Air pollution and antibodies against modified lipoproteins are associated with atherosclerosis and vascular remodeling in hyperlipemic mice

We analyzed the impact of chronic exposure to urban air pollution on the development of atherosclerosis. Hyperlipemic mice (LDLR(-/-)) were submitted to a high fat diet and air pollution for four months. We measured the susceptibility of LDL to oxidative modifications (TBARS), the presence of anti-oxLDL and an apoB-derived peptide (apoB-D) in blood and the degree of atherosclerosis in the aortic arch. Air pollution increased the susceptibility of LDL to oxidation as well as anti-oxLDL and anti-apo-B levels. These levels were even higher than in mice submitted to a high fat diet and non-polluted air. The lipid content of the atherosclerotic plaques in the aorta was increased in groups with a high cholesterol diet independently of the air quality. However, the thickness of the arterial wall was greater in mice fed a high lipid diet with polluted air. Thus, we conclude that urban air pollution exacerbates the susceptibility of LDL to oxidation, atherogenesis and vascular remodeling in hyperlipemic mice and that an immune response accompanies this process. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Long-Term Pulmonary Vascular Reactivity After Orthotopic Heart Transplantation by the Biatrial Versus the Bicaval Technique

Introduction. Advantages of the bicaval versus the biatrial technique have been reported, emphasizing atrial electrical stability and less tricuspid regurgitation. Objective. To analyze the impact of the surgical technique on long-term pulmonary pressures, contractility, and graft valvular behavior after heart transplantation. Methods. Among 400 orthotopic heart transplantation recipients from 1985 to 2010, we selected 30 consecutive patients who had survived beyond 3 years. The biatrial versus bicaval surgical technique groups included 15 patients each. Their preoperative clinical characteristics were similar. None of the patients displayed a pulmonary vascular resistance or pulmonary artery pressure over 6U Wood or 60 mm Hg, respectively. We evaluated invasive hemodynamic parameters during routine endomyocardial biopsies. Two-dimensional echocardiographic parameters were obtained from routine examinations. Results. There were no significant differences regarding right atrial pressure, systolic pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, systolic blood pressure, left ventricular ejection fraction, and mitral regurgitation (P > .05). Tricuspid regurgitation increased significantly over the 3 years of observation only among the biatrial group (P = .0212). In both groups, the right atrial pressure, pulmonary wedge capillary pressure, transpulmonary gradient, and pulmonary vascular resistance decreased significantly (P < .05) from the pre- to the postoperative examination. In both groups cardiac index and systemic blood pressure increased significantly after transplantation (P < .05). Comparative analysis of the groups only showed significant differences regarding right atrial pressure and degree of tricuspid regurgitation; the bicaval group showing the best performance. Conclusions. Both surgical techniques ensure adequate left ventricular function in the long term; however, the bicaval technique provided better trends in hemodynamic performance, as well as a lower incidence and severity of tricuspid valve dysfunction.

Intramyocardial transplantation of fibroblasts expressing vascular endothelial growth factor attenuates cardiac dysfunction

In this study, we analyzed whether transplantation of cardiac fibroblasts (CFs) expressing vascular endothelial growth factor (VEGF) mitigates cardiac dysfunction after myocardial infarction (MI) in rats. First, we observed that the transgene expression lasts longer (45 vs 7 days) when fibroblasts are used as vectors compared with myoblasts. In a preventive protocol, induction of cardiac neovascularization accompanied by reduction in myocardial scar area was observed when cell transplantation was performed 1 week before ischemia/reperfusion and the animals analyzed 3 weeks later. Finally, the therapeutic efficacy of this approach was tested injecting cells in a fibrin biopolymer, to increase cardiac retention, 24 h post-MI. After 4 weeks, an increase in neovascularization and a decrease in myocardial collagen were observed only in rats that received cells expressing VEGF. Basal indirect or direct hemodynamic measurements showed no differences among the groups whereas under pharmacological stress, only the group that received cells expressing VEGF showed a significant reduction in end-diastolic pressure and improvement in stroke volume and cardiac work. These results indicate that transplantation of CFs expressing VEGF using fibrin biopolymer induces neovascularization and attenuates left ventricle fibrosis and cardiac dysfunction in ischemic heart. Gene Therapy (2010) 17, 305-314; doi:10.1038/gt.2009.146; published online 10 December 2009

Improved detection of incipient vascular changes by a biotechnological platform combining post mortem MRI in situ with neuropathology

The histopathological counterpart of white matter hyperintensities is a matter of debate. Methodological and ethical limitations have prevented this question to be elucidated. We want to introduce a protocol applying state-of-the-art methods in order to solve fundamental questions regarding the neuroimaging-neuropathological uncertainties comprising the most common white matter hyperintensities [WMHs] seen in aging. By this protocol, the correlation between signal features in in situ, post mortem MRI-derived methods, including DTI and MTR and quantitative and qualitative histopathology can be investigated. We are mainly interested in determining the precise neuroanatomical substrate of incipient WMHs. A major issue in this protocol is the exact co-registration of small lesion in a tridimensional coordinate system that compensates tissue deformations after histological processing. The protocol is based on four principles: post mortem MRI in situ performed in a short post mortem interval, minimal brain deformation during processing, thick serial histological sections and computer-assisted 3D reconstruction of the histological sections. This protocol will greatly facilitate a systematic study of the location, pathogenesis, clinical impact, prognosis and prevention of WMHs. (C) 2009 Elsevier B.V. All rights reserved.

Adult rats are more sensitive to the vascular effects induced by hyperhomocysteinemia than young rats

We aimed to investigate the vascular effects of hyperhomocysteinemia (HHcy) on carotid arteries from young and adult rats. With this purpose young and adult rats received a solution of DL-homocysteine-thiolactone (1 g/kg body weight/day) in the drinking water for 7, 14 and 28 days. Increase on plasma homocysteine occurred in young and adult rats treated with DL-homocysteine-thiolactone in all periods. Vascular reactivity experiments using standard muscle bath procedures showed that HHcy enhanced the contractile response of endothelium-intact, carotid rings to phenylephrine in both young and adult rats. However, in young rats, the increased phenylephrine-induced contraction was observed after hyperhomocysteinemia for 14 and 28 days, whereas in adult rats this response was already apparent after 7 day treatment. HHcy impaired acetylcholine-induced relaxation in arteries from adult but not young rats. The contraction induced by phenylephrine in carotid arteries in the presence of Y-27632 was reversed to control values in arteries from young but not adult rats with hyperhomocysteinemia. HHcy did not alter the contraction induced by CaCl(2) in carotid arteries from young rats, but enhanced CaCl(2)-induced contraction in the arteries from adult rats. HHcy increased the basal levels of superoxide anion in arteries from both groups. Finally, HHcy decreased the basal levels of nitrite in arteries from adult but not young rats. The major new finding of the present work is that arteries from young rats are more resistant to vascular changes evoked by HHcy than arteries from adult rats. Also, we verified that the enhanced vascular response to phenylephrine observed in carotid arteries of DL-homocysteine thiolactone-treated rats is mediated by different mechanisms in young and adult rats. (C) 2010 Published by Elsevier Inc.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

Vieira RP, de Andrade VF, Duarte AC, dos Santos AB, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR. Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol 295: L670-L679, 2008. First published August 29, 2008; doi: 10.1152/ajplung.00465.2007.-Recent evidence suggests that asthma leads to inflammation and remodeling not only in the airways but also in pulmonary vessels and parenchyma. In addition, some studies demonstrated that aerobic training decreases chronic allergic inflammation in the airways; however, its effects on the pulmonary vessels and parenchyma have not been previously evaluated. Our objective was to test the hypothesis that aerobic conditioning reduces inflammation and remodeling in pulmonary vessels and parenchyma in a model of chronic allergic lung inflammation. Balb/c mice were sensitized at days 0, 14, 28, and 42 and challenged with ovalbumin ( OVA) from day 21 to day 50. Aerobic training started on day 21 and continued until day 50. Pulmonary vessel and parenchyma inflammation and remodeling were evaluated by quantitative analysis of eosinophils and mononuclear cells and by collagen and elastin contents and smooth muscle thickness. Immunohistochemistry was performed to quantify the density of positive cells to interleukin (IL)-2, IL-4, IL-5, interferon-gamma, IL-10, monocyte chemotatic protein (MCP)-1, nuclear factor (NF)-kappa B p65, and insulin-like growth factor (IGF)-I. OVA exposure induced pulmonary blood vessels and parenchyma inflammation as well as increased expression of IL-4, IL-5, MCP-1, NF-kappa B p65, and IGF-I by inflammatory cells were reduced by aerobic conditioning. OVA exposure also induced an increase in smooth muscle thickness and elastic and collagen contents in pulmonary vessels, which were reduced by aerobic conditioning. Aerobic conditioning increased the expression of IL-10 in sensitized mice. We conclude that aerobic conditioning decreases pulmonary vascular and parenchymal inflammation and remodeling in this experimental model of chronic allergic lung inflammation in mice.

Reprocessing and reuse of single-use medical devices used during hemodynamic procedures in Brazil: A widespread and largely overlooked problem

Background. Several medical devices used during hemodynamic procedures, particularly angiographic diagnostic and therapeutic cardiac catheters, are manufactured for single use only. However, reprocessing and reuse of these devices has been reported, to determine the frequency of reuse and reprocessing of single-use medical devices used during hemodynamic procedures in Brazil and to evaluate how reprocessing is performed. Design. National survey, conducted from December 1999 to July 2001. Methods. Most of the institutions affiliated with the Brazilian Society of Hemodynamic and Interventional Cardiology were surveyed by use of a questionnaire sent in the mail. Results. The questionnaire response rate was 50% (119 of 240 institutions). Of the 119 institutions that responded, 116 (97%) reported reuse of single-use devices used during hemodynamic procedures, and only 26 (22%) reported use of a standardized reprocessing protocol. Cleaning, flushing, rinsing, drying, sterilizing and packaging methods varied greatly and were mostly inadequate. Criteria for discarding reused devices varied widely. Of the 119 institutions that responded, 80 (67%) reported having a surveillance system for adverse events associated with the reuse of medical devices, although most of these institutions did not routinely review the data, and only 38 (32%) described a training program for the personnel who reprocessed single-use devices. Conclusions. The reuse of single-use devices used during hemodynamic procedures was very frequent in hospitals in Brazil. Basic guidance on how to reuse and reprocess single-use medical devices is urgently needed, because, despite the lack of studies to support reusing and reprocessing single-use medical devices, such devices are necessary in limited-resource areas in which these practices are current.

Markers of vascular differentiation, proliferation and tissue remodeling in juvenile nasopharyngeal angiofibromas

Juvenile nasopharingeal angiofibroma (JNA) is a histologically benign locally aggressive tumor characterized by irregular vessels embedded. in a fibrous stroma. Excessive vascularity results in bleeding complications, and the inhibition of angiogenesis is a promising strategy for managing extensive JNA tumors. To better characterize the endothelial components of JNA, we aimed to evaluate markers of vascular differentiation and proliferation, such as friend leukemia integration-1 (FLI-1) and endoglin, lymphatic markers, including podoplanin and vascular endothelial growth factor receptor 3 (VEGFR3) and its cognate ligand VEGFC, GLUT-1, a diagnostic marker that discriminates between hemangiomas and vascular malformations, and two markers of tissue remodeling, stromelysin 3 (ST3) and secreted acid protein rich in cysteine (SPARC). Antigens were assessed immunohistochemically in vessels and stromal cells of JNA archival cases (n=22). JNA endothelial cells were positive for endoglin, VEGFC and FLI-1, whereas podoplanin and VEGFR3 were negative in all cases. Both endothelial cells and fibroblasts stained for ST3 and SPARC. GLUT-1 was investigated in JNA cases, in infantile hemangiomas (n=123) and in vascular malformations (n=135) as controls. JNAs and vascular malformations were GLUT-1-negative, while hemangiomas showed positive staining. The presence of markers of endothelial differentiation and proliferation highlighted the hyper-proliferative state of JNA vessels. The absence of podoplanin and VEGFR3 underscores their blood endothelial cell characteristic. The absence of GLUT-1 discriminates JNAs from hemangiomas. ST3 and SPARC up-regulation in endothelial cells and fibroblasts may contribute to a compensatory signaling for controlling angiogenesis. Some of these markers may eventually serve as therapeutic targets. Our results may aid in the understanding of JNA pathophysiology.

Comparison of Quantitative Imaging Devices and Subjective Optic Nerve Head Assessment by General Ophthalmologists to Differentiate Normal From Glaucomatous Eyes

Purpose: To compare the ability of Subjective assessment of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) by general ophthalmologists and by a glaucoma expert with objective measurements by optical coherence tomography (Stratus OCT, Carl Zeiss Meditec Inc), confocal scanning laser ophthalmoscope (HRT III; Heidelberg Engineering, Heidelberg. Germany), and scanning laser polarimetry (GDx enhanced corneal compensation; Carl Zeiss Meditec Inc, Dublin, CA) in discriminating glaucomatous and normal eyes. Methods: Sixty-one glaucomatous and 57 normal eyes or 118 subjects Were included in the study. Three independent general ophthalmologists and I glaucoma expert evaluated ONH stereo-photographs. Receiver operating characteristic curves were constructed for each imaging technique and sensitivity at fixed specificity was estimated. Comparisons or areas under these curves (aROCs) and agreement (k) were determined between stereophoto grading and best parameter from each technique. Results: Best parameter from each technique showed larger aROC (Stratus OCT RNFL 0.92; Stratus OCT ONH vertical integrated area = 0.86; Stratus OCT macular thickness = 0.82; GDx enhanced corneal compensation = 0.91, HRT3 global cup-to-disc ratio = 0.83; HRT3 glaucoma probability score numeric area score 0.83) compared with stereophotograph grading by general ophthalmologists (0.80) in separating glaucomatous and normal eyes. Glaucoma expert stereophoto grading provided equal or larger aROC (0.92) than best parameter of each computerized imaging device. Stereophoto evaluated by a glaucoma expert showed better agreement with best parameter of each quantitative imaging technique in classifying eyes either as glaucomatous or normal compared with stereophoto grading by general ophthalmologists, The combination Of Subjective assessment of the optic disc by general ophthalmologists with RNFL objective parameters improved identification of glaucoma patients in a larger proportion than the combination of these objective parameters with Subjective assessment of the optic disc by a glaucoma expert (29.5% vs. 19.7%, respectively). Conclusions: Diagnostic ability of all imaging techniques showed better performance than subjective assessment of the ONH by general ophthalmologists, but not by It glaucoma expert, Objective RNFL measurements may provide improvement in glaucoma detection when combined with subjective assessment of the optic disc by general ophthalmologists or by a glaucoma expert.

Vascular endothelial growth factor and beta-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

Objective: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and beta-hCG and to assess its predictive value. Design: Prospective study. Setting: Tertiary care university hospital. Patient(s): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and beta-hCG serum concentrations on the day of surgery. Result(s): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and beta-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s): Maternal serum VEGF and beta-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall. (Fertil Steril (R) 2010;94:1595-600. (C) 2010 by American Society for Reproductive Medicine.)

Biofilm formation on intrauterine devices in patients with recurrent vulvovaginal candidiasis

A biofilm is a complex community of surface-associated cells enclosed in a polymer matrix. They attach to solid surfaces and their formation can be affected by growth conditions and co-infection with other pathogens. The presence of biofilm may protect the microorganisms from host defenses, as well as significantly reduce their susceptibility to antifungal agents. Pathogenic microbes can form biofilms on the inert surfaces of implanted devices such as catheters, prosthetic cardiac valves and intrauterine devices (IUDs). The present study was carried out to analyze the presence of biofilm on the surface of intrauterine devices in patients with recurrent vulvovaginal candidiasis, and to determine the susceptibility profile of the isolated yeasts to amphotericin B and fluconazole. Candida albicans was recovered from the IUDs and it was found to be susceptible to the antifungal agents when tested under planktonic growing conditions. These findings indicate the presence of the biofilm on the surface of the IUD as an important risk factor for recurrent vulvovaginal candidiasis.

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum

Objective: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium. and in three different sites of endometriosis: the ovary, bladder, and rectum. Design: Prospective study. Setting: University hospital. Patient(s): Thirty women with endometriosis (10 ovarian, 1.0 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). Intervention(s): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. Main Outcome Measure(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. Result(s): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. Conclusion(s): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.

Vascular diseases and old age mental disorders: an update of neuroimaging findings

Purpose of review To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer`s disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. Recent findings Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. Summary As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Collagen V and vascular injury promote lung architectural changes in systemic sclerosis

Background: Systemic sclerosis (SSc) is a multisystem disorder characterized by inflammation, fibrosis and vascular damage. The aim of this study was to evaluate the interactions between basement membrane disruption, endothelial injury and collagen V deposition on the vascular wall, as well as their association with pulmonary function tests in patients with SSc. Method: The endothelial apoptosis was assessed by TUNEL and electron microscopy, and quantified through the point-counting technique. To evaluate basement membrane integrity, laminin immunostaining and electron microscopy were used. Immunofluorescence and morphometric analysis were used to determine the amount of collagen V in the vascular walls in 23 open lung biopsies of patients with SSc without pulmonary hypertension. Normal lung tissue was obtained from five individuals who had died of traumatic injuries. Results: The apoptosis index in SSc was higher in the endothelial cells (13.83 +/- 6.83) when compared with the control (2.51 +/- 2.06) group (P < 0.001) and confirmed by electron microscopy. We observed an important disruption of the basement membrane on the vascular wall shown by discontinuous laminin immunostaining and electron microscopy. An increase in collagen V on the vascular wall of the SSc group was observed (45.28 +/- 13.21), when compared with control group (22.90 +/- 4.13, P < 0.001), and this difference was statistically significant. An inverse correlation was found between vital capacity, forced vital capacity, forced expiratory volume in 1 s, vascular collagen V and endothelial apoptosis (P < 0.05). Conclusions: We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential. Please cite this paper as: Parra ER, Aguiar AC Jr, Teodoro WR, de Souza R, Yoshinari NH and Capelozzi VL. Collagen V and vascular injury promote lung architectural changes in systemic sclerosis. The Clinical Respiratory Journal 2009; 3: 135-142.

Nodules Less Than 20 mm and Vascular Invasion are Predictors of Survival in Small Hepatocellular Carcinoma

Background: The aims of this study were to analyze the overall survival of patients with cirrhosis and small hepatocellular carcinoma (HCC) and identify independent pretreatment predictors of survival in Brazil. Methods: Between 1998 and 2003, 74 patients with cirrhosis and small HCC were evaluated. Predictors of survival were identified using the Kaplan-Meier survival curves and the Cox model. Results: The overall survival rates were 80%, 41%, and 17% at 12, 36, and 60 months, respectively. The mean length of follow-up after HCC diagnosis was 23 months (median 22 mo, range: I to 86 mo) for the entire group. Univariate analysis showed that model for endstage liver disease (MELD) score (P = 0.016), Child-Pugh classification (P = 0.007), alpha-fetoprotein level (P = 0.006), number of nodules (P = 0.041), tumor diameter (P = 0.009), and vascular invasion (P < 0.0001) were significant predictors Of Survival. Cox regression analysis identified vascular invasion (relative risk = 14.60, confidence interval 95% = 3.3-64.56, P < 0.001) and tumor size > 20 mm (relative risk = 2.14, confidence interval 95% = 1.07-4.2, P = 0.030) as independent predictors of decreased survival. Treatment of HCC was related to increased overall survival. Conclusions: Identification of HCC smaller than 20 mm is associated with longer survival. Presence of vascular invasion, even in small tumors, maybe associated with poor prognosis. Treatment of small tumors Of LIP to 20 mm diameter is related to increased survival.