. A dose of 20 Gy may be preferable versus a dose of 40 Gy to reduce neointimal hyperplasia. Copyright 2010 SIR. Published by Elsevier Inc. All rights reserved.

  16. Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery.

    PubMed

    Ferrer, Lucas M; Monroy, Alexandra M; Lopez-Pastrana, Jahaira; Nanayakkara, Gayani; Cueto, Ramon; Li, Ya-Feng; Li, Xinyuan; Wang, Hong; Yang, Xiao-Feng; Choi, Eric T

    2016-04-01

    To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase(-/-) mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase(-/-) mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase(-/-) tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.

  17. Relative contribution of wall shear stress and injury in experimental intimal thickening at PTFE end-to-side arterial anastomoses.

    PubMed

    Loth, Francis; Jones, Steven A; Zarins, Christopher K; Giddens, Don P; Nassar, Raja F; Glagov, Seymour; Bassiouny, Hisham S

    2002-02-01

    Intimal hyperplastic thickening (IHT) is a frequent cause of prosthetic bypass graft failure. Induction and progression of IHT is thought to involve a number of mechanisms related to variation in the flow field, injury and the prosthetic nature of the conduit. This study was designed to examine the relative contribution of wall shear stress and injury to the induction of IHT at defined regions of experimental end-to-side prosthetic anastomoses. The distribution of IHT was determined at the distal end-to-side anastomosis of seven canine Iliofemoral PTFE grafts after 12 weeks of implantation. An upscaled transparent model was constructed using the in vivo anastomotic geometry, and wall shear stress was determined at 24 axial locations from laser Doppler anemometry measurements of the near wall velocity under conditions of pulsatile flow similar to that present in vivo. The distribution of IHT at the end-to-side PTFE graft was determined using computer assisted morphometry. IHT involving the native artery ranged from 0.0+/-0.1 mm to 0.05+/-0.03 mm. A greater amount of IHT was found on the graft hood (PTFE) and ranged from 0.09+/-0.06 to 0.24+/-0.06 mm. Nonlinear multivariable logistic analysis was used to model IHT as a function of the reciprocal of wall shear stress, distance from the suture line, and vascular conduit type (i.e. PTFE versus host artery). Vascular conduit type and distance from the suture line independently contributed to IHT. An inverse correlation between wall shear stress and IHT was found only for those regions located on the juxta-anastomotic PTFE graft. The data are consistent with a model of intimal thickening in which the intimal hyperplastic pannus migrating from the suture line was enhanced by reduced levels of wall shear stress at the PTFE graft/host artery interface. Such hemodynamic modulation of injury induced IHT was absent at the neighboring artery wall.

  18. TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts.

    PubMed

    Bai, Xiao; Xi, Jie; Bi, Yanwen; Zhao, Xin; Bing, Weidong; Meng, Xiangbin; Liu, Yimin; Zhu, Zhonglai; Song, Guangmin

    2017-03-07

    The oxidative stress caused by endothelial injury is involved in intimal hyperplasia (IH) in vein grafts. Mesenchymal stem cells (MSCs) can home to injured intima and promote endothelial repair. However, MSC apoptosis is increased accompanied by decreased functional activity under oxidative stress. Thus, we investigate whether tumour necrosis factor-α (TNF-α) can promote the survival and activity of MSCs under oxidative stress to reduce IH more effectively, and establish what role the NF-κB pathway plays in this. In this study, we preconditioned MSCs with TNF-α ((TNF)(-α-PC) MSCs) for 24 hrs and measured the activation of the IKK/NF-κB pathway. EdU and transwell assays were performed to assess proliferation and migration of (TNF)(-α-PC) MSCs. Apoptosis and migration of (TNF)(-α-)(PC) MSCs were evaluated in conditions of oxidative stress by analysis of the expression of Bcl-2 and CXCR4 proteins. (TNF)(-α-)(PC) MSCs were transplanted into a vein graft model, so that cell homing could be tracked, and endothelial apoptosis and IH of vein grafts were measured. The results demonstrated that TNF-α promotes proliferation and migration of MSCs. Furthermore, survival and migration of (TNF)(-α-)(PC) MSCs under oxidative stress were both enhanced. A greater number of MSCs migrated to the intima of vein grafts after preconditioning with TNF-α, and the formation of neointima was significantly reduced. These effects could be partially abolished by IKK XII (NF-κB inhibitor). All these results indicate that preconditioning with TNF-α can promote survival and migration of MSCs under oxidative stress via the NF-κB pathway and thus attenuate IH of vein grafts.

  19. Animal models of catheter-induced intimal hyperplasia in type 1 and type 2 diabetes and the effects of pharmacologic intervention.

    PubMed

    McNamara, D B; Murthy, S N; Fonseca, A N; Desouza, C V; Kadowitz, P J; Fonseca, V A

    2009-01-01

    Diabetes is a complex disorder characterized by impaired insulin formation, release or action (insulin resistance), elevated blood glucose, and multiple long-term complications. It is a common endocrine disorder of humans and is associated with abnormalities of carbohydrate and lipid metabolism. There are two forms of diabetes, classified as type 1 and type 2. In type 1 diabetes, hyperglycemia is due to an absolute lack of insulin, whereas in type 2 diabetes, hyperglycemia is due to a relative lack of insulin and insulin resistance. More than 90% of people with diabetes have type 2 with varied degrees of insulin resistance. Insulin resistance is often associated with impaired insulin secretion, and hyperglycemia is a common feature in both types of diabetes, but failure to make a distinction between the types of diabetes in different animal models has led to confusion in the literature. This is particularly true in relation to cardiovascular disease in the presence of diabetes and especially the response to vascular injury, in which there are major differences between the two types of diabetes. Animal models do not completely mimic the clinical disease seen in humans. Animal models are at best analogies of the pathologic process they are designed to represent. The focus of this review is an analysis of intimal hyperplasia following catheter-induced vascular injury, including factors that may complicate comparisons between different animal models or between in vitro and in vivo studies. We examine the variables, pitfalls, and caveats that follow from the manner of induction of the injury and the diabetic state of the animal. The efficacy of selected antidiabetic drugs in inhibiting the development of the hyperplastic response is also discussed.

  20. γ-Secretase inhibitor DAPT attenuates intimal hyperplasia of vein grafts by inhibition of Notch1 signaling.

    PubMed

    Xiao, Yong Guang; Wang, Wei; Gong, Dan; Mao, Zhi Fu

    2014-06-01

    The proliferation and high plasticity of vascular smooth muscle cells (vSMCs) are the major reasons for restenosis of vein grafts. N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), specific inhibitor of γ-secretase, has been shown to regulate vSMC proliferation and differentiation through the Notch signaling pathway, but the pathophysiological importance of these findings in venous grafts has not yet been determined. A rat vein graft model was employed wherein the left jugular vein was surgically interposed into the left common carotid artery. Daily subcutaneous injections of DAPT or placebo (DMSO) were administered postoperatively (control animals received no treatment). We showed that DAPT can inhibit restenosis of vein grafts by inhibiting vSMC proliferation and increasing apoptosis in vivo. Notch1 signaling was highly active during the development of intima thickening. By blocking the Notch signaling pathway, the γ-secretase inhibitor DAPT can significantly attenuated intima thickening. These changes in vein grafts coincided with enhanced binding of myocardin to the smooth muscle-specific protein SM22 and smooth muscle myosin heavy chain at the promoters of vSMC differentiation-specific genes. These studies showed that DAPT can restore the vSMC phenotype and inhibit vSMC proliferation through suppression of the Notch1 signaling pathway, and thus opens a new avenue for the treatment of restenosis in vein grafts.

  1. Perivenous application of cyanoacrylate tissue sealants reduces intimal and medial thickening of the vein graft and inflammatory responses in a rabbit model of carotid artery bypass grafting.

    PubMed

    Dai, Longsheng; Gao, Mingxin; Gu, Chengxiong; Zhang, Fan; Yu, Yang

    2016-02-01

    Effective therapies to prevent vein graft failure after coronary artery bypass grafting (CABG) are still lacking. α-Cyanoacrylate (α-CA, 99% n-octyl-α-cyanoacrylate + n-butyl-α-cyanoacrylate) has been increasingly used as a tissue sealant for wound closure because of its bacteriostatic, biodegradable and haemostatic properties. As a strong tissue adhesive, α-CA might prevent an arterial circulation-induced mechanical stretch on vein graft to attenuate intimal hyperplasia. Here, we investigated the effects of perivenous application of α-CA on the vein graft in a rabbit model of carotid artery bypass grafting. Healthy New Zealand white rabbits were randomized into no graft, graft or graft + α-CA group (n = 10 per group). Rabbit carotid artery was bypassed with the jugular vein. α-CA sealants were sprayed on the entire jugular graft including both anastomotic sites after completion of anastomoses. Blood flow parameters and histological characteristics of the vein grafts including vessel wall thickness, number of medial elastic lamina and proliferation index were evaluated 4 weeks after the surgery. The mRNA or protein levels of proinflammatory factors, chemokine (C-C motif) ligand-2 (CCL-2) and tumour necrosis factor-α (TNF-α) were measured 4 weeks after the operation by quantitative reverse transcription polymerase chain reaction or enzyme-linked immunosorbent assay. Compared with the untreated vein grafts at Week 4 after the operation, the α-CA spray significantly improved graft flow (39.4 ± 1.5 vs 27.8 ± 2.9 ml/min, P < 0.01), attenuated intimal and medial thickening (116.3 ± 1.0 vs 159.7 ± 0.9 μm, P < 0.01), reduced anti-proliferating cell nuclear antigen proliferation index of the vein grafts (15.0 ± 0.4 vs 23.6 ± 0.4%, P < 0.01), decreased the mRNA levels of plasminogen activator inhibitor-1 and CCL-2, and reduced the serum levels of TNF-α (92.9 ± 1.7 vs 102.7 ± 1.8 pg/ml, P < 0.01). Perivenous application of α-CA sealants exerts short

  2. Occult closed posterior elbow dislocation with intimal rupture of the brachial artery in a 71-year-old male†

    PubMed Central

    Dabboussi, Naji Abdallah; Fakih, Riad Rifaat; Kassar, Talal Adnan; Abtar, Houssam Khodor

    2014-01-01

    Posterior elbow dislocation with vascular injury is rarely encountered, but it is crucial for every emergency physician to diagnose it. Missing these injuries can result in neurovascular compromise, which in turn can lead to limb ischemia, compartment syndrome and potential limb loss. Having a normal X-ray on presentation makes this injury more difficult to diagnose. In this study, we present a case of occult posterior elbow dislocation with an intimal injury of the brachial artery. The rarity of these cases, the diagnostic modalities and the treatment options will be reviewed. PMID:25527603

  3. Occult closed posterior elbow dislocation with intimal rupture of the brachial artery in a 71-year-old male†.

    PubMed

    Dabboussi, Naji Abdallah; Fakih, Riad Rifaat; Kassar, Talal Adnan; Abtar, Houssam Khodor

    2014-12-19

    Posterior elbow dislocation with vascular injury is rarely encountered, but it is crucial for every emergency physician to diagnose it. Missing these injuries can result in neurovascular compromise, which in turn can lead to limb ischemia, compartment syndrome and potential limb loss. Having a normal X-ray on presentation makes this injury more difficult to diagnose. In this study, we present a case of occult posterior elbow dislocation with an intimal injury of the brachial artery. The rarity of these cases, the diagnostic modalities and the treatment options will be reviewed.

  4. Oxidative stress, endothelial function, carotid artery intimal thickness and their correlates among chronic peritoneal dialysis patients

    PubMed Central

    Khaira, A.; Mahajan, S.; Kumar, A.; Prakash, S.; Saraya, A.; Singh, B.; Bora, M.; Tiwari, S. C.; Agarwal, S. K.; Bhowmik, D.

    2011-01-01

    We evaluated important nontraditional cardiovascular risk factors, endothelial function and oxidative stress (OS) among stable peritoneal dialysis (PD) patients. Their association with carotid intimal medial thickness (CIMT) was also assessed. Thirty-eight adult patients (13 diabetics, 20 males) on PD for >6 months and 15 age and sex-matched controls were studied. Duration of dialysis (DOD), residual urine output (UO), weekly Kt/V urea, detailed biochemical and lipid profile were noted. OS was measured by serum concentration of antioxidants; vitamin C and ferric reducing ability of plasma (FRAP) and pro-oxidant; thiobarbituric acid-reactive substances (TBARS). High-resolution ultrasonography was used to determine CIMT and flow-mediated dilatation of brachial artery [endothelium-dependent dilatation (EDD)] and dilatation subsequent to nitrate spray [endothelium-independent dilatation (EID)]. Mean age, DOD, UO and Kt/V of study population were 49.3 ± 11.6 years, 19.4 ± 11.8 months, 508.2 ± 422.9 ml/day and 1.73 ± 0.24, respectively. As compared to controls PD patients had higher CIMT (0.46 ± 0.05 vs 0.50 ± 0.07 mm, P = 0.003) and TBARS (1.5 ± 0.4 vs 5.1 ± 2.3 nM/ml, P < 0.001) but lower Vitamin C (1.7 ± 0.3 vs 0.6 ± 0.2 mg%, P < 0.001), FRAP (990.8 ± 78.1 vs 328.7 ± 183.5 μM/L, P < 0.001) and EDD (26.2 ± 5.4 vs 9.8 ± 4.6 %, P < 0.001). TBARS correlated positively with DOD and negatively with hemoglobin. Vitamin C and FRAP correlated positively with serum albumin. EDD correlated positively with UO, Kt/V and hemoglobin. CIMT correlated negatively with Kt/V and hemoglobin. Among themselves CIMT correlated negatively with EDD and vitamin C. EDD correlated positively with vitamin C, while FRAP correlated positively with vitamin C and negatively with TBARS. PD patients have higher OS, poorer endothelial function and higher structural atherosclerosis. These parameters are closely linked to each other, hemoglobin, DOD, residual UO, serum albumin and small

  5. Development of intimal thickening of coronary arteries over the lifetime of Atlantic salmon, Salmo salar L., fed different lipid sources.

    PubMed

    Seierstad, S L; Svindland, A; Larsen, S; Rosenlund, G; Torstensen, B E; Evensen, Ø

    2008-06-01

    The objective of the present study was to investigate the development of intimal changes of coronary arteries over the lifetime of farmed Atlantic salmon, Salmo salar L., fed either a 100% fish oil or a 100% vegetable oil blend. The study was performed as a randomized observer blinded controlled trial with parallel group design. At the start of the project, the fish were divided in two groups and sampled at five different time points throughout their life span. The total study sample consisted of 259 healthy fish. Serial sections were taken from the coronary artery lying on the bulbus arteriosus for histopathological evaluation and for area measurements using semi-quantitative and quantitative methods. The earliest onset of vascular changes was detected in fish from both groups in the freshwater stage prior to smoltification. The mean range lesion (MRL), used to describe the severity of the lesions observed, increased significantly for both groups from sea transfer throughout the study period. Comparison of the two groups based on the overall material corrected for time of sampling did not show any difference (P = 0.20) between the two groups with regard to MRL. The percentage lumen loss (PLL) measured by a quantitative method and used as a measure to indicate lesion severity showed an incremental, non-significant increase from week 72 to week 92 and further to week 115 in both diet groups during the seawater phase. Comparison of the groups corrected for time of sampling indicated a difference of PLL in favour of VO (P = 0.02). Heart weight, body weight and body length were all positively and significantly correlated to Log MRL. The partial correlation analysis indicated that heart weight was the most dominant variable in the set. Early vascular changes were found in the major bifurcation of the coronary artery at the apex and beyond the flow divider into the daughter branches. The latter represented the dominant changes and were found throughout the entire

  6. Reduction of Intimal Hyperplasia with Re-188-labeled Stents in a Rabbit Model at 7 and 26 Weeks: An Experimental Study

    SciTech Connect

    Tepe, Gunnar Dietrich, Tobias; Grafen, Franziska; Brehme, Ute; Muschick, Peter; Dinkelborg, Ludger M.; Greschniok, Annette; Claussen, Claus D.; Duda, Stephan H.

    2005-06-15

    The aim of this study was to analyze the feasibility of {sup 188}Re-labeled stents to reduce neointimal formation in a rabbit atherosclerosis model and to test the long-term effects at 7 and 26 weeks. Fifty-nine male New Zealand White rabbits were fed a 0.5% cholesterol diet for 4 weeks before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were sacrificed 7 and 26 weeks after stent implantation. Control stents were compared with {sup 188}Re stents: (dose 1) 11.3 {+-} 1.8 MBq; (dose 2) 37.3 {+-} 4.2 MBq, and (dose 3) 80.1 {+-} 7.8 MBq. Each activity group consisted of a short-term (7 weeks) and a long-term group (26 weeks), resulting in a total of eight study groups. No thrombotic occlusion was observed. The neointimal formation in the control group was 2.11 [95% confidence interval (CI): 0.68-6.52] mm{sup 2} at 7 weeks and 2.10 (0.62-7.11) at 26 weeks. In the treatment groups, neointima reduction was detectable at 7 weeks [dose 1: 0.33 (0.09-1.22) mm{sup 2}; dose 2: 0.17 (0.05-0.57) mm{sup 2}; dose 3: 0.03 (0.01-0.13) mm{sup 2}]. After 26 weeks, a catch-up of neointimal formation in the radioactive groups was most obvious in the low-dose group [dose 1: 0.80 (0.28-2.29) mm{sup 2}; dose 2: 0.18([0.06-0.52) mm{sup 2}; dose 3: 0.50 (0.17-1.42) mm{sup 2}]. Compared to the long-term control group, neointimal reduction was still >60%. No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed re-endothelialization. {sup 188}Re stents were capable to reduce intimal hyperplasia and did not cause thrombosis. The edge effect, which was the major limitation of {sup 32}P stents, was not observed in {sup 188}Re stents.

  7. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale.

    PubMed

    Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M

    2016-02-01

    Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α1-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studies on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.

  8. Prostatic Artery Embolization (PAE) for Symptomatic Benign Prostatic Hyperplasia (BPH): Part 2, Insights into the Technical Rationale

    SciTech Connect

    Sun, Fei Crisóstomo, Verónica Báez-Díaz, Claudia Sánchez, Francisco M.

    2016-02-15

    Rationale of prostatic artery embolization (PAE) in the treatment of symptomatic benign prostatic hyperplasia is conventionally believed to include two parts: shrinkage of the enlarged prostate gland as a result of PAE-induced ischemic infarction and potential effects to relax the increased prostatic smooth muscle tone by reducing the number and density of α{sub 1}-adrenergic receptor in the prostate stroma. This review describes new insights into the likely mechanisms behind PAE, such as ischemia-induced apoptosis, apoptosis enhanced by blockage of androgens circulation to the embolized prostate, secondary denervation following PAE, and potential effect of nitric oxide pathway immediately after embolization. Studies on therapeutic mechanisms in PAE may shed light on potentially new treatment strategies and development of novel techniques.

  9. Resistive index of prostate capsular arteries: a newly identified parameter to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia.

    PubMed

    Zhang, Xuefeng; Li, Gang; Wei, Xuedong; Mo, Xiaodong; Hu, Linkun; Zha, Yueqin; Hou, Jianquan

    2012-09-01

    We evaluated the association of the resistive index of the prostate capsular arteries and bladder outlet obstruction severity in men with benign prostatic hyperplasia. A total of 74 patients histologically diagnosed with benign prostatic hyperplasia were ultimately enrolled in this prospective study. Urodynamics were performed by a urologist to determine bladder outlet obstruction. Baseline parameters measured in patients with benign prostatic hyperplasia were the prostate capsular artery resistive index, International Prostate Symptom Score, quality of life score, total prostate and transition zone volume, and the transition zone index. ROC curves were produced to calculate the ROC AUC and evaluate the diagnostic performance of the prostate capsular artery resistive index, International Prostate Symptom Score, obstructive symptoms, total prostate and transition zone volume, and the transition zone index for bladder outlet obstruction. Significant difference between patients with and without bladder outlet obstruction was observed in the resistive index, which showed the highest coefficient with the degree of obstruction (r = 0.712, p <0.0001). At a cutoff of 0.69 the resistive index distinguished patients with and without bladder outlet obstruction with 78% sensitivity and 86.4% specificity. The prostate capsular artery resistive index had the maximum AUC of 0.823. The prostate capsular artery resistive index is significantly higher in patients with benign prostatic hyperplasia related bladder outlet obstruction than in those without such obstruction. The resistive index might serve as a novel indicator to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors.

    PubMed

    Zhao, Jianming; Roth, Jürgen; Bode-Lesniewska, Beata; Pfaltz, Madeleine; Heitz, Philipp U; Komminoth, Paul

    2002-05-01

    Identification of gene amplifications in human tumors is important for the understanding of tumorigenesis and may lead to discovery of diagnostic and prognostic markers. In this study, we used a microarray-based comparative genomic hybridization (CGH) technique, combined with conventional CGH, to identify gene amplifications in 43 tumors including eight pulmonary artery intimal sarcomas and 35 adrenocortical tumors. Conventional CGH revealed gains or amplifications of 12q13-q15 in six sarcomas and in two adrenocortical carcinomas. Using microarrays, we demonstrated that, among genes located on 12q13-q15, SAS/CDK4 were amplified in six sarcomas, and MDM2 and GLI in five and four sarcomas, respectively. The two adrenocortical tumors showed coamplifications of SAS/CDK4 and MDM2. Furthermore, PDGFRA (located on 4q12) amplification was identified in five sarcomas. Our data demonstrate: (1) amplifications of SAS/CDK4, MDM2, GLI, and PDGFRA are strongly associated with the tumorigenesis of pulmonary artery intimal sarcomas, whereas SAS/CDK4 and MDM2 coamplification may contribute to the progression of adrenocortical tumors; (2) microarray-based CGH is a useful tool for simultaneous detection of multiple gene amplifications, with a high sensitivity and resolution compared to that of conventional CGH.

  11. PET-positive fibrous dysplasia--a potentially misleading incidental finding in a patient with intimal sarcoma of the pulmonary artery.

    PubMed

    Strobel, Klaus; Bode, Beata; Lardinois, Didier; Exner, Ulrich

    2007-06-01

    Benign bone tumors can show an increased FDG uptake in FDG-PET/CT investigations. In the presented case, an incidentally detected PET-positive asymptomatic fibrous dysplasia was initially misinterpreted as a metastasis in a patient with intimal sarcoma of the pulmonary artery.

  12. Quantitative Measurement of Dissection Resistance in Intimal and Medial Layers of Human Coronary Arteries.

    PubMed

    Wang, Ying; Johnson, John A; Spinale, Francis G; Sutton, Michael A; Lessner, Susan M

    2014-04-01

    The left anterior descending (LAD) coronary artery is the most frequently involved vessel in coronary artery dissection, a cause of acute coronary syndrome or sudden cardiac death. The biomechanical mechanisms underlying arterial dissection are not well understood. This study investigated the dissection properties of LAD specimens harvested from explanted hearts at the time of cardiac transplantation, from patients with primary dilated cardiomyopathy (n=12). Using a previously validated approach uniquely modified for these human LAD specimens, we quantified the local energy release rate, G, within different arterial layers during experimental dissection events (tissue tearing). Results show that the mean values of G during arterial dissection within the intima and within the media in human LADs are 20.7±16.5 J/m(2) and 10.3±5.0 J/m(2), respectively. The difference in dissection resistance between tearing events occurring within the intima and within the media is statistically significant. Our data fall in the same order of magnitude as most previous measurements of adhesive strength in other human arteries, with the differences in measured values of G within the layers most likely due to histologically observed differences in the structure and composition of arterial layers.

  13. A case report of chemo-sensitive intimal pulmonary artery sarcoma.

    PubMed

    Chen, Xiaoxia; Ren, Shengxiang; Li, Aiwu; Zhou, Caicun

    2014-01-01

    The incidence rate of pulmonary artery sarcoma is very low, but its prognosis is extremely poor. In this case report, after various initial diagnoses at the early stage, pulmonary artery sarcoma was confirmed by surgery. 1 year later, the tumor recurred. After chemotherapy, the patient showed improvement of the subjective complaint of tightness in the chest, and radiological lesion decreased in size. The survival time was extended by 2.5 years. This is the first case report of pulmonary artery sarcoma with such chemo-sensitivity.

  14. Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rat model of arterial injury.

    PubMed

    Wu, Bian; Mottola, Giorgio; Chatterjee, Anuran; Lance, Kevin D; Chen, Mian; Siguenza, Iris O; Desai, Tejal A; Conte, Michael S

    2017-01-01

    Lipid mediators derived from omega-3 polyunsaturated fatty acids such as resolvin D1 (RvD1) accelerate the resolution of inflammation and have potential as vascular therapeutics. The objective of this study was to evaluate local perivascular delivery of RvD1 as a means to attenuate neointimal hyperplasia in a rat model of arterial injury. Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 through thin biodegradable three-layered poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury. RvD1 attenuated rat arterial vascular smooth muscle cell inflammatory pathways, proliferation, migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of cytotoxicity. RvD1-loaded wraps reduced neointimal formation after carotid angioplasty by 59% vs no-wrap controls (P = .001) and by 45% vs vehicle-wrap controls (P = .002). RvD1-loaded Pluronic gels similarly reduced neointimal formation by 49% vs no-gel controls (P = .02) and by 52% vs vehicle-gel controls (P = .02). No group was associated with infection, thrombosis, or negative vessel remodeling. Wraps were found to be easier to apply than gel constructs. Ki67 proliferation index was significantly lower in RvD1-loaded wrap-treated arteries compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both control groups at day 14; P < .05). Similarly, oxidative stress (30% and 29%; P < .05) and nuclear factor κB activation (42% and

  15. Halofuginone Stimulates Adaptive Remodeling and Preserves Re-Endothelialization in Balloon-Injured Rat Carotid Arteries

    PubMed Central

    Guo, Lian-Wang; Wang, Bowen; Goel, Shakti A.; Little, Christopher; Takayama, Toshio; Shi, Xu Dong; Roenneburg, Drew; DiRenzo, Daniel; Kent, K. Craig

    2014-01-01

    Background Three major processes, constrictive vessel remodeling, intimal hyperplasia and retarded re-endothelialization, contribute to restenosis after vascular reconstructions. Clinically used drugs inhibit intimal hyperplasia but delay re-endothelialization and also cause constrictive remodeling. Here we have examined halofuginone (HF), a herbal derivative, for its beneficial effects on vessel remodeling and differential inhibition of intimal hyperplasia versus re-endothelialization. Methods and Results Two weeks after perivascular application to balloon-injured rat common carotid arteries, HF versus vehicle (n=6 animals) enlarged luminal area 2.14 fold by increasing vessel size (adaptive remodeling, 123%), reducing intimal hyperplasia (74.3%) without inhibiting re-endothelialization. Consistent with its positive effect on vessel expansion, HF reduced collagen type-1 (but not type-3) production in injured arteries as well as that from adventitial fibroblasts in vitro. In support of its differential effects on intimal hyperplasia versus re-endothelialization, HF produced greater inhibition of vascular smooth muscle cell versus endothelial cell proliferation at concentrations around 50 nM. Furthermore, HF at 50 nM effectively blocked Smad3 phosphorylation in smooth muscle cells which is known to promote smooth muscle cell proliferation, migration, and intimal hyperplasia, but HF had no effect on phospho-Smad3 in endothelial cells. Conclusions Periadventitial delivery of HF dramatically increased lumen patency via adaptive remodeling and selective inhibition of intimal hyperplasia without affecting endothelium recovery. HF is the first reported small molecule that has favorable effects on all three major processes involved in restenosis. PMID:25074254

  16. Reduction of myointimal hyperplasia after arterial anastomosis by local injection of transforming growth factor beta3.

    PubMed

    Ghosh, Jonathan; Baguneid, Mohammed; Khwaja, Nadeem; Murphy, Michael O; Turner, Neill; Halka, Anatassi; Ferguson, Mark W; Kielty, Cay M; Walker, Michael G

    2006-01-01

    The transforming growth factor (TGF)-beta family of cytokines exerts pleiotropic actions on vascular smooth muscle cell phenotype, proliferation, and extracellular matrix synthesis. This in vivo study assessed the use of TGF-beta3 in attenuating the development of postanastomotic smooth muscle cell proliferation. Under general anesthesia, 10 adult goats underwent transection and reanastomosis of both common carotid arteries. After reanastomosis, one artery was infiltrated with 50 ng of TGF-beta3 in 100 microL of pH buffer around the anastomosis, and the other side was infiltrated with buffer only. After surgery, each animal received 150 mg of aspirin daily. The arteries were explanted after 3 months for histologic examination. Vessel wall thickness surrounding the anastomosis was reduced by 30% after TGF-beta3 treatment compared with placebo (P = .003), with a 20% (P = .002) reduction in cellular content. Although total collagen content was not significantly different between TGF-beta3 and placebo, collagen type VIII content was reduced around the TGF-beta3 anastomoses (P = .011). A reduction in the total elastin content (P = .003) and number of elastic fiber lamellae (P = .042) was found surrounding TGF-beta3-treated anastomoses, but not placebo-treated anastomosis. A 29% increase in vasa vasorum (P = .044) was present around TGF-beta3-treated anastomoses. No differences in inflammatory cell infiltration were seen between sides. Direct subadventitial infiltration of TGF-beta3 immediately after creation of an arterial anastomosis attenuates cell proliferation, with a reduction in elastin and collagen type VIII content and vessel wall thickness.

  17. Comparison of Nonspherical Polyvinyl Alcohol Particles and Microspheres for Prostatic Arterial Embolization in Patients with Benign Prostatic Hyperplasia

    PubMed Central

    Hwang, Jin Ho; Chang, Il Soo; Jung, Sung Il; Jeon, Hae Jeong; Lho, Yong Soo; Kim, Hyeong Gon; Paick, Sung Hyun; Park, Hyoung Keun

    2017-01-01

    Purpose To report early results following prostatic artery embolization (PAE) and compare outcomes between nonspherical polyvinyl alcohol (PVA) particles and microspheres to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). Methods PAE was performed in nine patients (mean age: 78.1 years) with symptomatic BPH. Embolization was performed using nonspherical PVA particles (250–355 μm) in four patients and microspheres (300–500 μm) in five patients. Results PAE was technically successful in all nine patients (100%). During a mean follow-up of 10.1 months, improvements in mean International Prostate Symptom Score (IPSS), Quality of Life (QoL), prostatic volume (total volume and transition zone), and peak urinary flow (Qmax) were 9.8 points, 2.3 points, 28.1 mL, 17.8 mL, and 4.5 mL/s, respectively. Clinical success was obtained in seven of nine patients (78%). Patients in the microsphere group showed greater improvement in IPSS, QoL, prostatic volume, and Qmax compared to patients in the nonspherical PVA particle group. However, significant difference was noted only in the prostatic volume. Conclusion PAE is a feasible, effective, and safe treatment option for BPH with LUTS. Use of microspheres showed greater prostatic volume reduction compared to nonspherical PVA particles. PMID:28717651

  18. Allium sativum Compared to Cilostazol as an Inhibitor of Myointimal Hyperplasia

    PubMed Central

    Lima, Paulo Roberto da Silva; Bandeira, Francisco Chavier Vieira; Rolim, Janio Cipriano; Nogueira, Manuel Ricardo Sena; Pordeus, Mizael Armando Abrantes; de Oliveira, Andressa Feitosa Bezerra; Pitta, Guilherme Benjamin Brandão

    2016-01-01

    Objective Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol. PMID:27849301

  19. Association of Serum HMGB2 Levels With In-Stent Restenosis: HMGB2 Promotes Neointimal Hyperplasia in Mice With Femoral Artery Injury and Proliferation and Migration of VSMCs.

    PubMed

    He, Yu Hu; Wang, Xiao Qun; Zhang, Jian; Liu, Zhu Hui; Pan, Wen Qi; Shen, Ying; Zhu, Zheng Bin; Wang, Ling Jie; Yan, Xiao Xiang; Yang, Ke; Zhang, Rui Yan; Shen, Wei Feng; Ding, Feng Hua; Lu, Lin

    2017-04-01

    In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in coronary artery disease patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls. Serum HMGB2 levels were significantly higher in patients with ISR than in those without ISR and were associated with ISR severity. Multivariable logistic regression analysis showed that HMGB2 level was independently associated with ISR. In experiments, HMGB2 expression was increased in vascular tissue after injury. Perivascular HMGB2 administration promoted injury-induced neointimal hyperplasia in C57Bl/6 mice compared with in the control, whereas such pathophysiological features were attenuated in Hmgb2(-/-) mice. Mechanistically, HMGB2 enhanced neointimal hyperplasia in mice and proliferation and migration in human aortic smooth muscle cells by inducing reactive oxygen species through increased p47phox phosphorylation. Knocking down p47phox, however, inhibited HMGB2-induced effects in human aortic smooth muscle cells. Finally, HMGB2-induced effects were significantly declined in receptor of advanced glycation end products knockdown or deficient cells, but not in Toll-like receptor 4 knockdown or deficient cells. Serum HMGB2 levels were associated with ISR in patients. HMGB2 promoted neointimal hyperplasia in mice with arterial wire injury through reactive oxygen species activation. © 2017 American Heart Association, Inc.

  20. To assess the intimal thickness, flow velocities, and luminal diameter of carotid arteries using high-resolution B-mode ultrasound doppler imaging

    NASA Astrophysics Data System (ADS)

    Vemuru, Madhuri; Jabbar, Afzal; Chandra, Suman

    2004-04-01

    Carotid imaging is a Gold Standard test that provides useful information about the structure and functions of carotid arteries. Spectral imaging helps to evaluate the vessel and hemodynamic changes. High resolution B-mode imaging has emerged as one of the methods of choice for determining the anatomic extent of atherosclerosis and its progression and for assessing cardiovascular risks. The measurements made with Doppler correlate well with pathologic measurements. Recent prospective studies have clearly demonstrated that these measurements of carotid intimal thickness are potent predictors of Myocardial Infarction and Stroke. This method appears very attractive as it is non-invasive, extremely safe, well accepted by the patient and relatively inexpensive. It can be performed serially and has the advantage of visualizing the arterial wall in contrast to angiographic techniques which provide only an outline of the arterial lumen. Recently, there has been an interest in the clinical use of this technique in making difficult clinical decisions like deciding on preventive therapies. 30 subjects aged 21-60 years and 30 subjects aged 61-85 years of both sexes are selected after doing a baseline study to exclude Hypertension, Diabetes, Obesity and Hyperlipidemia. The carotid arteries were examined for intimal thickening, blood flow velocities and luminal diameter. With aging there is a narrowing of the carotid vessels and significant increase in intimal thickening with a consequent increase in the blood flow velocities. Inter-observer, intra-observer and instrument variations are seen and there is no significant change in the values when the distal flow pattern is considered for measurements. Aging produces major cardiovascular changes including decreased elasticity and compliance of great arteries leading to structural and functional alterations in heart and vessels. With aging there is increased intimal thickness and increased pulse wave velocity which is clearly

  1. Characterization of sarcoma-like cells derived from endarterectomized tissues from patients with CTEPH and establishment of a mouse model of pulmonary artery intimal sarcoma.

    PubMed

    Jujo, Takayuki; Sakao, Seiichiro; Kantake, Masashi; Maruoka, Miki; Tanabe, Nobuhiro; Kasahara, Yasunori; Kurosu, Katsushi; Masuda, Masahisa; Harigaya, Kenichi; Tatsumi, Koichiro

    2012-08-01

    In general, intravascular thrombus formation in the pulmonary arteries is considered to be the most common cause of chronic thromboembolic pulmonary hypertension (CTEPH). The current mainstay of therapy for patients with CTEPH is pulmonary endarterectomy (PEA). Recently, the existence of myofibroblast-like cells in endarterectomized tissues has been demonstrated. At the 2nd passage of these myofibroblast-like cells, a pleomorphic cell type was isolated. Pulmonary intimal sarcoma is a very uncommon neoplastic tumor thought to originate from subendothelial-mesenchymal cells of the pulmonary vascular wall. Because these pleomorphic cells were isolated from the pulmonary vascular beds, it is believed that the analysis of these cells may contribute to the understanding of pulmonary intimal sarcoma. We isolated cells from the endarterectomized tissue from patients with CTEPH and identified one type as sarcoma-like cells (SCLs). The SCLs were characterized as hyperproliferative, anchorage-independent, invasive and serum-independent. Moreover, C.B-17/lcr-scid/scidJcl mice injected subcutaneously with SCLs developed solid, undifferentiated tumors at the site of injection, and those injected intravenously with SCLs via the tail vein developed tumors which grew along the intimal surface of the pulmonary vessels, thus, demonstrating the high tumorigenic potential of these cells. The behavior of SCLs indicated that these cells may have a vascular cell-like potential which can affiliate them with the intimal surface of the pulmonary artery, and which may be shared with pulmonary intimal sarcoma. A further investigation of this mouse model with SCLs may elucidate the mechanism(s) underlying the development of pulmonary intimal sarcoma.

  2. The Effect of Creating a Moderate Stenosis on the Localization of Intimal Thickening in the Common Carotid Artery of the Rabbit Fed on a Cholesterol-Rich Diet

    NASA Astrophysics Data System (ADS)

    Wada, Shigeo; Koujiya, Makoto; Karino, Takeshi

    The effect of a locally disturbed flow on intimal thickening was studied by creating a moderate axisymmetric stenosis (mean diameter reduction: 26%) in common carotid arteries of the rabbit and feeding a cholesterol-rich diet. In eight of nine specimens obtained from four rabbits, intimal thickening occurred at the distal side of the stenosis, mainly in a restricted region which extended from the apex of the stenosis to the distal end, the point of the maximum thickness locating approximately a half of the vessel diameter downstream of the apex of the stenosis. The result was compared with the distributions of wall shear stress and surface concentration of low-density lipoproteins (LDL) which were calculated using a theoretical model of blood flow and LDL transport through the stenosed artery. It was found that the site of intimal thickening well corresponded to the region where wall shear stress was relatively low and surface concentration of LDL was locally elevated. These results suggest that blood flow plays an important role in the localized pathogenesis and development of intimal thickening by locally augmenting concentration polarization of LDL at a blood/endothelium boundary.

  3. Acute effects of short-term intimal heating by laser-heated thermal balloon angioplasty in canine stenotic femoral arteries in vivo

    NASA Astrophysics Data System (ADS)

    Miyamoto, Akira; Sakurada, Masami; Arai, Tsunenori; Mizuno, Kyoichi; Sugiyabu, Yasunori; Kurita, Akira; Nakamura, Haruo; Kikuchi, Makoto; Watanabe, Tamishige; Utsumi, Atsushi; Akai, Yoshiro; Takeuchi, Kiyoshi

    1993-06-01

    Short-term intimal heating may be effective to improve luminal geometry without deep medial injury which can induce restenosis. We developed a new laser-heated thermal balloon catheter which can quickly raise and lower the balloon temperature. To investigate the acute effect of short-term thermal balloon angioplasty (STBA) for stenotic lesions, we performed STBA following balloon angioplasty (BA) in 8 canine stenotic femoral arteries. Cw Nd:YAG laser delivery (10 W, 15 s) induced the maximum temperature of 83 degree(s)C on average. Angiography and angioscopy were performed at pre-BA, post-BA and post-STBA. The angiographical mean stenotic diameter was 1.8 mm at pre-BA, 2.2 mm* at post-BA, 2.9 mm** at post-STBA (*:p < 0.05 pre-BA vs post-BA, **:p < 0.05 pre- and post-BA vs post-STBA). The angioscopic observation revealed intimal flaps and tears in 7 lesions after BA. The luminal geometry after STBA was symmetrically expanded. However, the intimal injury was still observed although the intimal flaps were partly sealed by STBA. These results suggested that the dilatation mechanism of STBA for stenotic lesions might be attributed to preventing elastic recoil rather than to sealing intimal fragments induced by BA.

  4. Mechanical functional role of non-atherosclerotic intimal thickening.

    PubMed

    Glagov, S; Zarins, C K; Masawa, N; Xu, C P; Bassiouny, H; Giddens, D P

    1993-01-01

    Arteries adjust to alterations in wall shear stress or tensile stress by changes in diameter, wall thickness, structure and composition. The intima participates in these adaptive reactions, particularly when changes in mechanical stresses are imposed after physiologic stress levels have been established during growth. Decreased wall shear stress due to decreased flow, flow separation or complex flow patterns, or increases in tensile stress due to increases in pressure or radius stimulate non-atherosclerotic intimal proliferation. Intimal fibrocellular hypertrophy (IFH), in the form of compact fibrocellular layers resembling the media, stabilizes when the lumen diameter is reduced sufficiently or wall thickness is increased sufficiently to restore baseline wall shear or tensile stress. Reactive-adaptive intimal proliferation is not necessarily self-limiting and may continue in the form of intimal hyperplasia (IH) which is relatively matrix-free and poorly organized. If mural and intimal changes do not result in restoration of baseline wall shear and tensile stress, IH may proceed to further narrowing and stenosis. Identification of the cellular and molecular mechanisms which underly the responses which link flow to diameter, diameter and pressure to mural restructuring, and mural restructuring to intimal thickening should provide new insights into the nature of vessel adaptations in the absence or presence of atherogenesis.

  5. Medium- and Long-Term Outcome of Prostate Artery Embolization for Patients with Benign Prostatic Hyperplasia: Results in 630 Patients.

    PubMed

    Pisco, João M; Bilhim, Tiago; Pinheiro, Luis C; Fernandes, Lucia; Pereira, Jose; Costa, Nuno V; Duarte, Marisa; Oliveira, António G

    2016-08-01

    To confirm that prostatic artery embolization (PAE) has a positive medium- and long-term effect in symptomatic benign prostatic hyperplasia (BPH). Between March 2009 and October 2014, 630 consecutive patients with BPH and moderate-to-severe lower urinary tract symptoms refractory to medical therapy for at least 6 months or who refused any medical therapy underwent PAE. Outcome parameters were evaluated at baseline; 1, 3, and 6 months; every 6 months between 1 and 3 years; and yearly thereafter up to 6.5 years. Mean patient age was 65.1 years ± 8.0 (range, 40-89 y). There were 12 (1.9%) technical failures. Bilateral PAE was performed in 572 (92.6%) patients and unilateral PAE was performed in 46 (7.4%) patients. The cumulative clinical success rates at medium- and long-term follow-up were 81.9% (95% confidence interval [CI], 78.3%-84.9%) and 76.3% (95% CI, 68.6%-82.4%). There was a statistically significant (P < .0001) change from baseline to last observed value in all clinical parameters: International Prostate Symptom Score (IPSS), quality-of-life (QOL), prostate volume, prostate-specific antigen, urinary maximal flow rate, postvoid residual, and International Index of Erectile Function. There were 2 major complications without sequelae. PAE had a positive effect on IPSS, QOL, and all objective outcomes in symptomatic BPH. The medium- (1-3 y) and long-term (> 3-6.5 y) clinical success rates were 81.9% and 76.3%, with no urinary incontinence or sexual dysfunction reported. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

  6. In vivo treatment of rat arterial adventitia with interleukin-1β induces intimal proliferation via the JAK2/STAT3 signaling pathway

    PubMed Central

    WANG, XIAO; CHEN, LIHUA; LIU, JIE; YAN, TAO; WU, GANGYONG; XIA, YANG; ZONG, GANGJUN; LI, FENGSHENG

    2016-01-01

    Previous studies have indicated that adventitial inflammation is involved in the development of atherosclerosis. The aim of this study was to investigate the effect of arterial adventitia inflammation induced by interleukin (IL)-1β on intimal proliferation and the mechanisms involved in this process. The left common carotid artery adventitia of male rats in the experimental and control groups (25 rats/group) was wrapped with agar containing or without a sustained-release suspension of 2.5 µg IL-1β, respectively. Five animals in each group were randomly selected for sacrifice at 2 h, 8 h, 24 h, 48 h, and 1 week post-treatment. Hematoxylin and eosin staining was performed for to analyze the morphology of the adventitia. The expression of janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, phosphorylated (p-)JAK2 and p-STAT3 were detected by western blot analysis or immunohistochemistry staining. A model of adventitial inflammation was successfully created by wrapping IL-1β around the rat carotid artery. IL-1β treatment induced vascular smooth muscle cell proliferation and migration as well as intimal proliferation. In addition, the expression of p-JAK2 and p-STAT3 increased after IL-1β treatment. Furthermore, an inhibitor of JAK2/STAT3 pathway, AG490, suppressed IL-1β-induced intimal proliferation and phosphorylation of JAK2 and STAT3. Thus, the JAK2/STAT3 signaling pathway is involved in intimal proliferation caused by vascular adventitial inflammation. Inhibiting the JAK2/STAT3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis. PMID:26955959

  7. Early results and complications of prostatic arterial embolization for benign prostatic hyperplasia.

    PubMed

    Lebdai, Souhil; Delongchamps, Nicolas Barry; Sapoval, Marc; Robert, Grégoire; Amouyal, Gregory; Thiounn, Nicolas; Karsenty, Gilles; Ruffion, Alain; de La Taille, Alexandre; Descazeaud, Aurélien; Mathieu, Romain

    2016-05-01

    To review current knowledge on clinical outcomes and peri-operative complications of prostatic arterial embolization (PAE) in patients treated for lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). A systematic review of the literature published from January 2008 to January 2015 was performed on PubMed/MEDLINE. Fifty-seven articles were identified, and four were selected for inclusion in this review. Only one randomized clinical trial compared transurethral resection of the prostate (TURP) to PAE. At 3 months after the procedure, mean IPSS reduction from baseline ranged from 7.2 to 15.6 points. Mean urine peak-flow improvement ranged from +3.21 ml/s to +9.5 ml/s. When compared to TURP, PAE was associated with a significantly lower IPSS reduction 1 and 3 months after the procedure. A trend toward similar symptoms improvement was however reported without statistical significance from 6 to 24 months. Major complications were rare with one bladder partial necrosis due to non-selective embolization. Mild adverse events occurred in 10 % of the patients and included transient hyperthermia, hematuria, rectal bleeding, painful urination or acute urinary retention. Further comparative studies are mandatory to assess post-operative rates of complications, especially acute urinary retention, after PAE and standard procedures. Early reports suggest that PAE may be a promising procedure for the treatment of patients with LUTS due to BPO. However, the low level of evidence and short follow-up of published reports preclude any firm conclusion on its mid-term efficiency. Further clinical trials are warranted before any use in clinical practice.

  8. Intimal sarcoma of the abdominal aorta and common iliac arteries presenting as epithelioid angiosarcoma of the skin: a case report

    PubMed Central

    Tajima, Shogo; Hoshina, Katsuyuki; Oushik, Tets; Shigematsu, Kunihiro; Fukayama, Masashi

    2015-01-01

    Intimal sarcoma (IS) is the most common type of sarcoma of the aorta. IS tumor emboli can involve various organs, including the skin. However, a limited number of IS cases with an initial presentation of skin metastasis has been reported. Cutaneous metastasis as a form of epithelioid angiosarcoma (EAS) has not been well described. Herein, we present a 61-year-old Japanese man with an initial presentation of EAS of the skin, followed by multiple metastases to the skin as a form of EAS prior to detection of IS of the infrarenal aorta and common iliac arteries. In our case, the IS was CD31 and cytokeratin positive but did not express CD34 and factor VIII-related antigen. The EASs in our case exhibited diffuse CD31 expression, and focal factor VIII-related antigen and cytokeratin expression were observed throughout the tumor, including the neoplastic vascular structure; CD34 expression was not identifiable. IS metastasis to the skin has been documented as a form of angiosarcoma. However, IS metastasis has not been well described as a form of EAS. Our case could prove a morphological change from IS to EAS. Given the rarity of primary cutaneous EAS, it is recommended that primary sites other than the skin should be thoroughly investigated when EAS of the skin is encountered. PMID:26191309

  9. Long-term survival of a patient with pulmonary artery intimal sarcoma after sequential metastasectomies of the thyroid and adrenal glands.

    PubMed

    Choi, Yun Mi; Jang, Eun Kyung; Ahn, Seong Hee; Jeon, Min Ji; Han, Ji Min; Kim, Seong Chul; Han, Duck Jong; Gong, Gyungyup; Kim, Tae Yong; Shong, Young Kee; Kim, Won Bae

    2013-03-01

    Cancer metastases to the thyroid or adrenal gland are uncommon. Furthermore, cases showing long-term survival after surgical resection of those metastatic tumors are rare. We report a case of pulmonary artery intimal sarcoma with metastases to the thyroid and adrenal glands sequentially that was successfully treated with sequential metastasectomies. A 62-year-old woman presented with a 4-week history of dyspnea on exertion and facial edema in November 1999. Echocardiography and chest computed tomography (CT) revealed an embolism-like mass in the pulmonary trunk. Pulmonary artery endarterectomy with pulmonary valve replacement was performed, and histopathology revealed pulmonary artery intimal sarcoma. A thyroid nodule was found by chest CT in November 2001 (2 years after initial surgery). During follow-up, this lesion showed no change, but we decided to obtain fine needle aspiration cytology (FNAC) in August 2004 (4.7 years after initial surgery). FNAC revealed atypical spindle cells suggestive of metastatic intimal sarcoma. She underwent total thyroidectomy. During follow-up, a right adrenal gland mass was detected by chest CT in March 2006 (6.3 years after initial surgery), and adrenalectomy was done, which also revealed metastatic sarcoma. She has been followed up without any evidence of recurrent disease until May 2012 (12.5 years after initial surgery).

  10. Nobiletin Inhibits PDGF-BB-induced vascular smooth muscle cell proliferation and migration and attenuates neointimal hyperplasia in a rat carotid artery injury model.

    PubMed

    Guan, Siyu; Tang, Qizhu; Liu, Wenwei; Zhu, Rui; Li, Bin

    2014-12-01

    Preclinical Research The abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) plays a pivotal role in the development of neointimal hyperplasia after vascular injury. Nobiletin, a citrus bioflavonoid, exhibits anti-inflammatory and anti-oxidative activities. The present study evalutaed whether nobiletin could inhibit platelet-derived growth factor (PDGF)-BB- stimulated VSMC proliferation and migration and decrease neointimal hyperplasia in a rat carotid artery injury model. Cultured VSMCs from rat thoracic aortas were treated with nobiletin before being stimulated with 20 ng/ml PDGF-BB, and rats were subjected to carotid artery injury. Nobiletin inhibited PDGF-BB-induced VSMC proliferation and migration, attenuated reactive oxygen species (ROS) production and reduced phosphorylation of ERK1/2 and the expression of nuclear NF-κB p65 in PDGF-BB-stimulated VSMCs. Nobiletin decreased the intima area and the ratio of neointima to media in balloon-injured rat carotid arteries. Serum levels of TNF-α and IL-6 in nobiletin-treated rats were decreased. These results indicated that nobiletin could be a potential protective agent for the prevention and treatment of restenosis after angioplasty.

  11. MicroRNA-24 Attenuates Neointimal Hyperplasia in the Diabetic Rat Carotid Artery Injury Model by Inhibiting Wnt4 Signaling Pathway.

    PubMed

    Yang, Jian; Fan, Zhixing; Yang, Jun; Ding, Jiawang; Yang, Chaojun; Chen, Lihua

    2016-05-24

    The long-term stimulation of hyperglycemia greatly increases the incidence of vascular restenosis (RS) after angioplasty. Neointimal hyperplasia after vascular injury is the pathological cause of RS, but its mechanism has not been elucidated. MicroRNA-24 (miR-24) has low expression in the injured carotid arteries of diabetic rats. However, the role of miR-24 in the vascular system is unknown. In this study, we explore whether over-expression of miR-24 could attenuate neointimal formation in streptozotocin (STZ)-induced diabetic rats. Adenovirus (Ad-miR-24-GFP) was used to deliver the miR-24 gene to injured carotid arteries in diabetic rats. The level of neointimal hyperplasia was examined by hematoxylin-eosin (HE) staining. Vascular smooth muscle cell (VSMC) proliferation in the neointima was evaluated by immunostaining for proliferating cell nuclear antigen (PCNA). The mRNA levels of miR-24, PCNA, wingless-type MMTV integration site family member 4 (Wnt4), disheveled-1 (Dvl-1), β-catenin and cell cycle-associated molecules (Cyclin D1, p21) were determined by Quantitative Real-Time PCR (qRT-PCR). PCNA, Wnt4, Dvl-1, β-catenin, Cyclin D1 and p21 protein levels were measured by Western blotting analysis. STZ administration decreased plasma insulin and increased fasting blood glucose in Sprague-Dawley (SD) rats. The expression of miR-24 was decreased in the carotid artery after a balloon injury in diabetic rats, and adenoviral transfection (Ad-miR-24-GFP) increased the expression of miR-24. Over-expression of miR-24 suppressed VSMC proliferation and neointimal hyperplasia in diabetic rats at 14 days. Furthermore, compared with Sham group, the mRNA and protein levels of PCNA, Wnt4, Dvl-1, β-catenin, and Cyclin D1 were strikingly up-regulated in the carotid arteries of diabetic rats after a balloon injury. Interestingly, up-regulation of miR-24 significantly reduced the mRNA and protein levels of these above molecules. In contrast, the change trend in p21 mRNA and

  12. Repetitive hypoglycemia increases circulating adrenaline level with resultant worsening of intimal thickening after vascular injury in male Goto-Kakizaki rat carotid artery.

    PubMed

    Yasunari, Eisuke; Mita, Tomoya; Osonoi, Yusuke; Azuma, Kosuke; Goto, Hiromasa; Ohmura, Chie; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2014-06-01

    Hypoglycemia associated with diabetes management is a potential risk for cardiovascular diseases. However, the effect of hypoglycemic episodes including a surge of sympathetic activity on the progression of neointima formation after vascular injury remains largely unknown. In this study, insulin was injected intraperitoneally into nonobese diabetic Goto-Kakizaki (GK) rats, once every 3 days for 4 weeks after balloon injury of carotid artery to induce hypoglycemia. Then, we evaluated balloon injury-induced neointima formation. Insulin treatment enhanced neointima formation and increased the number of proliferating cell nuclear antigen (PCNA)-positive cells in the carotid artery. Injection of glucose with insulin prevented hypoglycemia and abrogated intimal thickening. Also, bunazosin, an α1 adrenergic receptor antagonist, prevented intimal thickening and accumulation of PCNA-positive cells induced by insulin treatment despite the presence of concomitant hypoglycemia and high adrenaline levels. Incubation of cultured smooth muscle cells with adrenaline resulted in a significant increase in their proliferation and G0/G1 to S phase progression, which was associated with activation of extracellular signal-regulated kinase, enhanced expression of cell cycle regulatory molecules such as cyclin D1, and cyclin E, and phosphorylation of retinoblastoma protein. These adrenaline-induced effects were abrogated by bunazosin. Our data indicated that increased adrenaline induced by repetitive hypoglycemia promotes intimal thickening and smooth muscle cell proliferation after endothelial denudation in GK rats.

  13. Prostatic arterial embolization for the treatment of lower urinary tract symptoms as a result of large benign prostatic hyperplasia: A prospective single-center investigation.

    PubMed

    Wang, Maoqiang; Guo, Liping; Duan, Feng; Yuan, Kai; Zhang, Guodong; Li, Kai; Yan, Jieyu; Wang, Yan; Kang, Haiyan; Wang, Zhijun

    2015-08-01

    To evaluate the effectiveness and safety of prostatic arterial embolization as a primary treatment for patients with lower urinary tract symptoms as a result of large benign prostatic hyperplasia. A total of 64 patients with prostates >80 mL were included in the study. Prostatic arterial embolization was carried out using a combination of 50-µm and 100-µm particles. Clinical follow up was carried out using the International Prostate Symptom Score, quality of life, peak urinary flow, postvoid residual volume, International Index of Erectile Function Short Form, prostate-specific antigen, and prostatic volume at 1, 3, 6 and every 6 months thereafter. Prostatic arterial embolization was technically successful in 60 of 64 patients (93.8%). Follow-up data were available for 60 patients with a mean of 18 months. A clinical improvement, defined as reduction of International Prostate Symptom Score and increase of peak urinary flow, at 1 month, 3 months, 6 months, 12 months and 24 months, was achieved in 95.0%, 95.0%, 93.3%, 92.6% and 90.5%, respectively. A total of 42 patients had completed the follow up at 24 months after prostatic arterial embolization. There was an improvement in terms of mean International Prostate Symptom Score (pre-prostatic arterial embolization vs post-prostatic arterial embolization 27.0 vs 8.0; P < 0.01), mean quality of life (5.5 vs 2.0; P < 0.01), mean peak urinary flow (7.0 vs 13.0; P < 0.01), mean postvoid residual volume (130 vs 45.0; P < 0.05) and prostatic volume (121.0 vs 71.5, reduction of 40.9%; P < 0.01) were significantly different with respect to baseline. Prostatic arterial embolization seems to be a safe and effective treatment method for patients with lower urinary tract symptoms as a result of large benign prostatic hyperplasia, and it might play an important role for patients in whom medical therapy has failed, who are not candidates for surgical treatment. © 2015 The Japanese Urological Association.

  14. Lymphofollicular hyperplasia

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001377.htm Lymphofollicular hyperplasia To use the sharing features on this page, please enable JavaScript. Lymphofollicular hyperplasia is an increase in the size of the ...

  15. A Mechanical and Biochemical Model of Intimal Atherosclerotic Lesions

    NASA Astrophysics Data System (ADS)

    Fok, Pak-Wing; Vandiver, Rebecca

    2014-03-01

    We investigate a 1D axisymmetric model of intimal hyperplasia using hyperelasticity theory. Our model incorporates growth of the intima due to cell proliferation which in turn is driven by the release of a cytokine such as Platelet-Derived Growth Factor (PDGF). The main novelty of our model is that the growth rate is tied to local stresses and the local concentration of PDGF. The resulting system is a triple free boundary problem with different regions of the vessel wall having different homeostatic stress, depending on the local PDGF concentration. This system is coupled to force-balance equations that yield distributions for the stress and deformation. We find that rapid intimal thickening coupled to a quiescent media puts the intima in a state of compression and results in slow time scales of evolution. Our results are compared with intima-media thickness measurements of carotid arteries from previous clinical studies. Funded by a Simons Collaboration Grant.

  16. Gains of 12q13-14 and overexpression of mdm2 are frequent findings in intimal sarcomas of the pulmonary artery.

    PubMed

    Bode-Lesniewska, B; Zhao, J; Speel, E J; Biraima, A M; Turina, M; Komminoth, P; Heitz, P U

    2001-01-01

    The characterization of clinical, histopathological, immunohistochemical, and genetic features of intimal sarcomas arising in the pulmonary artery is presented in this study. Four resected lungs, one endarterectomy specimen and three biopsies from eight patients (four males and four females; median age 41 years) suffering from intimal sarcomas of the pulmonary artery using conventional stains, immunohistochemistry, and comparative genomic hybridization (CGH) were analyzed. The predominant clinical presentation was dyspnea (all eight patients) and febrile pulmonary disease (six of eight). Signs of embolic lung disease were present in all patients. One patient died postoperatively, six patients died of disease 8-35 months after presentation, and one patient was alive 6 months after surgery. Histopathological examination of the submitted material showed spindle cell, partially myxoid and pleomorphic sarcomas. Metastases were histologically confirmed in three patients (lung, pleura, and skull). Immunohistochemically, vimentin was strongly expressed in all tumors. Focal positivity was observed for alpha smooth muscle actin, CD117, CD68, p53, and bcl2. No reaction could be obtained for endothelial markers. The proliferation index Ki-67 was between 5% and 80%. Six examined tumors were positive for mdm2. In the CGH analysis, gains and amplifications in the 12q13-14 region were found in six of eight tumors (75%). Other, less consistent alterations, were losses on 3p, 3q, 4q, 9p, 11q, 13q, Xp, and Xq, gains on 7p, 17p, and 17q, and amplifications on 4q, 5p, 6p, and 11q. Intimal sarcomas of the pulmonary artery are tumors with an unfavorable prognosis and poorly differentiated morphology. A majority of tumors show a consistent genetic alteration (gains and amplifications in the 12q13-14 region) and overexpression of mdm2, implicating the mdm2/p53 pathway as a possible mechanism in the tumor pathogenesis.

  17. Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: an experimental study.

    PubMed

    Stefanadis, Christodoulos; Toutouzas, Konstantinos; Stefanadi, Elli; Lazaris, Andreas; Patsouris, Efstratios; Kipshidze, Nicholas

    2007-12-01

    Neovascularization is associated with destabilization of atheromatic plaques. Increased expression of vascular endothelial growth factor (VEGF) is important in the process of neovascularization. We assessed the effect of bevacizumab, a monoclonal antibody specific for VEGF, on neovascularization. We used 12 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a phosphorycholine coated stent into a solution of 4 ml bevacizumab according to previous studies. Twelve eluting stents and 12 non-eluting stents were implanted in the middle segment of the rabbit's iliac arteries. Follow-up angiography was performed at 4 weeks and tissues were obtained for histological analysis. The procedure of stent loading with bevacizumab and stent implantation was successful. There was no difference in angiographic measurements before, after implantation and at follow-up between the two groups. mean neointimal thickness (0.09+/-0.02 versus 0.12+/-0.02 mm, p<0.01), and mean neointimal area (1.08+/-0.09 versus 1.20+/-0.12 mm(2), p<0.01) were less in the bevacizumab treated segments. bevacizumab-treated arterial segments demonstrated significantly decreased microvessel density compared with the control group (1.69+/-0.06 CI: 1.65-1.73 versus 15.68+/-0.56 CI: 15.32-16.04 vessels per mm(2), p<0.001) and vegf expression was decreased in the media and adventitia of bevacizumab group. Endothelialization, inflammation and injury scores were similar between the two groups. These results suggest that bevacizumab-eluting stent implantation in rabbit iliac arteries is safe, and inhibits neovascularization without affecting the endothelialization.

  18. Neointimal Hyperplasia after Silverhawk Atherectomy versus Percutaneous Transluminal Angioplasty (PTA) in Femoropopliteal Stent Reobstructions: A Controlled, Randomized Pilot Trial

    SciTech Connect

    Brodmann, Marianne Rief, Peter; Froehlich, Harald; Dorr, Andreas; Gary, Thomas; Eller, Philipp; Hafner, Franz; Deutschmann, Hannes; Seinost, Gerald; Pilger, Ernst

    2013-02-15

    Due to intimal hyperplasia instent reobstruction in the femoropopliteal arterial segment is still an unsolved problem. Different techniques have been discussed in case of reintervention to guarantee longlasting patency rate. We conducted a randomized, controlled, pilot trial comparing Silverhawk atherectomy with percutaneous transluminal angioplasty (PTA) in patients with a first instent reobstruction in the femoropopliteal arterial segment, to evaluate intima media thickness (IMT) within the treated segment, as a parameter of recurrence of intimal hyperplasia. In a total 19 patients were included: 9 patients in the atherectomy device and 10 patients in the PTA arm. IMT within the treated segment was statistically significantly elevated in all patients treated with the Silverhawk device versus the patients treated with PTA. The obvious differentiation in elevation of IMT in nonfavor for patients treated with the Silverhawk device started at month 2 (max IMT SH 0.178 mm vs. IMT PTA 0.1 mm, p = 0.001) with a spike at month 5 (max IMT SH 0.206 mm vs. IMT PTA 0.145 mm, p = 0.003) and a decline once again at month 6 (max IMT SH 0.177 mm vs. IMT PTA 0.121 mm, p = 0.02). The values for mean IMT performed the same way. Although Silverhawk atherectomy provides good results at first sight, in the midterm follow-up of treatment of first instent restenosis it did not perform better than PTA as it showed elevated reoccurrence of intimal media hyperplasia.

  19. [[Impact of plestazol preparation on hyperplasia of inter vascular layer in the patients, suffering obliterating atherosclerosis of the lower extremities arteries after reconstructive operations].

    PubMed

    Nikuhinikov, P I; Bytsay, A N; Lysak, L I; Yatsenko, A I; Abramenko, A V

    2016-08-01

    In the clinic 60 patients were examined, in whom reconstructive operations on the main arteries were performed for obliterating atherosclerosis (OA) of the lower extremities vessels. Efficacy of impact of Plestazol (in a 200 mg/day dose) on neointima hyperpla- sia was studied. Clopidogrel (75 mg/day) was administered to patients of comparative group. Effective criteria for estimation of the migration-proliferation disorders state in endothelial dysfunction are concentration of the intercellular adhesion molecules (ICAM) and the basic factor of the fibroblasts growth (FGFb); morphological disorders in hyperplastic reactions of neointima - determination of thickness of "intima-media" complex in accordance to the ultrasound duplex scanning data. There was established, that Plestazol constitutes an effective disaggregate preparation, positively impacting decelerating reaction of neointima hyperplasia, including, deceleration of the smooth- muscle cells migration into subendotelial layer in the formation zone of the femoro- popliteal shunt distal anastomosis.

  20. Prostatic Urethral Lift Vs Prostate Arterial Embolization: Novel Nonablative Strategies in the Management of Lower Urinary Tract Symptoms Secondary to Benign Prostate Hyperplasia.

    PubMed

    Jones, Patrick; Rai, Bhavan Prasad; Aboumarzouk, Omar M; Somani, Bhaskar K

    2016-01-01

    Prostate urethral lift and prostate arterial embolization represent two evolving techniques with contrasting mechanisms of action (mechanical decompression vs angiographic embolization). Both yield relief of lower urinary tract symptoms over a period of several weeks. They display similar safety profiles with self-limiting pelvic discomfort characterizing the commonest minor adverse event. Both procedures have the potential to be carried out under local anesthesia and in the outpatient setting with suitability for patients with cardiovascular comorbidities. Neither has been found to cause degradation of sexual function. Further randomized studies are needed to delineate the formal position of these techniques in the surgical management of benign prostate hyperplasia. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Insights into the Effect of Nitric Oxide and its Metabolites Nitrite and Nitrate at Inhibiting Neointimal Hyperplasia

    PubMed Central

    Vavra, Ashley K.; Havelka, George E.; Martinez, Janet; Lee, Vanessa R.; Fu, Bo; Jiang, Qun; Keefer, Larry K.; Kibbe, Melina R.

    2011-01-01

    Objective Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate. Methods and Results In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n=8–11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, p<0.001). Only modest inhibition was noted with nitrite or nitrate (45% and 41% inhibition of intimal area, and 31% and 29% inhibition of medial area, respectively, p<0.001). No effects on blood pressure were noted with any treatment groups. In vivo, only PROLI/NO inhibited cellular proliferation and increased arterial lumen area compared to injury alone (p<0.001). However, all three treatments inhibited inflammation (p<0.001). Conclusions PROLI/NO was more effective at inhibiting neointimal hyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate. PMID:21554972

  2. Successful small diameter arterial grafting using cryopreserved allograft arteries.

    PubMed

    Eskew, T D; Ollerenshaw, J D; Philpott, J M; Dennis, K; Dawson, P; Sun, Y S; Chitwood, W R; Lust, R M

    1997-01-01

    Intimal hyperplasia (IH) limits the long-term success of veins as arterial grafts. IH occurs in veins partly as an adaptive process to arterial pressure conditions. The authors have previously reported early success with cryopreserved (CP) saphenous veins as aortocoronary bypass grafts, and they have hypothesized that CP arterial segments were already structurally adapted for arterial conditions. Six femoral arterial segments were harvested from three adult donor dogs, and cryopreserved. The segments were thawed and implanted into six recipient dogs, in end-to-end fashion, as interpositional grafts in the femoral artery. A similar length of native femoral artery was removed from the implant site and grafted in the contralateral femoral artery of the same animal to serve as native autograft-matched controls. Grafts were harvested bilaterally after 2 (n = 3) and 4 weeks (n = 3), perfusion fixed (80 mmHg, 15 min), and analyzed histologically. All grafts were patent at harvest, and flows distal to the grafted segments were not significantly different between grafts within an animal either at implant or subsequent harvest. Although CP arterial grafts still showed slight but significant dilation compared with native autograft, the dilation was much less than seen previously with either CP or native venous segments. No evidence of inflammation or IH was seen in CP arterial grafts. The absence of early IH or inflammation suggests that CP small diameter arteries may perform better than many currently available allograft tissues and synthetic prosthetics.

  3. Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: The roles of medial and luminal factors in arterial healing

    PubMed Central

    West, Jennifer L.; Hubbell, Jeffrey A.

    1996-01-01

    The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20-μm thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF. PMID:8917566

  4. [Role of cytokine-matrix metalloproteinase axis on promoting vascular neointima hyperplasia in mice].

    PubMed

    Liu, Y; Ning, W H; Shen, X H; Guo, D L; Guo, L

    2016-11-24

    Objective: To observe the effects of tumor necrosis factor-α (TNF-α) and platelet derived growth factor (PDGF) on vascular neointimal hyperplasia on matrix metalloproteinase 9/2 gene knockout (MMP9/2(-/-)) mice and explore related mechanisms. Methods: Mice of control group, MMP9(-/-) group, MMP2(-/-) group and MMP9/2(-/-) group were studied. Femoral artery was injured by transluminal wire, the mRNA expression levels of TNF-α and PDGF on femoral artery were detected by RT-PCR; the protein expression of MMP9 and MMP2 were assessed by Western blot on day 0, 1, 3, 7, 14 and 28 post injury. Mice in control group received TNF-α(5 ng/ml, 0.10 ml), TNF-α(0.05 ml)+ MMP inhibitor SB-3CT(0.50 ng/ml, 0.05 ml) injection, or PDGF-bb (10 ng/ml, 0.10 ml)and PDGF-bb(0.05 ml)+ SB-3CT(0.05 ml)injection around injured artery, intimal hyperplasia at 2 and 4 weeks after injury was observed. Intimal hyperplasia at 2 and 4 weeks after injury was also observed in MMP9/2(-/-) mice. TNF-α(5 ng/ml, 0.10 ml)was injected to MMP2(-/-) mice, PDGF-bb (0.1 ml) was injected to MMP9(-/-) mice around injured artery, intimal hyperplasia at 2 and 4 weeks after injury was observed. The degree of neointimal hyperplasia were observed by the Elastica-van Gieson staining and the area of neointima and media of the arteries were measured by SigmaPlot and intima ratio was calculated. Vascular smooth muscle cell (VSMC) mediums of MMP9(-/-) and MMP2(-/-) mice were stimulated by TNF-α and PDGF-bb, respectively, and migration assay, and proliferation assay were performed, relative migration and proliferation cells numbers were counted. Results: (1) mRNA expression of TNF-α (235.33±23.68) and PDGF-bb (3.30±0.56) in femoral arteries peaked at 1 day after injury, while MMP9 or MMP2 protein expression peaked at 7 or 28 days after injury. (2)In control mice, TNF-α intervention significantly enhanced intimal hyperplasia at 2 weeks after injury (2.21±0.05 vs. 1.55±0.03 in blank control group, P<0.05), while

  5. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery.

    PubMed

    Suzuki, Yasuhiro; Kondo, Kazunao; Matsumoto, Yuji; Zhao, Bing-Qing; Otsuguro, Kenichi; Maeda, Tetsuya; Tsukamoto, Yoshinori; Urano, Tetsumei; Umemura, Kazuo

    2003-07-25

    We have previously demonstrated that natto-extracts containing nattokinase (NK) inactivates plasminogen activator inhibitor type 1 and then potentiates fibrinolytic activity. In the present study, we investigated the effects of dietary supplementation with natto-extracts on neointima formation and on thrombolysis at the site of endothelial injury. Endothelial damage in the rat femoral artery was induced by intravenous injection of rose bengal followed by focal irradiation by transluminal green light. Dietary natto-extracts supplementation containing NK of 50 or 100 CU/body was started 3 weeks before endothelial injury and then continued for another 3 weeks. Intimal thickening in animals given supplementation was significantly (P<0.01) suppressed compared with controls and the intima/media ratio in animals with 50 and 100 CU/body NK and control group was 0.09 +/- 0.03, 0.09 +/- 0.06 and 0.16 +/- 0.12, respectively. Although femoral arteries were reopened both in control animals and those treated with NK within 8 hours after endothelial injury, mural thrombi were histologically observed at the site of endothelial injury. In the control group, the center of vessel lumen was reopened and mural thrombi were attached on the surface of vessel walls. In contrast, in NK-treated groups, thrombi near the vessel wall showed lysis and most of them detached from the surface of vessel walls. In conclusion, dietary natto-extracts supplementation suppressed intimal thickening produced by endothelial injury in rat femoral artery. These effects may partially be attributable to NK, which showed enhanced thrombolysis near the vessel wall.

  6. Occurrence of occlusive intimal changes in an expanded polytetrafluoroethylene graft.

    PubMed

    Carson, S N; Hunter, G; French, S; Lord, P; Wong, H N

    1980-01-01

    A case report is presented demonstrating pathologic changes in the neointima that formed when a polytetrafluoroethylene (PTFE) graft was placed in a 35 year old white male with severe arteriosclerosis. Representative sections of the patient's artery and graft were taken which demonstrated considerable smooth muscle proliferation in both along with full wall healing in the latter. Partial oclusion of the total length of the PTFE graft by a process similar to that occurring in the patient's own arteriosclerotic arteries was found. The consistency and extent of the involvement (> 10 cm in length) would appear to preclude entities such as neointimal fibrous hyperplasia and may point to another consequence of intimal injury and full wall graft healing which may be an undesirable effect of arteriosclerotic metabolism in the human. It is conceivable that full wall graft healing in an arteriosclerotic individual may have untoward events that need to be further investigated as new graft materials are developed.

  7. Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls.

    PubMed

    Ru, Xiaochen; Zheng, Changbo; Zhao, Qiannan; Lan, Hui-Yao; Huang, Yu; Wan, Song; Mori, Yasuo; Yao, Xiaoqiang

    2015-07-01

    A hallmark of atherosclerosis is progressive intimal thickening (namely neointimal hyperplasia), which leads to occlusive vascular diseases. Over-production of reactive oxygen species (ROS) and alteration of Ca2+ signaling are among the key factors contributing to neointimal growth. In the present study, we investigated the role of TRPM2, a ROS-sensitive Ca2+ entry channel, in neointimal hyperplasia. Perivascular cuffs were used to induce neointimal hyperplasia in rat/mouse arteries. Immunostaining showed numerous TRPM2-positive smooth muscle cells in neointimal regions. ROS were over-produced and PCNA-positive proliferating cells were numerous in the neointimal regions. The neointimal hyperplasia was substantially reduced in Trpm2 knockout mice compared with wild-type mice. In the cultured rat/mouse aortic smooth muscle cells, H2O2 treatment was found to stimulate cell proliferation and migration. The effect of H2O2 was reduced by a TRPM2-specific blocking antibody TM2E3 or Trpm2 knockout. The signaling molecules downstream of TRPM2 were found to be Axl and Akt. These data suggest a critical functional role of TRPM2 in the progression of neointimal hyperplasia. The study also highlights the possibility of targeting TRPM2 as a potential therapeutic option for the treatment of occlusive vascular diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Mass transport disturbances in the distal graft/artery junction of a peripheral bypass graft.

    PubMed

    Devereux, P D; O'Callaghan, S M; Walsh, M T; McGloughlin, T

    2005-11-01

    Intimal hyperplasia (IH) development is a primary cause of failure of reconstructive bypass surgery. While the exact mechanism by which IH initiates and proliferates has yet to be fully elucidated, it is clear that the abnormal haemodynamics present in the downstream graft/artery junction are intrinsic in its development. Mass transport disturbances owing to abnormal haemodynamics have been associated with atherogenesis and it is for this reason that an investigation into transport of platelet-derived growth factor (PDGF), a known promoter of the intimal hyperplastic response, at the downstream graft/artery junction was carried out. A steady flow analysis in a three-dimensional, idealized, downstream graft/artery junction was carried out using commercial computational fluid dynamics software. It was found that there is a two-and-half fold increase in the transport of PDGF to the artery wall at the bed of the junction when compared with an idealized, healthy artery. The presence of secondary flows in the downstream arterial section also leads to large disturbances in mass transport. It was concluded that PDGF transport in the downstream graft/artery junction tends to be highly disturbed and that there may be a role of this disturbance in the initiation and subsequent development of distal anastomotic intimal hyperplasia.

  9. Therapeutic Targeting of RNA Polymerase I With the Small-Molecule CX-5461 for Prevention of Arterial Injury-Induced Neointimal Hyperplasia.

    PubMed

    Ye, Qing; Pang, Shu; Zhang, Wenjing; Guo, Xiaotong; Wang, Jianli; Zhang, Yongtao; Liu, Yang; Wu, Xiao; Jiang, Fan

    2017-03-01

    RNA polymerase I (Pol I)-dependent rRNA synthesis is a determinant factor in ribosome biogenesis and thus cell proliferation. The importance of dysregulated Pol I activity in cardiovascular disease, however, has not been recognized. Here, we tested the hypothesis that specific inhibition of Pol I might prevent arterial injury-induced neointimal hyperplasia. CX-5461 is a novel selective Pol I inhibitor. Using this tool, we demonstrated that local inhibition of Pol I blocked balloon injury-induced neointima formation in rat carotid arteries in vivo. Neointimal development was associated with augmented rDNA transcriptional activity as evidenced by the increased phosphorylation of upstream binding factor-1. The beneficial effect of CX-5461 was mainly mediated by inducing G2/M cell cycle arrest of proliferating smooth muscle cells without obvious apoptosis. CX-5461 did not induce p53 stabilization but increased p53 phosphorylation and acetylation and activated the ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related (ATR) pathway. Inhibition of ATR, but not of ataxia telangiectasia mutated, abolished the cytostatic effect of CX-5461 and p53 phosphorylation. In addition, inhibition of p53 or knockdown of the p53 target GADD45 mimicked the effect of ATR inhibition. In vivo experiments showed that the levels of phospho-p53 and acetyl-p53, and activity of the ataxia telangiectasia mutated/ATR pathway were all augmented in CX-5461-treated vessels. Pol I can be therapeutically targeted to inhibit the growth of neointima, supporting that Pol I is a novel biological target for preventing arterial restenosis. Mechanistically, Pol I inhibition elicited G2/M cell cycle arrest in smooth muscle cells via activation of the ATR-p53 axis. © 2017 American Heart Association, Inc.

  10. Mir-22-3p Inhibits Arterial Smooth Muscle Cell Proliferation and Migration and Neointimal Hyperplasia by Targeting HMGB1 in Arteriosclerosis Obliterans.

    PubMed

    Huang, Shui-Chuan; Wang, Mian; Wu, Wei-Bin; Wang, Rui; Cui, Jin; Li, Wen; Li, Zi-Lun; Li, Wen; Wang, Shen-Ming

    2017-08-22

    Aberrant vascular smooth muscle cell (VSMC) proliferation and migration contribute to the development of vascular pathologies, such as atherosclerosis and post-angioplasty restenosis. The aim of this study was to determine whether miR-22-3p plays a role in regulating human artery vascular smooth muscle cell (HASMC) function and neointima formation. Quantitative real-time PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect miR-22-3p expression in human arteries. Cell Counting Kit-8 (CCK-8) and EdU assays were performed to assess cell proliferation, and transwell and wound closure assays were performed to assess cell migration. Moreover, luciferase reporter assays were performed to identify the target genes of miR-22-3p. Finally, a rat carotid artery balloon-injury model was used to determine the role of miR-22-3p in neointima formation. MiR-22-3p expression was downregulated in arteriosclerosis obliterans (ASO) arteries compared with normal arteries, as well as in platelet-derived growth factor-BB (PDGF-BB)-stimulated HASMCs compared with control cells. MiR-22-3p overexpression had anti-proliferative and anti-migratory effects and dual-luciferase assay showed that high mobility group box-1 (HMGB1) is a direct target of miR-22-3p in HASMCs. Furthermore, miR-22-3p expression was negatively correlated with HMGB1 expression in ASO tissue specimens. Finally, LV-miR-22-3p-mediated miR-22-3p upregulation significantly suppressed neointimal hyperplasia specifically by reducing HMGB1 expression in vivo. Our results indicate that miR-22-3p is a key molecule in regulating HASMC proliferation and migration by targeting HMGB1 and that miR-22-3p and HMGB1 may be therapeutic targets in the treatment of human ASO. © 2017 The Author(s). Published by S. Karger AG, Basel.

  11. Adenomatous-Dominant Benign Prostatic Hyperplasia (AdBPH) as a Predictor for Clinical Success Following Prostate Artery Embolization: An Age-Matched Case-Control Study.

    PubMed

    Little, M W; Boardman, P; Macdonald, A C; Taylor, N; Macpherson, R; Crew, J; Tapping, C R

    2017-05-01

    To investigate the clinical impact of performing prostate artery embolization (PAE) on patients with adenomatous-dominant benign prostatic hyperplasia (AdBPH). Twelve patients from the ongoing proSTatic aRtery EmbolizAtion for the treatMent of benign prostatic hyperplasia (STREAM) trial were identified as having AdBPH; defined as two or more adenomas within the central gland of ≥1 cm diameter on multi-parametric MRI (MP-MRI). These patients were age-matched with patients from the STREAM cohort, without AdBPH. Patients were followed up with repeat MP-MRI at 3 months and 1 year. International prostate symptom score (IPSS), international index for erectile function (IIEF), and quality of life assessment from the IPSS and EQ-5D-5S questionnaires were recorded pre-PAE and at 6 weeks, 3 months, and 1 year. The mean age of patients was 68 (61-76). All patients had PAE as a day-case procedure. The technical success in the cohort was 23/24 (96%). There was a significant reduction in prostate volume following embolization with a median reduction of 34% (30-55) in the AdBPH group, compared to a mean volume reduction of 22% (9-44) in the non-AdBPH group (p = 0.04). There was a significant reduction in IPSS in the AdBPH group following PAE when compared with the control group [AdBPH median IPSS 8 (3-15) vs. non-AdBPH median IPSS 13 (8-18), p = 0.01]. IPSS QOL scores significantly improved in the AdBPH group (p = 0.007). There was no deterioration in sexual function in either group post-PAE. This is the first time that AdBPH has been identified as being a predictor of clinical success following PAE.

  12. Endometrial Hyperplasia

    MedlinePlus

    ... menopause (in women who have not had a hysterectomy ) Irregular menstrual periods, especially associated with polycystic ovary ... atypical hyperplasia, the risk of cancer is increased. Hysterectomy usually is the best treatment option if you ...

  13. Comparison of Coronary Intimal Plaques by Optical Coherence Tomography in Arteries With Versus Without Internal Running Vasa Vasorum.

    PubMed

    Amano, Hideo; Koizumi, Masayuki; Okubo, Ryo; Yabe, Takayuki; Watanabe, Ippei; Saito, Daiga; Toda, Mikihito; Ikeda, Takanori

    2017-05-15

    It has been reported that the internal running vasa vasorum (VV) was associated with plaque vulnerability, and microchannels in optical coherence tomography (OCT) are consistent pathologically with VV. We investigated plaque vulnerability and incidence of slow flow during percutaneous coronary intervention of the internal longitudinal running VV. Subjects were 71 lesions that underwent OCT before percutaneous coronary intervention. Internal running VV was defined as intraplaque neovessels running from the adventitia to plaque. Lesions with internal running VV were found in 47% (33 of 71). Compared with lesions without internal running VV, lesions with internal running VV showed significantly higher incidence of intimal laceration (64% [21 of 33] vs 16% [6 of 38], p <0.001), lipid-rich plaque (79% [26 of 33] vs 26% [10 of 38], p <0.001), plaque rupture (52% [17 of 33] vs 13% [5 of 38], p <0.001), thin-cap fibroatheroma (58% [19 of 33] vs 11% [4 of 38], p <0.001), macrophage accumulation (61% [20 of 33] vs 26% [10 of 38], p = 0.004), intraluminal thrombus (36% [12 of 33] vs 3% [1 of 38], p <0.001), and slow flow after stent implantation (42% [14 of 33] vs 13% [5 of 38], p = 0.007). The multivariable analysis showed that internal running VV was an independent predictor of slow flow after stent implantation (odds ratio 4.23, 95% confidence interval 1.05 to 17.01, p = 0.042). In conclusion, compared with those without, plaques with internal running VV in OCT had high plaque vulnerability with more intimal laceration, lipid-rich plaque, plaque rupture, thin-cap fibroatheroma, macrophage accumulation, and intraluminal thrombus, and they had high incidence of slow flow after stent implantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Prevention of neointimal hyperplasia in balloon-injured rat carotid artery via small interference RNA mediated downregulation of osteopontin gene.

    PubMed

    Xu, Jian; Sun, Yingxian; Wang, Tairan; Liu, Guinan

    2013-05-01

    The aim of the present study was to take osteopontin (OPN) as molecular target to study its effects on injured intima model of carotid artery in rat using perivascular transfer of OPN-small interference RNA (siRNA). OPN mRNA in cultured VSMCs was quantified by real-time RT-PCR, and OPN-siRNA-002 was determined as the most sensitive sequence and used as transfected siRNA in the subsequent animal experiments. We established rat carotid arterial intima-injured model with balloon-injured method, and then perivascularly transfected OPN-siRNA-002 to study the role of OPN-siRNA in regulating several related genes including proliferating cell nuclear antigen (PCNA), transforming growth factor β1(TGF-β1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-14 (MMP-14), as well as its role in neointimal formation. OPN mRNA and protein decreased about 50 % with corresponding decrease in intima thickness after transfecting with specific OPN-siRNA-002 compared with Pluronic control group and OPN-SCR-siRNA group on each time point (n = 6, p < 0.001), and this inhibiting effects persisted up to 14 days after balloon injury. PCNA, TGF-β1, MMP-2, and MMP-14 mRNA and protein correlated directly with the respective levels of OPN, suggesting its functions via regulating these downstream factors (n = 6, p < 0.001). OPN may be a potential target gene in reducing the risk for arterial restenosis after vascular intervention.

  15. Natural Progression of Atherosclerosis from Pathologic Intimal Thickening to Late Fibroatheroma in Human Coronary Arteries: A Pathology Study

    PubMed Central

    Otsuka, Fumiyuki; Kramer, Miranda C.A.; Woudstra, Pier; Yahagi, Kazuyuki; Ladich, Elena; Finn, Aloke V.; de Winter, Robbert J.; Kolodgie, Frank D.; Wight, Thomas N.; Davis, Harry R.; Joner, Michael; Virmani, Renu

    2015-01-01

    Objective Smooth muscle cells, macrophage infiltration and accumulation of lipids, proteoglycans, collagen matrix and calcification play a central role in atherosclerosis. The early histologic changes of plaque progression from pathologic intimal thickenings (PIT) to late fibroatheroma lesions have not been fully characterized. Methods A total of 151 atherosclerotic coronary lesions were collected from 67 sudden death victims. Atherosclerotic plaques were classified as PIT without macrophage infiltration, PIT with macrophages, and early and late fibroatheromas. Presence of macrophages and proteoglycans (versican, decorin and biglycan) were recognized by specific antibodies while hyaluronan was detected by affinity histochemistry. Lipid deposition was identified by oil-red-O, and calcification was assessed following von Kossa and alizarin red staining. Results Lesion progression from PIT to late fibroatheroma was associated with increase in macrophage accumulation (p<0.001) and decreasing apoptotic body clearance by macrophages (ratio of engulfed-to-total apoptotic bodies) (p<0.001). Lipid deposition in lipid pool of PIT had a microvesicular appearance whereas those in the necrotic core were globular in nature. Overall, the accumulation of hyaluronan (p<0.001), and proteoglycan versican (p<0.001) and biglycan (p=0.013) declined along with lesion progression from PIT to fibroatheromas. Microcalcification was first observed only within areas of lipid pools and its presence and size increased in lesions with necrotic core. Conclusions PIT to fibroatheroma lesions are accompanied by early lipid accumulation, followed by macrophage infiltration with defective clearance of apoptotic bodies along with decrease in proteoglycan and hyaluronan in lipid pools that convert to necrotic cores. Calcification starts in PIT and increases with plaque progression. PMID:26058741

  16. Assessment of temporal bias in longitudinal measurements of carotid intimal-medial thickness in the Asymptomatic Carotid Artery Progression Study (ACAPS). ACAPS Research Group.

    PubMed

    Riley, W A; Craven, T; Romont, A; Furberg, C D

    1996-01-01

    A randomly selected subset of 100 pairs of baseline and 36-month follow-up carotid B-mode ultrasound examinations from the 919 patients participating in the Asymptomatic Carotid Artery Progression Study (ACAPS) were subjected to a blinded rereading at the conclusion of the trial to assess temporal bias in the measurement of carotid artery intimal-medial thickness (IMT). The original measurements of the primary outcome variable and five secondary outcome variables at baseline and 36 months, respectively, and the 3-year change in each of these variables, were compared with those obtained from the rereadings. For the primary outcome variable, the mean value of 12 IMT measurements obtained from predefined carotid segments, the mean difference (original-rereading) and the 95% confidence interval which resulted from the rereadings were -0.005 (-0.033, 0.023) mm at baseline and -0.009 (-0.031, 0.013) mm at 36 months. The difference in the 3-year change was -0.004 (-0.038, 0.028) mm. The 95% confidence interval for the mean difference between the rereadings and the original readings for the baseline and the 36-month follow-up examinations included zero for all of the six outcome variables as was also the case for the 3-year change in each variable. The magnitude of the mean differences for these 18 variables ranged from 0.004 to 0.034 mm. Intraclass correlation coefficients between the original readings and rereadings ranged from 0.56 to 0.87 with the 3-year changes in outcome variables tending to have lower correlations and the 36-month examinations higher correlations. The carotid IMT measurement process, when combined with uniform reader training, certification and monitoring of reading performance throughout the course of the study, can avoid the temporal bias observed in other studies.

  17. Efficacy and safety of prostate artery embolization on lower urinary tract symptoms related to benign prostatic hyperplasia: a systematic review and meta-analysis.

    PubMed

    Wang, Xiao-Yan; Zong, Huan-Tao; Zhang, Yong

    2016-01-01

    Prostate artery embolization (PAE) is emerging and is a promising minimally invasive therapy that improves lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). The purpose of this article was to evaluate the efficacy and safety of PAE on LUTS related to BPH. A literature review was performed to identify all published articles of PAE for BPH. The sources included MEDLINE, EMBASE and Cochrane Library from 1980 to 2016. A systematic review and meta-analysis was conducted. The outcome measurements were combined by calculating the mean difference with 95% confidence interval. Statistical analysis was carried out using Review Manager 5.3.0. Twelve studies involving 840 participants were included. Compared with baseline, the International Index of Erectile Function (IIEF-5; International Prostate Symptom Score) scores, the quality of life scores, peak urinary flow rate (Qmax) and postvoid residual volume all had significant improvements during the 24-month follow-up (all P<0.00001). Both prostate volume (PV) and prostate-specific antigen had significant decrease during the 12-month follow-up (P<0.00001 and P=0.005, respectively), except postoperative 24 months (P=0.47 and P=0.32, respectively). The IIEF-5 short form scores had significant increase at postoperative 6 months (P=0.002) and 12 months (P<0.0001), except postoperative 1 month (P=0.23) and 24 months (P=0.21). For large volume (PV ≥80 mL) BPH, the results were similar. There were no life-threatening complications. PAE is an effective, safe and well-tolerable treatment for LUTS related to BPH, including large volume (PV ≥80 mL) BPH, with a good short-term follow-up. Studies with large number of cases and longer follow-up time are needed to validate our results.

  18. Clinical, Laboratorial, and Urodynamic Findings of Prostatic Artery Embolization for the Treatment of Urinary Retention Related to Benign Prostatic Hyperplasia. A Prospective Single-Center Pilot Study

    SciTech Connect

    Antunes, Alberto A.; Carnevale, Francisco C. Motta Leal Filho, Joaquim M. da; Yoshinaga, Eduardo M.; Cerri, Luciana M. O.; Baroni, Ronaldo H.; Marcelino, Antonio S. Z.; Cerri, Giovanni G.; Srougi, Miguel

    2013-08-01

    PurposeThis study was designed to describe the clinical, laboratorial, and urodynamic findings of prostatic artery embolization (PAE) in patients with urinary retention due to benign prostatic hyperplasia (BPH).MethodsA prospective study of 11 patients with urinary retention due to BPH was conducted. Patients underwent physical examination, prostate specific antigen (PSA) measurement, transrectal ultrasound, and magnetic resonance imaging. International prostate symptom score (IPSS), quality of life (QoL), and urodynamic testing were used to assess the outcome before and after 1 year.ResultsClinical success was 91 % (10/11 patients) with a mean follow-up of 22.3 months (range, 12-41 months). At the first year follow-up, the mean IPSS score was 2.8 points (p = 0.04), mean QoL was 0.4 points (p = 0.001), mean PSA decreased from 10.1 to 4.3 ng/mL (p = 0.003), maximum urinary flow (Qmax) improved from 4.2 to 10.8 mL/sec (p = 0.009), and detrusor pressure (Pdet) decreased from 85.7 to 51.5 cm H{sub 2}O (p = 0.007). Before PAE, Bladder Outlet Obstruction Index (BOOI) showed values >40 in 100 % of patients. After PAE, 30 % of patients were >40 (obstructed), 40 % were between 20 and 40 (undetermined), and 30 % were <20 (unobstructed). Patients with a BOOI <20 had higher PSA values at 1-day after PAE.ConclusionsClinical and urodynamic parameters improved significantly after PAE in patients with acute urinary retention due to BPH. Total PSA at day 1 after PAE was higher in patients with unobstructed values in pressure flow studies.

  19. Intimal sarcoma of the pulmonary valve.

    PubMed

    Scheidl, Stefan; Taghavi, Shahrokh; Reiter, Ursula; Tröster, Natascha; Kovacs, Gabor; Rienmüller, Rainer; Lang, Susanna; Klepetko, Walter; Olschewski, Horst

    2010-04-01

    Pulmonary artery intimal sarcoma is a rare tumor of the cardiovascular system. Intimal sarcoma of the pulmonary valve itself has not been described. Embolization into pulmonary arteries originating from the pulmonary valve intimal sarcoma can mimic chronic thromboembolic pulmonary hypertension and mislead the diagnosis. We present and discuss a patient initially diagnosed as chronic thromboembolic pulmonary hypertension, treated by pulmonary endarterectomy. After 24 months, a tumor of the pulmonary valve was detected by echocardiography. The patient underwent removal and replacement of the pulmonary valve. Histology revealed pulmonary valve intimal sarcoma.

  20. Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.

    PubMed

    Wang, Xisheng; Mei, Yunqing; Ji, Qiang; Feng, Jing; Cai, Jianzhi; Xie, Shiliang

    2015-07-01

    The excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia. In a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry. Transfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA. We confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  1. Endometrial hyperplasia.

    PubMed

    Mills, Anne M; Longacre, Teri A

    2010-11-01

    Endometrial hyperplasia is a heterogeneous set of pathologic lesions that range from mild, reversible glandular proliferations to direct cancer precursors. These lesions comprise a continuum of morphologic appearances, with the earliest proliferation represented by crowded glands with simple tubular architecture lined by cells resembling proliferative endometrium, whereas advanced proliferations in this continuum are characterized by crowded glands with complex architecture, often containing cells with nuclear atypia resembling low-grade endometrioid adenocarcinoma. The former "early" proliferations may be isolated to an endometrial polyp, but advanced proliferations are generally more diffusely present throughout the endometrium. There are at least three major classification systems for endometrial carcinoma precursor lesions, each of which trend toward overlap at the complex end of the spectrum. Although some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), each classification scheme ultimately uses a series of histologic features, usually a combination of architecture and cytology, to establish a diagnosis of hyperplasia. Because different pathologists may apply different histologic criteria for endometrial hyperplasia depending on the classification system used, this article will provide an overview of the classifications used in current daily practice, present the histologic criteria and relative merits of each classification system, and discuss common and not so common causes of misclassification.

  2. Prostatic Arterial Embolization with Small Sized Particles for the Treatment of Lower Urinary Tract Symptoms Due to Large Benign Prostatic Hyperplasia: Preliminary Results

    PubMed Central

    Li, Qiang; Duan, Feng; Wang, Mao-Qiang; Zhang, Guo-Dong; Yuan, Kai

    2015-01-01

    Background: The clinical failure after prostatic artery embolization (PAE) with conventional particles was relatively high, in treatment for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). We reported the results of PAE with combined polyvinyl alcohol particles 50 μm and 100 μm in size as a primary treatment in 24 patients with severe LUTS secondary to large BPH. Methods: From July 2012 to June 2014, we performed PAE in 24 patients (65–85 years, mean 74.5 years) with severe LUTS due to large BPH (≥80 cm3) and refractory to medical therapy. Embolization was performed using combination of 50 μm and 100 μm in particles size. Clinical follow-up was performed using the International Prostate Symptom Score (IPSS), quality of life (QoL), peak urinary flow (Qmax), postvoid residual (PVR) volume, the International Index of Erectile Function (IIEF), prostatic specific antigen (PSA), and prostatic volume measured by magnetic resonance imaging at 1, 3, 6, and every 6-month thereafter. Technical success was defined when PAE was completed in at least one pelvic side. Clinical success was defined as the improvement of both symptoms and QoL. A Student's t-test for paired samples was used. Results: PAE was technically successful in 22 patients (92%). Bilateral PAE was performed in 19 (86%) patients and unilateral in 3 (14%) patients. Follow-up data were available for 22 patients observed for mean of 14 months. The clinical improvement at 1, 3, 6, and 12-month was 91%, 91%, 88%, and 83%, respectively. At 6-month follow-up, the mean IPSS, QoL, PVR, and Qmax were from 27 to 8 (P = 0.001), from 4.5 to 2.0 (P = 0.002), from 140.0 ml to 55.0 ml (P = 0.002), and from 6.0 ml/s to 13.0 ml/s (P = 0.001), respectively. The mean prostate volume decreased from 110 cm3 to 67.0 cm3 (mean reduction of 39.1%; P = 0.001). The PSA and IIEF improvements after PAE did not differ from pre-PAE significantly. No major adverse events were noted. Conclusions: The

  3. Prostatic Arterial Embolization Followed by Holmium Laser Enucleation of the Prostate as a Planned Combined Approach for Extremely Enlarged Benign Prostate Hyperplasia.

    PubMed

    Li, Pu; Wang, Chengming; Cao, Qiang; Zhang, Jiexiu; Shi, Haibin; Meng, Xiaoxin

    2017-08-03

    This study was aimed at reporting the initial experience with prostatic arterial embolization (PAE) followed by holmium laser enucleation of the prostate (HoLEP) as a planned combined approach for extremely enlarged benign prostate hyperplasia (BPH), and retrospectively estimating the efficacy and safety of this novel technique. Twenty-four BPH patients who underwent PAE and subsequent HoLEP were included. The PAE procedure was performed under local anesthesia at the supine position with polyvinyl alcohol spherical particles and gelatin sponge particles. HoLEP was performed 3 months after PAE by the "en-bloc" enucleation technique. Clinical data before and 6 months after the procedure were analyzed. PAE and HoLEP were technically successful in all 24 patients. The mean prostate volume was 219 ± 38 mL; the mean total operative time and enucleation time for HoLEP were 117.8 ± 21.9 and 83.5 ± 15.4 min, respectively; and the mean resected prostate weight was 118.3 ± 20.7 g. No transurethral resection of the prostate syndrome was observed during and after HoLEP. The estimated blood loss during HoLEP was 72.1 ± 33.7 mL, and no case required transfusion. International Prostate Symptom Score and post void residual volume decreased significantly (24.1 ± 2.84 vs. 13.5 ± 3.39, p < 0.001; 107.1 ± 40.8 vs. 21.8 ± 16.8, p < 0.001, respectively), maximal flow rate increased significantly (6.25 ± 1.42 vs. 17.63 ± 16.56, p < 0.001), and prostatic specific antigen level also decreased after the procedure (9.29 ± 2.28 vs. 4.99 ± 1.35, p < 0.001). PAE followed by HoLEP as a planned combined approach can be performed safely, feasibly, and efficiently in patients with extremely enlarged BPH. © 2017 S. Karger AG, Basel.

  4. Predictors of Clinical Outcome after Prostate Artery Embolization with Spherical and Nonspherical Polyvinyl Alcohol Particles in Patients with Benign Prostatic Hyperplasia.

    PubMed

    Bilhim, Tiago; Pisco, João; Pereira, José A; Costa, Nuno Vasco; Fernandes, Lúcia; Campos Pinheiro, Luís; Duarte, Marisa; Oliveira, António G

    2016-10-01

    Purpose To assess predictors of outcome after prostate artery embolization (PAE) for benign prostatic hyperplasia with spherical particle polyvinyl alcohol (sPVA) and compare outcomes with the use of nonspherical particle polyvinyl alcohol (nsPVA). Materials and Methods This was a single-center retrospective institutional review board-approved study conducted from 2009 to 2015 in patients undergoing PAE with sPVA (n = 186; mean age ± standard deviation, 65.5 years ± 7.7) and nsPVA (n = 300; mean age, 65.3 years ± 7.6). The two cohorts were compared and analyzed for predictors of outcome with a Cox proportional hazards model and linear regression. Post-PAE prostate ischemia was measured with contrast material-enhanced magnetic resonance (MR) imaging in 23 patients with nsPVA and 25 patients with sPVA. The 24-hour post-PAE prostate-specific antigen (PSA) level was registered in 133 patients with sPVA. Prognostic values of MR imaging and PSA levels 24 hours after PAE were assessed with Cox and random-effects regressions. Results Predictors of clinical failure were older age (age over 65 years, P = .002), unilateral procedure (P = .002), and higher baseline International Prostate Symptom Score (IPSS, P = .033). Adjusted hazard ratio for clinical failure of sPVA was 1.273 (P = .16). Acute urinary retention was a predictor of lower IPSS after PAE (P = .002). The mean proportion of prostate ischemia was 11% with sPVA and 10% with nsPVA (P = .65). Lower IPSS after PAE was associated with a higher proportion of prostate ischemia (P = .009). Patients with a PSA level of at least 75 ng/mL (75 μg/L) 24 hours after PAE had a greater decrease in IPSS (P = .01). Prostate ischemic volume and PSA level 24 hours after PAE were correlated (Pearson r = 0.64, P = .014). Conclusion Clinical outcome was similar after PAE with sPVA and nsPVA. Younger age (up to 65 years), bilateral PAE, lower baseline IPSS, and acute urinary retention were predictors of better clinical outcome. The

  5. Benign prostatic hyperplasia after prostatic arterial embolization in a canine model: A 3T multiparametric MRI and whole-mount step-section pathology correlated longitudinal study.

    PubMed

    Li, Basen; Xu, Anhui; Wang, Nan; Min, Xiangde; Feng, Zhaoyan; Deng, Ming; Li, Liang; Cai, Jie; Kang, Zhen; Jiang, Kehua; Kuang, Dong; Wang, Liang

    2017-10-01

    To explore the morphological and functional characteristics of prostatic arterial embolization (PAE) in a canine model of benign prostatic hyperplasia (BPH) with 3T multiparametric magnetic resonance imaging (mp-MRI) and whole-mount step-section pathology correlation. Eight adult male beagle dogs with hormone-induced BPH underwent 3T mp-MRI before and 1, 3, and 6 months after PAE, with subsequent whole-mount step-section pathologic assessment. Images were acquired using T1 -weighted images (T1 WI), T2 WI, 3D-SPACE, diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), T2 -mapping, and dynamic contrast-enhanced (DCE) sequences. Variance analysis was performed to assess statistical differences in prostatic volume (PV), apparent diffusion coefficient (ADC), and T2 values. Pearson correlation analysis was performed to correlate ADC, T2 , and PV. The PV decreased from baseline to 1, 3, and 6 months after PAE from (25.88 ± 7.09) cm(3) to (6.48 ± 2.08) cm(3) , (6.48 ± 3.39) cm(3) , (6.20 ± 2.88) cm(3) . The ADC values sequentially decreased from baseline to 1, 3, and 6 months after PAE from (1497.06 ± 222.72) × 10(-6) mm(2) /s to (1056.00 ± 189.46) × 10(-6) mm(2) /s, (950.48 ± 77.85) × 10(-6) mm(2) /s, (980.98 ± 107.78) × 10(-6) mm(2) /s. The T2 values decreased from baseline to 1, 3, and 6 months after PAE were (83.74 ± 5.29) msec, (68.72 ± 5.66) msec, (53.96 ± 15.04) msec, (49.81 ± 13.34) msec, respectively. ADC and T2 values were positively correlated with PV (r = 0.823 and 0.744, respectively). Microhemorrhages and hemosiderin were found on SWI after PAE. 3T mp-MRI may facilitate noninvasive assessment of morphological and functional changes of BPH after PAE. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1220-1229. © 2017 International Society for Magnetic Resonance in Medicine.

  6. Prevention of Neointimal Hyperplasia by Local Application of Lentiviral Vectors Encoding Pin1 shRNA in Pluronic F127.

    PubMed

    Lv, Lei; Shi, Yaxue; Duan, Rundan; Xie, Hui; Zhang, Jiwei; Liang, Wei; Xue, Guanhua; Zhang, Lan; Huang, Xiaozhong

    2015-01-01

    Inhibition of intimal hyperplasia plays an important role in preventing restenosis. Previously, we reported the provocative role of Pin1 in regulating vascular smooth muscle cell (VSMC) proliferation. Here we intended to identify whether locally delivered lentivirus-mediated siPin1 via pluronic F127 (PF127) could inhibit neointimal formation and further explore the potential mechanisms thereof. In vitro studies revealed that lentivirus-mediated siPin1 dispersed in PF127 suppressed proliferation and induced senescence in VSMCs. Reduction of Pin1 expression resulted in a decrease of phospho-Akt (p-Akt) expression level in VSMCs. Reactivation of Akt phosphorylation overcame the siPin1-mediated senescence. In a rat wire injury model, periadventitial delivery of lentivirus-mediated siPin1 via PF127 produced inhibition of intimal hyperplasia 14 days after injury without evidence for toxicity. Furthermore, the reduction of intimal thickness was associated with a decreased amount of PCNA positive cells, decreased telomerase activity and shortened telomere length. Therefore, these results suggest that PF127 delivery of lentivirus-mediated siPin1 to artery may have a therapeutic potential for the treatment of restenosis.

  7. Hyperplasia (Ductal or Lobular)

    MedlinePlus

    ... is also known as epithelial hyperplasia or proliferative breast disease. It’s an overgrowth of the cells that line the ducts or the milk glands (lobules). Hyperplasia may be called either ductal hyperplasia ( ...

  8. Quantification of Adventitial Vasa Vasorum Vascularization in Double-injury Restenotic Arteries

    PubMed Central

    Ye, Meng; Zhang, Bai-Gen; Zhang, Lan; Xie, Hui; Zhang, Hao

    2015-01-01

    Background: Accumulating evidence indicates a potential role of adventitial vasa vasorum (VV) dysfunction in the pathophysiology of restenosis. However, characterization of VV vascularization in restenotic arteries with primary lesions is still missing. In this study, we quantitatively evaluated the response of adventitial VV to vascular injury resulting from balloon angioplasty in diseased arteries. Methods: Primary atherosclerotic-like lesions were induced by the placement of an absorbable thread surrounding the carotid artery of New Zealand rabbits. Four weeks following double-injury induced that was induced by secondary balloon dilation, three-dimensional patterns of adventitial VV were reconstructed; the number, density, and endothelial surface of VV were quantified using micro-computed tomography. Histology and immunohistochemistry were performed in order to examine the development of intimal hyperplasia. Results: Results from our study suggest that double injured arteries have a greater number of VV, increased luminal surface, and an elevation in the intima/media ratio (I/M), along with an accumulation of macrophages and smooth muscle cells in the intima, as compared to sham or single injury arteries. I/M and the number of VV were positively correlated (R2 = 0.82, P < 0.001). Conclusions: Extensive adventitial VV neovascularization occurs in injured arteries after balloon angioplasty, which is associated with intimal hyperplasia. Quantitative assessment of adventitial VV response may provide insight into the basic biological process of postangioplasty restenosis. PMID:26228224

  9. [Nodular regenerative hyperplasia associated with primary antiphospholipid syndrome].

    PubMed

    Cadranel, J F; Demontis, R; Guettier, C; Bouraya, D; Dautreaux, M; Ghazali, A; Poux, J M; Coutarel, P; Devergie, B; Fievet, P

    1996-01-01

    Nodular regenerative hyperplasia of the liver is characterized by diffuse nodularity of the hepatic parenchyma without fibrotic septa. It may be related to venous or arterial obstruction in the portal tract. We report a case of primary antiphospholipid syndrome associated with nodular regenerative hyperplasia in a 45-year old woman. The patient had an ischemic stroke, associated with an acute arterial ischemia of the left leg. She had high titers of serum anticardiolipin antibodies. Nodular regenerative hyperplasia of the liver was histologically confirmed and was associated with anicteric cholestasis. This case provides additional evidence that a thrombotic mechanism may play a role in the pathogenesis of nodular regenerative hyperplasia of the liver.

  10. Human Umbilical Cord Blood Endothelial Progenitor Cells Decrease Vein Graft Neointimal Hyperplasia in SCID Mice

    PubMed Central

    Zhu, Shoukang; Malhotra, Anuj; Zhang, Lisheng; Deng, Shanming; Zhang, Taifang; Freedman, Neil J.; Storms, Robert; Peppel, Karsten; Goldschmidt-Clermont, Pascal J.; Dong, Chunming

    2014-01-01

    Aims Vein graft endothelial damage is a key step in the development of neointimal hyperplasia, leading to vein graft failure. We sought to determine whether exogenous endothelial progenitor cells could promote vein graft re-endothelialization, and thereby ameliorate neointimal hyperplasia. Methods and Results Carotid artery interposition grafting was performed with syngeneic inferior vena cavae in mice with severe combined immunodeficiency (SCID). Lineage-negative human umbilical cord blood (hUCB) cells (or medium alone) were injected into vein-grafted mice intraoperatively and 2 weeks postoperatively. In vein grafts from hUCB cell-injected mice, we found human HLA-expressing endothelial cells, as well as increased levels of VEGF and FGF-2. Furthermore, hUCB cells secreted VEGF and FGF-2 in vitro. The markedly enhanced endothelial regeneration, likely resulting from both direct engraftment and paracrine actions of hUCB cells, inhibited inflammatory response, diminished intimal cell proliferation, and reduced neointimal hyperplasia in the vein grafts. Conclusions hUCB cells may accelerate vein graft re-endothelialization via both direct differentiation into endothelial cells and release of paracrine factors to enhance endothelial regeneration and reduce inflammation. These data highlight a potential therapeutic role for cellular therapy in vessel injury. PMID:20451204

  11. Effect of valsartan on ACAT-1 and PPAR-γ expression in intima with carotid artery endothelial balloon injury in rabbit

    PubMed Central

    Ma, Tao; Ma, Zhi-Qiang; Du, Xiao-Hui; Yu, Qiu-Shi; Wang, Rong; Liu, Li

    2015-01-01

    Objective: To study the effect of valsartan on ACAT-1 and PPAR-γ expression after vascular endothelial balloon injury in intimal hyperplasia process. Methods: 24 male New Zealand white rabbits were randomly divided into three groups with 8 in each group. Control group: rabbits were fed with normal diet; Balloon injury group: rabbits were fed with 0.5% cholesterol, 5% lard rabbit feed; balloon injury + valsartan group, rabbits were fed with 0.5% cholesterol, 5% lard rabbit feed added with 10 mg/(kg.d) valsartan gavage. RT-PCR and Western blotting method were used to detect the carotid ACAT-1, PPAR-γ mRNA and protein expression after 8 weeks of feeding. Results: In carotid artery balloon injury group, vascular smooth muscle cells (VSMC) proliferation and intimal hyperplasia were significantly higher 14 d after endothelial injury. In 14 days valsartan treatment group VSMC proliferation and intimal hyperplasia were lighter than the surgery group. Compared with the control group, ACAT-1, PPAR-γ mRNA and protein were significantly increased in balloon injury group and valsartan group (P < 0.01 or P < 0.05); the expression of ACAT-1 mRNA and protein were significantly lower in valsartan group and balloon injury group (P < 0.01 or P < 0.05). The expression of PPAR-γ mRNA and protein in valsartan group expression was significantly higher than that in the balloon injury group (P < 0.05). The expression level of ACAT-1 and PPAR-γ mRNA in balloon injury group and valsartan group showed negative correlation (P < 0.05). Conclusion: The expression of ACAT-1, PPAR-γ mRNA and protein content were significantly increased in intimal hyperplasia process after vascular endothelial balloon injury. The effect of valsartan suppressed intimal hyperplasia correlated with the expression of down-regulated ACAT-1 and up-regulated PPAR-γ. PMID:26131133

  12. Verrucous Hyperplasia

    PubMed Central

    Grover, Sonal; Jha, Mihir; Sharma, Bhushan; Kapoor, Shekhar; Mittal, Kumud; Parakkat, Nithin K.; Shivappa, Anil B.; Kaur, Ravleen

    2017-01-01

    Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can transform into verrucous carcinoma (VC), its malignant but clinically similar counterpart. These entities can be distinguished by the lack of invasive growth in VH cases; as such, it is essential to include a margin with adequate depth when performing a biopsy of the epithelium of the lesion. We report an 80-year-old male patient who presented to the Bapuji Dental College & Hospital, Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the inside of his cheek. The patient was treated with wide surgical excision of the lesion and a diagnosis of VH was made based on histopathological features. There was no evidence of recurrence at a five-year follow-up. This report highlights the histological variations, pathogenesis and differential diagnosis of VH. PMID:28417036

  13. Is there a haemodynamic advantage associated with cuffed arterial anastomoses?

    PubMed

    Cole, J S; Watterson, J K; O'Reilly, M J G

    2002-10-01

    The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of PTFE grafts, results in an altered distribution of intimal hyperplasia and improved graft patency rates, especially for below-knee grafts. Numerical simulations have been conducted under physiological conditions to identify the flow behaviour in a typical cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flow patterns at the cuffed anastomosis are significantly different to those at the conventional end-to-side anastomosis. In the former case, the flow is characterised by an expansive, low momentum recirculation within the cuff. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act on the artery floor during systole. In contrast, a less disturbed flow prevails and the floor shear stress distribution is less adverse in the conventional model. In conclusion, aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The benefits associated with the cuffed grafts may be related primarily to the presence of venous material at the anastomosis. Therefore, caution is advised with regard to the use of PTFE grafts, pre-shaped to resemble a cuffed geometry.

  14. Computational and experimental simulations of the haemodynamics at cuffed arterial bypass graft anastomoses.

    PubMed

    Cole, J S; Wijesinghe, L D; Watterson, J K; Scott, D J A

    2002-01-01

    The development of intimal hyperplasia at arterial bypass graft anastomoses is a major factor responsible for graft failure. A revised surgical technique, involving the incorporation of a small section of vein (vein cuff) into the distal anastomosis of polytetrafluoroethylene (PTFE) grafts, alters the distribution of intimal hyperplasia and improves graft performance. Numerical and in vitro flow visualization experiments have been conducted to identify the flow behaviour in the cuffed bypass model and to determine whether the improved performance of the cuffed system can be accounted for by haemodynamic factors. The flowfield at the cuffed anastomosis is characterized by an expansive recirculation. Separation occurs at the graft heel, and at the cuff toe as the blood enters the recipient artery. Wall shear stresses in the vicinity of the cuff heel are low, but high shear stresses and large spatial gradients in the shearing force act for a time on the artery floor. In the conventional model, a less disturbed flow prevails while the gradients of shear stress on the floor are smaller. Aspects of the anastomotic haemodynamics are worsened when the cuff is employed. The superior patency rates of cuffed bypasses may not be explained purely on the basis of local haemodynamic factors.

  15. Pulmonary artery dissection causing haemothorax in a cat: potential role of Dirofilaria immitis infection and literature review.

    PubMed

    Biasato, I; Tursi, M; Zanet, S; Longato, E; Capucchio, M T

    2017-02-01

    A 7-year-old male castrated domestic short-haired cat suddenly died. Gross examination revealed severe right-sided haemothorax with blood clots, four adult filarial nematodes in the blood clots and the caudal vena cava and haemorrhage dissecting into the tunica media of the right pulmonary artery. Histopathological investigation showed fibrosis of the tunica intima and disorganization/fragmentation of the elastic fibres accompanied by fibrous tissue deposition in the tunica media of both branches of pulmonary artery. Degenerative vasculopathy (intimal fibromuscular hyperplasia and medial hypertrophy/hyperplasia) involving pulmonary arteries was also observed. The polymerase chain reaction amplification and sequencing confirmed the identification of the parasite as Dirofilaria immitis. A diagnosis of pulmonary artery dissection with haemothorax and concomitant heartworm disease was formulated. Degenerative processes of the tunica media have been reported to cause pulmonary artery dissection in both humans and animals. Pulmonary artery remodelling induced by heartworms may be considered the underlying cause in the first case of feline pulmonary artery dissection, herein described.

  16. An impedance matching of femoral-popliteal arterial grafts: a theoretical study.

    PubMed

    Hirayama, H; Nishimura, T; Fukuyama, Y

    1997-05-01

    We have proposed a mathematical method to investigate the matching conditions for an arterial graft in the femoral-popliteal region from a mechanical stand-point. Pulsatory blood flow, arterial wall motions, and conservation law are expressed by linear dynamical equations based on strict mechanical and constitutional considerations. To express the physiological blood flow in an actual arterial system, the tethering effects from the surrounding tissue and wall tensions were incorporated. The physiological parameters of arterial wall and tethering were utilized from reported experimental data. By complex analysis, mathematical expressions for the local impedance and reflection coefficient were obtained. They include not only blood properties such as viscosity and density, but also arterial properties including elastic modulus, radius, Poisson ratio, wall thickness, wall tension, frequency, and tethering effects from surrounding tissue. A matching condition was defined for minimizing the local impedance and reflection coefficient. The biophysical background was to reduce any mechanical mismatches, thus minimizing the disturbance of the flow velocity profile and shear stress distribution within the artery. Impedance matching in turn diminishes the negative factors for graft substitution represented by intimal hyperplasia and thrombosis. The calculated impedance and reflection coefficient inversed parabolically to functions of the resistance of the host artery, and there was one host arterial resistance that minimized the impedance and reflection coefficient. The present analysis revealed that for matching host artery with an elevated resistance, the dynamic elastic modulus of the wall of the graft that minimizes the impedance and reflection coefficient was increased. This indicates that for a host artery with a high resistance, an impedance matched stiff wall graft is preferable. For a large radius and a compliant host artery on the other hand, a large compliant graft

  17. Acute Pulmonary Artery Obstruction as the Primary Manifestation of a Rapidly Growing Intimal Sarcoma in a 54-Year-Old Patient.

    PubMed

    Westhofen, Sumi; Kugler, Christian; Reichenspurner, Hermann; Deuse, Tobias

    2016-12-01

    Pulmonary artery sarcoma is a rare malignant neoplasm that is often misdiagnosed and most often only recognized postmortem during the autopsy. We present the case of a male patient with a rapidly progressive pulmonary tumor who underwent urgent pneumonectomy for increasing symptoms of chest pain and septic clinical picture. Histological analysis revealed the diagnosis of a pulmonary artery sarcoma. Despite an R1-resection and adjuvant chemotherapy, the patient is in good clinical health and free of tumor relapse 1 year after the surgery.

  18. Acute Pulmonary Artery Obstruction as the Primary Manifestation of a Rapidly Growing Intimal Sarcoma in a 54-Year-Old Patient

    PubMed Central

    Westhofen, Sumi; Kugler, Christian; Reichenspurner, Hermann; Deuse, Tobias

    2016-01-01

    Pulmonary artery sarcoma is a rare malignant neoplasm that is often misdiagnosed and most often only recognized postmortem during the autopsy. We present the case of a male patient with a rapidly progressive pulmonary tumor who underwent urgent pneumonectomy for increasing symptoms of chest pain and septic clinical picture. Histological analysis revealed the diagnosis of a pulmonary artery sarcoma. Despite an R1-resection and adjuvant chemotherapy, the patient is in good clinical health and free of tumor relapse 1 year after the surgery. PMID:28018820

  19. Elastomeric PGS scaffolds in arterial tissue engineering.

    PubMed

    Lee, Kee-Won; Wang, Yadong

    2011-04-08

    Cardiovascular disease is one of the leading cause of mortality in the US and especially, coronary artery disease increases with an aging population and increasing obesity. Currently, bypass surgery using autologous vessels, allografts, and synthetic grafts are known as a commonly used for arterial substitutes. However, these grafts have limited applications when an inner diameter of arteries is less than 6 mm due to low availability, thrombotic complications, compliance mismatch, and late intimal hyperplasia. To overcome these limitations, tissue engineering has been successfully applied as a promising alternative to develop small-diameter arterial constructs that are nonthrombogenic, robust, and compliant. Several previous studies have developed small-diameter arterial constructs with tri-lamellar structure, excellent mechanical properties and burst pressure comparable to native arteries. While high tensile strength and burst pressure by increasing collagen production from a rigid material or cell sheet scaffold, these constructs still had low elastin production and compliance, which is a major problem to cause graft failure after implantation. Considering these issues, we hypothesized that an elastometric biomaterial combined with mechanical conditioning would provide elasticity and conduct mechanical signals more efficiently to vascular cells, which increase extracellular matrix production and support cellular orientation. The objective of this report is to introduce a fabrication technique of porous tubular scaffolds and a dynamic mechanical conditioning for applying them to arterial tissue engineering. We used a biodegradable elastomer, poly (glycerol sebacate) (PGS) for fabricating porous tubular scaffolds from the salt fusion method. Adult primary baboon smooth muscle cells (SMCs) were seeded on the lumen of scaffolds, which cultured in our designed pulsatile flow bioreactor for 3 weeks. PGS scaffolds had consistent thickness and randomly distributed macro

  20. Recurrent pulmonary intimal sarcoma involving the right ventricular outflow tract.

    PubMed

    Shah, Dipesh K; Joyce, Lyle D; Grogan, Martha; Aubry, Marie Christine; Miller, John A; Ding, Wei; Haddock, Michael G

    2011-03-01

    Intimal sarcoma of the pulmonary artery is commonly misdiagnosed as chronic pulmonary embolism. Rarely, it can involve the right ventricular outflow tract and the pulmonary valve. We report a patient who was treated surgically for an intimal sarcoma of the pulmonary artery involving the right ventricular outflow tract and the pulmonary valve. The sarcoma recurred in about 8 weeks. It responded favorably to chemoradiation therapy and shows some signs of regression.

  1. Benign prostate hyperplasia (BPH) - resources

    MedlinePlus

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse -- www. ...

  2. Oxygen Mass Transport in Stented Coronary Arteries.

    PubMed

    Murphy, Eoin A; Dunne, Adrian S; Martin, David M; Boyle, Fergal J

    2016-02-01

    Oxygen deficiency, known as hypoxia, in arterial walls has been linked to increased intimal hyperplasia, which is the main adverse biological process causing in-stent restenosis. Stent implantation has significant effects on the oxygen transport into the arterial wall. Elucidating these effects is critical to optimizing future stent designs. In this study the most advanced oxygen transport model developed to date was assessed in two test cases and used to compare three coronary stent designs. Additionally, the predicted results from four simplified blood oxygen transport models are compared in the two test cases. The advanced model showed good agreement with experimental measurements within the mass-transfer boundary layer and at the luminal surface; however, more work is needed in predicting the oxygen transport within the arterial wall. Simplifying the oxygen transport model within the blood flow produces significant errors in predicting the oxygen transport in arteries. This study can be used as a guide for all future numerical studies in this area and the advanced model could provide a powerful tool in aiding design of stents and other cardiovascular devices.

  3. Ginsenoside Rb₁ inhibits the carotid neointimal hyperplasia induced by balloon injury in rats via suppressing the phenotype modulation of vascular smooth muscle cells.

    PubMed

    Zhang, Shu; Deng, Jiang; Gao, Yang; Yang, Dan-li; Gong, Qi-hai; Huang, Xie-nan

    2012-06-15

    This study aims to investigate the effects of ginsenoside Rb(1) on vascular intimal hyperplasia in rats and explore the mechanisms. The rat vascular neointimal hyperplasia model was made by rubbing the endothelia of carotid artery with a balloon and Rb(1) (10 and 30 mg/kg/day) was given the day after surgery for 14 consecutive days. The neointimal hyperplasia level and the degree of vascular smooth muscle cells (VSMCs) proliferation were evaluated by histopathology and by calculating the proliferating cell nuclear antigen (PCNA) positive expression percentage; protein expressions of PCNA, phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2), smooth muscle α-actin (SM α-actin), and the mRNA expressions of proto-oncogene c-myc, SM α-actin, SM-emb (embryonic smooth muscle myosin heavy chain) and p38 MAPK were detected by immunohistochemistry and Real Time RT-PCR, respectively. Compared with the endothelia rubbing model group, Rb(1) 10 and 30 mg/kg/day medication significantly ameliorated the neointimal hyperplasia (P<0.05), and decreased the positive expression percentage of PCNA(P<0.05). Rb(1) medication also significantly decreased the elevated protein expression of pERK1/2 and the mRNA expression of c-myc(P<0.05), and tended to reduce the expression of p38 MAPK mRNA. Endothelial rubbing increased the SM-emb mRNA expression, but decreased the expression of SM α-actin mRNA which was reversed by Rb(1) (P<0.05). The results indicate that Rb(1) inhibits the vascular neointimal hyperplasia induced by balloon-injury in rats via suppressing the VSMC proliferation, which may be involved in part the inhibition of pERK1/2 protein and related to its inhibition on VSMC phenotype modulation.

  4. Estrogen replacement therapy and progression of intimal-medial thickness in the carotid arteries of postmenopausal women. ACAPS Investigators. Asymptomatic Carotid Atherosclerosis Progression Study.

    PubMed

    Espeland, M A; Applegate, W; Furberg, C D; Lefkowitz, D; Rice, L; Hunninghake, D

    1995-11-15

    The effect of estrogen replacement therapy (ERT) on 3-year changes in carotid intimal-medial thickness (IMT) was explored using serial B-mode ultrasound measurements collected during 1989-1993 as part of the Asymptomatic Carotid Atherosclerotic Progression Study (ACAPS). Eligibility included increased IMT and elevated low density lipoprotein cholesterol. Of the 186 postmenopausal ACAPS women randomly assigned to receive either placebo or lovastatin, 34% reported use of ERT. Users tended to be younger than nonusers by an average of 3 years, to have more favorable high and low density lipoprotein cholesterol levels, and to be more likely to have had hysterectomies. Baseline blood pressure, body mass index, and cross-sectional IMT were similar among ERT users and nonusers. In the placebo group, IMT tended to progress among ERT nonusers but to regress among ERT users: Mean covariate-adjusted progression rates were 0.015 +/- 0.007 mm/year versus -0.012 +/- 0.012 mm/year, respectively (p = 0.05). This difference appeared to be independent of lipoprotein concentrations. Lovastatin was associated with an approximately 25% lowering of low density lipoprotein cholesterol among both ERT users and nonusers and had a marked impact on IMT progression (p = 0.004) in these women. ERT appeared to have little additional effect on IMT in women assigned to lovastatin. ERT may reduce or halt the progression of early atherosclerosis in women not receiving active lipid-lowering medication.

  5. Hemodynamic Conditions in a Failing Peripheral Artery Bypass Graft

    PubMed Central

    McGah, Patrick M.; Leotta, Daniel F.; Beach, Kirk W.; Zierler, R. Eugene; Riley, James J.; Aliseda, Alberto

    2012-01-01

    Objective The mechanisms of restenosis in autogenous vein bypass grafts placed for peripheral artery disease are not completely understood. We seek to investigate the role of hemodynamic stress in a case study of a revised bypass graft that failed due to restenosis. Methods The morphology of the lumen is reconstructed from a custom 3D ultrasound system. Scans were taken at one, six, and sixteen months after a patch angioplasty procedure. Computational hemodynamic simulations of the patient-specific model provide the blood flow features and the hemodynamic stresses on the vessel wall at the three time points studied. Results The vessel was initially free of any detectable lesions, but a 60% diameter reducing stenosis developed over the 16 month interval of study. As determined from the simulations, chaotic and recirculating flow occurred downstream of the stenosis due to the sudden widening of the lumen at the patch location. Curvature and a sudden increase in the lumen cross-sectional area induce these flow features that are hypothesized to be conducive to intimal hyperplasia. Favorable agreement was found between simulation results and in vivo Doppler ultrasound velocity measurements. Conclusions Transitional and chaotic flow occurs at the site of the revision, inducing a complex pattern of wall shear are computed with the hemodynamic simulations. This supports the hypothesis that the hemodynamic stresses in the revised segment, produced by the coupling of vessel geometry and chaotic flow, led to the intimal hyperplasia and restenosis of the graft. PMID:22551907

  6. Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis.

    PubMed

    Carnevale, Francisco C; Iscaife, Alexandre; Yoshinaga, Eduardo M; Moreira, Airton Mota; Antunes, Alberto A; Srougi, Miguel

    2016-01-01

    To compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia. We prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL). All groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q max), both of which were significantly better in the TURP group, and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q max. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q max and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria. TURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.

  7. Transurethral Resection of the Prostate (TURP) Versus Original and PErFecTED Prostate Artery Embolization (PAE) Due to Benign Prostatic Hyperplasia (BPH): Preliminary Results of a Single Center, Prospective, Urodynamic-Controlled Analysis

    SciTech Connect

    Carnevale, Francisco C.; Iscaife, Alexandre Yoshinaga, Eduardo M.; Moreira, Airton Mota; Antunes, Alberto A. Srougi, Miguel

    2016-01-15

    PurposeTo compare clinical and urodynamic results of transurethral resection of the prostate (TURP) to original and PErFecTED prostate artery embolization (PAE) methods for benign prostatic hyperplasia.MethodsWe prospectively randomized 30 patients to receive TURP or original PAE (oPAE) and compared them to a cohort of patients treated by PErFecTED PAE, with a minimum of 1-year follow-up. Patients were assessed for urodynamic parameters, prostate volume, international prostate symptom score (IPSS), and quality of life (QoL).ResultsAll groups were comparable for all pre-treatment parameters except bladder contractility and peak urine flow rate (Q{sub max}), both of which were significantly better in the TURP group, and IIEF score, which was significantly higher among PErFecTED PAE patients than TURP patients. All groups experienced significant improvement in IPSS, QoL, prostate volume, and Q{sub max}. TURP and PErFecTED PAE both resulted in significantly lower IPSS than oPAE but were not significantly different from one another. TURP resulted in significantly higher Q{sub max} and significantly smaller prostate volume than either original or PErFecTED PAE but required spinal anesthesia and hospitalization. Two patients in the oPAE group with hypocontractile bladders experienced recurrence of symptoms and were treated with TURP. In the TURP group, urinary incontinence occurred in 4/15 patients (26.7 %), rupture of the prostatic capsule in 1/15 (6.7 %), retrograde ejaculation in all patients (100 %), and one patient was readmitted for temporary bladder irrigation due to hematuria.ConclusionsTURP and PAE are both safe and effective treatments. TURP and PErFecTED PAE yield similar symptom improvement, but TURP is associated with both better urodynamic results and more adverse events.

  8. Upregulated TRPC1 Channel in Vascular Injury In Vivo and Its Role in Human Neointimal Hyperplasia

    PubMed Central

    Kumar, B.; Dreja, K.; Shah, S.S.; Cheong, A.; Xu, S.-Z.; Sukumar, P.; Naylor, J.; Forte, A.; Cipollaro, M.; McHugh, D.; Kingston, P.A.; Heagerty, A.M.; Munsch, C.M.; Bergdahl, A.; Hultgårdh-Nilsson, A.; Gomez, M.F.; Porter, K.E.; Hellstrand, P.; Beech, D.J.

    2008-01-01

    Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure. PMID:16439693

  9. Exploration of the APC/beta-catenin (WNT) pathway and a histologic classification system for pulmonary artery intimal sarcoma. A study of 18 cases.

    PubMed

    Gaumann, A; Bode-Lesniewska, B; Zimmermann, D R; Fanburg-Smith, J C; Kirkpatrick, C J; Hofstädter, F; Woenckhaus, M; Stoehr, R; Obermann, E C; Dietmaier, W; Hartmann, A

    2008-11-01

    APC, a tumor suppressor gene in the Wnt pathway, stabilizes beta-catenin and controls cell growth. Mutation of APC or beta-catenin leads to nuclear accumulation of beta-catenin and transcription of cyclin D1/cyclin A. Pulmonary artery sarcoma (PAS) were studied by morphologic, immunohistochemical, and molecular genetic methods of the Wnt pathway. Eighteen cases were included: mean age 52 years, primary intraluminal location with typical clinical presentation. PAS were classified as epithelioid (n = 4) or malignant fibrous histiocytoma (MFH; spindled/pleomorphic, n = 4), myxofibrosarcoma (n = 8), and one each hemangiopericytoma-like or malignant inflammatory myofibroblastic tumor-like. The tumor cells demonstrated vimentin, focal actins, and rare focal desmin positivity. All but one were grade 2 or 3 by FNCLCC grading. Alteration in chromosome 5q21 (APC) was found in 4/14 PAS by LOH, mostly epithelioid-type; an MFH-type case demonstrated microsatellite instability (MSI) and nuclear beta-catenin. Cyclin D1 was expressed in seven tumors, all myxofibrosarcoma-type. No mutations were detected in APC or beta-catenin. In summary, PAS are predominantly intermediate grade myxofibrosarcoma in middle-aged males, and fatal in two-thirds of patients. Despite myofibroblastic phenotype, APC/beta-catenin pathway changes are rare. Cyclin D1, only expressed in the myxofibrosarcoma-type, is likely transcribed via factors other than beta-catenin.

  10. Pyrogallol abates VSMC migration via modulation of Caveolin-1, matrix metalloproteinase and intima hyperplasia in carotid ligation mouse.

    PubMed

    Ma, Yu-Dong; Thiyagarajan, Varadharajan; Tsai, May-Jywan; Lue, Sheng-I; Chia, Yi-Chen; Shyue, Song-Kun; Weng, Ching-Feng

    2016-12-01

    Migration of vascular smooth muscle cells (VSMCs) contributes to intimal hyperplasia and other vascular diseases. Caveolin-1 (Cav-1) has been recognized as a proliferative inhibitor of VSMCs and is likely to be an important regulator of VSMC migration. The underlying mechanism of pyrogallol on the VSMC migration is not fully understood. This study attempted to dissect the role of Cav-1 and matrix metalloproteinase (MMP) in VSMC migration and to investigate the effect of pyrogallol on VSMC mobility during carotid artery ligation mice. The mRNA expression of MMP-3 and MMP-13 was down-regulated in cultured VSMC prepared from Cav-1-deficient (Cav-1 KO) mice whereas MMP-14 expression was up-regulated. Pyrogallol effectively inhibited the migration of Cav-1 KO VSMC by promoting the expression of tissue inhibitors of metalloproteinase (TIMP)-2. Pyrogallol also inhibited the migration of Cav-1 wild type (WT) VSMC, however, by increasing TIMP-1 expression and repressing MMP-2 activity. In a parallel in vivo study, intra-peritoneal (ip) of pyrogallol to carotid artery ligated mice significantly suppressed intima formation in mice carotid artery. Furthermore, the proMMP-9 activity in pyrogallol-treated mice serum significantly increased from Day 0 to Day 2 and decreased from Day 2 to Day 7 in a time-dependent manner. In addition, WT mice treated with pyrogallol had significantly reduced neointima formation, whereas no differences were observed in Cav-1 knock out (KO) mice. These results suggest that pyrogallol not only inhibited VSMC migration but also effectively diminishes the severity of neointima hyperplasia, implying that pyrogallol possesses potential anti-atherogenic effects for the treatment of vascular diseases.

  11. The effect of supplemental oxygen on the transarterial wall oxygen gradients at a prosthetic vascular graft to artery anastomosis in the rabbit.

    PubMed

    Santilli, S M; Wernsing, S E; Lee, E S

    2001-07-01

    Artery wall hypoxia has been proposed to contribute to many kinds of artery wall pathology, including atherosclerosis and intimal hyperplasia. The purpose of this study was to determine the effect of supplemental oxygen on the transarterial wall oxygen gradients at a prosthetic vascular device (PVG)-to-artery anastomosis. The transarterial wall oxygen gradient in the infrarenal aorta of New Zealand White rabbits housed for 42 days in a 40% supplemental oxygen was measured with an oxygen microelectrode 2 mm distal to a PVG-to-artery anastomosis. Oxygen tensions were significantly increased throughout the artery wall at all time points in the supplemental oxygen groups compared to those in non-oxygen-supplemented groups. Within the oxygen-supplemented groups, the outer artery wall had diminished oxygen tensions immediately following creation of the anastomosis, with a slow return to control oxygen tensions on postanastomosis day 42 which correlated with a return of the vasa vasorum. These changes were noted without differences in blood pressure or arterial blood oxygen concentrations within the oxygen-supplemented group. Artery wall hypoxia noted following the creation of a PVG-to-artery anastomosis can be eliminated and artery wall oxygen tensions significantly increased by the administration of supplemental oxygen.

  12. Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine

    PubMed Central

    Zhang, Qi; Lu, Lin; Pu, LiJin; Zhang, RuiYan; Shen, Jie; Zhu, ZhengBing; Hu, Jian; Yang, ZhenKun; Chen, QiuJin; Shen, WeiFeng

    2007-01-01

    Background Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process. Methods Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-α protein level in the aortic intima was evaluated by Western blotting, and TNF-α, interleukin (IL)-1β and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction. Results The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 ± 24.0% vs. 20.2 ± 17.7%, p < 0.05), late lumen loss (0.33 ± 0.19 mm vs. 0.10 ± 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 ± 19.2% vs. 7.3 ± 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 ± 0.76 mm2 vs. 0.41 ± 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-α protein and TNF-α, IL-1β and IL-6 mRNA levels were observed in aortic intima in the diabetic group

  13. INCIDENCE OF ENDOMETRIAL HYPERPLASIA

    PubMed Central

    REED, Susan D.; NEWTON, Katherine M.; CLINTON, Walter L.; EPPLEIN, Meira; GARCIA, Rochelle; ALLISON, Kimberly; VOIGT, Lynda F.; Weiss, Noel S.

    2009-01-01

    Objective Estimate age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. Study design Women ages 18–90 years with endometrial pathology specimens (1985–2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. Results Endometrial hyperplasia peak incidence was: simple-142/100,000 woman-years, complex-213/100,000 woman-years, both in the early 50s; and atypical-56/100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. Conclusions Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence. PMID:19393600

  14. New Developments in Our Understanding of Neointimal Hyperplasia.

    PubMed

    Lee, Timmy; Ul Haq, Naveed

    2015-11-01

    The vascular access remains the lifeline for the hemodialysis patient. The most common etiology of vascular access dysfunction is venous stenosis at the vein-artery anastomosis in arteriovenous fistula and at the vein-graft anastomosis in arteriovenous grafts (AVG). This stenotic lesion is typically characterized on histology as aggressive venous neointimal hyperplasia in both arteriovenous fistula and AVG. In recent years, we have advanced our knowledge and understanding of neointimal hyperplasia in vascular access and begun testing several novel therapies. This article will (1) review recent developments in our understanding of the pathophysiology of neointimal hyperplasia development in AVG and fistula failure, (2) discuss atypical factors leading to neointimal hyperplasia development, (3) highlight key novel therapies that have been evaluated in clinical trials, and (4) discuss future opportunities and challenges to improve our understanding of vascular access dysfunction and translate this knowledge into novel and innovative therapies. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. [Focal epithelial hyperplasia].

    PubMed

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  16. Congenital Adrenal Hyperplasia

    PubMed Central

    Speiser, Phyllis W.

    2015-01-01

    Congenital adrenal hyperplasia associated with deficiency of steroid 21-hydroxylase is the most common inborn error in adrenal function and the most common cause of adrenal insufficiency in the pediatric age group. As patients now survive into adulthood, adult health-care providers must also be familiar with this condition. Over the past several years, F1000 has published numerous commentaries updating research and practical guidelines for this condition. The purposes of this review are to summarize basic information defining congenital adrenal hyperplasia and to highlight current knowledge and controversies in management. PMID:26339484

  17. Intimate partner homicide.

    PubMed

    Leth, Peter Mygind

    2009-01-01

    Intimate partner homicides represent the most severe outcome of intimate partner violence, and constitute more than a quarter (26%) of all homicides in adults over 15 years of age in Southern Denmark. In our experience the victims of partner homicides are primarily women, often from socially disadvantaged families, and that these homicides usually are the result of an impulsive act, with the perpetrator often committing suicide after the act. The aim of this study was to investigate these hypotheses further, and to provide an up-to-date overview of intimate partner homicides in Southern Denmark.

  18. Subareolar Sclerosing Ductal Hyperplasia.

    PubMed

    Cheng, Esther; D'Alfonso, Timothy M; Arafah, Maria; Marrero Rolon, Rebecca; Ginter, Paula S; Hoda, Syed A

    2017-02-01

    Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

  19. Congenital adrenal hyperplasia

    MedlinePlus

    ... or inappropriately). Congenital adrenal hyperplasia can affect both boys and girls. About 1 in 10,000 to 18,000 ... penis but normal testes Well-developed muscles Both boys and girls will be tall as children, but much shorter ...

  20. Atypical adenomatous hyperplasia

    Cancer.gov

    Focal and diffuse lesions involving alveoli and terminal bronchioles and consisting of relatively uniform atypical cuboidal to columnar cells with dense chromatin. Degrees of cellular hypertrophy and hyperchromasia are variable. Cellular and nuclear atypia are the distinctive features as compared with hyperplasia. Their relevance to human AAH and mouse adenomas remains to be determined.

  1. Oral focal epithelial hyperplasia.

    PubMed

    Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A

    2000-01-01

    Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.

  2. Effects of an artery/vascular graft compliance mismatch on protein transport: a numerical study.

    PubMed

    Stewart, Sandy F C; Lyman, Donald J

    2004-07-01

    Small-diameter vascular graft failure by intimal hyperplasia and thrombosis may result from flow disturbances and disruption of chemical transport in the fluid at the distal anastomosis, because of compliance mismatch between the graft and host artery. In previous studies. lower-than-normal wall shear stress (WSS), particle trapping, and high particle residence times were observed at the distal anastomosis due to a pulsatile tubular expansion effect caused by nonuniform radial deformations. This study was undertaken to examine effects of compliance and radius mismatch on the distribution of a model protein released at the graft-fluid interface. Finite element simulations of end-to-end vascular grafting were performed under pulsatile flow, using fluid-structure coupling to give physiologic wall displacements. Results showed that protein is convected smoothly downstream in a uniform compliant tube. A compliance mismatch disturbed the transport, causing positive and negative gradients in the concentration profile at the distal anastomosis. This was seen when the graft and artery radii were matched at zero pressure and at mean arterial pressure; low WSSs were only observed in the former case. Thus the distal intimal hypertrophy seen in noncompliant grafts may be caused partly by decreased WSS, and partly by concentration gradients of dissolved chemicals affecting chemotaxis of cells.

  3. Oral focal epithelial hyperplasia.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  4. Improved Patency of Transjugular Intrahepatic Portosystemic Shunt: The Efficacy of Cilostazol for the Prevention of Pseudointimal Hyperplasia in Swine TIPS Models

    SciTech Connect

    Park, Sang Woo Cha, In Ho; Kim, Chul Hwan; Jeon, Hae Jeong; Park, Jeong Hee; Hong, Suk Joo; Lee, In Sik

    2007-07-15

    Purpose. To investigate the efficacy of oral administration of cilostazol to inhibit pseudointimal/intimal hyperplasia in swine TIPS models. Methods. Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25 kg). In the treatment group (n = 6), both cilostazol and aspirin were administered daily, from the first day of TIPS creation. The control group (n = 5) was administered only aspirin. The animals were followed-up for 2 weeks and then killed. The specimen (including portal vein, hepatic parenchymal tract, hepatic vein, and inferior vena cava) and stents were carefully bisected in a longitudinal fashion. The control group was compared with the treatment group by means of a gross and histologic evaluation of the degree of pseudointimal/intimal hyperplasia in the shunt. Results. At the gross evaluation, the control group showed considerably more pseudointimal/intimal hyperplasia than the treatment group. Using microscopic evaluation, there was a statistically significant difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia thickness between the control group (2.97 {+-} 0.33 mm) and treatment group (0.73 {+-} 0.27 mm). Conclusion. Oral administration of cilostazol may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.

  5. improved patency of transjugular intrahepatic portosystemic shunt: the efficacy of cilostazol for the prevention of pseudointimal hyperplasia in swine TIPS models.

    PubMed

    Park, Sang Woo; Cha, In Ho; Kim, Chul Hwan; Jeon, Hae Jeong; Park, Jeong Hee; Hong, Suk Joo; Lee, In Sik

    2007-01-01

    To investigate the efficacy of oral administration of cilostazol to inhibit pseudointimal/intimal hyperplasia in swine TIPS models. Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25 kg). In the treatment group (n = 6), both cilostazol and aspirin were administered daily, from the first day of TIPS creation. The control group (n = 5) was administered only aspirin. The animals were followed-up for 2 weeks and then killed. The specimen (including portal vein, hepatic parenchymal tract, hepatic vein, and inferior vena cava) and stents were carefully bisected in a longitudinal fashion. The control group was compared with the treatment group by means of a gross and histologic evaluation of the degree of pseudointimal/intimal hyperplasia in the shunt. At the gross evaluation, the control group showed considerably more pseudointimal/intimal hyperplasia than the treatment group. Using microscopic evaluation, there was a statistically significant difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia thickness between the control group (2.97 +/- 0.33 mm) and treatment group (0.73 +/- 0.27 mm). Oral administration of cilostazol may have been effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.

  6. Pathologic pancreatic endocrine cell hyperplasia

    PubMed Central

    Ouyang, Debra; Dhall, Deepti; Yu, Run

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to non-insulinoma pancreatogenous hypoglycemia in adults, which may or may not be associated with bariatric surgery. α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia. Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels, and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors. PMID:21245985

  7. IL-19 Reduces Ligation-Mediated Neointimal Hyperplasia by Reducing Vascular Smooth Muscle Cell Activation

    PubMed Central

    Ellison, Stephen; Gabunia, Khatuna; Richards, James M.; Kelemen, Sheri E.; England, Ross N.; Rudic, Dan; Azuma, Yasu-Taka; Munroy, M. Alexandra; Eguchi, Satoru; Autieri, Michael V.

    2015-01-01

    We tested the hypothesis that IL-19, a putative member of the type 2 helper T-cell family of anti-inflammatory interleukins, can attenuate intimal hyperplasia and modulate the vascular smooth muscle cell (VSMC) response to injury. Ligated carotid artery of IL-19 knockout (KO) mice demonstrated a significantly higher neointima/intima ratio compared with wild-type (WT) mice (P = 0.04). More important, the increased neointima/intima ratio in the KO could be reversed by injection of 10 ng/g per day recombinant IL-19 into the KO mouse (P = 0.04). VSMCs explanted from IL-19 KO mice proliferated significantly more rapidly than WT. This could be inhibited by addition of IL-19 to KO VSMCs (P = 0.04 and P < 0.01). IL-19 KO VSMCs migrated more rapidly compared with WT (P < 0.01). Interestingly, there was no type 1 helper T-cell polarization in the KO mouse, but there was significantly greater leukocyte infiltrate in the ligated artery in these mice compared with WT. IL-19 KO VSMCs expressed significantly greater levels of inflammatory mRNA, including IL-1β, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to tumor necrosis factor α stimulation (P < 0.01 for all). KO VSMCs expressed greater adhesion molecule expression and adherence to monocytes. Together, these data indicate that IL-19 is a previously unrecognized counterregulatory factor for VSMCs, and its expression is an important protective mechanism in regulation of vascular restenosis. PMID:24814101

  8. Female Perpetrators of Intimate Abuse

    ERIC Educational Resources Information Center

    Dutton, Donald G.; Nicholls, Tonia L.; Spidel, Alicia

    2005-01-01

    A review is made of female intimate abuse. It is concluded that females are as abusive as males in intimate relationships according to survey and epidemiological studies. This is especially so for younger "cohort" community samples followed longitudinally. Predictors of intimate violence with women appear to be similar to those of men; including…

  9. Female Perpetrators of Intimate Abuse

    ERIC Educational Resources Information Center

    Dutton, Donald G.; Nicholls, Tonia L.; Spidel, Alicia

    2005-01-01

    A review is made of female intimate abuse. It is concluded that females are as abusive as males in intimate relationships according to survey and epidemiological studies. This is especially so for younger "cohort" community samples followed longitudinally. Predictors of intimate violence with women appear to be similar to those of men; including…

  10. [Focal epithelial hyperplasia].

    PubMed

    Delgado, Yolanda; Torrelo, Antonio; Colmenero, Isabel; Zambrano, Antonio

    2005-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferation of the oral mucosa with well defined clinical and histological characteristics. It has been associated with infection of the oral mucosa by types 13 and 32 of the human papillomavirus (HPV), and to a lesser extent, with other types. Its clinical course is variable, although it usually persists for months or years; cases with spontaneous resolution have been described, as have others with prolonged persistence. We present the case of an Ecuadorian boy whose visit was motivated by lesions in the oral mucosa consistent with a diagnosis of FEH, which were confirmed in the histological study, and in which HPV type 13 DNA was identified.

  11. Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats.

    PubMed

    Gregory, Elaine K; Webb, Antonio R; Vercammen, Janet M; Flynn, Megan E; Ameer, Guillermo A; Kibbe, Melina R

    2014-11-15

    Oral all-trans retinoic acid (atRA) has been shown to reduce the formation of neointimal hyperplasia; however, the dose required was 30 times the chemotherapeutic dose, which already has reported side effects. As neointimal formation is a localized process, new approaches to localized delivery are required. This study assessed whether atRA within a citrate-based polyester, poly(1,8 octanediolcitrate) (POC), perivascular membrane would prevent neointimal hyperplasia following arterial injury. atRA-POC membranes were prepared and characterized for atRA release via high-performance liquid chromatography with mass spectrometry detection. Rat adventitial fibroblasts (AF) and vascular smooth muscle cells (VSMC) were exposed to various concentrations of atRA; proliferation, apoptosis, and necrosis were assessed in vitro. The rat carotid artery balloon injury model was used to evaluate the impact of the atRA-POC membranes on neointimal formation, cell proliferation, apoptosis, macrophage infiltration, and vascular cell adhesion molecule 1 (VCAM-1) expression in vivo. atRA-POC membranes released 12 μg of atRA over 2 wk, with 92% of the release occurring in the first week. At 24 h, atRA (200 μmol/l) inhibited [(3)H]-thymidine incorporation into AF and VSMC by 78% and 72%, respectively (*P = 0.001), with negligible apoptosis or necrosis. Histomorphometry analysis showed that atRA-POC membranes inhibited neointimal formation after balloon injury, with a 56%, 57%, and 50% decrease in the intimal area, intima-to-media area ratio, and percent stenosis, respectively (P = 0.001). atRA-POC membranes had no appreciable effect on apoptosis or proliferation at 2 wk. Regarding biocompatibility, we found a 76% decrease in macrophage infiltration in the intima layer (P < 0.003) in animals treated with atRA-POC membranes, with a coinciding 53% reduction in VCAM-1 staining (P < 0.001). In conclusion, perivascular delivery of atRA inhibited neointimal formation and restenosis. These data

  12. Oncocytic hyperplasia of the larynx.

    PubMed

    Thawley, S E; Berlin, B P; Berkowitz, W P

    1977-07-01

    Oncocytic hyperplasia of the larynx is rare. The lesion most commonly arises from the false vocal chord. A distinction arises between oncocytomas of the salivary glands which are considered to be neoplasms and extrasalivary oncocytic lesions which are secondary to hyperplasia. Oncocytic lesions of the larynx are benign and treatment is excision. They may be multiple, but recurrences are rare.

  13. Drug-eluting stents in superficial femoral artery treatment: could they be the standard of care?

    PubMed

    Bosiers, Marc; Deloose, Koen; Callaert, Joren; Peeters, Patrick; Bosiers, Michel

    2016-12-01

    Endovascular techniques have improved markedly over the past several decades. Plain old balloon angioplasty can only reach patencies around 40% after 1 year. Scaffolding stents have resulted in improved short-term results but encountered limitations for longer-term durability. With the introduction of drug-eluting technologies the process of intimal hyperplasia might be slowed, resulting in improved long-term patency results. At first, limus-eluting technologies were not able to transfer the enthusiasm from the coronaries to the infrainguinal vascular bed. However, the newer generation paclitaxel-eluting technologies perform significantly better in femoropopliteal arteries than their non-eluting or non-coated counterparts. The results of a prospective randomized trial comparing DES versus DCB is eagerly awaited. For the moment there seems, based on the meta-analysis, no difference between the two treatment modalities. Although, we need to keep in mind that DCB perform worse in long calcified lesions.

  14. Congenital adrenal hyperplasia.

    PubMed

    Merke, Deborah P; Bornstein, Stefan R

    Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a disorder of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Patients with the most severe form also have abnormalities of the adrenal medulla and epinephrine deficiency. The severe classic form occurs in one in 15,000 births worldwide, and the mild non-classic form is a common cause of hyperandrogenism. Neonatal screening for CAH and gene-specific prenatal diagnosis are now possible. Standard hormone replacement fails to achieve normal growth and development for many children with CAH, and adults can experience iatrogenic Cushing's syndrome, hyperandrogenism, infertility, or the development of the metabolic syndrome. This Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and management of CAH, and provides an overview of clinical challenges and future therapies.

  15. Extensive focal epithelial hyperplasia.

    PubMed

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

  16. The effect of in-plane arterial curvature on blood flow and oxygen transport in arterio-venous fistulae

    NASA Astrophysics Data System (ADS)

    Iori, F.; Grechy, L.; Corbett, R. W.; Gedroyc, W.; Duncan, N.; Caro, C. G.; Vincent, P. E.

    2015-03-01

    Arterio-Venous Fistulae (AVF) are the preferred method of vascular access for patients with end stage renal disease who need hemodialysis. In this study, simulations of blood flow and oxygen transport were undertaken in various idealized AVF configurations. The objective of the study was to understand how arterial curvature affects blood flow and oxygen transport patterns within AVF, with a focus on how curvature alters metrics known to correlate with vascular pathology such as Intimal Hyperplasia (IH). If one subscribes to the hypothesis that unsteady flow causes IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto the outer-curvature of a curved artery. However, if one subscribes to the hypothesis that low wall shear stress and/or low lumen-to-wall oxygen flux (leading to wall hypoxia) cause IH within AVF, then the results suggest that in order to avoid IH, AVF should be formed via a vein graft onto a straight artery, or the inner-curvature of a curved artery. We note that the recommendations are incompatible—highlighting the importance of ascertaining the exact mechanisms underlying development of IH in AVF. Nonetheless, the results clearly illustrate the important role played by arterial curvature in determining AVF hemodynamics, which to our knowledge has been overlooked in all previous studies.

  17. Tissue concentration of heparin, not administered dose, correlates with the biological response of injured arteries in vivo

    PubMed Central

    Lovich, Mark A.; Edelman, Elazer R.

    1999-01-01

    Drug activity is often studied in well controlled and characterized cellular environments in vitro. However, the biology of cells in culture is only a part of the tissue behavior in vivo. Quantitative studies of the dose response to drugs in vivo have been limited by the inability to reliably determine or predict the concentrations achieved in tissues. We developed a method to study the dose response of injured arteries to exogenous heparin in vivo by providing steady and predictable arterial levels of drug. Controlled-release devices were fabricated to direct heparin uniformly and at a steady rate to the adventitial surface of balloon-injured rat carotid arteries. We predicted the distribution of heparin throughout the arterial wall by using computational simulations of intravascular drug binding and transport, and we correlated these concentrations with the biologic response of the tissues. This allowed the estimation of the arterial concentration of heparin required to maximally inhibit intimal hyperplasia after injury in vivo, 0.3 mg/ml. This estimation of the required concentration of drug seen by a specific tissue is independent of the route of administration and holds for all forms of drug release. In this way we may now be able to evaluate the potential of widely disparate forms of drug release and to finally create some rigorous criteria by which to guide the development of particular delivery strategies for local diseases. PMID:10500138

  18. Healing after arterial dilatation with radiofrequency thermal and nonthermal balloon angioplasty systems.

    PubMed

    Kaplan, J; Barry, K J; Connolly, R J; Nardella, P C; Hayes, L L; Lee, B I; Waller, B F; Becker, G J; Callow, A D

    1993-01-01

    Thermal balloon angioplasty has been proposed as a means of reducing acute and delayed reclosure of arteries after percutaneous transluminal balloon angioplasty. A radiofrequency (rf) balloon catheter was used to perform thermal balloon angioplasty on canine arteries in vivo. The histologic appearance of rf-treated sites was compared with that of control sites treated by conventional percutaneous transluminal angioplasty. Acutely, rf-treated sites showed a reduced medial cellularity with preservation of internal elastic lamina except at the transitional zone between thermal injury and normal artery, where localized internal elastic lamina disruption was found. Nonthermal sites showed generalized disruption of internal elastic lamina and normal medial cellularity. Both thermal and nonthermal sites displayed a return of intimal cover commencing at 1 to 2 weeks and completed by 4 weeks. Diffuse myointimal hyperplasia appeared by 2 weeks after injury at breaks in the internal elastic lamina along the nonthermal vessels but was localized to the transitional zone in thermal injury sites. In rf-treated vessels, repopulation of the acellular thermally modified media had commenced by 4 weeks, and by 8 weeks the media was diffusely repopulated by spindle-shaped cells resembling smooth muscle cells lying between and aligned with preserved connective tissue laminae. Overall, the distribution and extent of the proliferative response after rf thermal balloon angioplasty were less than those seen after nonthermal balloon angioplasty. Thermal sites, which underwent reintimalization before medial cells returned, were considerably less prone to the development of myointimal hyperplasia. These results suggest that this modality may have beneficial effects on arterial healing after angioplasty.

  19. A nonantibiotic chemically modified tetracycline (CMT-3) inhibits intimal thickening.

    PubMed

    Islam, Muzharul M; Franco, Christopher D; Courtman, David W; Bendeck, Michelle P

    2003-10-01

    Recent research has shown that the tetracycline antibiotics are pluripotent drugs that inhibit the activity of matrix metalloproteinases (MMPs) and affect many cellular functions including proliferation, migration, and matrix remodeling. We have shown that doxycycline inhibits MMP activity and intimal thickening after injury of the rat carotid artery, however we do not know whether these effects are because of the antibiotic, anti-MMP, or other actions of doxycycline. Recently, chemically modified tetracyclines have been synthesized that lack antibiotic activity but retain anti-MMP activity (CMT-3), or lack both antibiotic and anti-MMP activity (CMT-5). In the current study we have assessed the effects of treatment with CMT-3 or CMT-5 on intimal thickening after balloon catheter injury of the rat carotid artery. Rats were treated by oral gavage with 15 mg/kg/day CMT-3 or CMT-5. CMT-3 significantly reduced smooth muscle cell (SMC) proliferation in both the medial and intimal layers of the injured rat carotid artery compared to CMT-5. Furthermore, CMT-3 inhibited SMC migration from the media to the intima by 86% at 4 days after injury. CMT-3 also decreased MMP-2 activity. Finally, we found that CMT-3 treatment resulted in a significant reduction in intimal cross-sectional area from 0.23 +/- 0.01 mm(2) in the CMT-5 control group to 0.19 +/- 0.01 mm(2). There was also a reduction in elastin and collagen accumulation within the intima. We conclude that CMT-3 attenuated intimal thickening after arterial injury by inhibiting SMC proliferation, migration and MMP activity, and accumulation of extracellular matrix. The inhibitory effects of CMT-3 were independent of the antibiotic properties, but were dependent on the anti-MMP activity of the tetracycline family.

  20. Amlodipine-induced gingival hyperplasia.

    PubMed

    Lafzi, Ardeshir; Farahani, Ramin Mostofi Zadeh; Shoja, Mohammad Ali Mohajjel

    2006-11-01

    Drug-induced gingival hyperplasia is a serious concern both for the patient and the clinician. A 45 year-old Caucasian male patient with hypertension, who received amlodipine (10 mg/day, single dose orally) for two months, sought medical attention because of the new-onset gingival enlargement. On clinical examination a generalized and firm overgrowth of the gingival throughout the maxilla and the mandible were evident. The lack of gingival inflammation and purulent discharge were other features of the clinical scenario. Histological assessment of the biopsy specimen revealed the hyperplasia of connective tissue, epithelial acanthosis, and elongated rete ridges along with few inflammatory cells. The histological and the clinical evidences were consistent with amlodipine-induced gingival hyperplasia. We believe that the present report indicates the most rapidly developed case of amlodipine-induced gingival hyperplasia reported to date. The related literature is reviewed and the underlying pathogenic mechanisms of this rare side-effect are discussed here.

  1. Increased Expression of Phosphorylated Polo-Like Kinase 1 and Histone in Bypass Vein Graft and Coronary Arteries following Angioplasty

    PubMed Central

    Sur, Swastika; Swier, Vicki J.; Radwan, Mohamed M.; Agrawal, Devendra K.

    2016-01-01

    Interventional procedures, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) to re-vascularize occluded coronary arteries, injure the vascular wall and cause endothelial denudation and medial vascular smooth muscle cell (VSMCs) metaplasia. Proliferation of the phenotypically altered SMCs is the key event in the pathogenesis of intimal hyperplasia (IH). Several kinases and phosphatases regulate cell cycle in SMC proliferation. It is our hypothesis that increased expression and activity of polo-like kinase-1 (PLK1) in SMCs, following PTCA and CABG, contributes to greater SMC proliferation in the injured than uninjured blood vessels. Using immunofluorescence (IF), we assessed the expression of PLK1 and phosphorylated-PLK1 (pPLK1) in post-PTCA coronary arteries, and superficial epigastric vein grafts (SEV) and compared it with those in the corresponding uninjured vessels. We also compared the expressions of mitotic marker phospho-histone, synthetic-SMC marker, contractile SMC marker, IFN-γ and phosphorylated STAT-3 in the post-PTCA arteries, SEV-grafts, and the uninjured vessels. Immunostaining demonstrated an increase in the number of cells expressing PLK1 and pPLK1 in the neointima of post PTCA-coronary arteries and SEV-grafts compared to their uninjured counterparts. VSMCs in the neointima showed an increased expression of phospho-histone, synthetic and contractile SMC markers, IFN-γ and phosphorylated STAT-3. However, VSMCs of uninjured coronaries and SEV had no significant expression of the aforementioned proteins. These data suggest that PLK1 might play a critical role in VSMC mitosis in hyperplastic intima of the injured vessels. Thus, novel therapies to inhibit PLK1 could be developed to inhibit the mitogenesis of VSMCs and control neointimal hyperplasia. PMID:26820885

  2. [Congenital Adrenal Hyperplasia in Adults].

    PubMed

    Vrbíková, Jana

    2016-01-01

    Congenital adrenal hyperplasia is a life-long disease requiring an integrated therapy. It may negatively influence the quality of life. In childhood, the main problems of the care of these patients involve sex determination and ensuring optimum growth and puberty. The therapeutic goals for adults are the prevention of Addisonian crisis and ensuring the best possible quality of life, including fertility.Key words: androgens - cardiovascular risk - congenital adrenal hyperplasia - bone density - testicular rest tumors.

  3. PDT-induced apoptosis in arterial smooth muscles cells

    NASA Astrophysics Data System (ADS)

    Nyamekye, Isaac; Renick, R.; Gilbert, C.; McEwan, Jean R.; Evan, G.; Bishop, Christopher C. R.; Bown, Stephen G.

    1995-03-01

    PDT kills smooth muscle cells (SMC) in vivo and thus prevents intimal hyperplasia after angioplasty. It causes little inflammation and structural integrity of the artery is not compromised. We have studied the process of the SMC death in vitro. Cultured rat SMC (cell line sv40 ATCC) were sensitized with aluminum disulphonated phthalocyanine (AlS2Pc), and then irradiated with 675 nm laser light (2.5 J/cm2). Controls were studied using only sensitizer or laser for treatment. The cells were incubated and the dying process observed with a time lapse video and microscope system. PDT caused a characteristic pattern of death. Cells lost contact with neighbors, shrank, and showed hyperactivity and membrane ruffling. The cells imploded into active and condensed membrane bound vesicles which were terminally reduced to residual bodies. These are the morphological changes of apoptosis. The control cells which were given AlS2Pc alone or laser alone showed no death. PDT induced cultured arterial SMC death by apoptosis rather than necrosis. An apoptotic mechanism of cell death in vivo would explain the relative lack of inflammation and local tissue destruction in the face of massive death.

  4. Autocrine role of vascular IL-15 in intimal thickening

    SciTech Connect

    Cercek, Miha . E-mail: DimayugaP@cshs.org

    2006-01-13

    Interleukin 15 (IL-15) is a pro-inflammatory cytokine that modulates T cell recruitment and activation, independent of antigen. It has been detected in human atherosclerotic plaques and atherosclerotic plaques of apoE-/- mice. IL-15 regulates fractalkine (FKN)-CX3CR1 chemokine signaling which is involved in atherogenesis and promotes SMC proliferation. We investigated the role of IL-15 in intimal thickening after arterial injury. Treatment of serum-stimulated SMC with IL-15 in vitro attenuated proliferation and suppressed CX3CR1 and FKN mRNA expression. The role of endogenous IL-15 in vivo was investigated in injured carotid arteries of mice. Periadventitial arterial injury resulted in increased IL-15 expression in the media and neointima, paralleled by increased IL-15 receptor {alpha} expression. Blockade of endogenous IL-15 increased intimal thickening. FKN and CX3CR1 expression increased after injury and were further augmented after IL-15 blockade. These data suggest that endogenous IL-15 attenuated intimal thickening after arterial injury. The potential mechanism of action is suppression of CX3CR1 signaling.

  5. New Insights into Dialysis Vascular Access: Impact of Preexisting Arterial and Venous Pathology on AVF and AVG Outcomes.

    PubMed

    Vazquez-Padron, Roberto I; Allon, Michael

    2016-08-08

    Despite significant improvements in preoperative patient evaluation and surgical planning, vascular access failure in patients on hemodialysis remains a frequent and often unforeseeable complication. Our inability to prevent this complication is, in part, because of an incomplete understanding of how preexisting venous and arterial conditions influence the function of newly created arteriovenous fistulas and grafts. This article reviews the relationship between three preexisting vascular pathologies associated with CKD (intimal hyperplasia, vascular calcification, and medial fibrosis) and hemodialysis access outcomes. The published literature indicates that the pathogenesis of vascular access failure is multifactorial and not determined by any of these pathologies individually. Keeping this observation in mind should help focus our research on the true causes responsible for vascular access failure and the much needed therapies to prevent it. Copyright © 2016 by the American Society of Nephrology.

  6. Congenital lipoid adrenal hyperplasia

    PubMed Central

    2014-01-01

    Congenital lipoid adrenal hyperplasia (lipoid CAH) is the most fatal form of CAH, as it disrupts adrenal and gonadal steroidogenesis. Most cases of lipoid CAH are caused by recessive mutations in the gene encoding steroidogenic acute regulatory protein (StAR). Affected patients typically present with signs of severe adrenal failure in early infancy and 46,XY genetic males are phenotypic females due to disrupted testicular androgen secretion. The StAR p.Q258X mutation accounts for about 70% of affected alleles in most patients of Japanese and Korean ancestry. However, it is more prevalent (92.3%) in the Korean population. Recently, some patients have been showed that they had late and mild clinical findings. These cases and studies constitute a new entity of 'nonclassic lipoid CAH'. The cholesterol side-chain cleavage enzyme, P450scc (CYP11A1), plays an essential role converting cholesterol to pregnenolone. Although progesterone production from the fetally derived placenta is necessary to maintain a pregnancy to term, some patients with P450scc mutations have recently been reported. P450scc mutations can also cause lipoid CAH and establish a recently recognized human endocrine disorder. PMID:25654062

  7. C-cell hyperplasia.

    PubMed

    Guyétant, S; Bléchet, C; Saint-André, J-P

    2006-06-01

    Routine calcitonin assay programs and recent studies on the natural history of familial medullary thyroid carcinoma (MTC) have greatly added to our understanding of C-cell hyperplasia (CCH) and refined its classification. This article is an update on CCH physiopathology related to clinical presentation. With this combined approach, two types of CCH that differ by their physiological characteristics can be identified: neoplastic CCH and reactive (also called physiological) CCH. Neoplastic CCH is caused by a germline mutation of the RET protooncogene in a multiple endocrine neoplasia type 2 (MEN 2) syndrome. It progresses to MTC following a time line that depends on the RET mutation involved. CCH may actually be a misnomer for a neoplastic condition that some authors have proposed to call "in situ-MTC". Reactive CCH is considered to be caused by a stimulus that is external to the C-cell, and its premalignant potential is not documented. Many situations such as hypercalcemia, hyperparathyroidy, chronic lymphocytic thyroiditis or follicular tumors have been associated with reactive CCH, the pathogenesis of which remains unclear. But C-cell density in normal patients is subject to important variability, and several studies have demonstrated the dramatic male predominance in physiological CCH when hypercalcitoninemia was a random discovery. These data suggest that a number of conditions which were previously associated with reactive CCH might be purely fortuitous. Our clinical/pathological confrontation contributes to appropriately distinguishing between various CCH types, and in turn to identify the best way of managing patients.

  8. Benign prostatic hyperplasia

    PubMed Central

    2006-01-01

    Introduction Symptomatic benign prostatic hyperplasia (BPH) may affect up to 30% of men in their early 70s, causing urinary symptoms of bladder outlet obstruction. Symptoms can improve without treatment, but the usual course is a slow progression of symptoms, with acute urinary retention occurring in 1-2% of men with BPH per year. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical, surgical, and herbal treatments? We searched: Medline, Embase, The Cochrane Library and other important databases up to May 2005 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5 alpha-reductase inhibitors, alpha-blockers, beta-sitosterol plant extract, less-invasive surgical techniques, pygeum africanum, rye grass pollen extract, saw palmetto plant extracts, transurethral microwave thermotherapy, transurethral needle ablation, and transurethral resection.

  9. Ruptured pseudoaneurysm of the pulmonary artery--rare manifestation of a primary pulmonary artery sarcoma.

    PubMed

    Koch, Achim; Mechtersheimer, Gunhild; Tochtermann, Ursula; Karck, Matthias

    2010-01-01

    A 64-year-old male developed chest pain while gardening. Aortic dissection and coronary artery disease were excluded but chest computed tomography (CT) scan showed an aneurysmic enlargement of the pulmonary artery and a fluttering structure within. He underwent immediate sternotomy for replacement of the pulmonary artery. Histology showed an intimal sarcoma of both branches of the pulmonary artery. The pulmonary artery was replaced by a T-shaped Gore-Tex-prosthesis.

  10. Evaluating intimate partner violence.

    PubMed

    Valente, Sharon M

    2002-11-01

    To describe the incidence, assessment, and management of intimate partner violence (IPV) from a cultural perspective emphasizing the values, strengths, and health care needs of African-American women. Review of the published scientific literature, U.S. Bureau of Justice Statistics and the National Crime Victimization Survey (NCVS) supplemented with hypothetical cases. Violence is a social and public health emergency affecting over 10% of the population during their lives and 22% of women who are physically assaulted by an intimate. Roughly 3 million to 4.4 million women report being battered annually, although this is a low estimate. Neither gender nor age nor sexual orientation protects one from IPV. Violent crime causes 2.2 million known injuries with a huge cost in hospital days and other expenses. Women often hesitate to report violence; health care professionals detect as few as 5% of battered women. Women suffer for months and years before accurate diagnosis. Clinicians need to be vigilant in case finding, education, prevention, and treatment. Cultural differences in values and beliefs, and behavioral norms influence evaluation, treatment, and referral.

  11. Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro.

    PubMed

    Svegliati, Silvia; Amico, Donatella; Spadoni, Tatiana; Fischetti, Colomba; Finke, Doreen; Moroncini, Gianluca; Paolini, Chiara; Tonnini, Cecilia; Grieco, Antonella; Rovinelli, Marina; Funaro, Ada; Gabrielli, Armando

    2017-01-01

    One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia.

  12. Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro

    PubMed Central

    Svegliati, Silvia; Amico, Donatella; Spadoni, Tatiana; Fischetti, Colomba; Finke, Doreen; Moroncini, Gianluca; Paolini, Chiara; Tonnini, Cecilia; Grieco, Antonella; Rovinelli, Marina; Funaro, Ada; Gabrielli, Armando

    2017-01-01

    One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia. PMID:28228756

  13. Pharmacotherapy for benign prostatic hyperplasia.

    PubMed Central

    Narayan, P; Indudhara, R

    1994-01-01

    Benign prostatic hyperplasia is a benign neoplasm of the prostate seen in men of advancing age. Microscopic evidence of the disorder is seen in about 70% of men by 70 years of age, whereas symptoms requiring some form of surgical intervention occur in 30% of men during their lifetime. Although the exact cause of benign prostatic hyperplasia is not clear, it is well recognized that high levels of intraprostatic androgens are required for the maintenance of prostatic growth. In recent years, extensive surveys of patients undergoing transurethral resection of the prostate reveal an 18% incidence of morbidity that has essentially not changed in the past 30 years. This procedure is also the second highest reimbursed surgical therapy under Medicare. These findings have resulted in an intensive search for alternative therapies for prostatic hyperplasia. An alternative that has now been well defined is the use of alpha-adrenergic blockers to relax the prostatic urethra. This is based on findings that a major component of benign prostatic hyperplasia symptoms is spasm of the prostatic urethra and bladder neck, which is mediated by the alpha-adrenergic nerves. A second approach is to block androgens involved in maintaining prostate growth. Several such drugs are now available for clinical use, and we discuss their side effects and use. We also include the newer recommendations on evaluating benign prostatic hyperplasia that are cost-effective yet comprehensive. Images PMID:7528957

  14. Dietary supplementation with fermented soybeans suppresses intimal thickening.

    PubMed

    Suzuki, Yasuhiro; Kondo, Kazunao; Ichise, Hideyuki; Tsukamoto, Yoshinori; Urano, Tetsumei; Umemura, Kazuo

    2003-03-01

    Although soy foods have been consumed for more than 1000 y, it is only in the past 20 y that they have made inroads into Western diets. We investigated the effect of dietary supplementation with natto extracts produced from fermented soybeans on intimal thickening of arteries after vessel endothelial denudation. Natto extracts include nattokinase, a potent fibrinolytic enzyme having four times greater fibrinolytic activity than plasmin. Intimal thickening was induced in the femoral arteries by intravenous infusion of rose bengal followed by focal irradiation with a transluminal green light. Dietary natto extract supplementation was started 3 wk before endothelial injury and continued for another 3 wk after. In ex vivo studies, euglobulin clot lysis times were measured 3 wk after the initial supplementation. Neointima formation and thickening were also initiated successfully. The intima media ratio 3 wk after endothelial injury was 0.15 +/- 0.03 in the control group. Dietary natto extract supplementation suppressed intimal thickening (0.06 +/- 0.01; P < 0.05) compared with the control group. Natto extracts shortened euglobulin clot lysis time, suggesting that their thrombolytic activities were enhanced. These findings suggest that natto extracts, because of their thrombolytic activity, suppress intimal thickening after vascular injury as a result of the inhibition of mural thrombi formation.

  15. Over-expression of neuron-derived orphan receptor-1 (NOR-1) exacerbates neointimal hyperplasia after vascular injury.

    PubMed

    Rodríguez-Calvo, Ricardo; Guadall, Anna; Calvayrac, Olivier; Navarro, María A; Alonso, Judith; Ferrán, Beatriz; de Diego, Alicia; Muniesa, Pedro; Osada, Jesús; Rodríguez, Cristina; Martínez-González, José

    2013-05-15

    We have previously shown that NOR-1 (NR4A3) modulates the proliferation and survival of vascular cells in culture. However, in genetically modified animal models, somewhat conflicting results have been reported concerning the involvement of NOR-1 in neointimal formation after vascular injury. The aim of this study was to generate a transgenic mouse model over-expressing NOR-1 in smooth muscle cells (SMCs) and assess the consequence of a gain of function of this receptor on intimal hyperplasia after vascular injury. The transgene construct (SM22-NOR1) was prepared by ligating the full-length human NOR-1 cDNA (hNOR-1) and a mouse SM22α minimal promoter able to drive NOR-1 expression to SMC. Two founders were generated and two stable transgenic mouse lines (TgNOR-1) were established by backcrossing the transgene-carrying founders with C57BL/6J mice. Real-time PCR and immunohistochemistry confirmed that hNOR-1 was mainly targeted to vascular beds such as aorta and carotid arteries, and was similar in both transgenic lines. Vascular SMC from transgenic animals exhibit increased NOR-1 transcriptional activity (assessed by electrophoretic mobility shift assay and luciferase assays), increased mitogenic activity (determined by [(3)H]-thymidine incorporation; 1.58-fold induction, P < 0.001) and increased expression of embryonic smooth muscle myosin heavy chain (SMemb) than wild-type cells from control littermates. Using the carotid artery ligation model, we show that neointima formation was increased in transgenic versus wild-type mice (2.36-fold induction, P < 0.01). Our in vivo data support a role for NOR-1 in VSMC proliferation and vascular remodelling. This NOR-1 transgenic mouse could be a useful model to study fibroproliferative vascular diseases.

  16. A model of stress-induced geometrical remodeling of vessel segments adjacent to stents and artery/graft anastomoses.

    PubMed

    Rachev, A; Manoach, E; Berry, J; Moore, J E

    2000-10-07

    The mismatch between the elastic properties and initial geometry of a host artery and an implanted stent or graft cause significant stress concentration at the zones close to junctions. This may contribute to the often observed intimal hyperplasia, resulting in late lumen loss and eventual restenosis. This study proposes a mathematical model for stress-induced thickening of the arterial wall at the zones close to an implanted stent or graft. The host artery was considered initially as a cylindrical shell with constant thickness that was clamped to the stent or graft, which was assumed to be non-deformable in the circumferential direction. It was assumed that the abnormal circumferential and axial stresses due to the bending of the arterial wall cause wall thickening that tends to restore the stress state close to that existing far from the junction. The linear equations of a cylindrical shell with variable thickness were coupled to an evolution equation for the wall thickness. These equations were solved numerically and a parametric study was performed using finite difference method and explicit time step. The results show that the remodeling process is self-limiting and leads to local thickening that gradually decreases with distance from the edge of the stent/graft. Model predictions were tested against morphological findings existing in the literature. Recommendations on stent designs that reduce stress concentrations are discussed. Copyright 2000 Academic Press.

  17. Pulmonary intimal sarcoma treated by a left pneumonectomy with pulmonary arterioplasty under cardiopulmonary bypass: report of a case.

    PubMed

    Nakajima, Jun; Morota, Tetsuro; Matsumoto, Jun; Takazawa, Yutaka; Murakawa, Tomohiro; Fukami, Takeshi; Yamamoto, Tetsufumi; Takamoto, Shinichi

    2007-01-01

    Intimal sarcoma of the pulmonary artery is a rare disease. This neoplasm was characterized by an aggressive extension to the lumen of the pulmonary artery, thus mimicking a pulmonary thromboembolism. We herein report a 44-year-old woman who was diagnosed as having primary intimal sarcoma of the left lung preoperatively by transbronchial biopsy. The tumor originated in the pulmonary artery in the left lung, extending to the main pulmonary trunk via the pulmonary arterial lumen, thus resulting in stenosis of the main pulmonary trunk. A complete resection of the tumor with the left pneumonectomy and the pulmonary arterioplasty was successfully performed under cardiopulmonary bypass with vacuum assisted venous drainage.

  18. Reactive lymphoid hyperplasia of the thyroid followed by systemic autoimmune diseases: a case report

    PubMed Central

    2014-01-01

    Introduction Reactive lymphoid hyperplasia is a benign nodular lesion characterized by marked proliferation of non-neoplastic, polyclonal lymphocytes forming follicles. The lesion is found in various organs such as skin, orbit, lung, gastrointestinal tract, and liver. However, reactive lymphoid hyperplasia in the thyroid gland is extremely rare. Here, we present an interesting case of reactive lymphoid hyperplasia in the thyroid, which suggests the nature of the disease. Case presentation A 74-year-old Japanese man was referred to our institute because of a growing well-demarcated irregular-shaped mass in the right lobe of the thyroid. Malignant lymphoma was suspected by cytology, and right lobectomy was conducted. A final diagnosis of reactive lymphoid hyperplasia was made by the intimate investigation of the surgical specimen, with evidence of polyclonal and non-neoplastic lymphatic proliferations forming follicles with an active germinal center. After an initial uneventful postoperative course, our patient developed severe symptoms of systemic rheumatic arthritis, and alterations in autoimmune reaction, including clinically overt chronic thyroiditis, were identified. Conclusions Our case demonstrated important clinical information on reactive lymphoid hyperplasia of the thyroid, and suggested the importance of differential diagnosis, and possible close correlation between systemic autoimmune disorder and the disease. PMID:25005726

  19. Myometrial dysplasia (atypical myometrial hyperplasia).

    PubMed

    Cramer, Stewart F; Newcomb, Patricia M; Bonfiglio, Thomas A

    2007-04-01

    Although precursor lesions are well known for cervical and endometrial neoplasms, precursor lesions are not currently recognized for the most common tumor of the uterus-leiomyomas. Myometrial hyperplasia has been recently described and evaluated by morphometry, but its relationship to uterine leiomyomas has not been systematically explored. Myometrial dysplasia (atypical myometrial hyperplasia) has not been previously recognized. We herein report a case of myometrial dysplasia with immunostains for proliferation marker MIB-1 (Ki-67) and for p53. The paradoxical rarity of myometrial dysplasia is considered in comparison to the striking frequency of uterine leiomyomas.

  20. Thymic hyperplasia in Graves' disease.

    PubMed

    Kotwal, Narendra; Singh, Yashpal; Menon, Anil; Behera, Vineet

    2013-05-01

    Graves' disease is an autoimmune thyroid condition characterized by the production of autoantibodies against the thyrotropin receptor. It is known to be associated with autoimmune conditions such as myasthenia gravis, Addison's disease, type 1 diabetes mellitus, and vitiligo. We present a case of rare autoimmune association of Graves' disease with thymic hyperplasia which regressed after treatment with antithyroid drugs. Exact pathophysiology of thymic hyperplasia in Graves' is not well understood; it is likely to be the result of rather than the cause of Graves' disease.

  1. Focal epithelial hyperplasia: Case report.

    PubMed

    Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas

    2011-01-01

    The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.

  2. Ovine femoral artery bypass grafting using saphenous vein: a new model.

    PubMed

    El-Kurdi, Mohammed S; Soletti, Lorenzo; Nieponice, Alejandro; Abuin, Gustavo; Gross, Christina; Rousselle, Serge; Greisler, Howard; McGrath, Jonathan

    2015-01-01

    Saphenous vein grafts (SVGs) are frequently used for multi-vessel coronary artery bypass grafting and peripheral arterial bypasses; however, the estimated 40% failure rate within the first 5 y due to intimal hyperplasia (IH) and the subsequent failure rate of 2%-4% per year pose a significant clinical problem. Here, we report a surgical model in sheep intended to study IH development in SVGs, which can also be used for the evaluation of potential alternative treatments. Autologous bilateral SVGs were implanted as femoral artery interposition grafts using end-to-side anastomoses in adult sheep (n = 23), which were survived for 30 (n = 6), 90 (n = 7), 180 (n = 7), or 365 (n = 3) days. Post-implant, mid-term, and pretermination angiograms were quantified, and harvested SVGs were evaluated using quantitative histomorphometry. We describe a peripheral arterial surgical technique that models the progression of SVG pathology. Angiographic analysis showed a progressive dilation of SVGs leading to worsening diametrical matching to the target artery and reduced blood flow; and histomorphometry data showed an increase in IH over time. Multivariable regression analysis suggested that statistically significant (P < 0.05) time-dependent relationships exist between SVG dilation and both reduction in blood flow and IH development. Bilateral SVGs implanted onto the femoral arteries of sheep produced, controlled and consistent angiographic and histomorphometric results for which direct correlations could be made. This preclinical investigation model can be used as a robust tool to evaluate therapies intended for cardiovascular pathologies such as occlusive IH in SVGs. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Pulmonary Arterial Lesions in New World Camelids in Association With Dicrocoelium dendriticum and Fasciola hepatica Infection.

    PubMed

    Hilbe, M; Robert, N; Pospischil, A; Gerspach, C

    2015-11-01

    In Switzerland, dicrocoeliasis is regarded as the most significant parasitic infection of llamas and alpacas. Fasciola hepatica infestation is also a problem but less common. The aim of the present retrospective study was to evaluate the lungs of New World camelids (NWCs) for evidence of arterial hypertension in association with liver changes due to liver fluke infestation. The lungs of 20 llamas and 20 alpacas with liver fluke infestation were histologically evaluated. The hematoxylin and eosin and van Gieson (VG)-elastica stains as well as immunohistology for the expression of α-smooth muscle actin (α-SMA) were used to visualize the structures of arterial walls. Parasitology of fecal matter (11 llamas and 17 alpacas) confirmed that most of these animals were infested with both Dicrocoelium dendriticum and other gastrointestinal parasites. In most cases (10/12 llamas, 4/6 alpacas), liver enzyme activity in serum was elevated. Histologically, arteries in the lungs of 9 of 20 llamas (45%) and 3 of 20 alpacas (15%) showed severe intimal and adventitial and slight to moderate medial thickening, which was confirmed with α-SMA and VG-elastica staining. All animals exhibited typical liver changes, such as fibrosis and biliary hyperplasia, in association with the presence of liver flukes. This study shows that liver flukes can induce proliferative changes in lung arteries in NWCs that resemble those seen with pulmonary arterial hypertension due to liver parasites in humans. However, the degree of liver fluke infestation was not correlated with the extent of liver damage, or with the amount of thoracic or abdominal effusion or pulmonary arterial changes.

  4. Intimal sarcoma of the descending aorta.

    PubMed

    Shirani, Shapour; Soleymanzadeh-Ardabili, Maryam; Arami, Mitra

    2007-04-01

    Primary intimal angiosarcoma of the aorta (i.e., mostly intraluminal sarcomas with evidence of endothelial differentiation) is extraordinarily rare. We report a case in which the diagnosis was accurately made using immunohistochemistry in an embolectomy specimen. The patient was a 78-year-old man with a two-month history of bilateral claudication. Doppler ultrasound proved an embolus in both popliteal arteries, which was removed. The highly atypical cells comprising these emboli were positive immunohistochemically for CD68, vimentin, and CD31. Magnetic resonance imaging also showed an irregular tumor (invasion to the left main bronchus). This case emphasizes the need for a wide panel of immunohistochemical studies in tumor emboli of unknown origin.

  5. [Regenerative nodular hyperplasia in HIV].

    PubMed

    González, Ramiro Javier Romo; Chaves, Emiliano; Mullen, Eduardo; Copello, Hercilia

    2011-12-01

    Nodular regenerative hyperplasia of the liver is a rare condition. We describe here the case of a patient with HIV who presented with a clinical syndrome of portal hypertension. After multiple evaluations the diagnosis was recognized by the histology. The findings were attributed to the prolonged use of didanosine.

  6. Rare presentation of sebaceous hyperplasia

    PubMed Central

    Lester, Rachael A; Torgerson, Rochelle R; Sandhu, Nicole P

    2014-01-01

    A 23-year-old woman presented with an 8-month history of asymptomatic thickening of the central areola bilaterally and oily nipple discharge. On examination, there were yellowish-pink papules coalescing into plaques bilaterally. Biopsy showed ectopic sebaceous glands (Montgomery tubercles), known as bilateral areolar sebaceous hyperplasia. PMID:24759166

  7. The Effect of Arterial Curvature on Blood Flow in Arterio-Venous Fistulae: Realistic Geometries and Pulsatile Flow.

    PubMed

    Grechy, L; Iori, F; Corbett, R W; Gedroyc, W; Duncan, N; Caro, C G; Vincent, P E

    2017-07-26

    Arterio-Venous Fistulae (AVF) are regarded as the "gold standard" method of vascular access for patients with End-Stage Renal Disease (ESRD) who require haemodialysis. However, up to 60% of AVF do not mature, and hence fail, as a result of Intimal Hyperplasia (IH). Unphysiological flow and oxygen transport patterns, associated with the unnatural and often complex geometries of AVF, are believed to be implicated in the development of IH. Previous studies have investigated the effect of arterial curvature on blood flow in AVF using idealized planar AVF configurations and non-pulsatile inflow conditions. The present study takes an important step forwards by extending this work to more realistic non-planar brachiocephalic AVF configurations with pulsatile inflow conditions. Results show that forming an AVF by connecting a vein onto the outer curvature of an arterial bend does not, necessarily, suppress unsteady flow in the artery. This finding is converse to results from a previous more idealized study. However, results also show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can suppress exposure to regions of low wall shear stress and hypoxia in the artery. This finding is in agreement with results from a previous more idealized study. Finally, results show that forming an AVF by connecting a vein onto the inner curvature of an arterial bend can significantly reduce exposure to high WSS in the vein. The results are important, as they demonstrate that in realistic scenarios arterial curvature can be leveraged to reduce exposure to excessively low/high levels of WSS and regions of hypoxia in AVF. This may in turn reduce rates of IH and hence AVF failure.

  8. [Frequency of Kongenital Adrenal Hyperplasia (author's transl)].

    PubMed

    Müller, W; Prader, M; Kofler, J; Glatzl, J; Geir, W

    1979-01-01

    The frequency of homozygous congenital adrenal hyperplasia in Tyrol is found to be 1 : 8991, the gene-frequency for congenital adrenal hyperplasia 1 : 95 and the frequency of heterozygous congenital adrenal hyperplasia 1 : 48. Our data is compared on a numerical and statistical base with that in Zürich and Munich with regard to the frequency of congenital adrenal hyperplasia, to its distribution with and without salt loss and to its sex-distribution. According to our study one may assume a frequency of homozygous congenital adrenal hyperplasia in Tyrol, Zürich and Munich of 1 : 7000--10,000.

  9. Sulodexide may alleviate neointimal hyperplasia by inhibiting angiopoietin‑2 in an arteriovenous fistula model.

    PubMed

    Lei, Yan; Zheng, Zhihua; Wang, Ying; Liu, Yuyun; Liu, Rongjun; Xu, Qingdong; Yu, Xueqing

    2013-03-01

    The present study was undertaken to confirm whether sulodexide aleviates neointimal hyperplasia by regulating angiopoietin/Tie in a rat femoral arteriovenous fistula (AVF) model. Sprague Dawley rats were divided into four groups: sham, model, treatment and treatment control. An arteriovenous shunt model was created in the model and treatment groups. Sulodexide was subcutaneously administered (10 mg/kg/day) 6 times per week for 8 weeks in the treatment and treatment control groups. Histology and immunofluorescence were analyzed and the protein expression of angiopoietin‑1, angiopoietin‑2, Tie‑2, p‑ERK and total‑ERK were tested by ELISA and/or western blotting after 8 weeks. HE staining revealed that sulodexide was able to partially alleviate intimal hyperplasia of remodeled veins in the AVF model. Additionally, sulodexide was able to decrease angiopoietin‑2 and Tie‑2 expression while increasing angiopoietin‑1 expression in AVF tissue. Sulodexide was also able to decrease ERK phosphorylation which was increased in the model. Serum levels of soluble Tie-2 (sTie‑2) were also significantly decreased by sulodexide compared with the model. Immunofluorescent analysis also confirmed that sulodexide was able to decrease angiopoietin‑2 expression, possibly partially by inhibiting endothelial cell proliferation. Sulodexide may alleviate venous intimal hyperplasia by regulating the angiopoietin/Tie system, which may play a significant role in assisting remodeled veins to cope with their new biomechanical environment, but whether the angiopoietin/Tie system is beneficial or not requires further study.

  10. An Autopsy Case of Aortic Intimal Sarcoma Initially Diagnosed as Polyarteritis Nodosa

    PubMed Central

    Toyoda, Yuko; Ozaki, Ryohiko; Kishi, Jun; Hanibuchi, Masaki; Kinoshita, Katsuhiro; Tezuka, Toshifumi; Goto, Hisatsugu; Ono, Hiroyuki; Nagai, Kojiro; Bando, Yoshimi; Doi, Toshio; Nishioka, Yasuhiko

    2016-01-01

    A 61-year-old man had hypertension with stenosis in the left renal artery. When his fever, abdominal pain, and renal dysfunction progressed, he was admitted to our hospital. He was diagnosed with polyarthritis nodosa. His renal function rapidly deteriorated despite immunosuppressive therapy. His digestive tract perforated twice, and he subsequently died. An autopsy revealed that aortic intimal sarcoma caused stenosis in multiple arteries. Both polyarteritis nodosa and aortic intimal sarcoma are very rare diseases and the diagnoses are very difficult. It is very important to consider these entities when making a differential diagnosis of vasculitis. PMID:27803418

  11. Effect of Nitric Oxide on Neointimal Hyperplasia based on Sex and Hormone Status

    PubMed Central

    Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Saavedra, Joseph E.; Keefer, Larry K.; Kibbe, Melina R.

    2011-01-01

    Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have only been performed in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete media, male VSMC proliferated at greater rates than female VSMC. In hormone-deplete media, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male versus female VSMC. These findings correlated with greater G0/G1 cell cycle arrest and changes in cell cycle protein expression in male versus female VSMC following exposure to NO. Next, the rat carotid artery injury model was performed to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males versus females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in both sexes in castrated animals. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males than females and in hormonally-intact compared to castrated rats, indicating that the effect of NO in the vasculature may be sex- and hormone-dependent. PMID:21256959

  12. Effect of nitric oxide on neointimal hyperplasia based on sex and hormone status.

    PubMed

    Hogg, Melissa E; Varu, Vinit N; Vavra, Ashley K; Popowich, Daniel A; Banerjee, Monisha N; Martinez, Janet; Jiang, Qun; Saavedra, Joseph E; Keefer, Larry K; Kibbe, Melina R

    2011-05-01

    Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have been performed only in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete medium, male VSMC proliferated at greater rates than female VSMC. In hormone-depleted medium, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male compared to female VSMC. These findings correlated with greater G₀/G₁ cell cycle arrest and changes in cell cycle protein expression in male compared to female VSMC after exposure to NO. Next, the rat carotid artery injury model was used to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males compared to females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly, NO was less effective at inhibiting neointimal hyperplasia in castrated animals of both sexes. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males compared to females and in hormonally intact compared to castrated rats, indicating that the effects of NO in the vasculature may be sex- and hormone-dependent.

  13. Histomorphologic superiority of internal thoracic arteries over right gastroepiploic arteries for coronary bypass.

    PubMed

    Nakajima, Tomohiro; Tachibana, Kazutoshi; Takagi, Nobuyuki; Ito, Toshiro; Kawaharada, Nobuyoshi

    2016-06-01

    In this study, we compared the histologic and morphometric properties of both internal thoracic arteries and the right gastroepiploic artery (GEA) in patients undergoing coronary artery bypass grafting (CABG). We microscopically examined transverse sections of segments of both internal thoracic arteries and the right GEA obtained from 83 consecutive patients who underwent CABG. There were no significant differences between the internal thoracic arteries. Significant differences were found between the left and right internal thoracic arteries and GEA in the intimal width (21.8, 21.5, and 71.7 μm, respectively; P < .01), intima-to-media ratio (0.286, 0.256, and 0.749, respectively; P < .01), and media width (148.5, 157.5, and 164.8 μm, respectively; P = .43). No atherosclerotic lesions, medial calcification, or intimal thickening were seen in the internal thoracic arteries; however, atherosclerotic lesions were seen in the GEA. The intima of the GEA was thicker than that of the internal thoracic arteries. Intimal thickening of the GEA, but not the internal thoracic arteries, was positively correlated with risk of arteriosclerosis. In patients with diabetes mellitus, dietary/drug therapy and insulin therapy were associated with GEA intimal thickness (P = .02 and .01, respectively). The internal thoracic arteries have equivalent histologic and morphometric properties that differ from those of the GEA only in intimal width. The former had no intimal thickening, and is thus preferable to the GEA for CABG. Copyright © 2016. Published by Elsevier Inc.

  14. Nitric oxide is less effective at inhibiting neointimal hyperplasia in spontaneously hypertensive rats.

    PubMed

    Tsihlis, Nick D; Vavra, Ashley K; Martinez, Janet; Lee, Vanessa R; Kibbe, Melina R

    2013-11-30

    Exogenous administration of nitric oxide (NO) markedly decreases neointimal hyperplasia following arterial injury in several animal models. However, the effect of NO on neointimal hyperplasia in hypertension remains unknown. Here, we employ the spontaneously hypertensive rat (SHR) strain, inbred from Wistar Kyoto (WKY) rats, and the carotid artery balloon injury model to assess the effects of NO on neointimal hyperplasia development. 2weeks after arterial injury, we showed that both rat strains developed similar levels of neointimal hyperplasia, but local administration of NO was less effective at inhibiting neointimal hyperplasia in the SHR compared to WKY rats (58% vs. 79%, P<0.001). Interestingly, local administration of NO did not affect systemic blood pressure in either rat strain. Compared to WKY, the SHR displayed more proliferation in the media and adventitia following balloon injury, as measured by BrdU incorporation. The SHR also showed more inflammation in the adventitia after injury, as well as more vasa vasorum, than WKY rats. NO treatment reduced the vasa vasorum in the SHR but not WKY rats. Finally, while NO decreased both injury-induced proliferation and inflammation in the SHR, it did not return these parameters to levels seen in WKY rats. We conclude that NO is less effective at inhibiting neointimal hyperplasia in the SHR than WKY rats. This may be due to increased scavenging of NO in the SHR, leading to diminished bioavailability of NO. These data will help to develop novel NO-based therapies that will be equally effective in both normotensive and hypertensive patient populations. Published by Elsevier Inc.

  15. Nitric Oxide is Less Effective at Inhibiting Neointimal Hyperplasia in Spontaneously Hypertensive Rats

    PubMed Central

    Tsihlis, Nick D.; Vavra, Ashley K.; Martinez, Janet; Lee, Vanessa R.; Kibbe, Melina R.

    2013-01-01

    Exogenous administration of nitric oxide (NO) markedly decreases neointimal hyperplasia following arterial injury in several animal models. However, the effect of NO on neointimal hyperplasia in hypertension remains unknown. Here, we employ the spontaneously hypertensive rat (SHR) strain, inbred from Wistar Kyoto (WKY) rats, and the carotid artery balloon injury model to assess the effects of NO on neointimal hyperplasia development. Two weeks after arterial injury, we showed that both rat strains developed similar levels of neointimal hyperplasia, but local administration of NO was less effective at inhibiting neointimal hyperplasia in the SHR compared to WKY rats (58% vs. 79%, P<0.001). Interestingly, local administration of NO did not affect systemic blood pressure in either rat strain. Compared to WKY, the SHR displayed more proliferation in the media and adventitia following balloon injury, as measured by BrdU incorporation. The SHR also showed more inflammation in the adventitia after injury, as well as more vasa vasorum, than WKY rats. NO treatment reduced the vasa vasorum in the SHR but not WKY rats. Finally, while NO decreased both injury-induced proliferation and inflammation in the SHR, it did not return these parameters to levels seen in WKY rats. We conclude that NO is less effective at inhibiting neointimal hyperplasia in the SHR than WKY rats. This may be due to increased scavenging of NO in the SHR, leading to diminished bioavailability of NO. These data will help to develop novel NO-based therapies that will be equally effective in both normotensive and hypertensive patient populations. PMID:24149190

  16. Histopathological characterization of aortic intimal sarcoma with multiple tumor emboli.

    PubMed

    Nishida, N; Yutani, C; Ishibashi-Ueda, H; Tsukamoto, Y; Ikeda, Y; Nakamura, Y

    2000-11-01

    A case of aortic intimal sarcoma with multiple tumor emboli and distal metastasis is reported. All metastasis (adrenal, spleen) were via the arteries. This case also had independent lung cancer. Macroscopically, the aortic tumor did not form a bulged mass, but had linear ulceration with abundant mural thrombi. Poorly cohesive large atypical cells were seen in the intima of the abdominal aorta without invasion into the media. Tumor cells were disseminated into the mural thrombi on the aorta and embolized its branches. In the metastatic tumor or tumor emboli of the distal artery, there were not only large atypical cells, but also the foci of spindle-shaped cells or epithelioid differentiation. Tumor cells in the aorta were immunohistochemically positive for only vimentin. Muscle-specific actin was positive focally for spindle-shaped cells of tumor emboli and metastatic tumors. Furthermore, cytokeratin-positive cells were scatteredly seen. All tumor cells were negative for factor VIII and did not have a histologic or phenotypic analogy with lung cancer. The primary intimal sarcoma in the present case was of undifferentiated non-endothelial intimal stromal cell origin, and may have had multipotential for differentiation. Investigation of the metastatic site was useful for recognizing the features of this tumor.

  17. Drug eluting devices for critically ill patients: can we apply lessons learned from the treatment of peripheral artery disease?

    PubMed

    Werner, Martin; Scheinert, Dierk

    2014-11-20

    To review the use of drug-eluting devices in peripheral arteries of critically ill patients Drug eluting stents and drug coated balloons are promising technologies and have become an important tool for the endovascular treatment of peripheral artery disease. The concept of local drug delivery to prevent restenosis due to intimal hyperplasia has been proven in several trials for different peripheral vascular beds. Especially for the treatment of patients with critical lower limb ischemia, improved patency could presumably improve wound healing, survival and limb salvage rates. However, until now, there is a paucity of evidence regarding these devices in critically ill patients and lessons learned must be extrapolated from non-critically ill patients at this time. Restenosis rates can be reduced by drug eluting devices. Further study of the clinical impact of the use of drug eluting devices in the peripheral arteries will be required to determine if improved patency rates also can be translated into clinical benefit for critically ill patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Genetics in Arterial Calcification

    PubMed Central

    Rutsch, Frank; Nitschke, Yvonne; Terkeltaub, Robert

    2011-01-01

    Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxan-thoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature. PMID:21852556

  19. Mathematical model of intimal thickening in atherosclerosis: vessel stenosis as a free boundary problem.

    PubMed

    Fok, Pak-Wing

    2012-12-07

    Atherosclerosis is an inflammatory disease of the artery characterized by an expansion of the intimal region. Intimal thickening is usually attributed to the migration of smooth muscle cells (SMCs) from the surrounding media and proliferation of SMCs already present in the intima. Intimal expansion can give rise to dangerous events such as stenosis (leading to stroke) or plaque rupture (leading to myocardial infarction). In this paper we propose and study a mathematical model of intimal thickening, posed as a free boundary problem. Intimal thickening is driven by damage to the endothelium, resulting in the release of cytokines and migration of SMCs. By coupling a boundary value problem for cytokine concentration to an evolution law for the intimal area, we reduce the problem to a single nonlinear differential equation for the luminal radius. We analyze the steady states, perform a bifurcation analysis and compare model solutions to data from rabbits whose iliac arteries are subject to a balloon pullback injury. In order to obtain a favorable fit, we find that migrating SMCs must enter the intima very slowly compared to cells in dermal wounds. This cell behavior is indicative of a weak inflammatory response which is consistent with atherosclerosis being a chronic inflammatory disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical engineering review

    PubMed Central

    2013-01-01

    In this paper, coronary arterial bypass grafting hemodynamics and anastomosis designs are reviewed. The paper specifically addresses the biomechanical factors for enhancement of the patency of coronary artery bypass grafts (CABGs). Stenosis of distal anastomosis, caused by thrombosis and intimal hyperplasia (IH), is the major cause of failure of CABGs. Strong correlations have been established between the hemodynamics and vessel wall biomechanical factors and the initiation and development of IH and thrombus formation. Accordingly, several investigations have been conducted and numerous anastomotic geometries and devices have been designed to better regulate the blood flow fields and distribution of hemodynamic parameters and biomechanical factors at the distal anastomosis, in order to enhance the patency of CABGs. Enhancement of longevity and patency rate of CABGs can eliminate the need for re-operation and can significantly lower morbidity, and thereby reduces medical costs for patients suffering from coronary stenosis. This invited review focuses on various endeavors made thus far to design a patency-enhancing optimized anastomotic configuration for the distal junction of CABGs. PMID:24330653

  1. Coronary artery bypass grafting hemodynamics and anastomosis design: a biomedical engineering review.

    PubMed

    Ghista, Dhanjoo N; Kabinejadian, Foad

    2013-12-13

    In this paper, coronary arterial bypass grafting hemodynamics and anastomosis designs are reviewed. The paper specifically addresses the biomechanical factors for enhancement of the patency of coronary artery bypass grafts (CABGs). Stenosis of distal anastomosis, caused by thrombosis and intimal hyperplasia (IH), is the major cause of failure of CABGs. Strong correlations have been established between the hemodynamics and vessel wall biomechanical factors and the initiation and development of IH and thrombus formation. Accordingly, several investigations have been conducted and numerous anastomotic geometries and devices have been designed to better regulate the blood flow fields and distribution of hemodynamic parameters and biomechanical factors at the distal anastomosis, in order to enhance the patency of CABGs. Enhancement of longevity and patency rate of CABGs can eliminate the need for re-operation and can significantly lower morbidity, and thereby reduces medical costs for patients suffering from coronary stenosis. This invited review focuses on various endeavors made thus far to design a patency-enhancing optimized anastomotic configuration for the distal junction of CABGs.

  2. Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery.

    PubMed

    Zhang, Tiemin; Qu, Guangjin

    2016-01-01

    New and efficient strategies to protect endothelium or to enhance endothelial regrowth are important for treatment of restenosis after percutaneous transluminal angioplasty. Magnetic DNA microspheres are used to accelerate vascular endothelial growth factor (VEGF) re-endothelialization and to attenuate intimal hyperplasia in balloon-injured artery. This study aimed to assess DNA-gelatin magnetic nanospheres containing VEGF expression plasmids in vascular restenosis attenuation. Ninety-six rabbits underwent balloon injury and were randomly divided for gene transfer with naked VEGF plasmids (NAK group), magnetic VEGF microspheres (MIC group), and LacZ (CON group: naked LacZ plasmid and LacZ nanosphere subgroups). Serum and tissue VEGF levels were measured. Also, the ratios of intima area to media area were determined to assess neointima formation. Microsphere gene delivery through the artery by a magnet resulted in VEGF overexpression in transfected arterial segments. Tissue VEGF integral optical densities were significantly increased in MIC rabbits compared with NAK animals. Serum VEGF was below detection in all animals. X-Gal staining showed higher transfection efficiency in the CON group. The impact of neointimal thickening was evaluated by light microscopy as the ratio of intima area to media area in cross sections. Significant differences in the ratio of intima area to media area were obtained between the NAK group (0.12 ± 0.02, 0.41 ± 0.03, 0.61 ± 0.05, and 0.72 ± 0.04 at 1, 2, 3, and 4 weeks, respectively) and the MIC group (0.06 ± 0.03, 0.20 ± 0.05, 0.25 ± 0.04, and 0.26 ± 0.03 at 1, 2, 3, and 4 weeks, respectively) at 2, 3, and 4 weeks (P < .05). Intra-arterial VEGF gene delivery by magnetic microspheres significantly increased DNA stability, transfection efficiency, and targeting specificity, resulting in exogenous VEGF overexpression and attenuated intimal hyperplasia in balloon-injured artery. Copyright © 2016. Published by Elsevier Inc.

  3. Intimate Partner Violence. Prevention Update

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol, Drug Abuse, and Violence Prevention, 2011

    2011-01-01

    The Centers for Disease Control and Prevention (CDC) defines intimate partner violence (IPV) as violence between two people in a close relationship, including current and former spouses and dating partners. IPV occurs on a continuum from a single episode to ongoing battering and can include physical violence, sexual violence, threats, emotional…

  4. A Typology of Intimate Relationships

    ERIC Educational Resources Information Center

    Sager, Clifford J.

    1977-01-01

    A typology of marriages and other intimate relationships is offered based on seven behavioral profiles that partners can exhibit in their interactions with one another. The typology is relatively simple, based upon the main thrust of each partner's behavior in their dyadic system. (Author)

  5. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

    USDA-ARS?s Scientific Manuscript database

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

  6. Pituicytoma Coexisting With Corticotroph Hyperplasia

    PubMed Central

    Guo, Xiaopeng; Fu, Hanhui; Kong, Xiangyi; Gao, Lu; Wang, Wenze; Ma, Wenbin; Yao, Yong; Wang, Renzhi; Xing, Bing

    2016-01-01

    Abstract Pituicytoma is a rare, low-grade glial neoplasm that arises in the neurohypophysis or infundibulum and usually presents as pituitary gland enlargement. They are often misdiagnosed as pituitary adenomas. Causes have varied for high serum adrenocorticotropic hormone level reported in a few patients with pituicytoma. We report a rare case of pituicytoma accompanied by corticotroph hyperplasia—a challenging diagnosis guided by clinical presentations, radiological signs, and biopsy. We present a case of pituicytoma with corticotroph hyperplasia in a 46-year-old woman with typical Cushing syndrome. Magnetic resonance imaging revealed a lesion in the sellar area with equal T1 and T2 signals and marked homogeneous enhancement. We present detailed analysis of the patient's disease course and review pertinent literature. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. The patient underwent a surgical exploration and tumor resection through a trans-sphenoidal approach. Pathologic results revealed pituicytoma and corticotroph hyperplasia. As adrenocorticotropic hormone and cortisol levels did not decrease to normal, the patient received radiotherapy and recovered uneventfully. No recurrence was found over 8 years of follow-up. Pituicytoma is a rare type of sellar tumor. Pituicytomas in patients with Cushing syndrome are rarer still. To our knowledge, this is the first report of Cushing syndrome caused by corticotroph hyperplasia in a pituicytoma patient. PMID:26962837

  7. Focal epithelial hyperplasia: Heck disease.

    PubMed

    Cohen, P R; Hebert, A A; Adler-Storthz, K

    1993-09-01

    Two sisters of Mexican ancestry had focal epithelial hyperplasia (FEH). The lesions on the oral mucosa of the older child were initially misinterpreted as representing sexual abuse. Microscopic evaluation of a hematoxylin and eosin-stained section from a lower lip papule demonstrated the histologic features of FEH. Although human papillomavirus (HPV) type 13 and HPV32 have been most consistently present in FEH lesions, types 6, 11, 13, and 32 were not detected in the paraffin-embedded tissue specimen of our patient using an in situ hybridization technique. The lesions persisted or recurred during management using destructive modalities; subsequently, they completely resolved spontaneously.

  8. Benign Prostatic Hyperplasia: An Overview

    PubMed Central

    Roehrborn, Claus G

    2005-01-01

    Despite the deceptively simple description of benign prostatic hyperplasia (BPH), the actual relationship between BPH, lower urinary tract symptoms (LUTS), benign prostatic enlargement, and bladder outlet obstruction is complex and requires a solid understanding of the definitional issues involved. The etiology of BPH and LUTS is still poorly understood, but the hormonal hypothesis has many arguments in its favor. There are many medical and minimally invasive treatment options available for affected patients. In the intermediate and long term, minimally invasive treatment options are superior to medical therapy in terms of symptom and flow rate improvement; tissue ablative surgical treatment options are superior to both minimally invasive and medical therapy. PMID:16985902

  9. Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model

    PubMed Central

    Huang, Y; Salu, K; Liu, X; Li, S; Wang, L; Verbeken, E; Bosmans, J; De Scheerder, I

    2004-01-01

    Objective: To evaluate the effect of stent based methotrexate delivery on neointimal hyperplasia. Methods: Stainless steel coronary stents and biological polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs with a stent to artery ratio of 1.1:1. The pigs were killed after five days (10 stents) or four weeks (20 stents). Second, stainless steel coronary stents were dip coated in a 10 mg/ml methotrexate–SAE polymer solution, resulting in a total load of 150 μg methotrexate/stent. SAE coated stents and methotrexate loaded stents were randomly implanted in porcine coronary arteries with a stent to artery ratio of 1.2:1 and followed up to four weeks. Results: SAE coated stents and bare stents elicited a similar tissue response at five days. At four weeks, neointimal hyperplasia induced by the coated stents was less pronounced than with the bare stents (1.32 (0.66) v 1.73 (0.93) mm2, p > 0.05). In vitro drug release studies showed that 50% of the methotrexate was released in 24 hours, and all drug was released within four weeks. No impact on vascular smooth muscle cell proliferation or viability was observed in in vitro cell cultures. At four weeks the arteries with methotrexate loaded stents had decreased peristrut inflammation and neointimal hyperplasia (1.22 (0.34) v 2.25 (1.28) mm2, p < 0.01). Conclusions: SAE coating had an excellent biocompatibility with vascular tissue. Stent based delivery of methotrexate in the SAE coating effectively reduced neointimal hyperplasia in a porcine coronary stent model, potentially due to reduced peristrut inflammation. PMID:14729797

  10. Flow limitations in the iliac arteries in endurance athletes. Current knowledge and directions for the future.

    PubMed

    Schep, G; Bender, M H; Kaandorp, D; Hammacher, E; de Vries, W R

    1999-10-01

    are possible, although long-term follow-up is lacking. Percutaneous transluminal angioplasty and intravascular stent are contra-indicated because of high risks for dissection and reactive intimal hyperplasia, respectively.

  11. [Placing an endoprosthesis to maintain arterial canal permeability in lamb neonates].

    PubMed

    Godart, F; Jaillard, S; Corseaux, D; Houyel, L; Storme, L; Jude, B; Vincentelli, A; Rey, C

    2003-05-01

    Placing an endoprosthesis in the arterial canal in order to maintain permeability is a possible alternative to performing a modified Blalock-Taussig type surgical systemico-pulmonary anastomosis. This was studied in an animal model. Twelve newborn lambs, weighing from 1.8 to 3.5 kg, were catheterised in the neonatal period in order to place a stent. Three had a partial ligature of the pulmonary artery in utero. During the initial angiography, the canal was occluded in ten of them. Different types of coronary endoprosthesis were used: Multi link tetra TM and RX Herculink TM (Guidant Europe SA), Niroyal (Boston Scientific International), Bx Velocity (Cordis, Johnson and Johnson), Jostent (Jomed). The length of the endoprostheses varied from 12 to 18 mm and the diameter from 3.5 to 6 mm. Implantation was successful 10 out of 12 times: in one case, implantation was complicated by a fatal haemopericardium, and in another by pulmonary artery embolism. Nine animals out of 10 were followed up for 1 to 2 months. At autopsy verification, the canal was permeable in 7 cases with the development of a neointima and zones of moderate stenosis with intimal hyperplasia. In 2 animals the canal was occluded at the aortic level in a zone not covered by the endoprosthesis. Three animals died after implantation: the 2 implantation failures. A third animal with a well inserted prosthesis and a permeable canal died on day 1 from an unknown cause. Placing a stent in the arterial canal is a possible alternative to performing an aorto-pulmonary shunt. Coronary stents seem well adapted and this study does not allow any conclusions to be made at this time on the best type of stent. Further studies will be necessary in order to validate this concept before its use in congenital cardiopathies.

  12. Wnt2 and WISP-1/CCN4 Induce Intimal Thickening via Promotion of Smooth Muscle Cell Migration.

    PubMed

    Williams, Helen; Mill, Carina A E; Monk, Bethan A; Hulin-Curtis, Sarah; Johnson, Jason L; George, Sarah J

    2016-07-01

    Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs. Moreover, VSMC migration was induced by recombinant Wnt2 in vitro. Addition of recombinant Wnt2 protein increased Wnt1-inducible signaling pathway protein-1 (WISP-1) mRNA by ≈1.7-fold, via β-catenin/T-cell factor signaling, whereas silencing RNA knockdown of Wnt-2 reduced WISP-1 mRNA by ≈65%. Treatment with rWISP-1 significantly increased VSMC migration by ≈1.5-fold, whereas WISP-1 silencing RNA knockdown reduced migration by ≈40%. Wnt2 and WISP-1 effects were integrin-dependent and not additive, indicating that Wnt2 promoted VSMC migration via WISP-1. Additionally, Wnt2 and WISP-1 were significantly increased and colocated in human coronary arteries with intimal thickening. Reduced Wnt2 and WISP-1 levels in mouse carotid arteries from Wnt2(+/-) and WISP-1(-/-) mice, respectively, significantly suppressed intimal thickening in response to carotid artery ligation. In contrast, elevation of plasma WISP-1 via an adenovirus encoding WISP-1 significantly increased intimal thickening by ≈1.5-fold compared with mice receiving control virus. Upregulation of Wnt2 expression enhanced WISP-1 and promoted VSMC migration and thereby intimal thickening. As novel regulators of VSMC migration and intimal thickening, Wnt2 or WISP-1 may provide a potential therapy for restenosis and vein graft failure. © 2016 American Heart Association, Inc.

  13. Nodular extramammary Paget disease with fibroepitheliomatous hyperplasia.

    PubMed

    Kim, Joung Soo; Jeong, Myeong Gil; Kang, Ho Song; Yu, Hee Joon

    2014-12-01

    Extramammary Paget disease (EMPD) is a rare skin condition usually found in the anogenital region. Histologically, EMPD may be associated with varying degrees of epidermal hyperplasia classified as squamous, papillomatous, or fibroepitheliomatous. We report a case of EMPD in a 90-year-old man who presented with well-demarcated plaques and a nodule in the pubic area with fibroepitheliomatous hyperplasia.

  14. Hyperplasia in glands with hormone excess.

    PubMed

    Marx, Stephen J

    2016-01-01

    Five syndromes share predominantly hyperplastic glands with a primary excess of hormones: neonatal severe primary hyperparathyroidism, from homozygous mutated CASR, begins severely in utero; congenital non-autoimmune thyrotoxicosis, from mutated TSHR, varies from severe with fetal onset to mild with adult onset; familial male-limited precocious puberty, from mutated LHR, expresses testosterone oversecretion in young boys; hereditary ovarian hyperstimulation syndrome, from mutated FSHR, expresses symptomatic systemic vascular permeabilities during pregnancy; and familial hyperaldosteronism type IIIA, from mutated KCNJ5, presents in young children with hypertension and hypokalemia. The grouping of these five syndromes highlights predominant hyperplasia as a stable tissue endpoint and as their tissue stage for all of the hormone excess. Comparisons were made among this and two other groups of syndromes, forming a continuum of gland staging: predominant oversecretions express little or no hyperplasia; predominant hyperplasias express little or no neoplasia; and predominant neoplasias express nodules, adenomas, or cancers. Hyperplasias may progress (5 of 5) to neoplastic stages while predominant oversecretions rarely do (1 of 6; frequencies differ P<0.02). Hyperplasias do not show tumor multiplicity (0 of 5) unlike neoplasias that do (13 of 19; P<0.02). Hyperplasias express mutation of a plasma membrane-bound sensor (5 of 5), while neoplasias rarely do (3 of 14; P<0.002). In conclusion, the multiple distinguishing themes within the hyperplasias establish a robust pathophysiology. It has the shared and novel feature of mutant sensors in the plasma membrane, suggesting that these are major contributors to hyperplasia.

  15. Oral verrucous hyperplasia: a case report.

    PubMed

    Navaneetham, Anuradha; Dayanand Saraswathi, M C; Santosh, B S

    2014-09-01

    Oral verrucous hyperplasia is a whitish or pinkinsh elevated pre malignant lesion which occurs rarely. Its is also considered to be an early form of verrucous carcinoma. We have reported a case of verrucous hyperplasia which was diagnosed and treated with buccal fat pad as graft.

  16. Intimal sarcoma of the pulmonary trunk showing broad intimal extension and focal chondrosarcomatous differentiation: an autopsy case.

    PubMed

    Miyai, Kosuke; Takeo, Hiroaki; Matsukuma, Susumu

    2017-07-08

    We report an autopsy case of intimal sarcoma arising in the pulmonary artery with focal chondrosarcomatous differentiation. A 77-year-old woman presented with a thrombosis-like mass in the pulmonary trunk and underwent endarterectomy. Macroscopically, solid and myxomatous tumor expanded to the pulmonary valve and bilateral main pulmonary arteries. Microscopically, the tumor comprised atypical spindle cells proliferating in a fascicular fashion, as well as occasional bizarre multinucleated cells, within a myxomatous stroma. Less than 5% of the tumor cells showed chondrosarcomatous features. Immunohistochemically, tumor cells were diffusely positive for vimentin and partially positive for cytokeratin AE1/AE3, α-smooth muscle actin, and desmin. Electron microscopic analysis failed to reveal specific somatic differentiation of tumor cells. The patient died 2 days after the surgery because of uncontrollable heart failure. Upon autopsy, residual tumor cells were observed only in the left upper intrapulmonary portion of the pulmonary artery. Although the diagnosis of intimal sarcoma can be challenging, earlier histological confirmation of the tumor would lead to appropriate surgical treatment and improved outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Large Vessel Vasculitis with an Isolated Lesion of a Single-lobe Pulmonary Artery.

    PubMed

    Kitajima, Takamasa; Marumo, Satoshi; Shoji, Tsuyoshi; Huang, Cheng-Long; Yuba, Yoshiaki; Fukui, Motonari

    2016-01-01

    Chronic pulmonary arterial obstructions are caused mostly by chronic pulmonary artery thromboembolism and rarely by vasculitis or intimal sarcoma of the pulmonary artery. We herein report an unusual case of a 42-year-old woman with a solitary obstruction of the pulmonary artery in the right lower lobe of her lung. Because we could not exclude the possibility of intimal sarcoma, middle and lower lobectomy was performed. The resected specimens revealed large vessel vasculitis (LVV) and an isolated lesion in the right lower lobe pulmonary artery. LVV should therefore be considered in the differential diagnosis for single pulmonary arterial stenosis or obstruction.

  18. Angiolymphoid hyperplasia with eosinophilia and entrapment of the ulnar nerve

    PubMed Central

    Di Vitantonio, Hambra; De Paulis, Danilo; Ricci, Alessandro; Raysi, Soheila Dehcordi; Marzi, Sara; Del Maestro, Mattia; Galzio, Renato Juan

    2016-01-01

    Background: The angiolymphoid hyperplasia with eosinophilia (ALHE) is a sporadic vasoproliferative lesion of uncertain etiology involving the skin and the subcutaneous tissue. Occasionally, it involves also the large arteries compressing the near nerves. ALHE is commonly confused with Kimura's disease because of their clinical and histological similarities. Case Description: We report a case of a 52-year-old female suffering from a 6-month pain and paresthesias in the fourth and fifth finger of the right hand. The angiography showed a pseudoaneurysm in the proximal third of the right ulnar artery. A complete surgical excision of the vascular lesion was undertaken. The lesion forced the right ulnar nerve. The histopathological diagnosis deposed for ALHE. Conclusion: Up to now, literature has described 8 cases of ALHE involving the arteries, and only one case originating from the ulnar nerve. The authors report a case of a female with ALHE involving the ulnar artery that compressed the ulnar nerve. Clinical aspects, radiological features, surgical treatment, and operative findings are discussed reviewing the pertinent literature. PMID:27069750

  19. Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

    PubMed Central

    Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

    2014-01-01

    OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed

  20. [Primary pulmonary artery sarcoma in 36-year-old women: 3-years follow-up after partial resection and radiotherapy].

    PubMed

    Drożdż, Jarosław; Warchoł, Ewa; Fijuth, Jacek; Filipiak, Krzysztof; Spych, Michał; Maciejewski, Marek; Piestrzeniewicz, Katarzyna; Ludomir, Stafańczyk; Janaszek-Sitkowska, Hanna; Januszewicz, Andrzej; Zembala, Marian

    2013-01-01

    Intimal sarcoma of the heart and pulmonary artery is a very rare, malignant, primary tumour. The prognosis in patients with primary sarcoma of the pulmonary artery, including intimal sarcoma, is poor. We present the case and 3-years follow-up of 36-year-old woman who was successfully treated with surgical, partial resection of the tumour followed by radiotherapy.

  1. Effect of local heating on restenosis and in-stent neointimal hyperplasia in the atherosclerotic rabbit model: a dose-ranging study.

    PubMed

    Brasselet, Camille; Durand, Eric; Addad, Faouzi; Vitry, Fabien; Chatellier, Gilles; Demerens, Corinne; Lemitre, Mathilde; Garnotel, Roselyne; Urbain, Dominique; Bruneval, Patrick; Lafont, Antoine

    2008-02-01

    In-stent restenosis is related to neointimal hyperplasia. Heating reduces neointimal hyperplasia but promotes constrictive remodeling after balloon angioplasty. We aimed to assess the ability of local heating in inhibiting restenosis and in-stent neointimal hyperplasia and its potential side effects on arterial thrombosis. Atherosclerotic-like lesions were induced in iliac rabbit arteries. One month later, both iliac rabbit arteries were stented. In each animal, one artery was randomized to local heating at four temperatures (50, 60, 80, and 100 degrees C). The contra lateral artery was used as control. Angiographic and histomorphometric analysis were performed 42 days after angioplasty. Immunohistochemistry was performed 3, 15, and 42 days after angioplasty. Angiographic significant reduction of in-stent restenosis after moderate heating (50 degrees C) was related to in-stent neointimal hyperplasia trend to be lower after moderate local heating when compared with controls. In contrast, in-stent thrombosis was similar to controls. Higher temperatures (i.e. 80 and 100 degrees C) also reduced in-stent neointimal hyperplasia but were most frequently associated with severe in-stent thrombosis. Local heating was associated with decreased cell proliferation, collagen density, and increased smooth muscle cell apoptosis and heat shock protein expression. Moderate heating represents a promising approach to prevent in-stent restenosis via the limitation of the proliferative response without thrombosis induction.

  2. Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic.

    PubMed

    England, G C W; Moxon, R; Freeman, S L

    2012-10-15

    In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes in bitches with endometrial

  3. Trauma, attachment, and intimate relationships.

    PubMed

    Zurbriggen, Eileen L; Gobin, Robyn L; Kaehler, Laura A

    2012-01-01

    Intimate relationships can both affect and be affected by trauma and its sequelae. This special issue highlights research on trauma, attachment, and intimate relationships. Several themes emerged. One theme is the exploration of the associations between a history of trauma and relational variables, with an emphasis on models using these variables as mediators. Given the significance of secure attachment for healthy relationships, it is not surprising that attachment emerges as another theme of this issue. Moreover, a key component of relationships is trust, and so a further theme of this issue is betrayal trauma (J. J. Freyd, 1996 ). As the work included in this special issue makes clear, intimate relationships of all types are important for the psychological health of those exposed to traumatic events. In order to best help trauma survivors and those close to them, it is imperative that research exploring these issues be presented to research communities, clinical practitioners, and the public in general. This special issue serves as one step toward that objective.

  4. The role of accessory obturator arteries in prostatic arterial embolization.

    PubMed

    Bilhim, Tiago; Pisco, Joao; Pinheiro, Luís Campos; Rio Tinto, Hugo; Fernandes, Lúcia; Pereira, José A

    2014-06-01

    In 9 of 491 patients (1.8%) who underwent prostatic arterial embolization (PAE) for benign prostatic hyperplasia from March 2009-November 2013, prostatic arteries arose from the external iliac artery via an accessory obturator artery (AOA). Computed tomography angiography performed before the procedure identified the variant and allowed planning before the procedure. The nine AOAs were catheterized from a contralateral femoral approach. Bilateral PAE was technically successful in the nine patients. There was a mean decrease in international prostate symptom score of 6.5 points and a mean prostate volume reduction of 15.1% (mean follow-up, 4.8 mo) in the nine patients. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

  5. The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells

    SciTech Connect

    Perez-Vizcaino, Francisco . E-mail: fperez@med.ucm.es; Bishop-Bailley, David; Lodi, Federica; Duarte, Juan; Cogolludo, Angel; Moreno, Laura; Bosca, Lisardo; Mitchell, Jane A.; Warner, Timothy D.

    2006-08-04

    Quercetin, the most abundant dietary flavonol, exerts vasodilator, anti-hypertensive, and anti-atherogenic effects and reduces the vascular remodelling associated with elevated blood pressure. Here, we have compared the effects of quercetin in intimal- and medial-type rat vascular smooth muscle cells (VSMC) in culture. After 48 h, quercetin reduced the viability of a polyclonal intimal-type cell line derived from neonatal aorta but not of a medial-type cell line derived from adult aorta. These differential effects were similar in both proliferating and quiescent VSMC. Quercetin also preferentially reduced the viability of intimal-type over medial-type VSMC in primary cultures derived from balloon-injured carotid arteries. The effects of quercetin on cell viability were mainly dependent upon induction of apoptosis, as demonstrated by nuclear condensation and fragmentation, and were unrelated to PPAR{gamma}, pro-oxidant effects or nitric oxide. The expression of MAPKs (ERK, p38, and JNK) and ERK phosphorylation were not different between intimal- and medial-type VSMC. p38 phosphorylation was negligible in both cell types. Medial-type showed a weak JNK phosphorylation while this was markedly increased in intimal-type cells. Quercetin reduced JNK phosphorylation but had no consistent effect on ERK phosphorylation. In conclusion, quercetin preferentially produced apoptosis in intimal-type compared to medial-type VSMC. This might play a role in the anti-atherogenic and anti-hypertensive effects of quercetin.

  6. The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells.

    PubMed

    Perez-Vizcaino, Francisco; Bishop-Bailley, David; Lodi, Federica; Duarte, Juan; Cogolludo, Angel; Moreno, Laura; Bosca, Lisardo; Mitchell, Jane A; Warner, Timothy D

    2006-08-04

    Quercetin, the most abundant dietary flavonol, exerts vasodilator, anti-hypertensive, and anti-atherogenic effects and reduces the vascular remodelling associated with elevated blood pressure. Here, we have compared the effects of quercetin in intimal- and medial-type rat vascular smooth muscle cells (VSMC) in culture. After 48 h, quercetin reduced the viability of a polyclonal intimal-type cell line derived from neonatal aorta but not of a medial-type cell line derived from adult aorta. These differential effects were similar in both proliferating and quiescent VSMC. Quercetin also preferentially reduced the viability of intimal-type over medial-type VSMC in primary cultures derived from balloon-injured carotid arteries. The effects of quercetin on cell viability were mainly dependent upon induction of apoptosis, as demonstrated by nuclear condensation and fragmentation, and were unrelated to PPARgamma, pro-oxidant effects or nitric oxide. The expression of MAPKs (ERK, p38, and JNK) and ERK phosphorylation were not different between intimal- and medial-type VSMC. p38 phosphorylation was negligible in both cell types. Medial-type showed a weak JNK phosphorylation while this was markedly increased in intimal-type cells. Quercetin reduced JNK phosphorylation but had no consistent effect on ERK phosphorylation. In conclusion, quercetin preferentially produced apoptosis in intimal-type compared to medial-type VSMC. This might play a role in the anti-atherogenic and anti-hypertensive effects of quercetin.

  7. [Phytotherapy of benign prostatic hyperplasia].

    PubMed

    Bracher, F

    1997-01-01

    Phytopharmaceutical agents have been used for a long time in the treatment of symptomatic benign prostatic hyperplasia (BPH). However, until recently, it has been questioned whether phytotherapy is superior to a placebo treatment. In this article, the most widely used phytopharmaceutical agents, such as saw palmetto berry extracts, Radix urticae extracts, pumpkin seeds, pollen extracts and different phytosterols, are described. In addition, both in vitro and in vivo studies are discussed in an attempt to explain a possible mechanism of action. There are several new clinical studies which demonstrate a significant benefit compared with placebo treatment. Based on these results, the use of phytopharmaceutical agents for the treatment of mild to moderate symptomatic BPH seems to be well justified. So far, no significant inhibition of further prostate growth has been demonstrated. For this, a careful follow-up of the patients is necessary so as not to miss a deterioration and perhaps the need for an operation.

  8. Lasers for median lobe hyperplasia.

    PubMed

    Muschter, R; Gilling, A P

    2001-08-01

    Laser treatment encompases a variety of techniques using different laser wavelengths, application systems, and surgical techniques to achieve contrasting tissue effects such as incision, resection, vaporization, or coagulation. Many studies have proven the clinical efficacy of the various laser techniques for the treatment of benign prostatiuc hyperplasia, including randomized studies versus transurethral prostatectomy (TURP). Recently, long-term follow-up of up to 5 years has demonstrated the durability of the results, although in some of the studies, retreatment rates were higher than after TURP. Median lobes were never seen as a contraindication for treatment in the laser based procedures. Technically, laser treatment techniques such as side-firing transurethral coagulation, contact- and free-beam laser vaporization, interstitial laser coagulation, and the holmium laser-based resection and enucleation are fully suitable for treatment of median lobes. Surprisingly, no studies focussing specifically on laser treatment of median lobes have been published.

  9. Focal epithelial hyperplasia - an update.

    PubMed

    Said, Ahmed K; Leao, Jair C; Fedele, Stefano; Porter, Stephen R

    2013-07-01

    Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.

  10. Macromolecular Approaches to Prevent Thrombosis and Intimal Hyperplasia Following Percutaneous Coronary Intervention

    PubMed Central

    2015-01-01

    Cardiovascular disease remains one of the largest contributors to death worldwide. Improvements in cardiovascular technology leading to the current generation of drug-eluting stents, bioresorbable stents, and drug-eluting balloons, coupled with advances in antirestenotic therapeutics developed by pharmaceutical community, have had a profound impact on quality of life and longevity. However, these procedures and devices contribute to both short- and long-term complications. Thus, room for improvement and development of new, alternative strategies exists. Two major approaches have been investigated to improve outcomes following percutaneous coronary intervention including perivascular delivery and luminal paving. For both approaches, polymers play a major role as controlled research vehicles, carriers for cells, and antithrombotic coatings. With improvements in catheter delivery devices and increases in our understanding of the biology of healthy and diseased vessels, the time is ripe for development of novel macromolecular coatings that can protect the vessel lumen following balloon angioplasty and promote healthy vascular healing. PMID:24964369

  11. Laser tonsillotomy in children with tonsillar hyperplasia.

    PubMed

    Baharudin, A; Shahid, H; Rhendra, M Z

    2006-08-01

    Tonsillectomy in children is performed on a regular basis in ENT. The indications are chronic tonsillitis, sleep apnea to deeper structures. The natural history of tonsillar hyperplasia is regression when a child is six years beyond. In children with bilateral tonsillar hyperplasia we studied the use of laser as an alternative procedure to reduce the bulk of the tonsillar mass. Children with symptoms of bilateral tonsillar hyperplasia underwent laser tonsillotomy. The tonsils were dissected using carbon dioxide (CO2) laser. The tonsillar bed was left untouched. Intraoperative and postoperative conditions were noted.

  12. Intimate partner violence in African American women.

    PubMed

    Campbell, Doris Williams; Sharps, Phyllis W; Gary, Faye A; Campbell, Jacquelyn C; Lopez, Loretta M

    2002-01-01

    Violence against African American women, specifically intimate partner abuse, has a significant impact on their health and well being. Intimate partner femicide and near fatal intimate partner femicide are the major causes of premature death and disabling injuries for African American women. Yet, despite this, there is a paucity of research and interventions specific and culturally relevant for these women. This article focuses on issues relevant to intimate partner violence and abuse against African American women by examining existing empirical studies of prevalence and health outcomes of intimate partner violence against women in general, plus what limited research there is about African American women, specifically. It includes a discussion of specific recommendations for research, practice, education, and policy to reduce and prevent intimate partner violence against African American women.

  13. Retroperitoneal unicentric Castleman's disease (giant lymph node hyperplasia): case report.

    PubMed

    Waisberg, Jaques; Satake, Marie; Yamagushi, Nagamassa; Matos, Leandro Luongo de; Waisberg, Daniel Reis; Artigiani Neto, Ricardo; Franco, Maria Isete Fares

    2007-07-05

    Castleman's disease, or giant lymph node hyperplasia, is a rare disorder of the lymphoid tissue that causes lymph node enlargement. It is considered benign in its localized form, but aggressive in the multicentric type. The definitive diagnosis is based on postoperative pathological findings. The aim here was to describe a case of retroperitoneal unicentric Castleman's disease in the retroperitoneum. A 61-year old white male with weight loss and listlessness presented with moderate arterial hypertension and leukopenia. Abdominal tomography revealed a 5 x 4 x 5 cm oval mass of low attenuation, with inner calcification and intense enhancement on intravenous contrast, located in the retroperitoneal region, between the left kidney and the aorta, at the renal hilus. Exploratory laparotomy revealed a non-pulsatile solid oval mass situated in the retroperitoneum, adjacent to the left renal hilus. The retroperitoneal lesion was removed in its entirety. Examination of frozen samples revealed benign lymph node tissue and histopathological examination of the surgical sample revealed hyaline-vascular giant lymph node hyperplasia (Castleman's disease). The patient was discharged on the 12th day without significant events. Two months after the operation, the patient was readmitted with severe cardiac insufficiency, acute renal failure and bronchopneumonia, which progressed to acute respiratory insufficiency, sepsis and death.

  14. Coronary Arteries

    MedlinePlus

    ... and animations for grades K-6. The Coronary Arteries Coronary Circulation The heart muscle, like every other ... into two main coronary blood vessels (also called arteries). These coronary arteries branch off into smaller arteries, ...

  15. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Neuroendocrine Hyperplasia of Infancy.

    PubMed

    Carr, Laurie L; Kern, Jeffrey A; Deutsch, Gail H

    2016-09-01

    Although incidental reactive pulmonary neuroendocrine cell hyperplasia (PNECH) is seen on biopsy specimens in adults with chronic lung disease, disorders characterized by marked PNECH are rare. Primary hyperplasia of neuroendocrine cells in the lung and obstructive lung disease related to remodeling or physiologic constriction of small airways define diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH) in the adult and neuroendocrine cell hyperplasia of infancy (NEHI) in children. DIPENCH and NEHI share a similar physiology, typical imaging appearance, and increased neuroendocrine cells on biopsy. However, there are important differences related to the underlying disease mechanisms leading to disparate outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Altered dipeptidyl peptidase IV and prolyl endopeptidase activities in chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia.

    PubMed

    Larrinaga, Gorka; Pérez, Itxaro; Sanz, Begoña; Zarrazquin, Idoia; Casis, Luis; Anta, Jose Antonio; Martínez, Agustin; Santaolalla, Francisco

    2011-03-01

    To analyse peptidase activities in the removed tonsils and adenoids from patients with chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia. We have analyzed 48 tissue samples from patients undergoing tonsillectomy and adenoidectomy for chronic tonsillitis, tonsillar hyperplasia or adenoid hyperplasia. Tonsillectomy and adenoidectomy samples were collected and frozen for later enzyme analysis. The catalytic activity of a pool of peptidases (dipeptidyl peptidase IV, prolyl endopeptidase, aminopeptidase A, aminopeptidase N, aspartyl aminopeptidase, aminopeptidase B, neutral endopeptidase, pyroglutamyl peptidase I, puromycin-sensitive aminopeptidase and cystinyl aminopeptidase) was measured fluorometrically. The activity of prolyl endopeptidase was higher in tonsillar hyperplasia and adenoid hyperplasia than in chronic tonsillitis. On the contrary, dipeptidyl peptidase IV activity was higher in chronic tonsillitis than in hypertrophic tissues. When data were stratified by age and gender, dipeptidyl peptidase IV was also found to be more active in adult and male chronic tonsillitis tissues. Inversely, dipeptidyl peptidase IV activity was higher in tissues of females with tonsillar hyperplasia. These data indicate the involvement of dipeptidyl peptidase IV and prolyl endopeptidase in the mechanisms underlying chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia.

    PubMed

    Bahnson, Edward S M; Havelka, George E; Koo, Nathaniel C; Jiang, Qun; Kibbe, Melina R

    2016-10-01

    Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia; however, the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by (3)H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague-Dawley rats. Before balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels were assessed via immunofluorescence. Adipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature. Published by Elsevier Inc.

  18. Sebaceous hyperplasia: systemic treatment with isotretinoin*

    PubMed Central

    Tagliolatto, Sandra; Santos, Octavio de Oliveira; Alchorne, Maurício Mota de Avelar; Enokihara, Mauro Yoshiaki

    2015-01-01

    The study aimed to verify the therapeutic action of isotretinoin in the treatment of sebaceous hyperplasia. During two months, 20 patients with sebaceous hyperplasia took isotretinoin at a dosage of 1mg/kg per day. Their skin lesions were counted and photographed before and after treatment and re-evaluated two years later. The average number of sebaceous hyperplasia lesions before treatment was 24 per patient. At the end of two months of therapy, the number of lesions decreased to 2 per patient. The statistically analyzed data showed a reduction in the number of lesions following isotretinoin use (p < 0.05). Two years after the end of the treatment, the average number of sebaceous hyperplasia lesions was 4 per patient. There were no severe side effects. Thus, the data analysis suggests that isotretinoin is a safe and effective drug for treating the disease under study. PMID:25830991

  19. Diffuse villous hyperplasia of choroid plexus.

    PubMed

    Iplikcioglu, A C; Bek, S; Gökduman, C A; Bikmaz, K; Cosar, M

    2006-06-01

    Diffuse villous hyperplasia of choroid plexus (DVHCP) is a rare condition which is characterized by the presence of diffuse enlargement of the entire choroid plexus throughout the length of the choroidal fissure and overproduction of CSF. The diagnosis of diffuse villous hyperplasia of choroid plexus can be established by the MR demonstration of diffusely large, contrast enhanced choroid plexus in the cases of overproduction hydrocephalus. Although some authors recommend choroid plexus excision or coagulation, ventriculo-atrial shunt insertion is a simple and effective treatment modality in cases of diffuse villous hyperplasia of the choroid plexus. In this report we present a case of diffuse villous hyperplasia of the choroid plexus and a short review of the literature. To our knowledge, in the CT and MRI era only 5 cases of DVHCP cases have been reported.

  20. Oxidative stress in benign prostate hyperplasia.

    PubMed

    Zabaiou, N; Mabed, D; Lobaccaro, J M; Lahouel, M

    2016-02-01

    To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.

  1. Ancient history of congenital adrenal hyperplasia.

    PubMed

    New, Maria I

    2011-01-01

    Although there are many erudite reports on the history of endocrinology and endocrine disorders, the history of congenital adrenal hyperplasia has not been published. I have tried to review ancient as well as modern history of CAH.

  2. Sebaceous hyperplasia: systemic treatment with isotretinoin.

    PubMed

    Tagliolatto, Sandra; Santos Neto, Octavio de Oliveira; Alchorne, Maurício Mota de Avelar; Enokihara, Mauro Yoshiaki

    2015-01-01

    The study aimed to verify the therapeutic action of isotretinoin in the treatment of sebaceous hyperplasia. During two months, 20 patients with sebaceous hyperplasia took isotretinoin at a dosage of 1mg/kg per day. Their skin lesions were counted and photographed before and after treatment and re-evaluated two years later. The average number of sebaceous hyperplasia lesions before treatment was 24 per patient. At the end of two months of therapy, the number of lesions decreased to 2 per patient. The statistically analyzed data showed a reduction in the number of lesions following isotretinoin use (p < 0.05). Two years after the end of the treatment, the average number of sebaceous hyperplasia lesions was 4 per patient. There were no severe side effects. Thus, the data analysis suggests that isotretinoin is a safe and effective drug for treating the disease under study.

  3. Effects of wall shear stress in venous neointimal hyperplasia of arteriovenous fistulae.

    PubMed

    Jia, Lan; Wang, Lihua; Wei, Fang; Yu, Haibo; Dong, Hongye; Wang, Bo; Lu, Zhi; Sun, Guijiang; Chen, Haiyan; Meng, Jia; Li, Bo; Zhang, Ruining; Bi, Xueqing; Wang, Zhe; Pang, Haiyan; Jiang, Aili

    2015-05-01

    An arteriovenous fistulae (AVF) is the preferred vascular access for maintenance haemodialysis patients. Its dysfunction is often due to venous stenosis, which is mainly caused by neointimal hyperplasia. Additionally, haemodynamic forces, especially wall shear stress (WSS), as a mechanical stimuli to venous wall have a significant role in neointimal hyperplasia. The purpose of this study was to evaluate the association between WSS and neointimal hyperplasia. An 'end-to-side' AVF was created between the right femoral artery and vein of canines. Canines were killed at 7 and 28 days post-surgery. The velocity and WSS in the three-dimensional computational model of AVF were simulated using computational fluid dynamics (CFDs). The four typical sites of the vein evaluated in this study, chosen according to the haemodynamic analysis, included the arteriovenous anastomosis (A-V), the juxta-anastomotic segment (J-V), the juxta-ligation segment (L-V) and the proximal vein (P-V). The specimens were haematoxylin-eosin stained and the intima-media thickening was then measured. Neointimal hyperplasia was more obvious in the inner wall of the J-V and L-V (low-and-disturbed WSS) sites compared with the P-V and A-V sites, and the outer wall of the L-V and J-V segments (high or laminar WSS) (P < 0.01). In this study, we described the haemodynamic condition in the AVF and found that neointimal hyperplasia predisposed to occur in the inner wall of venous segment near the anastomosis. We also found that not only the neointimal hyperplasia has a strong inverse correlation with WSS levels, but also is related to flow patterns. © 2015 Asian Pacific Society of Nephrology.

  4. An uncommon focal epithelial hyperplasia manifestation.

    PubMed

    dos Santos-Pinto, Lourdes; Giro, Elisa Maria Aparecida; Pansani, Cyneu Aguiar; Ferrari, Junia; Massucato, Elaine Maria Sgavioli; Spolidório, Luis Carlos

    2009-01-01

    Focal epithelial hyperplasia is a rare, contagious disease associated with infection of the oral mucosa by human papillomavirus types 13 or 32, characterized by multiple soft papules of the same color as the adjacent normal mucosa. It mainly affects the lower lip, buccal mucosa, and tongue. The purpose of this case report was to describe a rare verrucal lesion located in the upper gingiva that was clinically and histologically consistent with focal epithelial hyperplasia.

  5. Management of adolescents with congenital adrenal hyperplasia.

    PubMed

    Merke, Deborah P; Poppas, Dix P

    2013-12-01

    The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Management of adolescents with congenital adrenal hyperplasia

    PubMed Central

    Merke, Deborah P; Poppas, Dix P

    2014-01-01

    The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed. PMID:24622419

  7. National Intimate Partner and Sexual Violence Survey: 2010 Highlights

    MedlinePlus

    ... an intimate partner. • 81% of women who experienced rape, stalking or physical violence by an intimate partner ... their experiences. IPV-Related Impacts Among Victims of Rape, Physical Violence, and/ or Stalking by an Intimate ...

  8. Undifferentiated Intimal Sarcoma of the Inferior Vena Cava with Extension to the Right Atrium and Renal Vasculature.

    PubMed

    Afzal, Aasim M; Alsahhar, Jamil; Podduturi, Varsha; Schussler, Jeffrey M

    2015-01-01

    Primary sarcomas of the great vessels (aorta, pulmonary artery, and inferior vena cava (IVC)) are exceedingly rare. We report a rare case of an undifferentiated intimal sarcoma of the IVC with extension to the right atrium, adrenal, and renal veins. The patient underwent extensive resection, reconstruction of the IVC, and subsequent adjuvant chemotherapy. Patient has tolerated chemotherapy and, at 17 months after resection, the patient remains free of tumor recurrence. Undifferentiated intimal sarcomas remain a rare entity with only five cases of venous undifferentiated intimal sarcomas reported in the literature, two of which occurred in the IVC. Intimal sarcomas tend to carry a poor prognosis with the limited literature available on treatment approaches. Our objective is to highlight this rare entity and possible treatment approach which we utilized. Primary sarcomas of IVC need to be included as part of a complete differential diagnosis in patients with atrial masses or recurrent pulmonary emboli.

  9. Undifferentiated Intimal Sarcoma of the Inferior Vena Cava with Extension to the Right Atrium and Renal Vasculature

    PubMed Central

    Afzal, Aasim M.; Alsahhar, Jamil; Podduturi, Varsha; Schussler, Jeffrey M.

    2015-01-01

    Primary sarcomas of the great vessels (aorta, pulmonary artery, and inferior vena cava (IVC)) are exceedingly rare. We report a rare case of an undifferentiated intimal sarcoma of the IVC with extension to the right atrium, adrenal, and renal veins. The patient underwent extensive resection, reconstruction of the IVC, and subsequent adjuvant chemotherapy. Patient has tolerated chemotherapy and, at 17 months after resection, the patient remains free of tumor recurrence. Undifferentiated intimal sarcomas remain a rare entity with only five cases of venous undifferentiated intimal sarcomas reported in the literature, two of which occurred in the IVC. Intimal sarcomas tend to carry a poor prognosis with the limited literature available on treatment approaches. Our objective is to highlight this rare entity and possible treatment approach which we utilized. Primary sarcomas of IVC need to be included as part of a complete differential diagnosis in patients with atrial masses or recurrent pulmonary emboli. PMID:26106489

  10. Pulmonary artery sarcoma mimicking massive pulmonary embolus: a case report.

    PubMed

    Alsoufi, Bahaaldin; Slater, Matthew; Smith, Pamela P; Karamlou, Tara; Mansoor, Atiya; Ravichandran, Pasala

    2006-08-01

    Intimal sarcomas of the pulmonary artery are rare tumors that are often difficult to distinguish from pulmonary thromboembolic disease, complicating accurate diagnosis and timely therapy. We report the case of a gentleman with a primary pulmonary artery sarcoma who presented with a massive pulmonary embolism and complete right ventricular outflow tract obstruction. The patient's condition was successfully managed with urgent pulmonary artery thromboendarterectomy, pulmonary valve replacement, and tricuspid valve annuloplasty.

  11. Dilemmas in intimate partner violence.

    PubMed

    Cook, Rebecca J; Dickens, Bernard M

    2009-07-01

    Intimate partner violence (IPV), usually men's violence against women, appears universal. It may be associated with pregnancy, but this may be because pregnant women receive more medical attention. Violence may cause bruises, abrasions, and cuts, but its extremes include hospitalization, death, and suicide. IPV is often disclosed when women are asked why they feel in poor health or depressed. A legal dilemma arises when healthcare providers consider that intervention such as law-enforcement is appropriate, but patients refuse approval. Patients may fatalistically accept violence, or fear loss of support for their children and themselves if their partners are held in custody. Legal reforms, such as punishing spousal rape, may provide some protection of women's autonomy. Ethical dilemmas concern intervention without patients' approval, and whether treating violent injuries without taking preventive action breaches the principle to Do No Harm. Professional advocacy and social action have been urged to expose and reduce IPV.

  12. Screening for Intimate Partner Violence.

    PubMed

    Paterno, Mary T; Draughon, Jessica E

    2016-05-01

    Intimate partner violence (IPV) is a serious concern for women that is associated with significant adverse health effects. Routine screening for IPV is recommended, but there are many barriers to screening that have been identified by providers, including discomfort, lack of training, and not knowing how to respond to a positive screen. This article reviews IPV screening and appropriate techniques for responding to a positive screen. IPV screening best practices include using a systematic protocol, developing a screening script, using a validated screening tool, and considerations for privacy and mandatory reporting. Responding to a positive screen should include acknowledging the experience, asking if the woman desires help, offering support and referrals, encouraging safety planning, and completing additional assessments to determine level of danger and to identify any comorbidities. Using these techniques along with therapeutic communication may increase IPV identification and create an environment in which women feel empowered to get help. © 2016 by the American College of Nurse-Midwives.

  13. Mig-6 Gene Knockout Induces Neointimal Hyperplasia in the Vascular Smooth Muscle Cell

    PubMed Central

    Lee, Ju Hee; Choung, Sorim; Kim, Ji Min; Lee, Jung Uee; Kim, Koon Soon; Kim, Hyun Jin; Jeong, Jae-Wook; Ku, Bon Jeong

    2014-01-01

    Although advances in vascular interventions can reduce the mortality associated with cardiovascular disease, neointimal hyperplasia remains a clinically significant obstacle limiting the success of current interventions. Identification of signaling pathways involved in migration and proliferation of vascular smooth muscle cells (SMCs) is an important approach for the development of modalities to combat this disease. Herein we investigate the role of an immediate early response gene, mitogen-inducible gene-6 (Mig-6), in the development of neointimal hyperplasia using vascular smooth muscle specific Mig-6 knockout mice. We induced endoluminal injury to one side of femoral artery by balloon dilatation in both Mig-6 knockout and control mice. Four weeks following injury, the artery of Mig-6 knockout mice demonstrated a 5.3-fold increase in the neointima/media ratio compared with control mice (P = 0.04). In addition, Mig-6 knockout vascular SMCs displayed an increase in both cell migration and proliferation compared with wild-type SMCs. Taken together, our data suggest that Mig-6 plays a critical role in the development of atherosclerosis. This finding provides new insight into the development of more effective ways to treat and prevent neointimal hyperplasia, particularly in-stent restenosis after percutaneous vascular intervention. PMID:25574067

  14. Mig-6 gene knockout induces neointimal hyperplasia in the vascular smooth muscle cell.

    PubMed

    Lee, Ju Hee; Choung, Sorim; Kim, Ji Min; Lee, Jung Uee; Kim, Koon Soon; Kim, Hyun Jin; Jeong, Jae-Wook; Ku, Bon Jeong

    2014-01-01

    Although advances in vascular interventions can reduce the mortality associated with cardiovascular disease, neointimal hyperplasia remains a clinically significant obstacle limiting the success of current interventions. Identification of signaling pathways involved in migration and proliferation of vascular smooth muscle cells (SMCs) is an important approach for the development of modalities to combat this disease. Herein we investigate the role of an immediate early response gene, mitogen-inducible gene-6 (Mig-6), in the development of neointimal hyperplasia using vascular smooth muscle specific Mig-6 knockout mice. We induced endoluminal injury to one side of femoral artery by balloon dilatation in both Mig-6 knockout and control mice. Four weeks following injury, the artery of Mig-6 knockout mice demonstrated a 5.3-fold increase in the neointima/media ratio compared with control mice (P = 0.04). In addition, Mig-6 knockout vascular SMCs displayed an increase in both cell migration and proliferation compared with wild-type SMCs. Taken together, our data suggest that Mig-6 plays a critical role in the development of atherosclerosis. This finding provides new insight into the development of more effective ways to treat and prevent neointimal hyperplasia, particularly in-stent restenosis after percutaneous vascular intervention.

  15. Eph-B4 activation reduces neointimal hyperplasia in human saphenous vein in vitro

    PubMed Central

    Wong, Daniel J; Lu, Daniel Y; Protack, Clinton D; Kuwahara, Go; Bai, Hualong; Sadaghianloo, Nirvana; Tellides, George; Dardik, Alan

    2014-01-01

    Background Vein bypass is an essential therapy for patients with advanced peripheral and coronary artery disease despite development of neointimal hyperplasia. We have shown that stimulation of the receptor tyrosine kinase Eph-B4 with its ligand Ephrin-B2 prevents neointimal hyperplasia in murine vein grafts. This study determines whether Eph-B4 in human veins is capable of phosphorylation, activation of downstream signaling pathways, and functional to release nitric oxide and prevent neointimal hyperplasia in vitro. Methods Discarded human saphenous veins were taken from the operating room and placed in organ culture without or with Ephrin-B2/Fc (2 μg/ml; 14 days) and the neointima:media ratio was measured in matched veins. Primary human umbilical vein endothelial cells (HUVEC) were treated with Ephrin-B2/Fc (2 μg/ml) and examined with qPCR, Western blot, immunoassays and for release of nitric oxide. Ephrin-B2/Fc (2 μg/ml) was placed in pluronic gel on the adventitia of saphenous veins treated with arterial shear stress for 24 hours in a bioreactor and activated Eph-B4 examined with immunofluorescence. Results The baseline intima:media ratio in saphenous vein rings was 0.456 ± 0.097 which increased to 0.726 ± 0.142 in untreated veins after 14 days in organ culture, but only to 0.630 ± 0.132 in veins treated with Ephrin-B2/Fc (p=.017; n=19). Ephrin-B2/Fc stimulated Akt, eNOS and caveolin-1 phosphorylation and NO release (p=0.007) from HUVEC (n=6). Ephrin-B2/Fc delivered to the adventitia stimulated endothelial Eph-B4 phosphorylation after 24 hours of arterial stress in a bioreactor (n=3). Discussion Eph-B4 is present and functional in adult human saphenous veins, with intact downstream signaling pathways capable of nitric oxide release and prevention of neointimal hyperplasia in vitro. Adventitial delivery of Ephrin-B2/Fc activates endothelial Eph-B4 in saphenous veins treated with arterial shear stress in vitro. These results suggest that stimulation of Eph

  16. Dynamic Autologous Reendothelialization of Small-Caliber Arterial Extracellular Matrix: A Preclinical Large Animal Study

    PubMed Central

    Dahan, Nitsan; Sarig, Udi; Bronshtein, Tomer; Baruch, Limor; Karram, Tony; Hoffman, Aaron

    2017-01-01

    Effective cellularization is a key approach to prevent small-caliber (<4 mm) tissue-engineered vascular graft (TEVG) failure and maintain patency and contractility following implantation. To achieve this goal, however, improved biomimicking designs and/or relatively long production times (typically several months) are required. We previously reported on porcine carotid artery decellularization yielding biomechanically stable and cell supportive small-caliber (3–4 mm diameter, 5 cm long) arterial extracellular matrix (scaECM) vascular grafts. In this study, we aimed to study the scaECM graft patency in vivo and possibly improve that patency by graft pre-endothelialization with the recipient porcine autologous cells using our previously reported custom-designed dynamic perfusion bioreactor system. Decellularized scaECM vascular grafts were histologically characterized, their immunoreactivity studied in vitro, and their biocompatibility profile evaluated as a xenograft subcutaneous implantation in a mouse model. To study the scaECM cell support and remodeling ability, pig autologous endothelial and smooth muscle cells (SMCs) were seeded and dynamically cultivated within the scaECM lumen and externa/media, respectively. Finally, endothelialized-only scaECMs—hypothesized as a prerequisite for maintaining graft patency and controlling intimal hyperplasia—were transplanted as an interposition carotid artery graft in a porcine model. Graft patency was evaluated through angiography online and endpoint pathological assessment for up to 6 weeks. Our results demonstrate the scaECM-TEVG biocompatibility preserving a structurally and mechanically stable vascular wall not just following decellularization and recellularization but also after implantation. Using our dynamic perfusion bioreactor, we successfully demonstrated the ability of this TEVG to support in vitro recellularization and remodeling by primary autologous endothelial and SMCs, which were seeded on the

  17. [Expression of telomerase genes in mamary atypical ductal hyperplasia].

    PubMed

    Song, Min; Mi, Xiaoyi; Li, Bailin; Zhu, Jijiang; Gao, Yingxian; Cui, Shuang; Song, Jiye

    2002-02-01

    To investigate the relationship of telomerase genes and the malignant transformation of atypical mammary ductal hyperplasia. Telomerase genes hTR and hTRT in 50 cases of mammary hyperplasia (the cases included 6 benign hyperplasia, 9 mild atypical hyperplasia, 12 medium atypical hyperplasia, 23 severe atypical hyperplasia) and 26 cases of breast carcinoma were detected by in situ hybridization. The expression of hTR and hTRT mRNA were weak or negative in benign hyperplasia (1/6, 0), weaker in mild-moderate atypical hyperplasia (2/9, 1/9, 4/12, and 3/12), strong in severe atypical hyperplasia (14/23, 60.9% and 12/23, 52.1%), while very strong expression (23/26, 88.5% and 21/25, 80.8%) in carcinoma of the breast. The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypital hyperplasia and intraductal carcinoma was not significant (P > 0.05). Telmerase genes (hTR, hTRT) expression is closely related to the malignant transformation of atypical hyperplasia. The reactivated telomerase may play a crucial role in the development of breast cancer.

  18. Intrathyroidal parathyroid hyperplasia in tertiary hyperparathyroidism

    PubMed Central

    Kim, Byung Seup; Ryu, Han Suk; Kang, Kyung Ho; Park, Sung Jun

    2013-01-01

    We report herein a case of intrathyroidal parathyroid hyperplasia in a patient with tertiary hyperparathyroidism. The patient was recommended for parathyroidectomy due to sustained hypercalcemia after kidney transplantation. Preoperative radiologic evaluations showed a benign-looking thyroid mass and three enlarged parathyroid glands. Intraoperative intact parathyroid hormone (iPTH) level and frozen biopsy results indicated a missed parathyroid gland after immediate subtotal parathyroidectomy. Then, a secondary partial resection of thyroid including the thyroid nodule was performed. An excised intrathyroid nodule was diagnosed to be parathyroid hyperplasia by frozen biopsy, and intraoperative iPTH level abruptly decreased. A benign-looking thyroidal mass in patients with secondary or tertiary hyperparathyroidism should be carefully evaluated considering the possibility of an intrathyroidal parathyroid hyperplasia. PMID:24964443

  19. Pseudocarcinomatous hyperplasia of the urinary bladder.

    PubMed

    Wu, Angela

    2014-10-01

    We review the morphology and differential diagnoses of pseudocarcinomatous hyperplasia of the bladder, using a study case to illustrate the discussion. Pseudocarcinomatous hyperplasia is a rare, reactive response to an ischemic insult, classically to radiation therapy, and consists of proliferative, pseudoinfiltrative urothelial nests within the stroma. The presence of background radiation therapy-related changes, such as numerous dilated thrombosed vessels, reactive-appearing endothelial and stromal cells, edema, and hemorrhage, can provide clues to the diagnosis. The main differential diagnoses include invasive urothelial carcinoma and the nested variant of urothelial carcinoma; morphologic features, such as the presence or absence of background therapy-related changes and the architecture and the cytologic atypia of the nests, can help distinguish between pseudocarcinomatous hyperplasia and urothelial carcinoma.

  20. [Modern pharmacotherapy of benign prostatic hyperplasia].

    PubMed

    Krysiak, Robert; Okopień, Bogusław; Szkróbka, Witold; Herman, Zbigniew Stanisław

    2005-11-01

    Benign prostatic hyperplasia is the most common medical problem affecting elderly men throughout the world. With increasing awareness of health issues amongst males, the morbidity caused by this disease is not longer being accepted as just part of growing old. Until about 10 years ago, surgery was the only effective treatment for symptomatic benign prostatic hyperplasia. Now, many men suffering from this disorder may be effectively treated with a medical therapy. This article provides an overview of the efficacy and safety of 5alpha-reductase inhibitors, alpha1-adrenoceptor antagonists and herbal remedies, putting special emphasis on the current place of these agents in the modem therapy of benign prostatic hyperplasia. Wherever possible, our opinion is based on the detailed analysis of the results of available clinical trials.

  1. Screening for Intimate Partner Violence During Pregnancy

    PubMed Central

    Deshpande, Neha A; Lewis-O’Connor, Annie

    2013-01-01

    Intimate partner violence (IPV) is defined as an actual or threatened abuse by an intimate partner that may be physical, sexual, psychological, or emotional in nature. Each year approximately 1.5 million women in the United States report some form of sexual or physical assault by an intimate partner; it is estimated that approximately 324,000 women are pregnant when violence occurs. Pregnancy may present a unique opportunity to identify and screen for patients experiencing IPV. This article provides health care practitioners and clinicians with the most current valid assessment and screening tools for evaluating pregnant women for IPV. PMID:24920977

  2. A review of pulmonary arterial hypertension

    PubMed Central

    Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.

    2004-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. PMID:25696347

  3. Outcome of congenital adrenal hyperplasia.

    PubMed

    Kuhnle, U; Bullinger, M

    1997-09-01

    In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, affected girls are born with ambiguous genitalia due to increased secretion of androgens in utero by the defective adrenal gland. Even though it is generally accepted that there are differences between male and female brain development, determining factors have been difficult to identify. Girls with CAH have frequently been studied to evaluate the impact of prenatal androgen exposure on psychological, psychosocial, and psychosexual development, and impairments in various areas have been identified. However, there is no comprehensive study available regarding the outcome of this chronic disorder in adult life. We studied the quality of life in women with CAH, with particular emphasis on how they cope with genital malformations, genital operations, and chronic disease as well as lifelong medication. The patients filled out questionnaires covering their physical state, psychological well-being, social relationships, and functional capacity, as well as questionnaires on psychosexual identification and psychosocial integration. The results were evaluated using a computerized statistical program for social studies. Out of a total of 94 patients above 18 years of age, 45 agreed to participate and were compared to 46 healthy, age-matched controls. Age at diagnosis was 2. 31 +/- 1.55 years and 38% suffered from the simple-virilizing, 45% from the salt-wasting, and 17.0% from the late-onset form of CAH. About one-third of patients had Prader stage 3 or 4 genital virilization. While the overall quality of life did not differ significantly, CAH patients were more often single (47.8% vs. 66.7%) and fewer of them had children (22.2% vs. 38.6%) compared to controls. Significant impairments were found in regard to body image and attitudes toward sexuality, but there was no increased homosexual preference. The women were successful in adjusting to illness and receiving social support. It is speculated that

  4. Pseudoepitheliomatous Hyperplasia in a Red Pigment Tattoo

    PubMed Central

    Kazlouskaya, Viktoryia

    2015-01-01

    Red pigment tattoos are known to cause pseudoepitheliomatous hyperplasia in the skin, frequently simulating squamous cell carcinoma or keratoacanthoma. Herein, the authors present two additional cases of red pigment tattoo pseudoepitheliomatous hyperplasia in which they noted a lichenoid tissue reaction. They reviewed the previously published cases and observed a lichenoid reaction in the histopathological images similar to hypertrophic lichen planus. The authors suggest that these reactions might best be referred to as “lichenoid reaction with pseudoepitheliomatous hyperplasia” or “hypertrophic lichen planus-like reaction.” Accordingly, recognition of an inflammatory component may allow additional treatment options. PMID:26705448

  5. Extensive Focal Epithelial Hyperplasia: A Case Report.

    PubMed

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  6. Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits.

    PubMed

    Noa, Miríam; Más, Rosa; Lariot, Carlos

    2007-09-01

    Policosanol is a cholesterol-lowering drug isolated from sugar cane wax with concomitant antiplatelet effects that prevents lipofundin-induced atherosclerotic lesions in rabbits and rats, including foam cell formation, and also reduces foam cell formation in carrageenan-induced granulomas in rats, while it inhibits proliferation of smooth muscle cells induced in rabbit cuffed artery. This study was undertaken to determine whether policosanol prevents endothelium damage and increase in arterial wall thickness in rabbits with arterial walls damaged with a forceps. Artery forceps were placed over the central artery of the right ear of all rabbits, and each artery was injured eight times. Animals were randomly distributed into four groups: a positive control group treated with Tween 20/H2O vehicle, two groups treated with policosanol (5 and 25 mg/kg, respectively), and a group treated with aspirin (8 mg/kg). Treatments were given for 30 days. Damaged arteries were examined by light and electron (transmission and scanning) microscopy. To evaluate intimal thickening, areas of intima were measured, and a significant reduction in policosanol-treated animals was observed. The endothelial surface, studied with scanning electron microscopy, revealed several types of damage. In control group, the endothelial surface was severely damaged. De-endothelialized areas were reduced in policosanol-treated animals. Platelet adhesion to subendothelium was seen in all animals of the control group, whereas policosanol-treated groups exhibited significantly reduced platelet adhesion. Policosanol also reduced, dose-dependently, the platelet sequestration induced in the damaged vessel wall, partially preventing the reduction in platelet count. It is concluded that policosanol prevents endothelium injury and reduces significantly intimal thickness of rabbit arteries damaged with forceps.

  7. Desistance From Intimate Partner Violence

    PubMed Central

    Bowen, Erica; Brown, Sarah; Sleath, Emma

    2015-01-01

    Intimate partner violence (IPV) is an international issue that social and criminal justice workers will encounter regularly. It has been identified that men can, and do stop using, or desist from, IPV although it is unclear how this process of change develops. This article introduces a conceptual model to outline how the process of desistance evolves and what it encompasses. Using thematic analysis of interview data from partner-violent men, survivors, and treatment facilitators, the resulting model demonstrates that the process of change is a dynamic one where men’s use of, and cessation from, violence needs to be understood within the context of each individual’s life. Three global themes were developed: (a) lifestyle behaviors (violent): what is happening in the men’s lives when they use violence; (b) catalysts for change: the triggers and transitions required to initiate the process of change; and (c) lifestyle behaviors (non-violent): what is different in the men’s lives when they have desisted from IPV. The purpose of this model is to offer a framework for service providers to assist them to manage the process of change in partner-violent men. PMID:25315483

  8. Pseudoepitheliomatous Hyperplasia in Oral Lesions: A Review

    PubMed Central

    Nayak, Vaidhehi Narayan; Uma, K; Girish, H C; Murgod, Sanjay; Shyamala, K; Naik, Ranajit B

    2015-01-01

    Pseudoepitheliomatous hyperplasia (PEH) is a histopathological reaction pattern to various stimuli, which includes trauma, infection, inflammation, neoplasia. It is seen as tongue like epithelial proliferation invading the connective tissue and should not be mistaken for squamous cell carcinoma (SCC). This review enlists oral lesions which exhibit PEH with a note on how to differentiate SCC from PEH. PMID:26435636

  9. Verrucous hyperplasia: A clinico-pathological study.

    PubMed

    Hazarey, Vinay K; Ganvir, Sindhu M; Bodhade, Ashish S

    2011-05-01

    Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. The present retrospective study was carried out to analyze the clinico-pathological features of verrucous hyperplasia (VH). Total 19 diagnosed cases of verrucous hyperplasia were retrospectively analyzed for demographic, clinical and histopathological features including dysplasia. Average age of occurrence of lesion was 4 (th) decade of life, with male predominance (2:1) and common site of occurrence being buccal mucosa. Clinically it present as verrucous exophytic growth with sharp or blunt projections on surface, which corresponds histologically. Tobacco lime quid placement in buccal vestibule was key etiologic factor. Histopathologicaly 68% cases showed dysplasia out of which moderate dysplasia predominates (42%). Moderately dysplastic cases were found to be associated with mixed habit pattern. Maximum cases were treated with excision. Biopsy specimen comprising of adjacent normal epithelium is key in distinguishing verrucous hyperplasia from verrucous carcinoma. Clinical behavior and recurrence potential needs to be assessed with long term follow up studies.

  10. Verrucous hyperplasia: A clinico-pathological study

    PubMed Central

    Hazarey, Vinay K; Ganvir, Sindhu M; Bodhade, Ashish S

    2011-01-01

    Context: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. Aims: The present retrospective study was carried out to analyze the clinico-pathological features of verrucous hyperplasia (VH). Materials and Methods: Total 19 diagnosed cases of verrucous hyperplasia were retrospectively analyzed for demographic, clinical and histopathological features including dysplasia. Results: Average age of occurrence of lesion was 4 th decade of life, with male predominance (2:1) and common site of occurrence being buccal mucosa. Clinically it present as verrucous exophytic growth with sharp or blunt projections on surface, which corresponds histologically. Tobacco lime quid placement in buccal vestibule was key etiologic factor. Histopathologicaly 68% cases showed dysplasia out of which moderate dysplasia predominates (42%). Moderately dysplastic cases were found to be associated with mixed habit pattern. Maximum cases were treated with excision. Conclusion: Biopsy specimen comprising of adjacent normal epithelium is key in distinguishing verrucous hyperplasia from verrucous carcinoma. Clinical behavior and recurrence potential needs to be assessed with long term follow up studies. PMID:22529578

  11. Hereditary pituitary hyperplasia with infantile gigantism.

    PubMed

    Gläsker, Sven; Vortmeyer, Alexander O; Lafferty, Antony R A; Hofman, Paul L; Li, Jie; Weil, Robert J; Zhuang, Zhengping; Oldfield, Edward H

    2011-12-01

    We report hereditary pituitary hyperplasia. The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. The study is a retrospective analysis of three cases from one family. The study was conducted at the National Institutes of Health, a tertiary referral center. A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. The condition was treated by total hypophysectomy. We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development.

  12. Intravascular papillary endothelial hyperplasia of the foot.

    PubMed

    Cisco, R W; McCormac, R M

    1994-01-01

    Intravascular papillary endothelial hyperplasia is a rare benign reactive lesion usually found in thrombosed subcutaneous blood vessels. The lesion resembles malignant angiosarcoma clinically and histopathologically, and must be diagnosed correctly to avoid inappropriate treatment. The following is a case presentation involving the foot.

  13. Multifocal epithelial hyperplasia. Report of nine cases.

    PubMed

    Ledesma-Montes, Constantino; Vega-Memije, Elisa; Garcés-Ortíz, Maricela; Cardiel-Nieves, Maritza; Juárez-Luna, Claudia

    2005-01-01

    Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease.

  14. [Focal epithelial hyperplasia. An unusual clinical aspect].

    PubMed

    Bodokh, I; Lacour, J P; Rainero, C; Orth, G; Perrin, C; Hoffman, P; Santini, J; Ortonne, J P

    1993-01-01

    We report a case of focal epithelial hyperplasia in a child born in France of Algerian parents. The clinical appearance was unusual in that certain lesions were verrucous and pediculate. A virological study revealed the presence of papillomavirus 32, one of the two types of HPV specifically associated with this entity.

  15. Myosin Regulatory Light Chain Diphosphorylation Slows Relaxation of Arterial Smooth Muscle*

    PubMed Central

    Sutherland, Cindy; Walsh, Michael P.

    2012-01-01

    The principal signal to activate smooth muscle contraction is phosphorylation of the regulatory light chains of myosin (LC20) at Ser19 by Ca2+/calmodulin-dependent myosin light chain kinase. Inhibition of myosin light chain phosphatase leads to Ca2+-independent phosphorylation at both Ser19 and Thr18 by integrin-linked kinase and/or zipper-interacting protein kinase. The functional effects of phosphorylation at Thr18 on steady-state isometric force and relaxation rate were investigated in Triton-skinned rat caudal arterial smooth muscle strips. Sequential phosphorylation at Ser19 and Thr18 was achieved by treatment with adenosine 5′-O-(3-thiotriphosphate) in the presence of Ca2+, which induced stoichiometric thiophosphorylation at Ser19, followed by microcystin (phosphatase inhibitor) in the absence of Ca2+, which induced phosphorylation at Thr18. Phosphorylation at Thr18 had no effect on steady-state force induced by Ser19 thiophosphorylation. However, phosphorylation of Ser19 or both Ser19 and Thr18 to comparable stoichiometries (0.5 mol of Pi/mol of LC20) and similar levels of isometric force revealed differences in the rates of dephosphorylation and relaxation following removal of the stimulus: t½ values for dephosphorylation were 83.3 and 560 s, and for relaxation were 560 and 1293 s, for monophosphorylated (Ser19) and diphosphorylated LC20, respectively. We conclude that phosphorylation at Thr18 decreases the rates of LC20 dephosphorylation and smooth muscle relaxation compared with LC20 phosphorylated exclusively at Ser19. These effects of LC20 diphosphorylation, combined with increased Ser19 phosphorylation (Ca2+-independent), may underlie the hypercontractility that is observed in response to certain physiological contractile stimuli, and under pathological conditions such as cerebral and coronary arterial vasospasm, intimal hyperplasia, and hypertension. PMID:22661704

  16. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia.

    PubMed

    Louiset, Estelle; Duparc, Céline; Young, Jacques; Renouf, Sylvie; Tetsi Nomigni, Milène; Boutelet, Isabelle; Libé, Rossella; Bram, Zakariae; Groussin, Lionel; Caron, Philippe; Tabarin, Antoine; Grunenberger, Fabienne; Christin-Maitre, Sophie; Bertagna, Xavier; Kuhn, Jean-Marc; Anouar, Youssef; Bertherat, Jérôme; Lefebvre, Hervé

    2013-11-28

    Bilateral macronodular adrenal hyperplasia is a rare cause of primary adrenal Cushing's syndrome. In this form of hyperplasia, hypersecretion of cortisol suppresses the release of corticotropin by pituitary corticotrophs, which results in low plasma corticotropin levels. Thus, the disease has been termed corticotropin-independent macronodular adrenal hyperplasia. We examined the abnormal production of corticotropin in these hyperplastic adrenal glands. We obtained specimens of hyperplastic macronodular adrenal tissue from 30 patients with primary adrenal disease. The corticotropin precursor proopiomelanocortin and corticotropin expression were assessed by means of a polymerase-chain-reaction assay and immunohistochemical analysis. The production of corticotropin and cortisol was assessed in 11 specimens with the use of incubated explants and cell cultures coupled with hormone assays. Corticotropin levels were measured in adrenal and peripheral venous blood samples from 2 patients. The expression of proopiomelanocortin messenger RNA (mRNA) was detected in all samples of hyperplastic adrenal tissue. Corticotropin was detected in steroidogenic cells arranged in clusters that were disseminated throughout the adrenal specimens. Adrenal corticotropin levels were higher in adrenal venous blood samples than in peripheral venous samples, a finding that was consistent with local production of the peptide within the hyperplastic adrenals. The release of adrenal corticotropin was stimulated by ligands of aberrant membrane receptors but not by corticotropin-releasing hormone or dexamethasone. A semiquantitative score for corticotropin immunostaining in the samples correlated with basal plasma cortisol levels. Corticotropin-receptor antagonists significantly inhibited in vitro cortisol secretion. Cortisol secretion by the adrenals in patients with macronodular hyperplasia and Cushing's syndrome appears to be regulated by corticotropin, which is produced by a subpopulation of

  17. Histopathological Differences Between the Anterior and Posterior Brain Arteries as a Function of Aging.

    PubMed

    Roth, William; Morgello, Susan; Goldman, James; Mohr, Jay P; Elkind, Mitchell S V; Marshall, Randolph S; Gutierrez, Jose

    2017-03-01

    We tested the hypothesis that posterior brain arteries differ pathologically from anterior brain arteries and that this difference varies with age. Brain large arteries from 194 autopsied individuals (mean age 56±17 years, 63% men, 25% nonwhite, 17% with brain infarcts) were analyzed to obtain the areas of arterial layers and lumen as well as the relative content of elastin, collagen, and amyloid. Visual rating was used to determine the prevalence of atheroma, calcification, vasa vasorum, pattern of intima thickening, and internal elastic lamina gaps. We used multilevel models adjusting for age, sex, ethnicity, vascular risk factors, artery type and location, and multiple comparisons. Of 1362 large artery segments, 5% had vasa vasorum, 5% had calcifications, 15% had concentric intimal thickening, and 11% had atheromas. Posterior brain arteries had thinner walls, less elastin, and more concentric intima thickening than anterior brain arteries. Compared to anterior brain arteries, the basilar artery had higher arterial area encircled by the internal elastic lamina, whereas the vertebral arteries had higher prevalence of elastin loss, concentric intima thickening, and nonatherosclerotic stenosis. In younger individuals, vertebral artery calcifications were more likely than calcification in anterior brain arteries, but this difference attenuated with age. Posterior brain arteries differ pathologically from anterior brain arteries in the degree of wall thickening, elastin loss, and concentric intimal thickening. © 2017 American Heart Association, Inc.

  18. Finasteride for benign prostatic hyperplasia.

    PubMed

    Tacklind, James; Fink, Howard A; Macdonald, Roderick; Rutks, Indy; Wilt, Timothy J

    2010-10-06

    Benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate in aging men, can cause bothersome urinary symptoms (intermittency, weak stream, straining, urgency, frequency, incomplete emptying). Finasteride, a five-alpha reductase inhibitor (5ARI), blocks the conversion of testosterone to dihydrotestosterone, reduces prostate size, and is commonly used to treat symptoms associated with BPH. To compare the clinical effectiveness and harms of finasteride versus placebo and active controls in the treatment of lower urinary tract symptoms (LUTS). We searched The Cochrane Library (which includes CDSR (Cochrane Database of Systematic Reviews), DARE (Database of Abstracts of Reviews of Effects), HTA (Heath Technology Assessments), and CENTRAL (Cochrane Central Register of Controlled Trials, and which includes EMBASE and MEDLINE), LILACS (Latin American and Caribbean Center on Health Sciences Information) and Google Scholar for randomized, controlled trials (RCTs). We also handsearched systematic reviews, references, and clinical-practice guidelines. Randomized trials in the English language with placebo and/or active arms with a duration of at least 6 months. JT extracted the data, which included patient characteristics, outcomes, and harms. Our primary outcome was change in a validated, urinary symptom-scale score, such as the AUA/IPSS. A clinically meaningful change was defined as 4 points. We also categorized outcomes by trial lengths of ≤ 1 year (short term) and > 1 year (long term). Finasteride consistently improved urinary symptom scores more than placebo in trials of > 1 year duration, and significantly lowered the risk of BPH progression (acute urinary retention, risk of surgical intervention, ≥ 4 point increase in the AUASI/IPSS). In comparison to alpha-blocker monotherapy, finasteride was less effective than either doxazosin or terazosin, but equally effective compared to tamsulosin. Both doxazosin and terazosin were significantly more

  19. Chemerin Stimulates Vascular Smooth Muscle Cell Proliferation and Carotid Neointimal Hyperplasia by Activating Mitogen-Activated Protein Kinase Signaling

    PubMed Central

    Xiong, Wei; Luo, Yu; Wu, Lin; Liu, Feng; Liu, Huadong; Li, Jianghua; Liao, Bihong; Dong, Shaohong

    2016-01-01

    Vascular neointimal hyperplasia and remodeling arising from local inflammation are characteristic pathogeneses of proliferative cardiovascular diseases, such as atherosclerosis and post angioplasty restenosis. The molecular mechanisms behind these pathological processes have not been fully determined. The adipokine chemerin is associated with obesity, metabolism, and control of inflammation. Recently, chemerin has gained increased attention as it was found to play a critical role in the development of cardiovascular diseases. In this study, we investigated the effects of chemerin on the regulation of vascular smooth muscle cells and carotid neointimal formation after angioplasty. We found that circulating chemerin levels increased after carotid balloon injury, and that knockdown of chemerin significantly inhibited the proliferative aspects of vascular smooth muscle cells induced by platelet-derived growth factor-BB and pro-inflammatory chemokines in vitro as well as prohibited carotid neointimal hyperplasia and pro-inflammatory chemokines in vivo after angioplasty. Additionally, inhibition of chemerin down-regulated the expression of several proteins, including phosphorylated p38 mitogen-activated protein kinase, phosphorylated extracellular signal regulated kinase 1/2, nuclear factor-kappa B p65, and proliferation cell nuclear antigen. The novel finding of this study is that chemerin stimulated vascular smooth muscle cells proliferation and carotid intimal hyperplasia through activation of the mitogen-activated protein kinase signaling pathway, which may lead to vascular inflammation and remodeling, and is relevant to proliferative cardiovascular diseases. PMID:27792753

  20. Witness of Intimate Partner Violence in Childhood and Perpetration of Intimate Partner Violence in Adulthood

    PubMed Central

    Roberts, Andrea L.; Gilman, Stephen E.; Fitzmaurice, Garrett; Decker, Michele R.; Koenen, Karestan C.

    2011-01-01

    Background At least half a million women are victims of intimate partner violence in the United States annually, resulting in substantial harm. However, the etiology of violence to intimate partners is not well understood. Witnessing such violence in childhood has been proposed as a principal cause of adulthood perpetration, yet it remains unknown whether the association between witnessing intimate partner violence and adulthood perpetration is causal. Method We conducted a propensity-score analysis of intimate partner violence perpetration to determine whether childhood witnessing is associated with perpetration in adulthood, independent of a wide range of potential confounding variables, and therefore might be a causal factor. We used data from 14,564 U.S. men ages 20 and older from the 2004–2005 wave of the National Epidemiologic Survey on Alcohol and Related Conditions. Results Nearly 4% of men reported violent behavior toward an intimate partner in the past year. In unadjusted models, we found a strong association between childhood witnessing of intimate partner violence and adulthood perpetration (for witnessing any intimate partner violence, risk ratio [RR] = 2.6 [95% confidence interval = 2.1–3.2]; for witnessing frequent or serious violence, 3.0 [2.3–3.9]). In propensity-score models, the association was substantially attenuated (for witnessing any intimate partner violence, adjusted RR = 1.6 [1.2–2.0]; for witnessing frequent or serious violence, 1.6 [1.2–2.3]). Conclusions Men who witness intimate partner violence in childhood are more likely to commit such acts in adulthood, compared with men who are otherwise similar with respect to a large range of potential confounders. Etiological models of intimate partner violence perpetration should consider a constellation of childhood factors. PMID:20811285

  1. Increased production of cytokines and growth factors by aortic allografts: A possible explanation for myointimal hyperplasia formation.

    PubMed

    Sterpetti, A V; Cucina, A; Randone, B; Guglielmi, M B; Fragale, A; Cavallaro, A

    1999-01-01

    Accelerated myointimal hyperplasia is a major complication of arterial allografts. The aim of our study was to analyze the role of growth factors in the genesis of myointimal hyperplasia in arterial allografts. Two groups of experiments were performed: Isografts and Allografts. The Isograft group consisted of 18 inbred Lewis rats in which a 1-cm long segment of aorta was inserted as abdominal aortic interposition graft. The aortic segments were obtained from syngeneic Lewis rats. The Allograft group consisted of 18 inbred Lewis rats, in which a 1-cm long segment of aorta was interposed at the level of the abdominal aorta. The aortic segments were obtained from allogeneic Brown-Norway rats. No immunosuppression was used. The animals were sacrificed 4 weeks after surgery and the aortic grafts were analyzed by light, electron microscopy (n = 3 for each group) and immunohistochemistry (n = 3 for each group). In addition, aortic segments (n = 12 for each group) were put in an organ culture to assess production of growth factors. All allografts showed evidence of severe myointimal hyperplasia, which was minimal in isografts. PDGF, bFGF and TGF-beta(1) production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts, whereas IL-1, TNF-alpha and GM-CSF production was increased in allografts and probably lymphocytes were the source of these cytokines (p < 0.001). We conclude that myointimal hyperplasia in aortic allografts is associated with an increase of IL-1, TNF-alpha and GM-CSF produced by lymphocytes.

  2. Rethinking estrangement, interventions, and intimate femicide.

    PubMed

    Ellis, D; Dekeseredy, W S

    1997-12-01

    This article aims to build on M. Wilson and M. Daly's male proprietariness thesis by integrating it with a theory of interventions. The challenge thesis contributed by a number of feminists focuses on the concepts of male proprietariness, estrangement, and intimate femicide, with mechanisms identified as exit, voice, and loyalty. An elaborated version of the challenge model shows male intimate partners on a continuum of proprietariness, female intimate partners are located on a continuum of resistance, mechanisms of resistance/change are linked with the choice of different kinds of interventions, harms experienced by estranged wives/cohabitating partners can be located on a continuum of harms, and person/situational factors are included because they help account for variations in male violence via their impact on proprietariness and deviance. Loyalty/love-invoked interventions could more likely reduce intimate femicide among coresiding female intimates. The criminal justice system is usually invoked by voice and these voice-invoked interventions increase the confidence of the battered wife symbolizing society's opposition to women abuse and could most probably end battering. Exit and exit-invoked mechanism are effective in ending battering for most battered women, although they may provoke a more fatal violence among dependent partners. The effectiveness of any of the chosen interventions varies with their appropriateness and timing.

  3. Analysis of Computational Fluid Dynamics and Particle Image Velocimetry Models of Distal-End Side-to-Side and End-to-Side Anastomoses for Coronary Artery Bypass Grafting in a Pulsatile Flow.

    PubMed

    Shintani, Yoshiko; Iino, Kenji; Yamamoto, Yoshitaka; Kato, Hiroki; Takemura, Hirofumi; Kiwata, Takahiro

    2017-08-19

    Intimal hyperplasia (IH) is a major cause of graft failure. Hemodynamic factors such as stagnation and disturbed blood flow are involved in IH formation. The aim of this study is to perform a comparative analysis of distal-end side-to-side (deSTS) and end-to-side (ETS) anastomoses using computational fluid dynamics (CFD) after validating the results via particle image velocimetry (PIV).Methods and Results:We investigated the characteristics of our target flow fields using CFD under steady and pulsatile flows. CFD via PIV under steady flow in a 10-times-actual-size model was validated. The CFD analysis revealed a recirculation zone in the heel region in the deSTS and ETS anastomoses and at the distal end of the graft, and just distal to the toe of the host artery in the deSTS anastomoses. The recirculation zone sizes changed with the phase shift. We found regions of low wall shear stress and high oscillating shear index in the same areas. The PIV and CFD results were similar. It was demonstrated that the hemodynamic characteristics of CFD and PIV is the difference between the deSTS and ETS anastomoses; that is, the deSTS flow peripheral to the distal end of the graft, at the distal end and just distal to the toe of the host artery is involved in the IH formation.

  4. [Experimental and clinical study of arterial damage induced by anti-cancer drug infusion].

    PubMed

    Ueda, E; Sako, M; Hirota, S

    1992-07-25

    In order to reduce the arterial damage following arterial chemo-infusion, arterial reaction to anti-cancer drugs and Corticosteroid were studied experimentally and clinically. In experiment, chemo-infusions (Mitomycin C, Adriamycin, Cisplatin) with or without Corticosteroid were carried out into the auricular and femoral arteries of rabbits, and the arterial changes were examined angiographically and histopathologically. The histologic examination showed the damages of various degrees characterized by intimal edema with pyknosis of endothelial cells, thrombus formation and detachment of intimal layer. The degree and frequency of the damage increased as the drug dose and concentration increased. However, higher blood flow and Corticosteroid could reduce the damages in some degrees. Clinically, bronchial arterial infusion of Cisplatin with or without Corticosteroid were studied. In conclusion, when angiography following ACI reveals narrowing and/or irregularity of the target artery, reduction of drug concentration and dose as well as elongation of infusion intervals are advised.

  5. Unilateral condylar hyperplasia: a treatment strategy.

    PubMed

    Ferreira, Sabrina; da Silva Fabris, André Luis; Ferreira, Gabriel Ramalho; Faverani, Leonardo Perez; Francisconi, Giovanna Barbosa; Souza, Francisley Avila; Garcia, Idelmo Rangel

    2014-05-01

    Condylar hyperplasia (CH) is a pathologic condition that causes overdevelopment of the condylar head and neck as well as the mandible. Slowly progressive unilateral enlargement of the head and the neck of the condyle causes crossbite malocclusion, facial asymmetry, and shifting of the midpoint of the chin to the unaffected side. The etiology and the pathogenesis of CH remain uncertain. The diagnosis is made by clinical and radiologic examinations and bone scintigraph. A difference in uptake of 10% or more between condyles is regarded as indicative of CH, and the affected condyles had a relative uptake of 55% or more. When the diagnosis of active CH is established, the treatment consists of removal of the growth center by a partial condylectomy. The authors present the case of a 46-year-old male patient with right active type II CH or hemimandibular hyperplasia who underwent a high condylectomy.

  6. Lymphoid papillary hyperplasia of the palatine tonsils.

    PubMed

    Carrillo-Farga, J; Abbud-Neme, F; Deutsch, E

    1983-09-01

    A rare case of papillary hyperplasia of the palatine tonsils is reported in a 9-year-old girl who presented with pharyngeal obstruction. The obstruction was due to the bilateral enlargement of the palatine tonsils with a papillary surface configuration so atypical that a diagnosis of malignant neoplasm was clinically considered. Histopathological study showed a peculiar form of lymphoid hyperplasia. No other members of the family were affected. As far as we know, this is the only case reported in recent years in an Occidental patient although a few similar cases have been reported from Japan. The importance of recognizing this peculiar abnormality rests in the fact that in spite of the clinical features simulating a cancer or multiple epithelial papillomas, the process is benign, probably non-neoplastic, and easily cured by bilateral tonsillectomy.

  7. Congenital adrenal hyperplasia with cholestatic jaundice.

    PubMed

    Ali, Nisreen Feroz; Zafar, Farhana; Bangash, Areeb Sohail; Malik, Abdul; Mohammedi, Karimunnisa

    2014-01-01

    Congenital Adrenal Hyperplasia describes a group of autosomal recessive disorders characterized by a decrease in Cortisol production. 11 beta hydroxylase deficiencies is the second most common form. However, its presentation with cholestatic jaundice is extremely rare. We present a case of a 29-day-old infant who came to us with unusual dark complexion, persistent jaundice, and electrolyte imbalance. On investigation he was diagnosed as a case of congenital adrenal hyperplasia. Treatment with hydrocortisone and fludrocortisone cleared his jaundice and complexion with subsequent improvement in electrolytes. The aim of this report is to illustrate an unusual presentation of CAH with Cholestatic jaundice. This is the first case to be reported from Pakistan. The case outlines the difficult workup that was encountered in the diagnosis and management of the patient.

  8. Extensive Focal Epithelial Hyperplasia: A Case Report

    PubMed Central

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501

  9. Myocardial hypertrophy induces carotid body hyperplasia.

    PubMed

    Sivridis, Efthimios; Pavlidis, Pavlos; Fiska, Aliki; Pitsiava, Dimitra; Giatromanolaki, Alexandra

    2011-01-01

    The carotid bodies tend to enlarge after long-standing cardiopulmonary disease. Our objective was to investigate whether cardiac hypertrophy is associated with carotid body hyperplasia. Fifteen autopsy cases with combined left and right ventricular hypertrophy were examined and compared with two control groups (16 cases). The study involved a meticulous dissection of carotid bifurcations, thin serial sections, and morphometric analysis of carotid body volume and cell types (progenitor, dark, light, and sustentacular). There was a significant increase in sustentacular cells in all individuals with cardiac hypertrophy, which was not drug-induced, and accompanied by a similar increase in carotid body volume. Dark or light cell accumulation was detected focally and only in three instances. It appears that the generalized sustentacular cell hyperplasia is the result of long-standing hypoxia, while a superimposed focal prominence of dark or light cells may be proliferative or metaplastic in nature and attributed to short-term hypoxia.

  10. Mandibular coronoid hyperplasia: a case report.

    PubMed

    Yura, Shinya; Ohga, Noritaka; Ooi, Kazuhiro; Izumiyama, Yuri

    2009-10-01

    A case of unilateral coronoid hyperplasia successfully treated by coronoidotomy with prolonged postoperative physiotherapy and reveal the postoperative radiographic changes between the sectioned part of the coronoid process and the mandibular ascending ramus is described. The patient was a 28-year-old man whose maximum mouth opening was 30 mm. A coronoidotomy of the left coronoid process was performed. Nine days after surgery, the patient started physiotherapy with a HU-OS(r) appliance. After coronoidotomy and physiotherapy, the maximum mouth opening had increased to 43 mm. Radiographic follow-up showed that the coronoid process apparently united with the mandibular ascending ramus, with moderate dislocation and inclination posteriorly. In the case presented, an intraoral coronoidotomy with postoperative physiotherapy for treatment of coronoid process hyperplasia allowed satisfactory and stable results in the correction of coronoid-malar interference.

  11. Hereditary Pituitary Hyperplasia with Infantile Gigantism

    PubMed Central

    Gläsker, Sven; Vortmeyer, Alexander O.; Lafferty, Antony R. A.; Hofman, Paul L.; Li, Jie; Weil, Robert J.; Zhuang, Zhengping

    2011-01-01

    Context: We report hereditary pituitary hyperplasia. Objective: The objective of the study was to describe the results of the clinical and laboratory analysis of this rare instance of hereditary pituitary hyperplasia. Design: The study is a retrospective analysis of three cases from one family. Setting: The study was conducted at the National Institutes of Health, a tertiary referral center. Patients: A mother and both her sons had very early-onset gigantism associated with high levels of serum GH and prolactin. Interventions: The condition was treated by total hypophysectomy. Main Outcome Measure(s): We performed clinical, pathological, and molecular evaluations, including evaluation basal and provocative endocrine testing, neuroradiological assessment, and assessment of the pituitary tissue by microscopic evaluation, immunohistochemistry, and electron microscopy. Results: All three family members had very early onset of gigantism associated with abnormally high serum levels of GH and prolactin. Serum GHRH levels were not elevated in either of the boys. The clinical, radiographic, surgical, and histological findings indicated mammosomatotroph hyperplasia. The pituitary gland of both boys revealed diffuse mammosomatotroph hyperplasia of the entire pituitary gland without evidence of adenoma. Prolactin and GH were secreted by the same cells within the same secretory granules. Western blot and immunohistochemistry demonstrated expression of GHRH in clusters of cells distributed throughout the hyperplastic pituitary of both boys. Conclusions: This hereditary condition seems to be a result of embryonic pituitary maldevelopment with retention and expansion of the mammosomatotrophs. The findings suggest that it is caused by paracrine or autocrine pituitary GHRH secretion during pituitary development. PMID:21976722

  12. [Hepatocellular nodular hyperplasias, adenomas and carcinomas].

    PubMed

    Altmann, H W

    1995-01-01

    Nodular hyperplasias ("hyperplasiomas") are new formations whose development as a required and regulated response can be traced either to compensatory reactions to the loss of cells (regeneration in a narrow sense) and to decreased cellular performance, or to primary growth impulses. Included in this group are: the "macroregenerative nodules" after extensive cell losses; solitary nodules of uncertain etiology; and the minute foci of "micronodular transformation" whose origin can be traced to a particular disturbance of the hepatic blood supply. The so-called "adenomatous hyperplasias" of the cirrhotic liver that have a tendency towards carcinomatous change are not included in this group and are perhaps better considered as "hyperplasiogenic adenomas". The so-called "focal nodular hyperplasia" too, it must be stressed, should be separated from the simple hyperplasias, for it is more closely related to the adenomas, but represents a new formation of limited growth potential. Morphologically it is conspicuously subdivided by multiple connective tissue bands and scars, but it is above all characterized by metaplastically derived neoductuli, and hence it is appropriately designated as a "combined nodule". Among the true uninodular adenomas there are several variants differing in their morphology,--the so-called "atypical" or "intermediate" forms, that can give rise to carcinomas. The hepatocellular carcinoma, that may arise in a variety of ways, presents multiple cytological and histological variants, but only the so-called "fibrolamellar carcinoma" presents also a clinical peculiarity. "Hepatoblastomas" differ from the common hepatocellular carcinomas by their origin in early childhood from immature early precursor cells and, in the later phases of life, from redifferentiated cells that can even give rise to mesenchymal elements. There is no evidence of the existence of particular pluripotential stem cells.

  13. Focal epithelial hyperplasia in a Turkish family.

    PubMed

    Gökahmetoğlu, Selma; Ferahbaş, Ayten; Canöz, Özlem

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.

  14. Extensive focal epithelial hyperplasia: case report.

    PubMed

    Durso, Braz Campos; Pinto, José Marcelo Vargas; Jorge, Jacks; de Almeida, Oslei Paes

    2005-11-01

    Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.

  15. Metformin for endometrial hyperplasia: a Cochrane protocol

    PubMed Central

    Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William

    2016-01-01

    Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination

  16. Inflammatory papillary hyperplasia: A systematic review.

    PubMed

    Gual-Vaqués, P; Jané-Salas, E; Egido-Moreno, S; Ayuso-Montero, R; Marí-Roig, A; López-López, J

    2017-01-01

    Inflammatory papillary hyperplasia (IPH) is a benign lesion of the palatal mucosa. It is usually found in denture-wearers but also has been reported in patients without a history of use of a maxillary prosthesis use. The aim of this study is to review the literature to assess the prevalence of denture stomatitis and inflammatory papillary hyperplasia and the etiological factors associated. A search was carried out in PubMed (January 2005 to October 2015) with the key words "inflammatory papillary hyperplasia", "denture stomatitis", "granular stomatitis" and "Newton's type III" The inclusion criteria were studies including at least a sample of 50 apparently healthy patients, articles published from 2005 to 2015 written in English. The exclusion criteria were reviews and non-human studies. Out of the 190 studies obtained initially from the search 16 articles were selected to be included in our systematic review. The prevalence of denture stomatitis was 29.56% and 4.44% for IPH. We found 5 cases of denture stomatitis among non-denture-wearer individuals. All IPH cases were associated with the use of prosthesis. Smoking and continued use of ill-fitting dentures turned out to be the most frequent risk factors for developing IPH. IPH is a rare oral lesion and its pathogenesis still remains unclear. Its presentation among non-denture-wearers is extremely unusual.

  17. Therapeutic strategies to combat neointimal hyperplasia in vascular grafts

    PubMed Central

    Collins, Michael J; Li, Xin; Lv, Wei; Yang, Chenzi; Protack, Clinton D; Muto, Akihito; Jadlowiec, Caroline C; Shu, Chang; Dardik, Alan

    2012-01-01

    Neointimal hyperplasia (NIH) in bypass conduits such as veins and prosthetic grafts is an important clinical entity that limits the long-term success of vascular interventions. Although the development of NIH in the conduits shares many of the same features of NIH that develops in native arteries after injury, vascular grafts are exposed to unique circumstances that predispose them to NIH, including surgical trauma related to vein handling, hemodynamic changes creating areas of low flow, and differences in biocompatibility between the conduit and the host environment. Multiple different approaches, including novel surgical techniques and targeted gene therapies, have been developed to target and prevent the causes of NIH. Recently, the PREVENT trials, the first molecular biology trials in vascular surgery aimed at preventing NIH, have failed to produce improved clinical outcomes, highlighting the incomplete knowledge of the pathways leading to NIH in vascular grafts. In this review, we aim to summarize the pathophysiologic pathways that underlie the formation of NIH in both vein and synthetic grafts and discuss current and potential mechanical and molecular approaches under investigation that may limit NIH in vascular grafts. PMID:22651839

  18. Role of Metabolic Environment on Nitric Oxide Mediated Inhibition of Neointimal Hyperplasia in Type 1 and Type 2 Diabetes

    PubMed Central

    Wang, Zheng; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.

    2014-01-01

    Nitric oxide (NO) is well known to inhibit neointimal hyperplasia following arterial injury. Previously, we reported that NO was more effective at inhibiting neointimal hyperplasia in a type 2 diabetic environment than control. We also found that NO was ineffective in an uncontrolled type 1 diabetic environment; however, insulin restored the efficacy of NO. Thus, the goal of this study was to more closely evaluate the effect of insulin and glucose on the efficacy of NO at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments using different doses of insulin as well as pioglitazone. Type 1 diabetes was induced in male Lean Zucker (LZ) rats with streptozotocin (60mg/kg IP). Groups included control, moderate glucose control, and tight glucose control. Zucker Diabetic Fatty (ZDF) rats fed Purina 5008 chow were used as a type 2 diabetic model. Groups included no therapy, insulin therapy, or pioglitazone therapy. After 4 weeks of maintaining group assignments, the carotid artery injury model was performed. Treatment groups included: control, injury, and injury plus NO. 2 weeks following arterial injury, in the type 1 diabetic rats, NO most effectively reduced the neointimal area in the moderate and tightly controlled groups (81% and 88% vs. 33%, respectively, p=0.01). In type 2 diabetic rats, the metabolic environment had no impact on the efficacy of NO (81%–82% reduction for all groups). Thus, in this study, we show NO is effective at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments. A greater understanding of how the metabolic environment may impact the efficacy of NO may lead to the development of more effective NO-based therapies for patients with diabetes. PMID:24333562

  19. Role of metabolic environment on nitric oxide mediated inhibition of neointimal hyperplasia in type 1 and type 2 diabetes.

    PubMed

    Rodriguez, Monica P; Emond, Zachary M; Wang, Zheng; Martinez, Janet; Jiang, Qun; Kibbe, Melina R

    2014-01-30

    Nitric oxide (NO) is well known to inhibit neointimal hyperplasia following arterial injury. Previously, we reported that NO was more effective at inhibiting neointimal hyperplasia in a type 2 diabetic environment than control. We also found that NO was ineffective in an uncontrolled type 1 diabetic environment; however, insulin restored the efficacy of NO. Thus, the goal of this study was to more closely evaluate the effect of insulin and glucose on the efficacy of NO at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments using different doses of insulin as well as pioglitazone. Type 1 diabetes was induced in male lean Zucker (LZ) rats with streptozotocin (60 mg/kg IP). Groups included control, moderate glucose control, and tight glucose control. Zucker diabetic fatty (ZDF) rats fed Purina 5008 chow were used as a type 2 diabetic model. Groups included no therapy, insulin therapy, or pioglitazone therapy. After 4 weeks of maintaining group assignments, the carotid artery injury model was performed. Treatment groups included: control, injury and injury plus NO. 2 weeks following arterial injury, in the type 1 diabetic rats, NO most effectively reduced the neointimal area in the moderate and tightly controlled groups (81% and 88% vs. 33%, respectively, p=0.01). In type 2 diabetic rats, the metabolic environment had no impact on the efficacy of NO (81-82% reduction for all groups). Thus, in this study, we show NO is effective at inhibiting neointimal hyperplasia in both type 1 and type 2 diabetic environments. A greater understanding of how the metabolic environment may impact the efficacy of NO may lead to the development of more effective NO-based therapies for patients with diabetes.

  20. Arterial insufficiency

    MedlinePlus

    ... is atherosclerosis or "hardening of the arteries." Fatty material (called plaque) builds up on the walls of your arteries. This causes them to become narrow and stiff. As a result, it is hard for blood to flow through your arteries. Blood flow may be suddenly ...

  1. [Primary hyperaldosteronism due to unilateral adrenal hyperplasia with surgical resolution].

    PubMed

    Rubio-Puchol, O; Garzón-Pastor, S; Salom-Vendrell, C; Hernández-Mijares, A

    Unilateral adrenal hyperplasia is a rare cause of primary hyperaldosteronism (around a 3%) that has surgical treatment. A case of a patient with hypertension resistant to conventional therapy in treatment with 7 drugs who presented with primary hyperaldosteronism due to unilateral adrenal hyperplasia is presented. A left adrenalectomy was performed, and the patient had a good clinical response, with no need of any drug after 2 years of surgery. Unilateral adrenal hyperplasia is a different entity and it is not an asymmetric variant of the bilateral adrenal hyperplasia. In the study of patients with primary hyperaldosteronism and imaging tests with absence of adenoma is a diagnosis that must be considered before cataloguing patients with bilateral adrenal hyperplasia and start a medical treatment, because unilateral adrenal hyperplasia would have a surgical resolution.

  2. 18F-FDG-avid brunner gland hyperplasia.

    PubMed

    Park, Seol Hoon; Park, Kwang-Min; Kim, Jae Seung

    2014-08-01

    Brunner gland hyperplasia, a rare duodenal tumor, usually presents with benign features. A 68-year-old man with a history of anemia presented with a polypoid duodenal mass that was detected by CT and esophagogastroduodenoscopy. This mass showed high F-FDG avidity on PET/CT and was histopathologically confirmed as Brunner gland hyperplasia. We suggest that Brunner gland hyperplasia should be considered in the differential diagnosis of F-FDG-avid duodenal tumors.

  3. Unilateral condylar hyperplasia: A case report and review of literature.

    PubMed

    Bharathi, Saravana C; Senthilnathan, S; Kumar, Lokesh D; Mohan, Anand C S; Taranath, M

    2014-01-01

    Condylar hyperplasia is (CH) an uncommon malformation of the mandible involving change in size and morphology of the condylar neck and head. CH is an anomaly that usually occurs unilaterally and equally affects in both men and women. Hyperplasia of the condyle 'differentiated into hemimandibular hyperplasia, hemimandibular elongation and CH. Here, we are presenting a case of 17-year-old male patient with unilateral CH and its review of the literature.

  4. Denture hyperplasia with areas simulating oral inverted ductal papilloma.

    PubMed

    Vargas, Pablo Agustin; Perez, Danyel Elias da Cruz; Jorge, Jacks; Rangel, Ana Lúcia Carrinho Ayrosa; León, Jorge Esquiche; Almeida, Oslei Paes de

    2005-07-01

    Denture hyperplasia is a reactive lesion of the oral mucosa, usually associated to an ill-fitting denture. This lesion is easily diagnosed and in some cases distinct microscopic variations such as osseous, oncocytic and squamous metaplasia may be found. These metaplastic alterations probably are associated with the lymphocytic infiltrate usually present in denture hyperplasia. We present a case of denture hyperplasia containing salivary gland tissue with ductal alterations mimicking an oral inverted ductal papilloma.

  5. Beak-Like Extension of the Pancreatic Uncinate Process on MDCT: Is It Hyperplasia or Movement?

    PubMed

    Omeri, Ahmad Khalid; Matsumoto, Shunro; Kiyonaga, Maki; Takaji, Ryo; Yamada, Yasunari; Mori, Hiromu

    2016-01-01

    We aimed to evaluate the pancreatic uncinate process with a beak-like extension (BLE) beyond the left border of the superior mesenteric artery, to define the cause of BLE, and to differentiate BLE from hyperplasia. We retrospectively reviewed 1042 triple-phase contrast-enhanced multidetector-row computed tomography (3P-CE-MDCT) examinations of 500 patients. Finally, 38 patients (28 men, 10 women; mean age, 66 years) with 140 3P-CE-MDCT images showing BLE were studied regarding BLE size, contour, and cause. The superior mesenteric artery position was also evaluated. Beak-like extensions were found in 7.6% of patients. Most were caused by movement of the small bowel mesentery (n = 21, 55%), with deviation of mesenteric vessels or mass effect from expanded adjacent organs (n = 3, 8%). Seven patients (18.5%) had true hyperplasia. Beak-like extension is caused by movement of the small bowel mesentery with deviation of mesenteric vessels or by adjacent organ expansion. Beak-like extension closely mimics other pathology on nonenhanced MDCT.

  6. Soluble N-cadherin: A novel inhibitor of VSMC proliferation and intimal thickening.

    PubMed

    Lyon, Cressida A; Wadey, Kerry S; George, Sarah J

    2016-03-01

    Reoccurrence of symptoms occurs in 30-50% of coronary artery disease patients receiving vein grafts or bare-metal stents due to intimal thickening (restenosis). Restenosis is caused by vascular smooth muscle cell (VSMC) migration and proliferation. New therapeutic approaches that reduce VSMC migration and proliferation while promoting endothelial cell (EC) coverage are required. We assessed the effect of a soluble form of N-cadherin (SNC-Fc, a fusion of the extracellular portion of N-Cadherin to a mutated Fc fragment of IgG), a cell-cell junction molecule, on human saphenous VSMC proliferation and migration in vitro. We also assessed its effect on intimal thickening in a validated human ex vivo organ culture model. We observed that SNC-Fc significantly inhibited VSMC proliferation and to a lesser extent migration. The anti-proliferative effect of SNC-Fc was mediated by the interaction of SNC-Fc with the FGFR, rather than through inhibition of β-catenin signalling. SNC-Fc also significantly reduced intimal thickening by ~85% in the ex vivo organ culture model. SNC-Fc treatment inhibited proliferation of the intimal cells but did not affect migration. SNC-Fc reduced EC apoptosis, without detrimental effects on EC proliferation and migration in vitro. Importantly SNC-Fc increased EC coverage in the ex vivo model of intimal thickening. In conclusion, we suggest that SNC-Fc may have potential as an anti-proliferative therapeutic agent for reducing restenosis which has no detrimental effects on endothelial cells.

  7. Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization.

    PubMed Central

    Barath, P.; Fishbein, M. C.; Cao, J.; Berenson, J.; Helfant, R. H.; Forrester, J. S.

    1990-01-01

    We used immunohistochemistry to detect tumor necrosis factor (TNF) and in situ hybridization to detect TNF messenger RNA (mRNA) in the intimal mesenchymal-appearing cells and in the medial smooth muscle cells of human atherosclerotic arteries. Medial smooth muscle cells showed localization of immunoreactive TNF on the cell surface and did not express TNF mRNA. Conversely, in intimal mesenchymal-appearing cells, TNF was localized in the cytoplasm and TNF mRNA was expressed by in situ hybridization. Thus 89% of intimal cells were immunohistochemically positive for TNF, 96% of them were positive by in situ hybridization, and 76% were positive for the smooth muscle cell marker, HHF35. Our results suggest that intimal mesenchymal-appearing cells are mostly, but not exclusively, derived from smooth muscle cells. These cells express TNF, whereas the medial smooth muscle cells in the atherosclerotic human arteries do not. The expression of TNF by these mesenchymal-appearing cells may have implications regarding the evolution of the atherosclerotic plaque. Images Figure 1 to Figure 4 Figure 3 PMID:1698022

  8. Risk Recognition and Intimate Partner Violence

    ERIC Educational Resources Information Center

    Witte, Tricia H.; Kendra, Rachel

    2010-01-01

    The objective of this study was to determine whether female victims of physical forms of intimate partner violence (IPV) displayed deficits in risk recognition, or the ability to detect danger, in physically violent dating encounters. A total of 182 women watched a video depicting a psychologically and physically aggressive encounter between…

  9. Intimate Debate Technique: Medicinal Use of Marijuana

    ERIC Educational Resources Information Center

    Herreid, Clyde Freeman; DeRei, Kristie

    2007-01-01

    Classroom debates used to be familiar exercises to students schooled in past generations. In this article, the authors describe the technique called "intimate debate". To cooperative learning specialists, the technique is known as "structured debate" or "constructive debate". It is a powerful method for dealing with case topics that involve…

  10. Risk Recognition and Intimate Partner Violence

    ERIC Educational Resources Information Center

    Witte, Tricia H.; Kendra, Rachel

    2010-01-01

    The objective of this study was to determine whether female victims of physical forms of intimate partner violence (IPV) displayed deficits in risk recognition, or the ability to detect danger, in physically violent dating encounters. A total of 182 women watched a video depicting a psychologically and physically aggressive encounter between…

  11. Power and Dependence in Intimate Exchange

    ERIC Educational Resources Information Center

    van de Rijt, Arnout; Macy, Michael W.

    2006-01-01

    A division of labor is mediated by exchange of valued goods and services. We use social exchange theory to extend this principal to "labors of love." Sexual activity in a close personal relationship seems outside the domain of bargaining and exchange. Nevertheless, we explore the possibility that this most intimate of human relations is influenced…

  12. Subtyping Male Perpetrators of Intimate Partner Violence

    ERIC Educational Resources Information Center

    Fowler, Katherine A.; Westen, Drew

    2011-01-01

    Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…

  13. Power and Dependence in Intimate Exchange

    ERIC Educational Resources Information Center

    van de Rijt, Arnout; Macy, Michael W.

    2006-01-01

    A division of labor is mediated by exchange of valued goods and services. We use social exchange theory to extend this principal to "labors of love." Sexual activity in a close personal relationship seems outside the domain of bargaining and exchange. Nevertheless, we explore the possibility that this most intimate of human relations is influenced…

  14. Physical Health Effects of Intimate Partner Abuse

    ERIC Educational Resources Information Center

    Sillito, Carrie LeFevre

    2012-01-01

    Although intimate partner violence has been recognized as both a social problem and health issue, the extent to which it is a health issue for both males and females in the general population is largely unknown. This longitudinal research uses data from the National Survey of Family and Households (1987-2003). Random effects logistic regression…

  15. Intimate Relationships of Female International Students

    ERIC Educational Resources Information Center

    Popadiuk, Natalee E.

    2008-01-01

    Five female international students studying at a western Canadian university were interviewed about their experiences of being in a difficult intimate heterosexual relationship. An in-depth interpretive analysis revealed that, according to the participants, these relational struggles influenced their adjustment to the host culture. Implications…

  16. Gender Symmetry, Sexism, and Intimate Partner Violence

    ERIC Educational Resources Information Center

    Allen, Christopher T.; Swan, Suzanne C.; Raghavan, Chitra

    2009-01-01

    This study of a predominantly Hispanic sample of 92 male and 140 female college students examines both gender symmetry in intimate partner violence (IPV) and inconsistent relationships found in previous studies between sexist attitudes and IPV. Results indicate that although comparable numbers of men and women perpetrate and are victimized in…

  17. Intimate Partner Violence in Older Women

    ERIC Educational Resources Information Center

    Bonomi, Amy E.; Anderson, Melissa L.; Reid, Robert J.; Carrell, David; Fishman, Paul A.; Rivara, Frederick P.; Thompson, Robert S.

    2007-01-01

    Purpose: We describe the prevalence, types, duration, frequency, and severity of intimate partner violence ("partner violence") in older women. Design and Methods: We randomly sampled a total of 370 English-speaking women (65 years of age and older) from a health care system to participate in a cross-sectional telephone interview. Using 5…

  18. Subtyping Male Perpetrators of Intimate Partner Violence

    ERIC Educational Resources Information Center

    Fowler, Katherine A.; Westen, Drew

    2011-01-01

    Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male…

  19. Intimate Debate Technique: Medicinal Use of Marijuana

    ERIC Educational Resources Information Center

    Herreid, Clyde Freeman; DeRei, Kristie

    2007-01-01

    Classroom debates used to be familiar exercises to students schooled in past generations. In this article, the authors describe the technique called "intimate debate". To cooperative learning specialists, the technique is known as "structured debate" or "constructive debate". It is a powerful method for dealing with case topics that involve…

  20. "The Intimate Machine"--30 Years On

    ERIC Educational Resources Information Center

    Frude, Neil; Jandric, Petar

    2015-01-01

    This conversation focuses on a book published in 1983 that examined "animism," the tendency to regard non-living entities as living and sentient. "The Intimate Machine" suggested that animism will be fully exploited by artificial intelligence (AI) and robotics, generating artefacts that will engage the user in…

  1. Physical Health Effects of Intimate Partner Abuse

    ERIC Educational Resources Information Center

    Sillito, Carrie LeFevre

    2012-01-01

    Although intimate partner violence has been recognized as both a social problem and health issue, the extent to which it is a health issue for both males and females in the general population is largely unknown. This longitudinal research uses data from the National Survey of Family and Households (1987-2003). Random effects logistic regression…

  2. "The Intimate Machine"--30 Years On

    ERIC Educational Resources Information Center

    Frude, Neil; Jandric, Petar

    2015-01-01

    This conversation focuses on a book published in 1983 that examined "animism," the tendency to regard non-living entities as living and sentient. "The Intimate Machine" suggested that animism will be fully exploited by artificial intelligence (AI) and robotics, generating artefacts that will engage the user in…

  3. Intimate Relationships of Female International Students

    ERIC Educational Resources Information Center

    Popadiuk, Natalee E.

    2008-01-01

    Five female international students studying at a western Canadian university were interviewed about their experiences of being in a difficult intimate heterosexual relationship. An in-depth interpretive analysis revealed that, according to the participants, these relational struggles influenced their adjustment to the host culture. Implications…

  4. Effective Listening: Key to Intimate Communication.

    ERIC Educational Resources Information Center

    Seiquist, Jack

    Intended for those who teach dyadic communication, this paper argues that each partner in an intimate relationship has two primary communication needs: (1) to listen, look at, and pay attention to the "self" in order to attain clear awareness as a source of information for self-disclosure; and (2) to listen, look at, and pay attention to…

  5. Gender Symmetry, Sexism, and Intimate Partner Violence

    ERIC Educational Resources Information Center

    Allen, Christopher T.; Swan, Suzanne C.; Raghavan, Chitra

    2009-01-01

    This study of a predominantly Hispanic sample of 92 male and 140 female college students examines both gender symmetry in intimate partner violence (IPV) and inconsistent relationships found in previous studies between sexist attitudes and IPV. Results indicate that although comparable numbers of men and women perpetrate and are victimized in…

  6. Intimate Partner Violence and Belief Systems in Liberia

    ERIC Educational Resources Information Center

    Allen, Mary; Devitt, Catherine

    2012-01-01

    Intimate partner violence is endemic in parts of the African continent. A small scale survey (n = 229) was conducted in 2009 in Northern Liberia, West Africa, to determine the prevalence and nature of intimate partner violence, and the cultural beliefs and gender norms that underpin respondent experiences and views towards intimate partner…

  7. Intimate Partner Violence and Belief Systems in Liberia

    ERIC Educational Resources Information Center

    Allen, Mary; Devitt, Catherine

    2012-01-01

    Intimate partner violence is endemic in parts of the African continent. A small scale survey (n = 229) was conducted in 2009 in Northern Liberia, West Africa, to determine the prevalence and nature of intimate partner violence, and the cultural beliefs and gender norms that underpin respondent experiences and views towards intimate partner…

  8. Association of adrenal medullar and cortical nodular hyperplasia: a report of two cases with clinical and morpho-functional considerations.

    PubMed

    Valdés, Gloria; Roessler, Eric; Salazar, Iván; Rosenberg, Helmar; Fardella, Carlos; Martínez, Pedro; Velasco, Alfredo; Velasco, Soledad; Orellana, Pilar

    2006-12-01

    Arterial hypertension of adrenal etiology is mainly attributed to primary hyperaldosteronism. However, subtle expressions of hyperadrenergic or glucocorticoid excess can also generate arterial hypertension. The present report describes two hypertensive patients cataloged as resistant essential hypertensives, in whom adrenal masses were found incidentally, who highlight the need to recognize these tenuous clinical or laboratory presentations. Case 1 was a 50-yr-old female with hyperadrenergic hypertension associated to a left adrenal node, normal cortisol and aldosterone:renin ratio, marginally increased urinary normetanephrine, and a positive 131I MIBG radioisotope scan. Adrenalectomy normalized blood pressure and urinary metanephrines. Pathology showed a hyperplastic adrenal medulla associated to a multinodular cortical hyperplasia. Case 2 was a 62- yr-old female with progressive hypertension, a slight Cushing phenotype, non-suppressible hypercortisolism, normal urinary metanephrines, and bilateral adrenal nodes. Bilateral adrenalectomy and subsequent replacement normalized blood pressure and phenotypic stigmata. Pathology demonstrated bilateral cortical multinodular hyperplasia and medullary hyperplasia. The clinical study in both patients was negative for MEN. The apparently rare association of cortical and medullary lesions presented by both patients is probably overlooked in routine pathology exams, but should be meticulously searched since the crosstalk between the adrenal cortex and medulla may prompt dual abnormalities.

  9. Computational estimation of fluid mechanical benefits from a fluid deflector at the distal end of artificial vascular grafts.

    PubMed

    Roos, M W; Wadbro, E; Berggren, M

    2013-02-01

    Intimal hyperplasia at the distal anastomosis is considered to be an important determinant for arterial and arteriovenous graft failure. The connection between unhealthy hemodynamics and intimal hyperplasia motivates the use of computational fluid dynamics modeling to search for improved graft design. However, studies on the fluid mechanical impact on intimal hyperplasia at the suture line intrusion have previously been scanty. In the present work, we focus on intimal hyperplasia at the suture line and illustrate potential benefits from the introduction of a fluid deflector to shield the suture line from unhealthily high wall shear stress.

  10. Men who use violence: intimate violence versus non-intimate violence profiles.

    PubMed

    Lawson, David M; Weber, Deborah; Beckner, Helen Minnette; Robinson, Lori; Marsh, Neal; Cool, Angela

    2003-06-01

    The current study examined the differences between three types of violent men based on Holtzworth-Munroe and Stuart's (1994) tripartite typology and a group of non-intimate violent men. First, a cluster analysis was conducted on a sample of 91 domestically violent men, resulting in three clusters that approximated the tripartite model for psychopathology as measured by the MMPI-2, that is, non-pathological, borderline/dysphoric, and antisocial. Based on the violence variables (i.e., severity of violence, family-only violence, and exposure to family of origin violence) only severity of violence approximated what would be expected across the three clusters, that is, the less the psychopathology, the less severe the violence. The other two violence variables had approximate frequencies/percentages of occurrence that would be expected for individual typologies with some but not all three typologies. In comparing the three intimate violent typologies to the non-intimate violent group, the non-intimate and non-pathological groups were within normal limits and did not differ significantly on any of the MMPI-2 scales. These non-intimate and non-pathological groups differed significantly from the antisocial and borderline/dysphoric groups on all the scales that defined the psychopathology of these two groups. On the violence variables, the non-intimate groups reported significantly less severe violence than the borderline/dysphoric and antisocial groups.

  11. Acute arterial occlusion - kidney

    MedlinePlus

    Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...

  12. Inflammatory papillary hyperplasia: A systematic review

    PubMed Central